People's Democratic Republic of Algeria

Ministry of Higher Education and Scientific Research

Mentouri University Constantine

Faculty of Natural Sciences and Life
Department of Natural Sciences and Life

N° d’ordre
N° de série

Markers for side complications among diabetic

mellitus patients

Submitted for the degree of Doctorat d'état in

Animal Biology and Physiology

Thesis presented by
Salah Attalah

Approval Sheet

President Prof. Zahia MERAIHI (University of Mentouri, Constantine)

Supervisor Prof. Ahmed M. IBRAHIM (National Research Centre, Egypt)

Co-Supervisor Prof. Cherifa BENLETRECHE (CHU Ibn Badis, Constantine)

Examiner Dr. Aicha MECHAKRA (University of Mentouri, Constantine)

Examiner Prof. Cherif ABDENNOUR (University of Badji Mokhtar, Annaba)

Examiner Prof. Saad SAKA (University of Badji Mokhtar, Annaba)

- 2007 -
 Acknowledgments
First, my gratitude and thanks should be submitted to "THE GOD" for
his kind support witch is in every success in my life.

I wish to express my deepest thanks and gratitude to the late Prof.

Mohamed Fathi El-Howary, Prof. of Biochemistry, National Research Centre,
for suggesting the topic of this work.

I wish to express my sincere thanks and gratitude to Prof. Ahmed

Mohamed Ibrahim, Prof. of Biochemistry, National Research Centre, for his
continuous advice, sincere supervisions help and encouragement throughout the
practical work and during the writing of the manuscript.

I wish to express my profoundly gratitude to Prof. Ben Latreche Chrifa,

Prof of Biochemistry , Hospital Centre University, Laboratory of Biochemistry ,
Ibn Badiss, Constantine, Algeria, for her kind supervision, guidance, continuous
advice, help and encouragement throughout the practical work.

I wish to express my deepest thanks and gratitude to Dr. Mamdouh AIi,

Ass, Prof. of Biochemistry, National Research Centre, for his support and for his
sincere help and encouragement, and sincere advices.

I am greatly indebted and grateful to Prof Abdelmohsen Saber Isamail,

Prof. of Biochemistry, National Research Centre, for his encouragement, and
sincere advices.

Deepest gratitude is indebted to the National Research Centre, and the

Institute of Diabetes, Ministry of Heath, Cairo, for the facilities that enabled
me to do this work.

Last but not least, I wish to express my deep gratitude to my wife for her
sacrifice and immolation, also for her constant help and sincere encouragement,
am really indebted for her. Also, I express my deep gratitude to my parents and
all family for the excellent efforts through the thesis preparation.

Lastly, I am grateful to all patients who shared in this study to whom I am

greatly indebted.
 ABSTRACT
Diabetes mellitus is a common metabolic disorder affecting the metabolism of
carbohydrate, lipids, proteins and enzymes activities. The purpose of this study is to
determine if the pancreatic or liver and kidney function tests are changed in diabetic patients
with or without ketosis and whether ketosis show any evidence of pancreatitis in juvenile or
adult diabetic patients. For this reason three groups of diabetic patients associated with
either ketotic or non-ketotic condition were selected and investigated.
60 diabetic patients were chosen for investigations on liver and pancreatic function
tests for serum GOT, GPT, ALP, lipase, and amylase enzymes. Kidney function tests were
also assed for blood urea, and serum creatinine. Serum total protein and protein fractions
were also studied. In addition, correlation of such finding with age, sex, ketotic state and type
of diabetics have been investigated.
Although many biochemical parameters are now available, investigations of diabetic patients
with pancreatic disease, yet any one of them alone was found unsatisfactory.
From our data, we concluded, the increased lipase and amylase activities are good
indicators for the diagnostic of tissue injury (pancreatitis), particularly in juvenile diabetic
patients associated with ketosis as compared to diabetic patients without ketosis.

Other 85 diabetic patients were also chosen for serum total lipids, triglycerides, free
fatty acids, cholesterol and phospholipids. In all diabetics, the mean value of serum total
lipids was significantly increased as compared to the control. In both ketotic and non-ketotic
females, the level of serum cholesterol was significantly increased while in males the level
was insignificantly increased as compared to control. Furthermore, serum triglyceride level
was significantly increased in both sexes of the ketotic than in the non-ketotic and the control.
In both sexes the serum triglyceride level, which showed high value in poorly-controlled
patients, revealed normal value with the proper control of blood glucose level by insulin
treatment. Thus, our results showed increased level of free fatty acids in all groups as
compared to the corresponding control.
Also, we concluded that the elevation of individual lipid components is very important to
be analyzed regularly in order to follow the modulation of risk condition in diabetic patients.
A great interest, also, to follow up the abnormal lipid metabolism to avoid any metabolic
complication.
115 Juvenile and adult diabetic patients were also subjected for urine protein
investigation by gel electrophoresis and the immunoelectrophoresis. The obtained results
were correlated with age, disease duration, sex and treatment type. In patients with diabetes
for less than 5 years and proteinuria not more than 100 mg/dl, albumin, transferrin and
ceruloplasmin were the protein components mostly excreted in urine and the proteinuria in
such cases was described as selective. In patients with diabetes of more than 5 years and
proteinuria exceeding 100 mg/dl, additional relatively high molecular weight proteins
including IgA and IgG were detected and the proteinuria in such cases can be considered as
non selective.
From the previous results, it can be concluded that, selective proteinuria was
encountered in young males as well as the same number of young females at the same age,
whereas the non-selective proteinuria seems to be of higher frequency among adult females
than adult males, and it can be considered as a sign of advanced nephritic status that would
require much more intensive medical care.

Key words: Diabetic ketoacidosis, NIDDM, IDDM, Juvenile diabetique, pancreatitis,

proteiuria, Selective, Non-selective, Nephropathy.
 CONTENTS

ABSTRACT PAGE

I CHAPTER I

INTRODUCTION AND AIM OF WORK 1

LITERATURE REVIEW 3
I-1 DIABETES MELLITUS 3
I-1.1 Definition 3
I-1.2 Origin of diabetes 4
I-1.3 Classification of diabetes 4
I-1.4 Diabetes symptoms 9
I-1.5 Cause of diabetes 10
I-1.6 The complications of diabetes mellitus 11
I-1.7 The pancreas functions 17
I-1.8 The liver functions 18
I-1.8.1 The role of the liver in glucose homeostasis 18
I-1.9 Lipid components in diabetes patients 21
I-1.9.1 Serum total lipids 21
I-1.9.2 Serum triglycerides 22
I-1.9.3 Lipase and amylase 23
I-1.9.4 Serum free fatty acids 24
I-1.9.5 Serum total cholesterol 25
I-1.9.6 Serum phospholipids 26
I-1.10 Diabetic nephropathy 27
I-1.10.1 Clinical significance of proteinuria in diabetes 27
I-1.10.2 Characteristics of diabetic patients with various degree of 30
renal involvement

II CHAPTER II

II.1 MATERIALS AND METHODS 32

A Investigation of blood glucose, liver and kidney and 32
pancreatic function tests in diabetic patients.
II-1.1 MATERIALS 32
II-2.1 METHODS 32
II-2.1.1 Determination of blood glucose, liver, kidney and pancreatic 33
function tests in different diabetic Patients (IDDM and
NIDDM) with and Without ketosis.
B Investigation of serum total lipids and Lipid components 34
II-1.2 MATERIALS 34
II-2.2 METHODS 36
II-2.1 Determination of serum glucose 36
II-2.2 Determination of serum total lipids 36
II-2.3 Determination of serum total cholesterol 37
II-2.4 Determination of serum phospholipids 37
II-2.5 Determination of serum triglycerides 38
II-2.6 Determination of serum free fatty acids 38
C Investigation of urinary proteins in diabetic patients 39
II-3 MATERIALS 39
II-2.3 METHODS 40
II-2.3.1 Determination of urine total protein, and protein compounds 40
II.4 Statistical analysis 40

III CHAPTER III

III-1 RESULTS 41
III-1.1 Determination of kidney, liver, and pancreatic function tests
in different diabetic Patients (IDDM and NIDDM) with and 41
without ketosis.
III-2 Determination of total lipids and lipids components in 58
diabetic patients
III-2-1 Serum total lipids 58
III-2-2 Serum cholesterol 59
III-2-3 serum phospholipids 60
III-2-4 serum triglycerides 61
III-2-5 serum free fatty acids 62
III-3 Determination of urinary protein and diabetic patient's 80
nephropathy in diabetic patients.

IV CHAPTER IV

DISCUSSION 96
RECOMMENDATION 110
REFERENCES 111
APPENDIX --
ARABIC SUMMARY --
 ABBREVIATIONS

A/G Albumin/Globulin
AER Albumin Excretion Rate
Alb Albumin
ALP Alkaline Phosphatase
ALT Alanine Transferase
AST Aspartate Transaminase
Apo Apoprotein
ATP Adenosine Triphosphate
CAD Coronary Artery Disease
cAMP cyclic Adenosine Monophosphate
DM Diabetes Mellitus
ESRD End Stage Renal Disease
FFA Free Fatty Acids
GDM Gestational Diabetes Mellitus
G-Hb Glycolated Heamoglobin
GFR Glomerular Filtration Rate
GOT glutamic oxalic transaminase
GPT glutamic pyruvic transaminase
HMG- CoA 3-Hydroxy- 3- Methylglutaryl- Coenzyme A
HNKS Hyperosmolar NonKetotic Syndrome
HLA Human Leukocyte Antigens
HbA1c Human Hemoglobin
HDL High Density Lipoprotein
LDL Low Density Lipoprotein
LCAT Lecithin Cholesterol Acyltransferase
LPL Lipoprotein Lipase
IGT impaired glucose tolerance
IDDM Insulin Dependent Diabetes Mellitus
MODY Maturity-Onset Diabetes of the young
NDDG National Diabetes Data Group
NIDDM Non- Insulin Dependent Diabetes Mellitus
NIDDM- I Non- Insulin Dependent Diabetes Mellitus - Insulin Treated
NADPH Nicotinamide Adenine Dinecliotide Phosphate
n.s non significance
O.D Optical Density
P Degree of probability
PL Phospholipids
p.m past meridian
SD Standard Deviation
S.S Slightly significant
TC Total Cholesterol
TL Total Lipid
T.P Total Protein
UAER Urinary Albumin Excretion Rate
v.h.s very high significant
VLDL Very Low Density Lipoprotein
W/V Weight / Volume
WHO World Health Organization
 CHAPTER I

LETERATURE REVIEW
II=======================================================Chapter I

INTRDUCTION AND AIM OF THE WORK

Diabetes mellitus is a common metabolic disorder affecting the

metabolism of carbohydrates, lipids, proteins and enzyme activities. The present
study deals with investigations on liver and pancreatic function tests for serum
aspartate, alanine amino transferase, alkaline phosphatase, total lipase and
amylase enzymes.

Kidney function tests were also assessed for blood urea and serum
creatinine, serum total proteins and protein fractions were also studied. In
addition, the correlation of such finding with age, sex, ketotic state & diabetics
(type 1 & type 2) have been studied. Although many biochemical parameters are
now available investigating of diabetic patients with pancreatic disease, a single
use of one of them was found unsatisfactory.

The actual work, therefore, has been divided into 3 main parts, each has been
studied separately.
Part 1 concerns the liver, kidney and pancreatic functions for the
following purposes:
-To determine if any complication related to the pancreas, liver and kidney
function tests if it can be changed or not in diabetic patients with or without
ketonuria.
-Also, if it can be possible that diabetic patients with ketosis may show or not
any evidence of pancreatitis in juvenile or adult diabetic patients.
For this reasons, 60 cases (28 males + 32 females) divided into three
groups were studied: Thus, juvenile group as well as two other groups of adult
diabetic patients associated with ketotic or non-ketotic condition were selected
and investigated.

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II=======================================================Chapter I

Part 2 investigates the controversy observed among the data reported by

many authors, due to diverse number of factors among which are race,
environmental, socio-economic, age, sex differences, mode of treatment and the
case level, a great interest in this study is also focused on changes and
abnormalities in lipid metabolism. Such abnormalities may lead generally to
undesirable complications following diabetes mellitus.
For this reasons, other 85 diabetic patients (45 males + 40 females) with
or without ketosis as compared to 38 control subjects were also studied.
All diabetic patients were divided into other different groups according to
variable mode of classification. In addition, since, nephropathy is the most
common and serious complication accompanying the diabetic patients.

Part 3 is concerned to the classification of the type and molecular weight of

either heavy or light protein components, and its nature, whether selective or
non selective in relation to age, duration, sex, and type of treatment.
For this reasons, the urine of 115 diabetic patients of 28 juveniles
(14 males + 14 females) and 87 adults (56 females + 31 males) were analyzed.

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II=======================================================Chapter I

I-1. DIABETES MELLITUS

I-1.1. Difinition:
Diabetes mellitus is one of the most common endocrine diseases,
associated with a group of metabolic disorder characterized by chronic
hyperglycemia with disturbances of carbohydrate, lipids, and protein
metabolism resulting from defects in insulin secretion, insulin action, or both
(Taylor, 1999). The effect of diabete mellitus include long-term damage,
dysfunction, and failure of various organs, especially the eyes, kidneys, nerves,
heart, and blood vessels (Zimmet and Alberti, 1998).

Greek and Roman physician used the term "diabetes" to refer to conditions
in which the cardinal finding was a large urine volume, and 2 types were
distinguished "diabetes mellitus" in which the urine lasted sweet and "diabetes
insipidus" in which the urine was tasteless. Today the term diabetes insipidus is
reserved for the action by deficiency of antidiuretic hormone from the posterior
pituitary gland and the unmodified word diabetes is generally used as a synonym
for diabetes mellitus (Ganong, 1983).

Diabetes is not a single disease but a heterogeneous group of disorders in

cause and type (Fajans et al., 1978). Heterogeneity of diabetes implies that
there are differences among various groups of patients in terms of etiology.
Pathogenesis (genetic, environmental and immune factors, in natural history and
in response to treatment. The disease may be found in a variety of clinical
presentations, ranging from asymptomatic states in patients with mild insulin
deficiency to debilitating conditions of weight loss, thirst polyuria, dehydration
and coma in those with severe insulin deprivation (Fajans, 1989; Owen &
Shuman, 1990).

-3-
II=======================================================Chapter I

Diabetes is a disease of global distribution, affecting individuals of all

ages with widely varying prevalence rates in different populations and within
the same population. Epidemiologic studies have shown an increased frequency
related to changes in life-style, urbanization, dietary changes, obesity and stress
are putative factors in this propensity for glucose intolerance and diabetes
mellitus in a certain population (Owen & Shuman, 1990).

I-1.2. Origin of Diabetes:

Diabete comes from a Greek word that means to siphon or "passing

though,". The most obvious sign of diabetes is excessive urination. Water passes
through the body of a person with diabetes as if it were being siphoned from the
mouth through the urinary system out of the body.

Mellitus comes from a Latin word that means sweet like honey. The
urine of a person with diabetes contains extra sugar (glucose).
In 1679, a physician tasted the urine of a person with diabetes and
described it as sweet like honey.This had been noticed long before in ancient
times by the Greeks, Chinese, Egyptians, and Indians.
In 1776 Matthew Dobson confirmed the sweet taste was because of an
excess of a kind of sugar in the urine and blood of people with diabetes
(Dobson, 1776).

I-1.3. Classification of Diabetes

According to the classification recommended by the (American Diabetes
Association, 2004), diabetes mellitus can be classified as type 1, type 2, other
specific types, and gestational diabetes mellitus as shown in table (1).

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II=======================================================Chapter I

Table 1: Etiologic Classification of Diabetes Mellitus

I. Type 1 diabetes* (β-cell destruction, usually leading to absolute insulin
deficiency)

1. Immune mediated
2. Idiopathic

II. Type 2 diabetes* (may range from predominantly insulin resistance with
relative insulin deficiency to a predominantly insulin secretory defect with
insulin resistance)
III. Other specific types

1. Genetic defects of b-cell function

2. Genetic defects in insulin action
3. Diseases of the exocrine pancreas
4. Endocrinopathies:
1. Acromegaly
2. Cushing's syndrome
3. Glucagonoma
4. Hyperthyrodism
5. Somatostatinoma
6. Aldosteronoma
5. Drug- or chemical-induced
6. Infections
1. Congenital rubella
2. Cytomegalovirus
3. Others
7. Uncommon forms of immune-mediated diabetes
1. "Stiff-man" syndrome
2. Anti-insulin receptor antibodies
3. Others
8. Other genetic syndromes sometimes associated with diabetes
1. Down's syndrome
2. Klinefelter's syndrome
3. Turner's syndrome

IV. Gestational diabetes-mellitus (GDM)

*Patients with any form of diabetes may require insulin treatment at some stage
of their disease. Such use of insulin does not, of itself, classify the patient.

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II=======================================================Chapter I

I-1.3.1. Type 1 Diabetes Mellitus:

Formerly known as insulin-dependent diabetes mellitus (IDDM),
childhood diabetes, this type of diabetes can affect children or adults but was
traditionally termed "juvenile diabetes" because it represents a majority of cases
of diabetes affecting children and young adults and accounts for approximately
15% of the total diabetic population (Owen and Shaman, 1990). About 40% of
people with type 1 develop severe nephropathy and kidney failure by the age of
50. It is characterized by the development of ketoacidosis in the absence of
insulin therapy or insulin deficiency caused by autoimmune or idiopathic
destruction of pancreatic β-cells (Atkinson and Maclaren, 1994), abrupt onset
of symptoms and absolute dependence on exogenous insulin not only to control
the hyperglycemia but to prevent the occurrence of ketoacidosis and sustain life
(American Diabetes Association, 2004).
Type 1 diabetes is thought to be inherited in genetically susceptible
individuals by environmental factors such as viral, toxic or chemical agents that
lead to autoimmune destruction of β-cells, resulting in the formation of altered
protein components. This material is a foreign antigen to the immuno system,
establishing the basis for an autoimmuno reaction against the cell of origin the
β-cell (Goruch et al., 1983 and Bosi, 1987).

I-1.3.2. Type 2 Diabetes Mellitus :

Previously known as non-insulin dependent diabetes mellitus (NIDDM),
adult-onset diabetes mellitus, maturity- onset diabetes mellitus, accounts for
more than 90% of all diabetes with unknown specific etiology, but hereditary
factors, aging, and obesity are important risk factors (American Diabetes
Association, 2004). Two groups of patients with NIDDM were recognized by
different body composition, obese and no obese. In addition, a third group called
maturity-onset diabetes of the young (MODY) had been described for those
individuals in whom the diagnosis of diabetes is made before the age of 25

-6-
II=======================================================Chapter I

years. With the disease being non-ketosis rarely leads to ketoacidosis and
typically response to diet and/or sulfonylurea urea drugs (Fajans, 1989).
Type 2 diabetes is usually associated with a positive family history, and
begins in middle life or beyond, often over the age of 40. Symptoms being more
gradually than in IDDM, and the diagnosis is frequently discovered when an
asymptomatic person is found to have elevated plasma glucose on routine
laboratory examination. In contrast to insulin-dependent disease, plasma insulin
levels are normal to high although there are an inability of insulin to lower
plasma glucose levels effectively an-abnormality termed insulin resistance.
Type 2 diabetes can result from genetics defects that cause both insulin
deficiency and insulin resistance (a term refers to impaired tissue response to
insulin) occurs during the early phase of NIDDM, but the disease frequently
goes undiagnosed for many years because hyperglycemia during the earlier
stages is not severe enough to cause symptoms (Foster., 1994, American
Diabetes Association, 2004).

The pathophysiologic alterations in type 2 diabetes include abnormal insulin

secretion and resistance to insulin action in target tissues. Although either
defects may be the initial pathogenic event that ultimately leads to the disease,
most patients with the fully developed syndrome show impairments of both
insulin secretion and insulin-mediated glucose disposal (insulin or insulin
antibodies) receptors (decreased number or diminished binding of insulin) or
post receptor (Abnormal signal transduction especially failure to activate
tyrosine kinase) abnormalities. Obesity is the most common cause of insulin
resistance (DeFronzo et al., 1992 and Sherwin, 1996). The comparison between
type 1 and type 2 is showed in table 1.

-7-
II=======================================================Chapter I

Table (1): Comparison between IDDM and NIDDM.

Type I (IDDM) Type II (NIDDM)

Age at onset Usually under 40 Usually over 40

Body weight Thin Usually overweight

Symptoms Appear suddenly Appear slowly

Insulin None Too little, or it is ineffective

produced
Insulin Must take insulin May require insulin (20-30%)
required
Other names Juvenile diabetes Adult onset diabetes

Usually abrupt, thirst, Frequently asymptomatic or

Symptoms polyuria, polyphagia, thirst, fatigue visual blurring
weight loss and easy fatigability
Nutritional Usually nonobese 60-80% obese
status
virus or other Family history and strong
Etiology environmental factors association with obesity.
Chronic autoimmunity Impaired insulin secretion
Pathogenesis against islet β-cells; islet and/or insulin resistance.
cell antibodies detected
years before clinical onset
Endogenous Negligible to absent Normal or higher levels, but
insulin and low in relation to blood sugar
C-peptide level
Acute Diabetic ketoacidosis Hyperosmolar state: ketosis,
complication rarely with infection or stress.
Sulfonylurea No response Effective for majority
Diet Mandatory Mandatory: diet alone may
control blood sugar.

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II=======================================================Chapter I

I-1.4. Symptoms of Diabetes:

Usually, the symptoms of type 1 diabetes are obvious. That is not true for
type 2. Many people with type 2 do not discover they have diabetes until they
are treated for a complication such as heart disease, blood vessel disease
(atherosclerosis), stroke, blindness, skin ulcers, kidney problems, nerve trouble
or impotence. The warning signs and symptoms for both types are:

Type 1: Frequent urination, increased thirst, extreme hunger, unexplained

weight loss, extreme fatigue, blurred vision, irritability, nausea and vomiting.

Type 2: Any type 1 symptom, plus: unexplained weight gain, pain, cramping,
tingling or numbness in your feet, unusual drowsiness, frequent vaginal or skin
infections, dry, itchy skin and slow healing sores.

If a person is experiencing these symptoms, they should see a doctor

immediately (The HealthScoud Network Contact US, 2001-2007)

• Frequent urination (even at night) (polyuria)

• Excessive thirst (polydispia)
• Always being very hungry (polyphagia).
• Dry skin
• Itchy skin
• Slow healing of cuts
• Blurry eyesight
• Feeling tired and weak
• Weight loss
• Skin infections
• Numbness or tingling in feet

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II=======================================================Chapter I

I-1.5. Causes of Diabetes:

Many factors, especially heredity and obesity are important in the
development of diabetes (The HealthScoud Network Contact US, 2001-2007):
Heredity: family history of diabetes. If you have a parent, grand parent, brother,
or sister who has diabetes, you are more likely to develop diabetes. There is
about a 5% risk of developing type 2 diabetes if your mother, father, or sibling
has diabetes. There is a higher risk (up to 50%) of developing type 2 diabetes if
your parent or siblings have type 2 diabetes and you are overweight.

Obesity: 80% of people with type 2 diabetes are overweight when diagnosed.
Diabetes symptoms disappear in many of these obese patients when they lose
weight.

Age: Advanced age cause improper functioning of the pancreas.

Viruses: Certain viruses may destroy β-cells in susceptible people.
Faulty immune system: There is not cause of diabetes, but multiple factors that
may trigger the immune system to destroy β-cells.
Physical trauma: An accident or injury may destroy the pancreas, where insulin
is normally produced.
Drugs: Drugs prescribed for another condition may unmask diabetes.
(Medication cortisone and some high blood pressure drugs).
Stress: Hormones released during periods of stress may block the effect of
insulin.
Pregnancy: Hormones produced during pregnancy may block the effect of
insulin.
Unhealthy diet: Bad diet can cause diabetes.

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II=======================================================Chapter I

I-1.6. The complications of diabetes mellitus:

The complications are far less common and less severe in people who
have well-controlled blood sugar levels, (Nathan et al., 2005). In fact, the better
the control, the lower the risk of complications. Hence patient education,
understanding and participation are vital. Healthcare professionals who treat
diabetes also address other health problems that may accelerate the deleterious
effects of diabetes. These include smoking (abstain), elevated cholesterol levels
(control with diet, exercise or medication), obesity (even modest weight loss can
be beneficial), high blood pressure, and lack of regular exercise (Ann Intern
Med, 1995).

I-1.6.1. Acute complication of diabetes mellitus:

The acute complications of diabetes are a direct result of abnormalities

in the plasma level: Hyperglycemia or hypoglycemia. Initial symptoms of
hyperglycemia are increased urination (Polyuria), fatigue or blurry vision. If
uncorrected, hyperglycemia eventually may lead to diabetic ketoacidosis (DKA)
or non-ketotic hyperosmolar coma. In actually, they represent parts of a
spectrum of a disease process characterized by varying degrees of insulin
deficiency over production of counter regulatory hormones and dehydration
hypoglycemia, another acute complication of diabetes, results from an
imbalance between the medication for diabetes treatment (insulin or
sulfonylurea) and the patient's food intake or exercise. Because the brain
depends almost entirely on glucose can lead to confusion, stupor or coma
(Clement and Torrens, 1995).

I-1.6.1.1. Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is an acute, dangerous complication and is
always a medical emergency. On presentation at hospital, the patient in DKA is
typically dehydrated and breathing both fast and deeply. Abdominal pain is

- 11 -
II=======================================================Chapter I

common and may be severe (Susan and Kecokes, 1993).The level of

consciousness is normal until late in the process, when lethargy (dulled or
reduced level of alertness or consciousness) may progress to coma. The
ketoacidosis can become severe enough to cause hypotension and shock. Prompt
proper treatment usually results in full recovery, though death can result from
inadequate treatment, delayed treatment or from a variety of complications. It is
much more common in type 1 diabetes than type 2, but can still occur in patients
with type 2 diabetes (Williams, 1996).

I-1.6.1.2. Non ketotic hyperosmolar coma :

While not always progressing to coma, this hyperosmolar non-ketotic
state (HNS) is another acute problem associated with diabetes mellitus. It has
many symptoms in common with DKA, but a different cause, and requires
different treatment. In anyone with very high blood glucose levels (usually
considered to be above 300 mg/dl or 16 mmol/l), water will be cosmetically
driven out of cells into the blood. The kidneys will also be "dumping" glucose
into the urine, resulting in concomitant loss of water, causing an increase in
blood osmolality. If the fluid is not replaced (by mouth or intravenously), the
osmotic effect of high glucose levels combined with the loss of water will
eventually result in such a high serum osmolality (dehydration). The body's cells
may become progressively dehydrated as water is drawn out from them and
excreted. Electrolyte imbalances are also common. This combination of
changes, especially if prolonged, will result in symptoms of lethargy (dulled or
reduced level of alertness or consciousness) and may progress to coma. As with
DKA urgent medical treatment is necessary, especially volume replacement.
This is the diabetic coma which more commonly occurs in type 2 diabetics.
Coma in diabetes can be due to acidosis and dehydration. However, the
blood glucose can be elevated to such a degree that independent of plasma pH,
the hyperosmolarity (hyperosmolarcoma) of the plasma causes unconsciousness.

- 12 -
II=======================================================Chapter I

Accumulation of lactic acid in the blood (lactic acidosis) may also complicate
diabetic ketoacidosis if the tissues become hypoxic and lactic acidosis may itself
cause coma (Ganong, 1983).

I-1.6.1.3. Hypoglycemia
Hypoglycemia, or abnormally low blood glucose, is a complication of
several diabetes treatments. It may develop if the glucose intake does not match
the treatment. The patient may become agitated, sweaty, and have many
symptoms of sympathetic activation of the autonomic nervous system resulting
in feelings similar to dread and immobilized panic. Consciousness can be
altered, or even lost, in extreme cases, leading to coma and/or seizures or even
brain damage and death. In patients with diabetes this can be caused by several
factors, such as too much or incorrectly timed insulin, too much exercise or
incorrectly timed exercise (which decreases insulin requirements) or not enough
food or insufficient amount of carbohydrates in food. In most cases,
hypoglycemia is treated with sweet drinks or food. In severe cases, an injection
of glucagon (a hormone with the opposite effects of insulin) or an intravenous
infusion of glucose is used for treatment, but usually only if the person is
unconscious. (Taylor, 1999).

I-1.6.2. Chronic complications of diabetes mellitus

The most patients with diabetes are susceptible to an extensive array of
medical complications; most of the problems can be attributed to particular
susceptibility to damage to the eye (retinopathy), the kidney (nephropathy), the
peripheral nerves (neuropathy), and the blood vessels (atherosclerosis). The first
three categories of complication are relatively specific for diabetes and are
characterized by pathologic endothelial changes, such as basement membrane
thickening and increased vascular permeability. For this reason, retinopathy,
nephropathy and neuropathy have been categorized as microvascular

- 13 -
II=======================================================Chapter I

complications of diabetes. The increased susceptibility to atherosclerosis and its

complications are categorized as macro vascular complications (Clement, 1995).
The functional and structural changes in the involved organs usually lead
in turn to the development of well-defined clinical entities, the so-called
"complications of diabetes", which most characteristically affect the eye, the
kidney and the nervous system (Reginald et al., 1975) suggest that, the term
"complication" may be rejected, arguing that the tissue changes are an integral
part of a "syndrome", preceding or even initiating hyperglycemia. However, the
complications of diabetes can be categorized into vascular complications
(arteriosclerosis, eyes and kidneys), infections (there is lowering resistance
towards infection especially if the diabetes is poorly-controlled) (George and
Cahill, 1985), and coma (Ketoacidosis and non-ketoacidosis).
The disease occurs when insulin activity (not necessarily the amount of
pancreatic insulin secretion) is deficient. Since the introduction of insulin for
diabetic therapy and the subsequent increased longevity of diabetics, the
vascular complications of diabetes have appeared as a major cause of morbidity
(Beach et al., 1979 and Tunbridge, 1981). Vascular complications can be
divided into two types; affecting glomeruli and arteriosclerosis involving the
cranial arteries, coronary arteries and peripheral arteries (Platon et al., 1978).
Involvements of the peripheral arteries frequently lead to claudication, ischemic
ulcers and amputation (Strandness et al., 1964). In fact, it is generally accepted
that, arteriosclerosis spears at an earlier age in diabetics, is more extensive and is
associated with a higher morbidity and mortality (Santen et al., 1972; West,
1978 and Tunbridge, 1981).

I-1.6.2.1. Microvasclar disease

Chronic elevation of blood glucose level leads to damage of blood vessels.
In diabetes, the resultant problems are grouped under "microvascular disease"
(due to damage to small blood vessels) and "macrovascular disease" (due to

- 14 -
II=======================================================Chapter I

damage to the arteries).The damage to small blood vessels leads to a

microangiopathy, which causes the following organ-related problems:Diabetic
retinopathy, growth of friable and poor-quality new blood vessels in the retina as
well as macular edema (swelling of the macula), which can lead to severe vision
loss or blindness. Retinal damage (from microangiopathy) makes it the most
common cause of blindness among non-elderly adults in the US.

• Diabetic neuropathy, abnormal and decreased sensation, usually in a

stocking distribution starting at the feet but potentially in other nerves.
When combined with damaged blood vessels this can lead to diabetic foot
(see below). Other forms of diabetic neuropathy may present as
mononeuritis or autonomic neuropathy.
• Diabetic nephropathy, damage to the kidney which can lead to chronic
renal failure, eventually requiring dialysis. Diabetes mellitus is the most
common cause of adult kidney failure worldwide.
• Diabetic nephropathy develops in close to 40% of patients with type 1
diabetes and in 5% to 40% of patients with type 2 diabetes. Genetics play
an important role: Patients who have one or two deletions of the
angiotensin-converting enzyme (ACE) gene, a defect in the sodium proton
pump, or a family history of hypertension are at increased risk for
progression to diabetic nephropathy (Parving et al., 1996). However, in
such patients, nephropathy does not occur until type 1 diabetes develops;
the worse and more prolonged the hyperglycemia, the greater the risk of
diabetic nephropathy (Parving et al., 1996).

- 15 -
II=======================================================Chapter I

I-1.6.2.2. Macrovascular disease:

Macrovascular disease leads to cardiovascular disease, mainly by
accelerating atherosclerosis:

• Coronary artery disease, leading to myocardial infarction ("heart attack")

• Peripheral vascular disease, which contributes to intermittent claudication
(exertion-related foot pain) as well as diabetic foot.
• Diabetic myonecrosis

Diabetic foot, often due to a combination of neuropathy and arterial

disease, may cause skin ulcer and infection and, in serious cases, necrosis and
gangrene. It is the most common cause of adult amputation, usually of toes and
or feet, in the US and other Western countries. However, diabetes does cause
higher morbidity, mortality and operative risks with these conditions (Weiss and
Sumpio, 2006).

- 16 -
II=======================================================Chapter I

I-1.7. The Pancreas functions:

The pancreas is a small organ located in the abdomen, behind the

stomach. It is attached to the small intestine and the spleen. Inside the pancreas
are small clusters of cells called "the islets of Langerhans". The islets of
Langerhans are endocrine tissue containing four types of cells. In order of
abundance, they are:

• Beta cells, which secrete insulin and amylin.

• Alpha cells, which secrete glucagons.
• Delta cells, which secrete somatostatin.
• Gamma cells, which secrete a polypeptide of unknown function.

Within the islets are β-cells, which produce insulin it is stored within
vacuoles pending release, via exocytosis, which is triggered by increased blood
glucose levels. β-cells have channels in their plasma membrane that serve as
glucose detectors. Insulin is the principal hormone for maintaining glucose
homeostasis and regulating carbohydrate, lipid, and protein metabolism by
suppressing gluconeogenesis and glycogenolysis in the liver and by stimulating
the uptake of glucose into skeletal muscle and fat (Saltiel and Kahn, 2001).
Insulin is a polypeptide hormone composed of 51 amino acid residues an alpha
chain called the A chain of 21 amino acids linked by two disulfide (S-S) bridges
to a beta chain called the B chain of 30 amino acids, and has a molecular weight
of 5808 Da. Insulin exerts its physiological actions by binding to its receptor on
cell membrane (Massague et al, 1980).

In people who do not have diabetes, glucose in the blood stimulates

production of insulin in the β-cells. β-cells "measure" blood glucose levels
constantly and deliver the required amount of insulin to funnel glucose into
cells. They keep blood sugar in the normal range of 60 mg to 120 mg. When
there is little or no insulin in the body, or when insulin is not working properly,

- 17 -
II=======================================================Chapter I

glucose has difficulty entering your cells. Also, when there is not enough
insulin, excess cannot be stored in the liver and muscle tissue. Instead, glucose
accumulates in your blood. This high concentration of glucose in the blood is
called hyperglycemia or high blood sugar (Taylor, 1999).

I-1.8. The liver functions:

The human liver performs multiple functions essential for life. The liver
directly receives processes and stores materials absorbed from the digestive tract
such as amino acids, carbohydrates, fatty acids, cholesterol and vitamins and is
capable of releasing metabolites of these compounds on demand. The liver
synthesize multiple plasma proteins including albumin, α-globulin, β-globulin,
blotting and transport proteins. These factors influence homeostasis, since
binding proteins modulate the circulating total concentrations of calcium,
magnesium and many drugs, while albumin concentrations regulate the plasma
oncotic pressure and thus influence the dynamics between the blood and the
tissues (Balistreri & Rej, 1994).

The liver responds to multiple hormonal and neutral stimuli to regulate the
blood glucose concentration and contributes to the body is immune system
(Whicher, 1983 and El-Shebl, 1993).

I-1.8.1. The role of the liver in glucose homeostasis:

The liver has a central role in glucose homeostasis (DeFranzo and
Ferrannini, 1987). In the post absorptive, fasting state and basal hepatic glucose
production is in precise equilibrium with basal glucose utilization by the brain
and other tissue that are obligate glucose consumers. The liver release both from
glycogen stores (glucogenolysis) and from newly synthesized glucose
(gluconeogenesis).In control the postprandial state, substrate-related meremental
Insulin secretion stimulates glucose utilization and storage, while inhibiting
hepatic glucose output. The liver also responds to hypoglycemia by providing

- 18 -
II=======================================================Chapter I

glucose acutely. This mediated by three distinct pathways (Moore &

Cherrington, 1996).
1- The action of epinephrine on the liver.
2- The action of glucagon on the liver.
3- The direct innervations of the liver.

The metabolic rate of ingested glucose within the liver appears to involve
the removal of about 30% to 40% of the glucose that enters the portal vein
following an oral glucose load. The liver replete its glycogen stores by both
direct and indirect pathways (Shulman et al., 1990). The regulation of hepatic
glucose uptake involves a complex interaction of neural and hormonal
mechanisms. Insulin and glucagons levels, the amount of glucose presented to
the liver, and the portal neural signal are important regulators of the liver's
response to glucose delivery (Moore and Cherrington, 1996).
Insulin increases hepatic glucose uptake and suppresses hepatic glucose
production (Bergman, 1977). On contrast, glucagons reduces net hepatic
glucose uptake during portal glucose delivery due to lack of suppression of
endogenous glucose production. Whereas, insulin activities glycogen syntheses
and increases glycogen deposition, glucagons reduces glycogen synthesis
activity and glycogen deposition. In addition to this, epinephrine alters hepatic
glucose production. A physiologic increment in plasma epinephrine increases
hepatic glucose production by increasing both the maximal gluconeogenic rate
and glycogenolysis, with gluconeogenesis being responsible for 60% of the
overall increase in glucose production.
In contrast, intraportal epinephrine, which elevates sinusoidal glucose
levels? Increases hepatic glucose production but does not change the maximal
gluconeogenic rate, thus its effect on glucose production is attributable solely to
an increase in glycogenolysis (Marks and Skyler, 1999). Moore and
Cherrington, (1996) reported that the neutral of hepatic glucose metabolism

- 19 -
II=======================================================Chapter I

includes a tonic block of glucose entry into the liver, probably mediated by both
sympathetic neural activity and low insulin: glucagons ratio. An increase in the
portal vein glucose level is detected by portal region sensors that cause a
decrease in the firing rate of the hepatic branch of the vagus nerve.
The change in the afferent firing rate is processed in the hypothalamus
and instigates a change in the efferent firing rate of the hepatic and pancreatic
branches of the vagus, with corresponding increases in insulin secretion and net
hepatic glucose uptake. The portal signal not only serves to direct glucose into
the liver but also appears to stimulate its deposition as glycogen. A saturable
pathway of insulin degradation is located in the liver. Most insulin is
metabolized by this way, and 50% of secreted insulin is extracted on the first
pass through the liver (Marchesini et al., 1990). The metabolic disturbances,
which involve the liver, have been recently reviewed (Stone & Van Theil, 1985
and Fagivoli and Van Theil, 1993).

In type I diabetes, resulting from insulin lack, the liver contributes to the
disturbances in carbohydrate metabolism. The hyperglycemia results from
breakdown of glycogen and over-production of glucose by the liver together
with a decreased uptake of glucose from the portal vein blood. The activity of
glucose-6-phosphatase is increased with resulting increased glycogenolysis and
decreased phosphorylation in the liver. Over-production of glucose also occurs
due to a loss of the normal feedback inhibition of gluconeogenesis by plasma
glucose levels (Wahren et al., 1972). The uptake of glucose from portal vein
blood is considerably reduced (Felig, 1977).

- 20 -
II=======================================================Chapter I

I-1.9 Lipid components in diabetic patients:

I-1.9.1 Serum Total Lipids:

Lipids are important dietary constituents, not only for their high energy
value, but also because of the fat-soluble vitamins and essential fatty acids
contained in the fat of natural foods. Lipid metabolic abnormalities play an
important role in various diseases such as hyperlipidemia, heart disease and
diabetes mellitus (Felts and Rudel, 1975), (Gurr and James, 1975) and
(Liebich, 1986). Diabetes and hyperlipidemia are frequently associated
pathologic states. Diabetes is considered causative or aggravating factors in
hyperlipidemia. Yet, the incidence of hyperlipidemia is high in this state, and the
severity of disturbed metabolism differs from one patient to another (Debry et
al., 1979). Hyperlipidemia is the result of an imbalance between the formation
and degradation of either the lipoprotein entity or any of its constituents. The
level of serum lipids are affected by a multitude of factors such as race, heredity,
age, sex, hormones, diet, physical activity, season and method of analysis
(Larsson et al., 1962).
Few of the materials in the literature are uniform in these respects and any
detailed comparison between the results of different investigators would
therefore be of limited value. Of interest to mention, is that serum lipids are
different among population of different countries. Thus in diabetics Senegalese,
serum lipids and its components were increased in relation to that of healthy
Senegalese, who show lower or less have the same levels as healthy Europeans
(Josselin, et al., 1976). The most common lipid abnormality in diabetic is
hyperglycerdemia (Bagdade et al., 1968), but plasma cholesterol also can be
increased. In addition, the chemical composition of lipoproteins is abnormal
(Schonfeld et al., 1974).

- 21 -
II=======================================================Chapter I

I- 9.1.2 Serum triglycerides :

Triglycerides are stored in adipose and act as a large energy reserve,
which can be made available when required by enzymatic hydrolysis to fatty
acids and glycerol. About 30-40% of people's daily caloric intake is normally in
the form of fat. After hydrolysis, the dietary fat is absorbed primarily
monoglycerides and fatty acids, and resynthesized into triglycerides in the
mucosal cells. The triglycerides are then combined with cholesterol,
phospholipids and apolipoprotein and secreted into the lymph system as
chylomicrons. The amount of fat is a meal appears to determine the amount of
triglycerides resyntheslized in the mucosal cells, the more the latter, the higher
and the proportional of chylomicrons to VLDL (Gangl and Ockner, 1975).
It has been established that diabetes is often associated with increased
plasma triglyceride level and (Laakso et al., 1985; 1987).
In insulin- dependent diabetes mellitus (Juvenile-onset diabetes), the change
in both males and females was insignificant (Beach et al., 1979).
Serum triglyceride level was significantly higher in alloxan-diabetic
rabbits than in non-diabetic rabbits (Kantardzhyan, 1976) and in young alloxan-
diabetic rats than in non-diabetic rats (Saatov et aI., 1980).

Multiple mechanisms may be responsible for the increase of serum trigly-

ceride level in diabetes. In absolute insulin-deficiency, there is an increased
concentration of serum free acids with increased endogenous synthesis of
triglycerides (Nikkila and Kekki, 1973) and a decreased activity of adipose
tissue lipoprotein lipase and post heparin lipoprotein lipase (Bagdade et aI.,
1968), which provide an adequate explanation for hypertriglyceridemia.

- 22 -
II=======================================================Chapter I

I-1.9.3 Lipase and amylase enzymes :

Lipase and amylase are two digestive enzymes produced by the pancreas
that can be measured in the blood (Miura et al., 2002). The pancreas has two
separate functions: the endocrine function of blood glucose regulation and the
exocrine function of digestion. When either of these functions is abnormal, it
may cause the other one to be disrupted. Diabetes can cause pancreatitis and
pancreatitis can cause diabetes. In pancreatitis, where the inflammation occurs
suddenly or gradually over a long period of time, acute pancreatitis causes little
or no permanent damage to the pancreas, while chronic pancreatitis can result in
scar tissue forming in the pancreas, which in turn decreases the ability of the
pancreas to function properly.
It is concluded that the serum activity of pancreatic enzymes increases
with the degree of diabetic disequilibrium and mainly correlate with metabolic
factors such as hyperglycemia, dehydration and acidosis. Amylase inhibition has
gastrointestinal and metabolic effects that may aid in the treatment of diabetes
and obesity or type 2 diabetes mellitus (Lankisch et al., 1998). So, the
pancreatic enzymes might be of value in determining the severity and chronicity
of human insulin-dependent diabetes, and can be used as a parameter in
evaluating the response to treatment (Aughsteen and Mohammed, 2002).
Yadav, et al., (2000), found that the estimation of amylase and lipase
enzymes are the standard testes to diagnose acute pancreatitis (AP). The aim of
their studies was to evaluate the incidence and magnitude of non specific
elevations of amylase and lipase in diabetic ketoacidosis (DKA). In DKA
nonspecific elevations of amylase and lipase occurred in 16-25% of the cases.
Amylase and lipase elevation are correlated with serum osmorality.

- 23 -
II=======================================================Chapter I

I-1.9.4 Serum free fatty acids (SFFA):

The so-called free fatty acids do not, in fact, exist in the plasma in a free
form but are always bound to albumin. Normally about 2-3 molecules of fatty
acid are transported on each molecule of albumin and the complex so formed
may be described as a special type of lipoprotein (Thomas and Gillham, 1989).
Fatty acids are present in plasma chiefly in esterified forms namely, triglycerides
45%, phospholipids 35%, cholesterol ester 15% and free fatty acids account for
less than 5% of the total fatty acids present in plasma. The released fatty acids in
adipose tissue can also reform triglycerides by uniting with α-glycerophosphate.
Since, the mammalian adipocyte lacks significant amounts of the enzyme
glycerokinase to phosphorylate glycerol, a new source of α-glycerophosphate
must be provided. Insulin provides this substrate by promoting the flux of
glucose intra-cellular and the production via glycolysis of α-glycerophophate
(Saudex and Eder, 1979).In diabetic subjects, it was found that serum FFA
concentration was markedly increased than in non-diabetic subjects (Golay et
aI., 1987). They also reported that, in diabetic children, the mean value of serum
FFA was significantly higher than control and similarly, in adult-onset diabetic
subjects, elevated serum FFA was observed by (Mingrone and Aldo, 1979).
Recently, significant relationship were seen between values for fasting plasma
glucose and fasting serum FFA in non-insulin dependent diabetes mellitus
(Fraze et aI., 1985; Golay et aI., 1987), and based upon these finding the
possibility has been raised that the elevated serum FFA levels are the cause of
the increase endogenous glucose production and resultant fasting hyperglycemia
(Bogardus et aI., 1984).

I-1.9.5 Serum total cholesterol:

The normal human body contains about 2 gm of cholesterol per Kg.

total body weight, but only about 5% of this value is present in the plasma
lipoproteins. Almost all animal tissues are capable of synthesizing cholesterol

- 24 -
II=======================================================Chapter I

from acetate, but the most activity synthesizing sites are the liver and
gastrointestinal tract (Grundy, 1978). However, it was reported that, the mean
level of serum cholesterol was significantly higher in normal girls than in
normal boys in Washington and Sanghai (Zhijia et aI., 1986). These authors
believed that cholesterol metabolism is influenced by hormones during the
adolescent period. Serum cholesterol in Egyptian male normal children (6-12
years) was insignificantly higher than in corresponding females (Sabry et aI.,
1983 b). However, (Wilding et aI., 1972) reported that in healthy subjects,
serum cholesterol concentration is significantly higher in male than in female.
The mean value for serum cholesterol was found to be significantly increased
with age (Hanz-hong et aI., 1986). An increase in blood cholesterol normally
occurs after end of the adolescent period (Wilding et aI., 1972).

Several studies confirmed that plasma cholesterol is elevated in diabetic

populations and there is evidence that other aspects of cholesterol metabolism
are abnormal (Florey et aI., 1973). This may play a role in the accelerated
development of the arteriosclerotic vascular disease that is a major long-term
complication of diabetes in humans (Palumbo et aI., 1976). The concentration
of serum cholesterol was increased in diabetic patients (Lowry and Barach,
1985). However, other authors, when compared between diabetic and non-
diabetic subjects, found no difference in the concentration of serum cholesterol
(Briones et aI., 1984; Taskinen et aI., 1986).

I-1.9.6 Serum phospholipids:

Phospholipids are complex lipids containing phosphate and a water

soluble nitrogenous base. Phospholipids are widely distributed in all tissues and
it is a major constituent of biological membranes. Bile phospholipids are
important in keeping cholesterol in solution and lecithin is an-essential
component of surfactant. Dietary phospholipids may be at least partially

- 25 -
II=======================================================Chapter I

absorbed as such because of their relative solubility in water or they may be

hydrolyzed before absorption, yet, plasma phospholipids are derived mainly
from synthesis in the liver (Van-Deenen, 1971). Mayes, (1988b) reported that
average serum phospholipids for healthy subjects were 215 mg/dl. In healthy
Egyptian males (4-75 years) serum phospholipids were found to show
significant increase with age (Abul-Fadl et aI., 1983). However, level of serum
phospholipids was significantly higher in non-diabetic Sweden girls than in
non-diabetic Sweden boys (Sterky et aI., 1963).

In diabetic patients, marked elevation of serum triglycerides and serum

lipids is associated with a less pronounced increase of serum cholesterol and
phospholipids (Spiro, 1972). In adequate diabetic control with insulin or
hypoglycemic drugs was associated with a superimposed elevation of
phospholipids level to normal value (George et aI., 1978). In alloxan-diabetic
rats, the level of serum phospholipids was above that of normal rats and
phospholipids / total cholesterol ratio was below that of normal rats (Uchida et
aI., 1979; Saatov et aI., 1980).

- 26 -
II=======================================================Chapter I

I-1.10. Diabetic and nephropathy

Diabetic nephropathy is a major cause of death in diabetes mellitus, and is

known to occur long time after clinical diabetes. For clinical proteinuria was
taken as a marker for diabetic nephropathy. Standard tests for urine albumin
excretion become positive around 100-150 microgram/min. The introduction of
immunoelectrophoresis and other techniques to detect much smaller
concentration of albumin in urine open a great knowledge diagnosis of diabetic
renal disease. Microalbuminuria can be defined as abnormality elevated albumin
excretion without clinical proteinuria such microalbuminuria is a good indicator
of microvascular complication.

Proteinuria is the first manifestation of the syndrome owing to increased

glomerular permeability. Later, progressive renal Failure is evidenced by
increasing blood urea nitrogen and creatinine levels, none of the histopathologic
changes observed in the kidney of diabetic patients is specific for diabetes
mellitus. Typical lesions include widening of glomerular basement membrane,
deposition of albumin and proteins in both and glomueruli and tubules, and
accumulation of eosinophilic material in the glomerular tuft (Kimmelstiel-
Wilson Nodules (Lavine, 1990).

I-1.10.1 Clinical significance of proteinuria in diabetes:

The proteinuria phase of diabetes mellitus may be characterized by its
associated features, and these may also help define its clinical relevance
(Mogensen, 1989). The abnormal albumin excretion is related both to the
duration of diabetes and the degree of glycemic control. Renal function is
usually well preserved with normal renal plasma flow, but early glomerular
hyper filtration. Histological alteration particulary mesangial expansion and
thickening of the glomerular basement membrane, may develop early and are

- 27 -
II=======================================================Chapter I

often progressive, however, their expression may be dependent on the presence

of concomitant hypertension.
Attention has also focused on two other major diabetic complications,
retinopathy and neuropathy. Available data strongly suggest that both are related
to the level of protein excretion including the micro albumin urine range
(Parving et al., 1988). In an elegant study of albumin metabolism in type I
diabetes abnormal movement or leakage of protein from the peripheral
vasculature was present only in those patients with micro or macroalbuminuria –
indicating extra renal vascular damage (Feldt, 1986).

Most of the microalbuminuria patients had developed overt nephropathy

with decreased renal function. Albumin excretion is also a strong indicator for
survival in NIDDM. When protein excretion is stratified according to the level
of early morning urinary albumin concentration (normal <15 mg/L) and
microalbuminuria (15-40 mg/l and 40-200 mg/l).
However , The presence and interactive effects of many of the conditions
associated with microalbuminuria,e.g.,elevated blood pressure or overt
hypertension , lipid and coagulation factor abnormalities , altered glomerular
homodynamic and structural lesions , suggest that microalbuminuria could be an
indicator of established , albeit early , nephropathy and generalized vascular
disease , rather than a predictor of these complications (Deckert et al., 1989).

Microalbuminuria and clinical proteinuria are common features combined

prevalence approximately 40% in NIDDM patients (Gall et al., 1991) and
Nelson, 1988) but renal failure is a less prominent consequence than in insulin
dependent diabetes mellitus (Mogensen, 1990). However, some factors are
correlated with renal failure:

- 28 -
II=======================================================Chapter I

1- Plasma glucose:
Fasting plasma glucose in the factor most consistently and strongly
associated with elevated urinary albumin levels in all analysis for both the total
population and diabetic subjects alone. Similar findings have been reported by
others for microalbuminuria and proteinuria (Schmitz and Veath, 1988)
although a study found no association between albuminuria and level of
glycemia and another found the association only in women (Gatting et al.,
1988).

2- Blood pressure:
The importance of the association between elevated blood pressure and
urinary albumin levels has been previously reported. Although other workers
have reported similar results for NIDDM subjects with microalbuminuria
(Gatting et al., 1988).

3- Duration of diabetes:
The duration of diabetes was not a significant independent correlate of
either micro- or macroalbuminuria in Neurguan diabetic subjects. A study by
(Suzuki et al., 1986), showed a relationship between urinary albumin excretion
and disease duration in patients with IDDM but not with NIDDM, whereas other
report found an independent association in women but not men with NIDDM
(Mattok et al., 1988).

4- Obesity:
Indices of obesity were important independent correlates of elevated
urinary albumin levels in all women and diabetic men and women with normal
glucose tolerance. The link between obesity and hyperinsulinemia is well
recognized and these results could suggest that association obesity and
albuminuria might be mediated by insulin (Modan, 1986).

- 29 -
II=======================================================Chapter I

I-1.10.2. Characteristics of Diabetic Patients with Various Degree

of kidney failure

Symptoms related to kidney failure usually occur only in late stages of the
disease, when kidney function has diminished to less than 10 to 25 % of normal
capacity. Scientists have described five stages in the progression to kidney
failure in patients with diabetes mellitus (The HealthScoud Network Contact
US, 2001-2007)

1- Stage I: The flow of blood through the kidneys, and therefore through the
glomeruli, increases--this is called hyper filtration--and the kidneys are larger
than normal. Some people remain in stage I indefinitely; others advance to
stage II after many years.

2- Stage II: The rate of filtration remains elevated or at near-normal levels and
the glomeruli begins to show damage. Small amounts of a blood protein
known as albumin leak into the urine, a condition known as
microalbuminuria. In its earliest stages, microalbuminuria may not be
detected on each evaluation. But as the rate of albumin loss increases from
20 to 200 micrograms per minute, the finding of microalbuminuria becomes
more constant. (Normal losses of albumin are less than 5 micrograms per
minute.) A special test similar to a urine dipstick is required to detect
microalbuminuria. People with type 1 and type 2 diabetes may remain in
stage II for many years, especially if they have good control of their blood
pressure and blood sugar levels.

3- Stage III: The loss of albumin and other proteins in the urine exceeds 200
micrograms per minute. It can be detected during routine urine tests. Because
such tests often involve dipping indicator strips into the urine, they are
referred to as "dipstick methods" Stage III sometimes is referred to as

- 30 -
II=======================================================Chapter I

"dipstick-positive proteinuria" (or "clinical albuminuria" or "overt diabetic

nephropathy"). The glomeruli suffer increased damage. The kidneys
progressively lose the ability to filter waste, and blood levels of creatinine
and urea-nitrogen rise. People with type 1 and type 2 diabete may remain at
stage III for many years.

4- Stage IV: This is referred to as "advanced clinical nephropathy". The

glomerular filtration rate decreases to less than 75 milliliters / minute, large
amounts of protein pass into the urine, and high blood pressure almost
always occurs. Levels of creatinine and urea-nitrogen in the blood rise
further.

5- Stage V: The final stage is kidney failure. The glomerular filtration rate
drops to less than 10 milliliters / minute. Symptoms of kidney failure become
apparent.

These stages describe the progression of kidney disease for most people
with type 1 diabetes who develop kidney failure. For people with type 1, the
average length of time required to progress from onset of kidney disease to stage
IV is 17 years. The average length of time to progress to kidney failure is 23
years. Progression to kidney failure may occur more rapidly (5-10 years) in
people with untreated high blood pressure. If proteinuria does not develop
within 25 years, the risk of developing advanced kidney disease begins to
decrease. Type 1 diabetes accounts for only 5 to 10 % of all diagnosed cases of
diabetes, but type 1 accounts for 30 percent of the cases of kidney failure caused
by diabetes.

- 31 -
 CHAPTER II

MATERIAL AND METHODS

II=======================================================Chapter II

II-1. MATERIALS AND METHODS

A. Investigation of blood glucose, liver, kidney and pancreatic

function tests in diabetic patients:

II-1.1. MATERIALS:
All studied cases were selected at random among patients seeking
medical care at the Hospital of Ibn Badiss and of Pediatric, Constantine, Algeria.
The number of patients comprised 60 diabetic cases (28 males + 32 females).
31 out of these patients had ketosis indicated by a positive test for ketone bodies
in their urine.

Cases were classified into:

1)- 16 adult diabetic cases with non insulin dependent diabetes mellitus

(NIDDM) divided into 8 cases (3 males + 5 females) (age range 30 - 60

years) associated with ketosis and 8 cases (5 males + 3 females) (age range
32 - 67 years) without ketosis.

2)- 24 adult diabetic cases with insulin dependent diabetes mellitus (IDDM)
divided into 13 cases (5 males + 8 females) age range (20 - 57 years)
associated with ketosis and 11 cases (5 males + 6 females) age range (20 - 49
years) without ketosis.

3)- 20 Juvenile insulin dependent diabetic mellitus (IDDM) cases divided into
10 children (4 males + 6 females) (age range 4 - 20 years) associated with
ketosis and 10 juvenile diabetic cases (6 males + 4 females) age range (4 - 16
years) without ketosis.

- 32 -
II=======================================================Chapter II

SAMPLES:
All subjects were asked to fast overnight for a period of about 8 hours
(12 pm –8 am), during which no treatment (insulin or hypoglycemic drugs) was
allowed to be taken. Morning urine sample was collected in sterilized container
to detect the sugar and ketone bodies in urine with glucostrip camper No. 3
(Boehringer Mannheim, Germany).

A sample of 5 ml venous blood was collected, allowed to clot and the

serum was separated for determination of serum urea and creatinine as kidney
function tests. The activities of alanine aminotransferase (ALT), aspartate
aminotransferase (AST), alkaline phosphatase (ALP), total lipase and amylase
enzymes were estimated as for liver and pancreatic function tests. Serum total
protein and the individual protein fractions were also studied.

II-1.1. Determination of kidney, liver, and pancreatic function

tests in different diabetic Patients:

II-2.1. METHODS:
The level of blood glucose was enzymatically estimated following the
method described by (Werner et al., 1970b). Urea and creatinin as kidney
function tests were determined as described by (Henry et al., 1974). The values
of (ALT and AST) transaminases and alkaline phosphatase enzyme were
estimated as reported by Bergmeyer (1968). The activities of lipase and amylase
enzymes was measured as described by (Huttunen et al., 1975), and (Baron,
1982), respectively. All the previous parameters were analyzed using
commercial kits of "BAYER Diagnostic, France".
Additionally, serum total protein and electrophoretic protein fractions was
investigated as described by (El-Hawary and Ibrahim, 1968).

- 33 -
II=======================================================Chapter II

B. Investigation of serum total lipids and Lipid components:

II-1.2. MATERIALS:

Another, number of 85 patients are also studied for total lipids and lipid
components (45 males and 40 females), of which 38 patients had ketosis with a
positive test for urinary ketone bodies. All studied patients were selected among
those seeking medical care in the Institute of Diabetes, Kasr EL-Aini Hospital,
Cairo, Egypt.
At the time of examination, all patients were under insulin treatment. The
mean age was 33 ± 1.6 years, with a range of 13-65 years. The average duration
of the diabetes ranges from less than one year to 18 years. Diabetic patients had
normal liver and kidney function as assessed by history, laboratory and physical
examination. None of them received lipid-lowering drugs. Women using oral
contraceptive were excluded from our groups.

The diabetic patients were divided into different groups according to variable
mode of classification:

1- The patients were divided into non-ketotic diabetics (23 males with age 34.2
± 3.1 and 24 females with age 37.5 ± 3.0 years) and ketotic diabetics (22
males with age 28.2 ± 2.3 and 16 females with age 30.3 ± 3.1 years).

2- The patients were also divided into insulin-dependent diabetes mellitus

(IDDM), formerly called juvenile-onset diabetes, in which diabetes was
detected at age before 25 years (23 males with age 19 ± 0.8 and 16 females
with age 18.9 ± 1.0 years) and non-insulin- dependent diabetes mellitus-
insulin treated (NIDDM-I), formerly called adult-onset diabetes, in which
diabetes was detected at age after 25 years (22 males with age 45 ± 1.8 and
24 females with age 45 ± 1.8 years).

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II=======================================================Chapter II

3- The patients were also divided as regards the duration of diabetes to patients
with duration < 3 years (15 males with age 35.6 ± 4.0 and 13 females with
age 29.4 ± 3.5 years), patients with duration 3-6 years (15 males with age
23.6 ± 3.0 and 12 females with age 38.4 ± 5.0 years) and patients with
duration > 6 years (15 males with age 36.3 ± 3.3 and 15 females with age 36
± 3.2 years).

4- The patients were also classified as regards diabetic control. Index patients
have been arbitrary divided into three groups on the basis of serum glucose
level as proposed by (Nikkila and Hormila, 1978):
a) Well- controlled (glucose < 200 mg/dl), consisted of 14 males with age 38 ±
4.0 and 12 females with age 36.7 ± 3.6 years.
b) Moderately-controlled (glucose 200-300 mg/dl), consisted of 12 males with
age 35 ± 3.6 and 14 females with age 41.5 ± 3.9 years.
c) Poorly-controlled (glucose > 300 mg/dl), consisted of 19 males with age 25 ±
2.9 and 14 females with age 25.9 ± 3.4 years.

CONTROL SUBJECTS:

38 healthy subjects, living under the same socic-economic conditions of

the diabetic patients, were selected to serve as controls. They had no symptoms
of diabetes and had fasting serum glucose levels less than 120 mg/dl. There was
no evidence of any acute illness. None were taking medications or had been
received hypolipidemic drug therapy. The age distribution of the control
subjects was approximately similar to that of the patients. They were divided
into 20 males (age 31.5 ± 2.6 years) and 18 females (age 31.5 ± 2.3 years). They
also were divided into those with less than 25 years (9 males and 8 females) and
those with more than 25 years (11 males and 10 females). These diabetic
patients and control subjects were examined over the same seasonal period.

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II=======================================================Chapter II

SAMPLES:
All subjects were asked to fast overnight for a period of about 12 hours
(8pm-8am overnight) during which no treatment was allowed to be taken. A
sample of 5 ml venous blood was collected, allowed to clot and the serum was
separated for determination of glucose, total lipids, total cholesterol,
phospholipids, triglyceride and free fatty acids.

II-2.2. METHODS:
All chemicals used in the present methods were of analytical grade (A.R).

1. Determination of serum glucose:

Principle:

Serum glucose was enzymatically estimated following the method

described by Werner et al., (1970b).
GOD
Glucose + O2 + H2O --------------- gluconate + H2O2

POD
H2O2 + ABTS ------------------ colored complex + H2O

Calculation:
OD of sample
Glucose concentration = 100 x --------------------- [mg/dl]
OD of standard

2. Determination of serum total lipids:

Principle:
Serum total lipids were determined by the method described by (Zoellner
and Kirsch, 1962). This method depends on the fact that lipids give a pink-
colored complex on treatment with sulfuric, phosphoric acid and vanillin.

- 36 -
II=======================================================Chapter II

Calculation: OD of sample
Concentration of total lipids = 1000 x -------------------- [mg/dl]
OD of standard

3. Determination of serum total cholesterol :

Principle:
Serum total cholesterol was determined by the method of (Watson, 1960).
The principle of this method depends on the Leiberman-Burchard reaction. The
acetic acid - acetic anhydride mixture, acts as a dehydrating agent, removing
water from cholesterol molecule. This is followed by oxidation and further
dehydration by concentrated sulfuric acid, to give cholestahexane sulfuric acid,
which is green in color. The reaction is time and temperature dependent.
Absolute dryness of test tubes, pipettes and cuvettes used is a must.

Calculation: OD of sample
Concentration of cholesterol = 200 x ------------------- [mg/dl]
OD of standard

4. Determination of serum phospholipids:

Principle:
This method depends on the fact that phospholipids are precipitated with
trichloroacetic acid and oxidized to inorganic phosphate with perchloric acid and
hydrogen peroxide. Phosphate forms a colored complex with molybdate and
vanadate in the presence of nitric acid (Zilversmit and Davis, 1950).

Calculation:
OD of sample
Concentration of phospholipids = 5.0 x ------------------ x 25 [mg/dl]
OD of standard

- 37 -
II=======================================================Chapter II

5. Determination of serum triglycerides:

Principle:
The method is based on enzymatic hydrolysis of triglycerides followed by
subsequent enzymatic determination of liberated glycerol according to the
modification, by Lange, H. - Beohringer Mannheim, of the method of (Bucole
and David, 1973).
Lipase/Estrase
Triglycerides + 3H 2o -------------------> glycerol + 3RcooH
Glycerol dehydrogenase
Glycerol + NAD + -----------------------------> dihydroxyacetone + NADH + H +

Diaphorase
NADH + MTT -------------------> Formazan + NAD+

Calculation:
Concentration of triglycerides = 498.5 x Absorbance of sample [mg/dl]

6. Determination of serum free fatty acids:

Principle:
The serum free fatty acids are converted to chloroform-soluble copper
salts, the copper in the organic layer is subsequently measured colorimetrically.
The concentration of free fatty acids is proportional to the absorbance of the
copper-containing chloroform (Duncombe, 1964).

Calculation: OD of sample
Concentration of free fatty acids= ---------------------à x 14.22 [mg/dl]
OD of standard

- 38 -
II=======================================================Chapter II

C. Investigation of urinary proteins in diabetic patients:

In fact nephropathy is one of the most common and serious complication

accompanying diabetes. There is much controversy about its etiology including
time of onset relation to the type of treatment, as well as to the extent of
controllability of the condition.
The present study deals with investigations on the type of proteinuria,
whether being light or heavy on one hand and its nature whether selective or non
selective on the other hand in relation to age, duration, sex and type of treatment
among diabetes. The nature of the proteinuria was judged by the type and
molecular weight of the proteins detected in urine as revealed by
immunoelectrophoresis.

II-1.3. MATERIALS:
All diabetic cases were selected at random among patients seeking
medical care at the Hospital of Ibn Badiss and of pediatric, Constantine, Algeria.
The number of patients comprised 115 diabetic cases. The obtained
results were correlated with, sex, disease duration, age and treatment type.

A- The sex:
1- 28 juveniles (14 females and 14 males)
2- 87 adults (56 females and 31 males).
B- The age range:
1- 10-25 years
2- 25-40 years
3- 40-50 years
4- > 50 years
C- The duration of disease:
1- Up to 6 month

- 39 -
II=======================================================Chapter II

2- 6-1 years
3- 1-5 years
4- 5-10 years
5- 10-15 years
6- 15-20 years
C- The line of therapy:
1- 72 cases were treated with insulin.
2- 25 cases were put on hypoglycemic drugs.
3- 18 patients had combined treatment.

SAMPLS:
Morning urine samples were collected before the patients had received
any food or fluids.

III-1. Determination of urine total protein and protein compounds:

II-2.3. METHODS:
Determination of urine total protein was carried out according to the
method described by Wootton (1971). Urine was concentrated by dialysis
against 30% (W/V): polyethylene glycol (M.W. 20.000) in 0.15M NaCl.
Electrophoresis of urine proteins was performed as described by Johansson
(1972) and the immunoelctrophoresis analysis as described by (El-Hawary et
al., 1968; Grabar and Butin, 1964).

IV. Statistical Analysis

The results were expressed as mean ± SEM. Student’s t-test has been
applied to compare between groups. The significant test was applied at p<0.05.

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 CHAPTER III

RESULTS
II====================================================== Chapter III

RESULTS

III-1.1. Determination of kidney, liver, and pancreatic function tests

in different diabetic patients (IDDM and NIDDM) with and
without ketosis

Table (1), shows that, in 8 cases of (NIDDM) ketosis, the values of serum
α1-globulin was moderately decreased as compared to values in 8 diabetic
patients without ketosis (fig 2).
In patients with (IDDM) ketosis, the total proteins, albumin and
β-globulin were slightly significant decreased in 13 cases as compared to their
corresponding values in 11 diabetic cases without ketosis (fig 1,2).
In juvenile patients with (IDDM) ketosis, serum albumin and A/G ratio
were slightly significant decreased in 10 cases as compared to their
corresponding values in 10 diabetic cases without ketosis (fig 2, 3).

- 41 -
 II====================================================== Chapter III

Table (1): Represents the values of serum total protein and protein fractions (g/dl) in different groups with diabetic patients
associated with or without ketosis.

Groups (n) T.P Protein fractions (g/dl)

A/G ratio
Albumin α1-globulin α 2-globulin β-globulin γ-globulin

NIDDMwithout KA (8) 6.45±0.23 3.50±0.18 0.31±0.04 0.50±0.04 0.81±0.06 1.33±0.11 1.19±0.06

NIDDMwith KA (8) 6.37±0.32 3.54±0.20 0.21±0.03* 0.61±0.07 0.71±0.11 1.33±0.09 1.22±0.10

IDDMwithout KA (11) 7.36±0.22 3.88±0.15 0.39±0.06 0.70±0.08 0.96±0.05 1.54±0.10 1.13±0.07

IDDMwith KA (13) 6.83±0.18* 3.45±0.12 * 0.37±0.03 0.70±0.07 0.83±0.03* 1.47±0.09 1.03±0.05

IDDMJuvenile without KA 7.67±0.31 4.52±0.30 0.26±0.04 0.75±0.10 0.90±0.05 1.25±0.10 1.45±0.11

(10)
IDDMJuvenile with KA 7.11±0.28 3.88±0.15 * 0.29±0.07 0.88±0.12 0.81±0.09 1.24±0.14 1.25±0.06 *
(10)

n: number of cases
NIDDM: non-insulin dependent diabetes mellitus.
IDDM: insulin dependent diabetes mellitus.
KA: ketosis.
T.P: total protein.
Data are expressed as means ± S.E.
*
indicates a significant difference between group with KA and groups without KA, at P<0.05 using Student’s t-test.

42
II====================================================== Chapter III

9
TP

7
*

6
Total protein (g/dl)

0
NIDDM NIDDM with IDDM IDDM with IDDM IDDM
without KA KA without KA KA Juvenile Juvenile
without KA with KA

Figure (1): Represents the values of serum toal protein (g/dl) in different
groups with diabetic patients associated with or without ketosis
(KA).

- 43 -
II====================================================== Chapter III

6
Albumin
Alfa1 -globulin
Alfa2-globulin
Beta-globulin
5 Gamma-globulin

*
Protein Fractions (g/dl)

4
*

1
*
*
0
NIDDM NIDDM with IDDM without IDDM with KA IDDM IDDM
without KA KA KA Juve nile Juv e nile
without KA with KA

Figure (2): Represents the values of protein fractions (mg/dl) in different groups
with diabetic patients associated with or without ketosis (KA).

- 44 -
II====================================================== Chapter III

1.8
A/G

1.6

1.4
*
1.2
A/G ratio (g/dl)

0.8

0.6

0.4

0.2

0
NIDDM NIDDM with IDDM IDDM with IDDM IDDM
without KA KA without KA KA Juvenile Juvenile
without KA with KA

Figure (3): Represents the values of A/G ratio (g/dl) in different groups with
diabetic patients associated with or without ketosis (KA).

- 45 -
II====================================================== Chapter III

Table (2), show that in 8 cases with (NIDDM) associated with ketosis, the
values of blood glucose (fig 4) and the activities of transaminases GOT and GPT
and alkaline phosphatase fig (7) enzyme were slightly significantly increased,
while the total lipase and amylase enzymes as pancreatic function were highly
significant increased (fig 5,6).
In addition, the values of urea and creatinine as kidney function tests
showed normal level as compared to their corresponding values in 8 cases
without ketosis (fig 8).
In patients with (IDDM) associated with ketosis, the level of blood
glucose was highly significantly increased (fig 4) and the urea, creatinine values
showed slightly increased in 13 cases as compared to their corresponding values
in 11 diabetic cases without ketosis (fig 8).
Regarding, the kidney function test, both serum urea and blood creatinine
values were slightly significant increased in 11 adults (IDDM) ketosis as
compared to their corresponding values in 13 adult diabetic cases without
ketosis Fig (9).
In 10 Juvenile (IDDM) ketosis, the level of blood glucose (fig 4), total
lipase and amylase enzymes were highly significantly increased in 10 cases as
compared to their corresponding values in 10 diabetic cases without ketosis
(fig 5,6).
Regarding the concentration of blood glucose level and the activities of
pancreatic enzymes, a positive relationship was found between blood glucose
and total lipase (Fig 10) as well as for blood glucose and amylase (Fig 11) in
Juvenile cases with insulin dependent diabetic ketosis.
Table (15-18) show the individual glucose level, liver function and kidney
function tests, total protein, albumin,globulin fractions and A/G ratio in juvenile
diabetics with either non-ketotic or ketotic.

- 46 -
 II====================================================== Chapter III

Table (2): glucose level, lipase and amylase activity, liver functions, and kidney function tests in different groups with
diabetic patients associated with or without ketosis.

Group (n) Glucose Lipase (µmol) Amylase GOT GPT ALP Urea Creatinine
mg/dl /FFA/ml) IU/L (IU/L) (mg/dl)

NIDDM without KA (8) 237±34.74 32.11±3.64 100.90±15.02 18.12±2.82 16.5±3.31 215.37±21.02 51±6.74 0.95±0.09

NIDDM with KA (8) 334±21.57* 69.96±5.08* 153.75±10.62* 33±8.21* 24.9±3.11* 300.13±47.45* 42±5.71 0.99±0.07

IDDM without KA (11) 172±25.80 22.16±2.25 65.20±15.22 26.91±5.2 22.27±2.29 271.91±44.8 46±11.45 1.68±0.31

IDDM with KA (13) 420±22.82* 25.48±2.24 66.20±6.45 25.30±2.09 46.92±19.84 296±35.76 62±12.24* 2.02±0.66*

IDDM Juvenile without 207±17.5 34.90±3.65 95.20±14.34 18.4±1.44 21.1±1.05 146.1±14.84 32±2.62 1.00±0.07
KA (10)
IDDM Juvenile with KA 343±22.55* 59.95±8.55* 248.1±27.74* 21.7±3.07 20.2±1.94 177.6±24.97 41±5.22 1.05±0.10
(10)

n: number of cases.
NIDDM: non-insulin dependent diabetes mellitus.
IDDM: insulin dependent diabetes mellitus.
KA: ketosis.
Data are expressed as means ± S.E.
*
indicates a significant difference between group with KA and groups without KA, at P<0.05 using Student’s-test.

- 47 -
II====================================================== Chapter III

500
Glucose

450
*

400
*
*
350
Glucose level (mg/dl)

300

250

200

150

100

50

0
NIDDM NIDDM with IDDM IDDM with IDDM IDDM
without KA KA without KA KA Juvenile Juvenile
without KA with KA

Figure (4): Represents Glucose level (mg/dl) in different studied groups with or
without ketosis (KA).

- 48 -
II====================================================== Chapter III

80
* Lipase

*
70

60
Lipase activity (µFFA/ml)

50

40

30

20

10

0
NIDDM NIDDM with IDDM IDDM with IDDM IDDM
without KA KA without KA KA Juvenile Juvenile
without KA with KA

Figure (5): Represents the Lipase Activity (mg/dl) in different studied groups
with or without ketosis (KA).

- 49 -
II====================================================== Chapter III

300
Amylase
*
250

200
Amylase activity (IU/l)

*
150

100

50

0
NIDDM NIDDM IDDM IDDM with IDDM IDDM
without KA with KA without KA KA Juvenile Juvenile

Figure (6): Represents the Amylase Activity (mg/dl) in different studied groups
with or without ketosis (KA).

- 50 -
II====================================================== Chapter III

400 GOT
GPT
ALP
350 *

300
Enzyme Activity (IU/L)

250

200

150

100

50 *
*
0
NIDDM NIDDM IDDM IDDM with IDDM IDDM
without KA with KA without KA KA Juvenile Juvenile
without KA with KA

Figure (7): Represents the mean values of serum GOT, GPT, and ALP (IU/L) in
different studied groups with or without ketosis (KA).

- 51 -
II====================================================== Chapter III

80
Urea
* Creatinine
70
serum urea and blood creatinine level (mg/dl)

60

50

40

30

20

10

*
0
NIDDM NIDDM with IDDM IDDM with IDDM IDDM
without KA KA without KA KA Juvenile Juvenile
without KA with KA

Figure (8): Represents the Level of serum urea and blood creatinine (mg/dl)
in different studied groups with or without ketosis (KA).

- 52 -
II====================================================== Chapter III

70 2.5
Urea
Creatinine
60
2

Blood Creatinine Level (mg/dl)

50
Serum Urea Level (mg/dl)

1.5
40

30
1

20

0.5
10

0 0
NIDDM without KA

IDDM without KA

NIDDM with KA

IDDM with KA

IDDM Juvenile with

IDDM Juvenile
without KA

KA

Figure (9): Represents the Level of serum urea and blood creatinine (mg/dl)
in different studied groups with or without ketosis (KA).

- 53 -
II====================================================== Chapter III

450 80

400 Glucose 70
Lipase
350
60

Lipase Activity (µg / FFA / ml)

Glucose Level (mg / dl)

300
50

250
40
200

30
150

20
100

50 10

0 0
NIDDM without KA

IDDM without KA

NIDDM with KA

IDDM with KA
IDDM Juvenile without

IDDM Juvenile with

KA
KA

Figure (10): Represents the relation between mean values of blood glucose
(mg/dl) and serum total lipase (µg/FFA/ml) in different studied
groups with or without ketosis (KA).

- 54 -
II====================================================== Chapter III

450 300

Glucose
400
Amylase
250
350

Amylase Activity (IU / L)

Glucose Level (mg / dl)

300 200

250
150
200

150 100

100
50
50

0 0
NIDDM without KA

IDDM without KA

NIDDM with KA

IDDM with KA
IDDM Juvenile

IDDM Juvenile with

without KA

KA

Figure (11): Represents the relation between the mean values of blood glucose
(mg/dl) and serum amylase (IU/L) in different studied groups with
or without ketosis (KA).

- 55 -
II====================================================== Chapter III

III-2. Determination of lipid components in diabetic patients:

II-2.1. Serum total lipids:

The value of serum total lipids of normal subjects ranged from 383-745
mg/dl with mean value ±SE. 557 ± 14 mg/dl. Serum lipid concentrations of all
diabetic patients were significantly higher as compared to the normal controls
(Table 3 and Figure 12). The level of total lipids was significantly higher in
male and female diabetic patients when compared to the corresponding normal
controls (Table 4 and Figure 13). Results demonstrate also that serum total lipid
concentrations were much higher in the ketotic and in the non-ketotic diabetic
patients in both males and females in comparison to the corresponding normal
controls (Table 5 and Figure 14a, 14b). In males with insulin-dependent diabetes
mellitus (IDDM), the serum total lipid level was significantly higher than that of
healthy control by 22%, while in females with non-insulin-dependent diabetes
mellitus- insulin treated (NIDDM-I) it was higher by 17% and 26% when
compared to the corresponding IDDM and control groups respectively (Table 6
and Figure 15a, 15b).

The results in table (7) and figure (16a, 16b) show the influence of
duration of diabetes on serum lipid pattern in diabetic of both sexes. The serum
total lipid concentrations of males with duration of diabetes < 3 years were
significantly higher from control by 29% and by 16% and 20% with duration of
3-6 and > 6 years respectively. The level of serum total lipids in males with
duration 3-6 years was significantly higher from the male control subjects. Thus
it is obvious that serum total lipids in males were decreased with the increasing
of the duration of diabetes. Females with duration of diabetes 3-6 and > 6 years
showed significant higher level of serum total lipids amounted to 16% and 25%
respectively than the control healthy subjects and 18% and 28% respectively as
compared to females with duration < 3 years. Regarding the influence of

- 56 -
II====================================================== Chapter III

diabetic control, table (8) and figure (17a, 17b) show a significant higher levels
of serum total lipids in male diabetics with well-, moderately –and poorly-
controlled diabetes as compared to control subjects by 19%, 20% and 14%
respectively, while in moderately –and poorly-controlled female diabetic
patients, the level of serum total lipids was significantly higher than normal
control, and normal level of serum total lipids in well-controlled patients.

II- 2.2. Serum cholesterol:

The value of serum cholesterol of normal subjects ranged from 110-279
mg/dl with mean value ±SE. 169 ± 6.0 mg/dl. The level of serum cholesterol of
all diabetic patients was significantly higher than that of controls (Table 3 and
Figure 12). Serum cholesterol concentration was significantly higher in female
diabetic patients as compared to controls (Table 4 and Figure 13). Serum
cholesterol concentration was significantly higher in the ketotic and the non-
ketotic female diabetic compared to control subjects. Among male diabetic
patients, no change in the level of cholesterol in the ketotic and the non-ketotic
diabetics was observed (Table 5 and Figure 14a, 14b). In normal subjects, the
level of serum cholesterol was significantly higher in the males with age >25
years as compared to the males with age < 25 years (Table 6). Thus, the
concentration of serum cholesterol rises with the age of normal male subjects.

Results show that, the level of serum cholesterol in males with IDDM was
higher by 20% than that of healthy control, while in females with NIDDM- I the
level of serum cholesterol revealed a significant higher level by 11% and 21% as
compared to the corresponding IDDM and control groups respectively (Table 6
and Figure 15a, 15b). Thus, the level of serum cholesterol was significantly
increased with the age of female patients.

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II====================================================== Chapter III

The concentration of serum cholesterol in female diabetics with duration

3-6 years was significantly higher as compared to control group. Female
diabetics with duration > 6 years showed also significant higher levels of serum
cholesterol by 17% and 24% comparing to females with duration < 3 years and
controls respectively (Table 7 and Figure 16a, 16b). In poorly-, moderately-or
well-controlled male diabetics, serum cholesterol level showed no significant
change as compared to control subjects. On the other hand, in poorly-and well-
controlled female diabetics, serum cholesterol concentration was significantly
higher as compared to control subjects. In poorly-controlled female diabetics,
there was a significant increase in serum cholesterol concentration as compared
to females with moderately-controlled diabetes (Table 8 and Figure 17a, 17b).
Thus, the concentration of serum cholesterol in females was much more affected
by the degree of the control of diabetes than has been found in males.

II-2.3. Serum phospholipids:

The value of phospholipids in normal subjects ranged from 106-269
mg/dl with mean value ± SE. 180 ± 8.0 mg/dl. Phospholipid concentrations of
all diabetic patient males and females were significantly higher as compared to
normal controls (Table 3 and Figure 12). The concentration of phospholipids
was also significantly higher in normal females than in normal males group. It
was significantly higher in normal females than in normal males group. It was
significantly higher in male diabetic patients as compared to controls (Table 4
and Figure 13). The level of phospholipids was significantly higher by 28% and
24% in both non-ketotic diabetic males and females respectively as compared to
the normal controls. In female diabetics, serum phospholipid concentrations
were significantly higher by 34% in the non-ketotic as compared to the ketotic
group (Table 5 and Figure 14a, 14b). The level of serum phospholipids was 30%
higher in normal males with age > 25 years as compared to normal males with
age < 25 years (Table 6). In males with IDDM, the level of serum phospholipids

- 58 -
II====================================================== Chapter III

showed a significant elevated concentration amount to 44% as compared to the

corresponding control. Serum phospholipid concentrations in females with
NIDDM-I were significantly higher by 45% than females with IDDM (Table 6
and Figure 15a, 15b).

In male diabetics with duration <3 years, serum phospholipid

concentrations were 40% significantly higher than control as well as 44% higher
than males with duration >6 years, however, in female diabetics, it showed no
significant change (Table 7 and Figure 16a, 16b).

II-2.4. Serum triglycerides :

The concentration of serum triglyceride ranged from 60-184 mg/dl with
mean value ± SE. 112 ± 6.0 mg/dl. Serum triglycride concentrations of all
diabetic patients were significantly higher as compared to normal control (Table
3 and Figure 12). Regarding the effect of sex in normal subjects, serum
triglyceride level was significantly higher in males as compared to females
group (Table 4). The level of serum triglycerides was significantly higher in
female diabetics as compared to control subjects (Table 4 and Figure 13). Serum
triglyceride concentrations were significantly higher by 58% in the ketotic male
and 63% in the ketotic female diabetic groups as compared to the respective
non-ketotic groups as well as significantly higher by 36% and 79% respectively
as compared to corresponding control subjects (Table 5 and Figure 14a, 14b).
Thus, the elevation of serum triglyceride level was more concomitant with the
ketotic state in either male or female patients and such elevation could not be
observed in the non-ketotic state. Level of serum triglycerides was significantly
higher in normal females with age <25 years as compared to normal females
with age >25 years (Table 6). Results show that in female diabetics, serum
triglyceride concentrations were significantly higher by 33% and 74% in both
IDDM and NIDDM-I groups respectively as compared to the corresponding

- 59 -
II====================================================== Chapter III

controls, but insignificant difference was obtained in male diabetics (Table 6 and
Figure 15a, 15b). Thus, the rise of serum triglycerides was more pronounced in
females, either IDDM or NIDDM-I groups.
The concentration of serum triglycerides in males with duration of
diabetes <3 years was significantly higher by 39% than corresponding controls
as well as by 36% and 50% than males with duration 3-6 and >6 years
respectively. Whereas, in females with duration 3-6 and >6 years, it was
significantly higher by 60% and 48% respectively as compared to controls
(Table 7 and Figure 16a, 16b). The level of serum triglycerides was significantly
higher in poorly-controlled male and females diabetics by 30% and 52%
respectively as compared to the corresponding control subjects and by 53% and
28% respectively as compared to the respective well-controlled diabetic groups.
In moderately-controlled male diabetics, it was significantly higher by 32% and
55% as compared to the corresponding control subjects and well-controlled
diabetics respectively, while in moderately-controlled female diabetics, it was
significantly lower by 26% as compared to poorly- controlled female diabetics
(Table 8 and Figure 17a, 17b).

II-2.5. Serume free fatty acids :

The concentration of serum FFA ranged from 8.0-19 mg/dl with mean
value ±SE. 13 ± 0.6 mg/dl in normal subjects. Serum FFA concentrations of all
diabetic patients were significantly higher as compared to normal controls
(Table 3 and Figure 12). The level of serum FFA was significantly higher in
both male and female diabetics as compared to corresponding controls (Table 4
and Figure 13). Serum FFA concentrations were significantly higher by 192%
and 100% in the ketotic and the non-ketotic male diabetics respectively and
143% and 107% in the ketotic and the non-ketotic female diabetics respectively
as compared to the corresponding control and were significantly higher by 46%
in the ketotic male as compared to the non-ketotic male diabetics (Table 5 and

- 60 -
II====================================================== Chapter III

Figure 14a, 14b). Serum FFA concentrations also were significantly higher by
142%, 114%, 185% and 162% in males and females with IDDM and males and
females with NIDDM-I respectively in comparison to the corresponding control
groups. Serum FFA concentrations were also 28% significantly higher in males
with NIDDM-I than corresponding IDDM group (Table 6 and Figure 15a, 15b).

Serum FFA concentrations were significantly higher in diabetic patients

independent of the duration of diabetes as compared to control (Table 7 and
Figure 16a, 16b). The level of serum FFA showed significant high level in all
diabetic groups with different degree of diabetics control as compared to control
subjects. In male diabetics with poorly-controlled, the level of serum FFA was
increased by 63% and 39% than in males with moderately- and well-controlled
diabetes respectively (Table 8 and Figure 17a, 17b).

Table (19-25) show the individual values of serum glucose level and lipid
components in normal subjects and different classes of diabetes.

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II====================================================== Chapter III

Table (3): serum glucose (mg/dl) and lipid components (mg/dl), (mean±SE.)
in diabetic patients (Figure in parenteses denote number of cases).

Groups Controls Diabetics

Parameters

Serum glucose 103±2.0 287± 24*

(mg/dl) (38) (85)

serum Lipid components

Total lipids 557±14 640±16*

(mg/dl) (38) (85)

Total cholesterol 169±6.0 188±4.0*

(mg/dl) (37) (85)

Phosholipids 180±8.0 208±10*

(mg/dl) (37) (85)

Triglycerides 112±6.0
(mg/dl) (36) 136±7.0*
(82)

Free fatty acids 13±0.6 30±2.0*

(mg/dl) (31) (76)

*: Significant difference from control at P <0.05.

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II====================================================== Chapter III

Table (4): Effect of sex on serum glucose (mg/dl) and lipid components (mg/dl),
(mean ± SE.) in diabetic patients (Figure in parentheses denote number
of cases).

Groups Male Female

Parameters Normal Diabetics Normal Diabetics

Serum glucose 101±3.0 288± 17* 104±3.0 287±18*

(mg/dl) (20) (45) (18) (40)

Serum Lipid
components

Total lipids 543±20 629±22* 571±21 652±24*

(mg/dl) (20) (45) (18) (40)

Total cholesterol 170±7.0 183±7.0 169±10 193±6.0*

(mg/dl) (19) (45) (18) (40)

Phosholipids 168±10 201±14* 194±11º 217±14*

(mg/dl) (20) (43) (17) (40)

Triglycerides 122±7.0 134±10 100±8.0 º 139±10*

(mg/dl) (19) (44) (17) (38)

Free fatty acids 12±1.0 29±2.3* 14±1.0 31±2.3*

(mg/dl) (16) (39) (15) (37)

*: Significant difference from the corresponding control at P<0.05.

ο : Significant difference from the corresponding male group at P<0.05.

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 II====================================================== Chapter III

Table (5): Serum glucose (mg/dl) and lipid components (mg/dl), (mean±SE.) in
Ketotic and non-ketotic diabetic patients (Figure in parentheses denotes
number of cases).

Groups Male Female

Non- Ketotic Non- Ketotic

Parameters
Controls ketotic diabetics Controls ketotic diabetic
diadetics diadetics

Serum glucose 101±3.0 256±22* 320± 24*# 104± 3.0 284± 24* 292± 29*
(mg/dl) (20) (23) (22) (18) (24) (16)

Serum Lipid
components

Total lipids 543±20 618±33* 654± 28* 571± 21 668± 33* 646± 32*
(mg/dl) (20) (22) (22) (18) (23) (16)

Total 170±7.0 182±8.0 184± 11 169± 10 169± 9.0* 195± 6.0*

cholesterol (20) (23) (22) (18) (24) (16)
(mg/dl)

Phosholipids 168±10 215±21* 184± 17 194± 11 241± 21* 180± 13#

(mg/dl) (20) (23) (20) (17) (24) (16)

Triglycerides 122±7.0 105±11 166± 15*# 100± 8.0 110± 9.0 179±16*#
(mg/dl) (19) (23) (21) (17) (22) (16)

Free fatty 12±100 24±3.0* 35± 3.0*# 14± 1.0 29 ±3.0* 34± 4.0*
acids (16) (21) (18) (15) (24) (13)
(mg/dl)

*: Significant difference from the corresponding control at P<0.05.

#: Significant difference from the corresponding non- ketotic diabetics at P<0.05.

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II====================================================== Chapter III

Table (6): serum glucose (mg/dl) and lipid components (mg/dl), (mean±SE.) in IDDM and NIDDM-I groups (Figure in
parenteses denote number of cases).

Parameters Glucose Total Total Phospho- Trigly- Free fatty

Sex Age lipids cholesterol Lipids Cerides Acids
Groups

Controls 99±6.0 520± 32 151± 6.0 144±13 125 ±13 12 ±1.0

(9) (9) (8) (9) (8) (8)
<25Years IDDM 329±25* 634± 26* 181± 8.0* 208± 20* 140± 14 29± 2.0*
(23) (23) (23) (21) (22) (20)
Male
Controls 102± 4.0 562± 24 184± 9.0º 187± 12º 120± 9.0 13± 1.0
>25Years (11) (11) (11) (11) (11) (8)
NIDDM-I 243± 18*º 623± 37 190± 10 179± 16 128±15 37± 4.0*º
(22) (22) (22) (21) (22) (17)
Controls 101± 4.0 598± 27 169 ±13 184± 20 125± 11 14± 1.0
(8) (8) (8) (8) (7) (7)
<25Years IDDM 367± 29* 593± 40 184± 8.0 160± 12 166± 11* 30± 3.0*
(16) (16) (16) (15) (14) (13)
Female
Controls 107± 4.0 550± 31 169 ±15 203 ±12 82± 8.0º 13 ±1.0
>25Years (10) (10) (10) (9) (10) (8)
NIDDM-I 234 ±16*º 691± 27*º 204± 8.0*º 232±14º 143 ±17* 34± 3.0*
(24) (24) (24) (23) (24) (2 1)

*: Significant difference from the corresponding control at P<0.05.

º: Significant difference from the corresponding IDDM group at P<0.05 and from the corresponding group with <25Years at
P<0.05.

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 II====================================================== Chapter III

Table (7): Effect of duration of diabetes on serum glucose (mg/dl) and lipid components (mg/dl) (mean±SE.) in male and
female diabetic patients (Figures in parenthese denote number of cases).

Parameters Glucose Total Total Phosho- Triglyce- Free

Sex Lipids Cholestrol lipids rides Fatty acids
Groups Duration(Years)

--- 101±3.0 543± 20 170 ±7.0 168± 10 122± 7.0 12 ±1.0

Controls (20) (20) (19) (20) (19) (16)
<3 250± 26* 701± 48* 183 ±12 235 28* 169± 17* 30± 3.0*
Male (15) (15) (15) (11) (12) (15)
3-6 322± 28* 603± 29*º 175± 9.0 205± 25 124± 13* 31± 3.0*
Diabetics (15) (15) (15) (14) (15) (13)
>6 290± 32* 582± 32* 191± 13 163 ±12* 113 ±18* 23± 3.0*#
(15) (15) (15) (15) (12) (8)
--- 104± 3.0 571± 21 169 ±10 194± 11 100± 8.0 14± 1.0
Controls (18) (18) (18) (17) (17) (15)
<3 264± 27* 558± 38 180± 8.0 203± 22 123± 14 31± 3.0*
Female (13) (13) (13) (13) (13) (13)
3-6 239± 21* 660± 37*º 195± 11* 213± 22 160± 27* 32± 4.6*
Diabetics (12) (12) (12) (12) (12) (10)
>6 345± 35*º# 414± 42*º 210 ±10*º 195 ±16 148± 14* 35± 4.0*
(15) (15) (15) (13) (14) (11)

* Significant difference from the corresponding control at P<0.05.

ο Significant difference from the corresponding diabetics with duration less than 3 years at P<0.05.
# Significant difference from the corresponding diabetics with duration 3- 6 years at P<0.05.

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II====================================================== Chapter III

Table (8): Serum glucose (mg/dl) and lipid components (mg/dl), (mean±SE.) in male and female index patients (figure
in parenteses denote number of cases).

Parametres Glucose Total Total Phospho- Triglycerides Free

Sex lipids cholesterol Lipids fattyAcids
Groups

Controls 101±3.0 543± 20 170± 7.0 168± 10 122± 7.0 12 ±1.0

(20) (20) (19) (20) (19) (16)
Well-controlled diabetics 164± 7.0* 645± 53* 187± 13 173± 12 104± 11 28± 2.0*
Male (14) (14) (14) (11) (13) (11)
Moderately- controlled diabetics 259±8.0* 653± 39* 181± 14 212± 27 161± 21*º 24± 3.0*
(12) (12) (12) (11) (11) (9)
Poorly-controlled diabetics 396± 16*º# 617± 23* 180± 10 186± 20 159± 10*º 39± 4.0*º#
(19) (18) (19) (19) (15) (15)
Controls 104± 3.0 571± 21 169± 10 194± 11 100± 8.0 14± 1.0
(18) (18) (18) (17) (17) (15)
Well-controlled diabetics 171± 9.0* 638± 39 196± 9.0* 211± 17 119± 17 35± 4.0*
Female (12) (11) (10) (12) (9) (9)
Moderately- controlled diabetics 256± 7.0*º 646± 32* 179± 7.0 200± 19 113± 14 32± 4.0*
(14) (13) (14) (12) (10) (13)
Poorly-controlled diabetics 417± 22*º# 654± 37* 198± 8.0*# 184± 18 152± 7.5*º# 32± 4.0*
(14) (14) (14) (13) (13) (12)

* Significant difference from the corresponding control at P<0.05.

ο Significant difference from the corresponding diabetics with well-controlled diabetics at P<0.05.
# Significant difference from the corresponding diabetics with moderately- controlled diabetics at P<0.05.

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II====================================================== Chapter III

360

320
*
% Change of normal control ± SE

280

240 *

200

160
* * *
120
*

80

40

G TL TC PL TG FFA

Figure (12): Serum glucose, lipid pattern, in all diabetic patients (the values are
expressed as percent change of normal control).
*significant difference from control at P <0.05.
G: glucose, TL: total lipids, TC: cholesterol, PL: phospholipids,
TG: triglycerides, FFA: free fatty acids.

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II====================================================== Chapter III

360
Male
320 Female
*
*
% Change of normal control ± SE

280

240
*
*
200

160
* *
* *
120
*

80

40

0
G TL TC PL TG FFA

Figure (13): Serum glucose, lipid pattern, in male and female diabetic patients
(the values are expressed as percent change of normal control).
* Significant difference from control at P<0.05.
G: glucose, TL: total lipids, TC: cholesterol, PL: phospholipids, TG:
triglycerides, FFA: free fatty acids.

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II====================================================== Chapter III

400
Non-ketotic
360 Male Ketotic
*
#
320
*#
% Change of normal control ± SE

280 *
240

200
*

160 * * * *#

120

80

40

0
G TL TC PL TG FFA

Figure (14a): Serum glucose, lipid pattern, in Male non-ketotic and ketotic
diabetic patients (the values are expressed as percent change of normal control).
* Significant difference from control at P<0.05.
# Significant difference from the corresponding non-ketotic diabetics at P<0.05.
G: glucose, TL: total lipids, TC: cholesterol, PL: phospholipids, TG:
triglycerides, FFA: free fatty acids.

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II====================================================== Chapter III

400

Female Non-ketotic
360 Ketotic

320 *
*
% Change of normal control ± SE

280

*
240
*
200 *#

160 * * *
* *
120 #

80

40

0
G TL TC PL TG FFA

Figure (14b): Serum glucose, lipid pattern, in Female non-ketotic and ketotic
diabetic patients (the values are expressed as percent change of normal control).
* significant difference from control at P<0.05.
# significant difference from the corresponding non-ketotic diabetics at P<0.05.
G: glucose, TL: total lipids, TC: holesterol, PL: phospholipids, TG:
triglycerides, and FFA: free fatty acids.

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II====================================================== Chapter III

400
IDDM
360 * Male
NIDDM

320
*#
% Change of normal control ± SE

280
*#
*
240

200

*
160
*
*
120

80

40

0
G TL TC PL TG FFA

Figure (15a): Serum glucose, lipid pattern, in Male diabetic patients with
IDDM and NIDDM (the values are expressed as percent change of normal
control).
* significant difference from control at P<0.05.
# significant difference from the corresponding non-ketotic diabetics at P<0.05.
G: glucose, TL: total lipids, TC: holesterol, PL: phospholipids, TG:
triglycerides, and FFA: free fatty acids

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II====================================================== Chapter III

440
IDDM
Female
400 * NIDDM

360
% Change of normal control ± SE

320

280 *
240 *#
*
200 *
160
*#
*# # *
120

80

40

0
G TL TC PL TG FFA

Figure (15b): Serum glucose, lipid pattern, in Female diabetic patients with
IDDM and NIDDM (the values are expressed as percent change of normal
control).
* significant difference from control at P<0.05.
# Significant difference from the corresponding non-ketotic diabetics at P<0.05.
G: glucose, TL: total lipids, TC: holesterol, PL: phospholipids, TG:
triglycerides, and FFA: free fatty acids

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II====================================================== Chapter III

400
Less than 3 years
Male
360 *# 3-6 years
More than 6 years

320 *
% Change of normal control ± SE

280 *
*
*
240

200 *º
* *
160 *# *
* #
120 #
*
80

40

0
G TL TC PL TG FFA

Figure (16a): Serum glucose, lipid pattern, in Male diabetic patients with
different duration of disease (the values are expressed as percent change of
normal control).
* Significant difference from control at P<0.05.
# Significant difference from the corresponding diabetics with duration of
disease less than 3 years at P<0.05.
º Significant difference from the corresponding diabetics with duration of
disease less than 3-6 years at P<0.05.
G: glucose, TL: total lipids, TC: holesterol, PL: phospholipids, TG: riglycerides,
and FFA: free fatty acids

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II====================================================== Chapter III

440
Less than 3 years
400 Female 3-6 years
*#º More than 6 years

360
% Change of normal control ± SE

320

280 *
*
*
*
240 *
200
*# *
160 *# *
*#
*
120

80

40

0
G TL TC PL TG FFA
Figure (16b): Serum glucose, lipid pattern, in Female diabetic patients with
different duration of disease (the values are expressed as percent change of
normal control).
* Significant difference from control at P<0.05.
# Significant difference from the corresponding diabetics with duration of
disease less than 3 years at P<0.05.
ºsignificant difference from the corresponding diabetics with duration of disease
less than 3-6 years at P<0.05.
G: glucose, TL: total lipids, TC: holesterol, PL: phospholipids, TG:
triglycerides, and FFA: free fatty acids

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II====================================================== Chapter III

480
Well-controlled
440 Male Moderately-controlled
*#o Poorly-controlled
400

360
% change of normal control ± SE

*#
320 o

280 *#
*
240
*
200 * *
* *#
160 *#
*
120

80

40

0
G TL TC PL TG FFA

Figure (17a): Serum glucose, lipid pattern, in male diabetic patients (the values
are expressed as percent change of normal control).
* Significant difference from control at P<0.05.
# significant difference from the corresponding diabetics with duration of
disease less than 3 years at P<0.05.
º Significant difference from the corresponding diabetics with duration of
disease less than 3-6 years at P<0.05.
G: glucose, TL: total lipids, TC: holesterol, PL: phospholipids, TG:
triglycerides, and FFA: free fatty acids

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II====================================================== Chapter III

480
Well-controlled
440 *#o Female
Moderately-controlled
Poorly-controlled

400

360
% Change of normal control ± SE

320

280
*# *
240 * *
200
* *#o
160 * *
* *o
120

80

40

0
G TL TC PL TG FFA

Figure (17b): Serum glucose, lipid pattern, in Female diabetic patients (the
values are expressed as percent change of normal control).
* Significant difference from control at P<0.05.
# Significant difference from the corresponding diabetics with duration of
disease less than 3 years at P<0.05.
º Significant difference from the corresponding diabetics with duration of
disease less than 3-6 years at P<0.05.
G: glucose, TL: total lipids, TC: holesterol, PL: phospholipids, TG:
triglycerides, and FFA: free fatty acids

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II====================================================== Chapter III

III-3. Determination of urinary protein and diabetic

nephropathy in diabetic patients

Data for distribution among juvenile and adult diabetic cases in relation to
the different parameters namely: age, duration of the disease and type of the
treatment are given in Table 9 (Fig 18), Table 10 (Fig 19) and Table 11 (Fig 20).
Values for urine total protein in 10 subjects of healthy controls varied from 10-
70 (mean 40±6.32 mg/dl).

Table (9): The distribution of age range among the 115 diabetic patients.

Age range Females Males

(years) (n=70) (n=45)

10 - 25 years 14 juvenile cases 14 juvenile cases

25 - 40 years 11 adult dibetics 11 adult diabetics

40 - 50 years 25 adult diabetics 7 adult diabetics

> 50 years 20 adult diabetics 13 adult diabetics

n= number

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II====================================================== Chapter III

30
Females
Males

25
Number of diabetic patients

20

15

10

0
10-25 years 25-40 years 40-50 years > 50 years

Figure (18): The distribution of age range among the 115 diabetic patients (45
males and 70 females).

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II====================================================== Chapter III

Table (10): The duration of the disease* among the 115 diabetic patients.

Duration N of females N of males

Up to 6 month 7 7

6 months to 1 year 7 7

1 – 5 years 17 8

5 - 10 years 28 9

10 - 15 years 7 7

15 - 20 years 4 7

* According to clinical notes and laboratory detection

N: Number of cases

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II====================================================== Chapter III

30
Females
Males

25
Number of diabetic patients

20

15

10

0
Up to 6 6 months to 1-5 years 5-10 years 10-15 years 15-20 years
month 1 year

Figure (19): The duration of the disease among the 115 diabetic patients (45
males and 70 females).

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 II====================================================== Chapter III

Table (11): The distribution according to line of treatment among the 115 diabetic
patients.

Type of treatment N of females N of males

Insulin 42 30

Hypoglycaemic drugs 17 8

Insuline+hypoglycaemic 11 7

N: Number of cases

- 83 -
II====================================================== Chapter III

45
Females
Males
40

35
Number of diabetic patients

30

25

20

15

10

0
Insulin Hypoglycaemic drugs Insuline+hypoglycaemic

Figure (20): The distribution according to the line of treatment among the
115diabetic patients (insulin, hypoglycemic drugs and insulin+
hypoglycemic drugs).

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II====================================================== Chapter III

Sample electrophoresis revealed a single spot of albumin, but the

immunoelectrophoretic analysis of concentrated urine revealed a well defined
albumin pattern. In addition, a hazy defined precipitation shadows could be
noticed in the area β-globulin in concentrated urine of few cases.

Distribution of the urinary total proteins according to age range is shown

in Table 12 (fig 21). The mean values of urinary total proteins have shown
highly significant values in diabetics as compared to control.

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 II====================================================== Chapter III

Table (12): Urinary total proteins (mg/dl) distribution among the different ages in juvenile and adult diabetic patients
groups.

Juvenile diabetic cases (28) Adult diabetic cases (87)

<25 Years >25 Years

Age range 10 - 25Years 25 – 40Years 40 - 50 Years > 50 Years

Sex Male Female Male Female Male Female Male Female

N (14) (14) (11) (11) (7) (25) (13) (20)

Range 51.2-130.9 39.5-81.55 40-96.4 55.3-102.3 38.21-90.45 58.8-369.4 42.7-112.2 44.1-725.8

Mean 94.700 64.43 65.14 72.20 69.27 94.27 71.58 111.90

±S.E. 0.173* 3.04* 4.79* 4.71* 6.53* 12.25* 4.95* 33.54*

* Statistically significant difference from the control group.

N: Number of cases.

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II====================================================== Chapter III

120
male *
female
The mean values of urinary total proteins (mg/dl)

100 * *
*
80
* * *
*
60

40

20

0
10-25years 25-40years 40-50years >50years

Figure (21): The mean values of urinary total proteins (mg/dl) distribution
among the different ages in juveniles (10-25 years) and adults
(> 25 years) diabetic patients groups.

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II====================================================== Chapter III

The distribution of urinary total proteins according to sex is shown in

Table 13 (Fig 22). Normal values of 40 mg or less/dl urine have been
demonstrated in only 2.60% of whole diabetic patients. Partial proteinuria (40-
100 mg/dl) occurred among 80.90%, whereas proteinuria (more than 100 mg/dl)
was demonstrated in 16.50% of whole patients.

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II====================================================== Chapter III

Table (13): Distribution of the level of urinary proteins (mg/dl) among the 115
Diabetic patients.

Level of proteins(mg/dl) % of female cases % of male cases

< 40 mg/dl ------- 6.66%

> 40 - 100 mg/dl 82.86% 77.78%

> 100 - 200 mg/dl 12.85 15.56%

> 200 – 300 mg/dl 1.43% -------

> 300 mg/dl 2.86% -------

- 89 -
II====================================================== Chapter III

90%
female cases
male cases
80%

70%

60%
% of diabetic patients

50%

40%

30%

20%

10%

0%
<40 mg/dl >40-100 >100-200 >200-300 >300 mg/dl
mg/dl mg/dl mg/dl

Figure (22): Distribution of the level of urinary proteins (mg/dl) among 115
Diabetic patients.

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II====================================================== Chapter III

The distribution of diabetic patients, according to the type proteinuria

among both sexes is shown in Table 14 (Fig 23). Proteinuria of not more than
100 mg protein per 100 ml urine have shown a type of selectivity in 83.50% of
whole patients; whereas proteinuria of more than 100 mg/dl, have shown a type
of non selectivity 16.50% among all of diabetic patients.

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II====================================================== Chapter III

Table (14): Distribution according to the type of proteinuria among the 115
diabetic patients.

Type of proteinuria % of female cases % of male cases

Selective 82.86% 84.44%

Non selective 17.14% 15.56%

90
Selective
Non-selective
80

70

60
% of diabetic patients

50

40

30

20

10

0
females males

Figure (23): Distribution according to the type of proteinuria (selective or non

selective) among 115 diabetic patients.

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II====================================================== Chapter III

Table 15, reveals the percentage numbers of occurrence of different

protein components among the cases showing proteinuria of less or more than
100 mg/dl. Albumin and occasionally transferrin and ceruloplasmin were
detected in the urine of selective group whereas proteins of relatively high
molecular weight such as; IgA and IgG were excreted in the urine of the non
selective group.

Selective proteinuria was demonstrated in 58 females (82.86%) and

38 males (84.44%), whereas the non selective type was seen only in 12 females
(17.14%) and 7 males (15.56%).

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 II====================================================== Chapter III

Table (15): Percentage number of urinary protein components as heavily detected by immunoelectrophoresis in diabetic
patients.

Type of Diabetics Sex Albumin α1-Acid α1-Anti- Gc- Cerulo- Hemo- Trans- IgA IgG
Proteinuria glycoprotein trypsin Globulin plasmin pxin ferrin

Juvenile M(12) 100% ----- ----- ----- ----- ----- ----- ----- -----
Selective (26) F(14) 100% ----- ----- ----- ----- ----- ----- ----- -----
( <100mg/dl)
Adults M(26) 100% ----- ----- ----- 3.85% ----- 15.4% ----- -----
(70) F(44) 100% ----- ----- ----- 9.10% ----- 27.3% ----- -----

Juvenile M(2) 100% 20.0% ----- ----- 100% ----- 100% 100% 100%
Non-selective (2) F---- ----- ----- ----- ----- ----- ----- ----- ----- -----
( >100mg/dl)
Adults M(5) 100% 20.0% 20.0% 20.0% 20.0% ----- 100% 60% 100%
(17) F(12) 100% 41.7% 41.7% 25.0% 100% 25.0% 100% 100% 100%

M: Male cases
F: Female cases
... Absent

- 94 -
 CHAPTER IV

DISCUSION
II=======================================================Chapter IV

DISCUSSION

Acidosis is a serious complication of uncontrolled diabetes which may

lead to diabetic coma and death if not treated. Acidosis results from a lack of
insulin preventing the diabetic from properly using sugar for energy production.
If this source of energy is not available, the body turns to fat stores for energy
and large amounts of fat are broken down, acid ketones are produced causing
acidosis. High amounts of ketones accumulate in blood eventually spill over into
the urine.

In ketotic diabetic patients, acidosis, dehydration and blood glucose can

be elevated to such degree that independent of plasma pH and the
hyperosmolarity of the plasma can cause unconsciousness. Accumulation of
lactic acid in the blood (lactic acidosis) may also complicate diabetic
ketoacidosis if the tissue becomes hypoxic and lactic acidosis may itself cause
coma, (Ganon, 1982) . (Yadav et al, 2000), reported that amylase and lipase
estimations are the standard tests to diagnose acute pancreatitis. Diagnostic
efficiency for pancreatic disease using serum pancreatic amylase, lipase and
total amylase tests were 94.1% 76.5% and 74.7%, respectively (Apple, et al
1991). These data may also suggest that, total amylase might be considered as
the routine laboratory test for the diagnosis of pancreatic tissue injury.

Although, the clinical diagnosis (anorexia, lethargy, vomiting, abdominal

pain and diarrhea) are difficult to predict the pancreatitis, the elevation of some
enzymes produced by the pancreas can be measured in the blood and may
suggest the disease. The exact cause of pancreatitis is unknown and pancreatitis
can cause diabetes or vise versa. In pancreatitis, inflammation can become
severe and the digestive enzymes that are normally inactive can become active
and cause damage to the pancreas. This initials a cycle of increasing
inflammation (Miura et al, 2002).

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II=======================================================Chapter IV

In our cases ( type 1 DM ), the kidney function test, both blood urea and
serum creatinine values were slightly significantly increased in adult insulin
dependent diabetic ketosis ( DK ) as compared to their corresponding values in
cases without ketosis.

In other cases (Ibrahim et al., 2006) with non insulin dependent diabetic
ketosis, the activity of both liver and pancreatic enzymes was significantly
increased as compared to their corresponding values in diabetic cases without
ketosis. In such cases, ketosis is not common at the time of diagnosis because
the pancreas can still secrete the minimal concentration of insulin required for
the suppression of lipolysis. However, with the progression of the disease,
especially when long-term glycemic control is not adequate, pancreatic β-cell
dysfunction can be so severe that insulin treatment is necessary (Mahler and
Adler, 1999). Vacca et al., (1964) found variable levels either high or low
serum amylase activity in human diabetes which might be due to chronic
pancreatitis involvement in this condition. However, striking elevation of serum
lipase levels and elevations of serum amylase in diabetic ketoacidosis with no
objective evidence of abdominal pain, suggest the association of asymptomatic
elevations with diabetic ketoacidosis (Nsein, et al., 1992). In children with
insulin dependent diabetes mellitus (IDDM) without ketosis, the exocrine
pancreatic function seemed to be normal (Lorini, et al., 1990) as no significant
variations could be observed in serum urinary amylase and lipase enzymes.
In the group of juvenile diabetic children, recurrent vomiting and abdominal
pain were associated with ketosis where in some of them the condition was
similar to that seen in peritonitis or appendicitis. Clinical examination often
reveals a deep pain on pressure over the pancreas. The recognition of the
condition of ketonuria is therefore of great importance (Emest and David,
1955). Operative interference in such cases without treatment of the acidosis is

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an extremely risky undertaking. Lipase and amylase are two digestive enzymes
produced by the pancreas and elevations in these enzymes may indicate
pancreatitis. (Henderson et al., 1981) also reported that the endocrine pancreas
has a marked influence on exocrine pancreatic secretions.
In our studies although the function of liver enzymes is normal the
pancreatic endocrine and exocrine enzymes are often elevated in juvenile
diabetic ketoacidosis. (Lorini et al., 1990), during their studies on pancreatic
function in children and adolescents, showed that exocrine pancreatic function
might be abnormal in children with IDDM. The exocrine pancreas in human
insulin dependent diabetics is much smaller than normal and it is thought that
insulin is required for the synthesis of pancreatic enzymes and maintenance of
the size of the pancreas (Henderson et al, 1981).

Serum pancreatic enzymes including amylase and lipase were

significantly increased in 10 juvenile ketotic diabetic cases (6F+4M) as
compared to 10 diabetic children with non ketosis (4F+6M). Such cases
developed ketotic diabetes and requiring intensive insulin therapy during the
course of disease.
Childhood diabetes mellitus is mostly insulin dependent and is caused by
autoimmune destruction of the pancreatic islet β-cell.
Bouhours and Coutant, (2005), found that the annual incidence is increasing in
France (10 new cases/100,000 children between 0 and 15 years of age) and
ketoacidosis occurs in 25% of newly diagnosed diabetes. β-cell auto antibodies
(ICA, anti-GAD, anti insulin and anti-IA2) are present in at least 90% of
children with newly diagnosed diabetes (Bouhours and Coutant, 2005).
In comparison to our non ketotic diabetic children, Ibrahim et al., (2006)
has observed that the mean values of both lipase and amylase enzymes were
concomitantly increased (2.3 and 3.4 times, respectively) in 5 out of 10 cases
associated with diabetic ketosis. These abnormalities could be explained by the

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fact that the pancreatic malfunction in these cases is injured and pancreatitis may
cause diabetes in such cases with ketosis. It can be also concluded that, the level
of pancreatic enzymes (lipase and amylase) may occur concomitantly due to
swelling of pancreas and the severity of disease in ketotic patients as compared
to non ketotic children.

In these patients with ketosis the ratio of females to males was markedly
high (60%) as compared with the group without ketosis (40%).
Otani et al., (1990) surveyed the age of onset of Japanese younger diabetics in
Tokyo and showed that many cases of diabetes had its onset during junior high
school. It is assumed that a rapid and large amount of glucose inflow and
relative insulin deficiency played an important in precipitating diabetic
ketonuria.
In France, type 1diabetes in children is frequently diagnosed at the stage
of ketoacidosis (Blanc and Tubiana, 2003) and the children in low economic
intake families exhibited more frequently a severe DKA and were more
frequently misdiagnosed before admission. Total calories intake per day and
dietary contents of carbohydrate were significantly higher in patients with
ketonuria (Matsui et al., 2005), than in those patients without ketonuria.
Although basal amylase and/or lipase in blood are reliable diagnosed in acute
pancreatitis, their utility is low in chronic pancreatic diseases (Lenti and
Emanulli, 1976).
From the present study (Ibrahim et al., (2006), it has been suggested that,
diabetes caused by insulin insufficiency and digestion defects or mal absorption
is a result of ketonuria and the diffuse pancreatic destruction. Coma is known to
be serious and unless proper treatment is available death would be the result.
In our results, the data given for serum lipid components in normal
subjects were somewhat deviated as compared to a number of authors in
different localities. The contradiction between these values is most probably due

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to differences in the socio-economic status between the normal groups or the

sensitivity of fatty acid levels to the nutritional state and exercise of the subjects
(Strafford, 1968).
The levels of the blood lipids are affected by a multitude of factors such
as race, heredity, age, sex, hormone, diet, physical activity, season and method
of analysis. In diabetic Senegalese, the lipid components of blood were
increased in relation to those of healthy Senegalese, which are lower than those
of diabetic Europeans. It appears that, diabetic Senegalese have the same lipid
level as healthy Europeans (Josselin et al., 1976). The variations of serum total
lipids with age and sex are different among different populations related to
dietary habits, and life style (Hanz-hong et al., 1986).

Thus, the higher fatty acids in diabetic persons may augment the
hyperglycemia observed in our results. Plasma free fatty acids (FFA)
concentration in diabetes mellitus may act on the liver to stimulate endogenous
glucose production by gluconeogensis. Oxidation of FFA produces acetyl CoA
which is important activator of pyruvate carboxylase, pyruvate carboxylase is
one of a key gluconeogenic enzyme which converts pyruvate to oxaloacetate in
the presence of carbon dioxide and ATP (Williamson et al., 1968).
Ferrannini et al., 1983, concluded that, in the well- insulinized state raised FFA
levels effectively compete with glucose for uptake by peripheral tissues,
regardless of the presence of hyperglycemia. When insulin is deficient, on the
other hand, elevated rate of lipolysis may contribute to hyperglycemia not by
competition for fuel utilization, but through an enhancement of endogenous
glucose output in normal subjects under certain condition.
In our group of diabetic patients as a whole, the mean value of serum total
lipids reported in the present results was significantly higher than that found in
the control healthy group. Such hyperlipidemia was in accordance to
observations reported by many investigators in human (Garcia et al., 1974;

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Debry et al., 1979) as well as in alloxan diabetic rats (Wilson et al., 1987). The
observed elevation of serum total lipids in our results was explicable in terms of
significant increased level in serum triglycerides, cholesterol, phospholipids and
free fatty acids.

There is much evidence of the increased frequency of hyperlipidemia in

the clinical diabetic, often associated with hypertriglyceridemia and occasionally
with hypercholesterolemia (Kennedy et al., 1978). The increased level in serum
triglycerides in diabetic patients is in agreement with what has been reported by
other authors in humans (Laakso et al., 1987) and in alloxan diabetic rats
(Durrington and Stephens, 1980).
The mechanism responsible for the elevation of serum triglycerides in
different types of diabetes is not uniform. Increased hepatic endogenous
synthesis of serum triglycerides has been demonstrated in diabetic animals and
humans (Nikkila and Kekki, 1973) through the incorporation of labeled glycerol
in triglycerides secreted from the liver to suprahepatic veins. One explanation to
the increased level of serum triglycerides in our results is the observed elevation
of serum FFA in diabetic subjects.

The lack of Insulin in diabetes mellitus probably affects adipose tissue

more than other tissues, because of its extreme sensitivity to this hormone; also
it may result in over mobilization of FFA from adipose tissue and increased
uptake by the liver (Elkeles, 1983; Williamson, 1988). FFA are released in
quantities that give rise to FAA levels in plasma more than twice than those in
fasting normal subject. Fasting diabetic patients often have elevated levels in
serum FFA (Yao et al., 1981; Abrams et al., 1982). Serum FFA play an
important role in determining VLDL-triglycerides output. There are two roads
for serum FFA metabolism, an oxidative pathway and the other is non–oxidative
one (Taskinen et al., 1985). The latter would be a component related to

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II=======================================================Chapter IV

triglycerides production (Taskinen et al., 1986). Increased level of serum FFA

was reported to stimulate the hepatic production of triglycerides (Weiland et al.,
1980).
Our results showed that the concentration of serum triglycerides is
positively correlated with the blood glucose concentrations in both male and
female patients. Moreover, the levels of serum triglycerides in moderately - and
poorly- controlled males were significantly higher than that of the corresponding
well- controlled and healthy subjects. In females, the level of serum
triglycerides in poorly-controlled patients was significantly higher than that of
the corresponding well-moderately-controlled and healthy subjects. This is in
agreement with the previous reports showing a direct relationship between
concentration of serum triglycerides and the degree of diabetic control. George
et al., (1978) and Sabry et al., (1983b) reported that insulin treatment could
lower triglycerides concentrations but the level was still higher than the healthy
subjects. Zimmerman et al., (1981), reported that there is a relation between
fasting blood glucose and triglyceride concentrations. However Wile Briones et
al., (1984) reported insignificant relation between glucose level and serum
triglycerides concentrations.
In our results, the observed decrease level in serum triglycerides in well-
controlled diabetics may be due to decrease in the level of serum FFA. Serum
FFA in well-moderately - controlled diabetic males were significantly decreased
as compared to poorly - controlled but still higher than in normal subjects.
Insulin stimulates also lipogenesis in adipose tissue by providing the
α1-glycerophosphate involved in triglyceride synthesis. It provides the
α1-glycerophosphate by promoting also the flux of glucose intracellularly and
the production via glycolysis of α1- glycerophosphate (Saudek and Eder, 1979).

The most significant effect of insulin is to promote the reesterification of

free fatty acids rather than to depress hormone - sensitive lipase (Saudek and

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II=======================================================Chapter IV

Eder., 1979). Murthy and Shipp (1979) found that insulin reversed the increase
of FFA in diabetic rats to normal value. However, George et al., (1978) found
that the treatment with insulin did not affect the level of FFA and that the
treatment with the oral hypoglycemics such as gilbenclamide, chlorpromazine
and biguanide caused reduction in FFA level in diabetic patients. Moreover,
insulin stimulates the de novo synthesis of fatty acids in mammalian liver,
adipose tissue, intestine and lactating mammary glands (Robinson and Speake,
1988) by providing the acetyl-CoA and NADPH required for fatty acid synthesis
(Granner, 1988).

In our results the rise of serum triglycerides was more pronounced in

females, either with insulin-dependent diabetes mellitus (IDDM) or with non-
insulin-dependent diabetes mellitus-insulin treated (NIDDM-I), than in male
patients. This is indicated by the increase of serum triglyceride concentrations in
females with IDDM and NIDDM-I by 33% and 74% respectively than in the
corresponding control. Similar observation was also, reported by Mattock et al.,
(1979) and Walden et al., (1984). However, the rise in serum triglyceride level
in our results is not detected in male patients. This was in agreement with
Winocour et al., (1986) who found no significant change in the level of serum
triglycerides in male diabetic patients as compared to control. These differences
in serum triglycerides may be related to a greater adverse effect of diabetes on
triglyceride concentration in diabetic females than in diabetic males. This may
explain the high risk of arteriosclerosis in diabetic females (Beach and
Strandness, 1980; Wingard et al., 1981), since in diabetic patients both
coronary and peripheral arteriosclerosis appear to be most closely associated
with hypertriglyceridemia (Beach et al., 1979). Knopp et al., (1981) observed a
great increase in circulated VLDL in pregnant and estrogen treated animals.
Moreover, Hazzard et al., (1969), suggested that estrogen may elevate serum
triglyceride levels through increased triglyceride synthesis and in put into

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II=======================================================Chapter IV

plasma. VLDL is formed in the liver and transport triglycerides formed from
fatty acids and carbohydrates in the liver to extra hepatic tissues (Mayes,
1988b). Also it has been reported by Nikkila, (1973), in diabetic patients and by
Kantardzhyan, (1976) and Saatov et al., (1980) in diabetic rats.
Since, in normal subjects, serum triglyceride levels reveal higher values
among males than in females, normal females usually have less arteriosclerosis
vascular disease than in males as reported by Beach and Strandness, (1980).
Similarly Sabry et al., (1983a), found that serum triglycerides showed constant
higher values in males than in females of healthy Egyptian subjects aged from
16-74 years. This may be also explained by the suggestion that administration of
estrogen facilitates the assimilation of VLDL and chylomicrons remnant by liver
in females (Kushwaha et al., 1977).
Our results showed that the significant increase of serum triglycerides in
normal females with age <25 years than in age >25 years. Our data showed that,
the elevation of serum triglyceride levels was more concomitant with the ketotic
state in either male or female diabetic patients and such elevation could not be
observed in the non-ketotic state. Similar finding were reported by Court et al.,
(1978) in diabetic children and by Wilson et al., (1987) in diabetic rats. This
increment may be due to the increase of hepatic triglyceride synthesis, since, the
hepatic cytosolic phosphatidate phosphohydrolase activity was markedly
increased in the ketotic diabetic state (Murthy and Shipp, 1979), by its
movement from the cytosol to the endoplasmic reticulum where phosphatidate,
the inter-mediate in the synthesis of triglycerides, is synthesized (Brindley,
1988).
Since, serum FFA play an important role in formation of ketone bodies, a
consequence of its increase cause accumulation of acetyl CoA and rapid
conversion to ketone bodies by the liver (Keller et al., 1977). However,
concentration of serum FFA can be elevated without ketosis (Watkins et al.,
1970). Our results showed that the level of serum FFA in ketotic state was

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II=======================================================Chapter IV

higher than in non-ketotic state in both sexes of either males or females but the
increment was only significant in male patients. Since, serum FFA are known to
be the sole precursors of the carbonyl carbon of acetoacetate, they are rate
limiting for maintenance of ketotic state in establishing acetoacetate diabetic
ketoacidosis (Axelrod et al., 1979).

In our diabetic group of patients, the observed increase of serum

cholesterol was in agreement with the results obtained in diabetic human by
other authors (Palmumbo et al., 1976; Mattock et al., 1979), as well as on
alloxan diabetic animals (Saatov et al., 1980). However, Sarlund et al., (1987)
found that, no significant difference was obtained in the level of serum
cholesterol in diabetic and non-diabetic subjects. The observed increase of
serum cholesterol level in diabetic patients may be due to increased synthesis of
cholesterol. The increased synthesis of cholesterol in diabetic patients was
reported by (Abrams et al., 1982).
The rise of cholesterol in diabetic patients is thought to originate from
increased production through synthesis from acetate fragments. The activity of
HMG-CoA (3- hydroxyl- 3- methylglutaryl - Coenzyme -A) reductase, the rate
limiting enzyme in cholesterol synthesis is increased in intestinal crypt cells of
diabetic rats (Nakayama and Nakagawa, 1977). Beside, insulin deficiency has
been found to stimulate intestinal synthesis of cholesterol (Nakayama and
Nakagawa, 1977), although, such deficiency has suppressing effect on hepatic
cholesterogenesis. Thus, insulin - deficiency, has been found as an opposing
effect on the two major cholesterol synthesizing organs. Abrams et al., (1982),
suggested that hypercholesterolemia in diabetic patients could be also due to the
increase in biliary secretion and synthesis of bile acids which enhanced the
absorption of cholesterol (Uchida et al., 1979).
In our results a significant increase of serum phospholipids in all diabetic
patients has been found as compared to controls. The increase of LCAT activity

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II=======================================================Chapter IV

in diabetics could also be related to the increased concentration of serum

phospholipid in diabetics (Billimoria et al., 1976), as the raising of serum
phospholipid levels could enhance LCAT enzyme activity (Wallentin and
Vikrot, 1976).
High levels for serum phospholipids have been also found in human
diabetics as well as in experimental alloxan- diabetic rats by (Saatov et al.,
1980). The increase in serum cholesterol in our diabetic patients was not
dependent on the presence or absence of ketosis. This is indicated by the
increased level of serum cholesterol in ketotic and non- ketotic females than in
control group, while in diabetic males, serum cholesterol was significantly
increased in ketotic and non - ketotic groups as compared to control. We
suggested to that these differences in serum cholesterol may be related to the sex
differences. This finding is in agreement with our results in diabetic patients
where the elevation was mainly detected in female patients and not in male
patients, this observation is compatible with other authors (Walden et al., 1984).

While in normal subjects, sex revealed no influence on the serum

cholesterol concentration. This is in accordance with the observation reported by
(Reed et al., (1972) and Goldberg et al., (1973).
Moreover, Sabry et al., (1983b), found that the concentration of serum
cholesterol was insignificantly increased in boys than in girls of healthy
Egyptian. However Zhijia et al., (1986) found that the concentration of serum
cholesterol was significantly increased in girls than in boys.

In our results, the level of serum cholesterol was significantly increased

with the age of female diabetic patients particularly in NIDDM-I group as
compared to IDDM and control groups. This was also in agreement with other
authors who reported that significant change of serum cholesterol was found
mainly in females with the advance of age. Furthermore, it has been found an

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II=======================================================Chapter IV

increase in serum cholesterol after the adolescent period in diabetic patients.

While in males, serum cholesterol was significantly increased in IDDM group as
compared to control. This was also in agreement with other authors (Chase and
Glasgow, 1976). From our results, the increased level of serum cholesterol and
phospholipids was found in males with IDDM as compared to control. HDL-
cholesterol in juvenile male diabetics was associated with high level of
cholesterol concentrations (Kennedy et al., 1978).

The prevalent increase of serum cholesterol in our diabetic females than

in males may be due to the more pronounced effect of the duration of what
shown in our results. From our results, a positive correlation has been confirmed
between serum cholesterol and the duration of diabetes in females. The level of
serum cholesterol was significantly higher than in control after duration of 3-6
and >6 years by 15% and 24% respectively. Our results are in agreement with
other reports (Kogp and hennenberger, 1979), but in contrast with the data
obtained by (Sterky et al., 1963) who found that the concentration of serum
cholesterol failed to show any significant relation with the duration of diabetes
in school children.

Our results also showed that the concentration of serum cholesterol in

poorly-controlled females was significantly higher than that in moderately-
controlled females and normal control subjects, but still remained higher in the
well - controlled females as compared to the healthy group. Kimiko et al., 1982,
and Sabry et al., 1983c, reported that the concentration of serum cholesterol was
significantly decreased in diabetic patients after receiving efficient insulin
therapy. Similar observations were also reported by Durrington and Stephens,
1980, in alloxan-diabetic rats.
Good control of blood glucose level would produce a gradual decline in
the synthesis rate of cholesterol in diabetes (Abrams et al., 1982). Previously,

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II=======================================================Chapter IV

Bennion and Grundy, 1977, reported that insulin therapy slightly reduced the
production of cholesterol in diabetes. The improvement of serum cholesterol by
insulin could be explained on the basis that the level of LCAT activity is within
normal limits in treated insulin - dependent diabetics (Mattock et al., 1979) and
usually the activity return to normal with the improved diabetic control (Norum,
1974).
The selective and non selective of urinary proteins in urine of Juvenile
and adult diabetic patients could be studied and classified by the immuno-
electrophoretic analysis (Attalah et al., 2004) into two groups: In the first group,
with duration of less than 5 years, albumin and /or transferrin as well as
ceruloplasmin were the only proteins that could be detected in proteinuria of not
more than 100 mg/dl.

The type of protein pattern is characterized by selective (Pesce et al.,

1970) and a condition of moderate renal function impairment may be associated
for such a group of patients. Campbell et al., (2003) found that diabetic
nephropathy is characterized by increased urinary albumin excretion and loss of
renal function. Increase urinary albumin (proteinuria) is a key component of this
disease. Previously, its development led to end-stage renal disease with
increased mortality and morbidity for diabetic patients versus non-diabetic
patients. The abnormality of increased excretion in uncontrolled diabetes was
explained by the increased glomerular passage of albumin and decreased tubular
reabsorption, and the exact cause of increase glomerular filtration rate is
unknown and may be due to increased permeability of glomerular basement
membrane or increased filtration areas.
In the second group of patients (total n=19), the composition of the
patients who excreted high molecular weight proteins in urine were as follows: 2
male juvenile diabetics + 7adult diabetics (5 males and 2 females with less than
50 years of age) + 10 adult female diabetics with more than 50 years of age.

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II=======================================================Chapter IV

In all of patients, the duration of the disease exceeded 5 and up 20 years.

Albumin, transferrin and IgG were the most excreted components in all patients
with proteinuria of more than 100 mg/dl and the proteinuria in this group of
patients was non selective (Pesce, 1970).
Furthermore, augmented abnormal urine protein pattern showing
additional of protein components, namely α1-acidglycoprotein, α1-antitrypsin,
ceruloplasmin, hemopexin, and IgA were demonstrated in urine of females
rather than the male adult diabetic's urine. Heavy proteinuria met within a few
adult diabetics could be indicated as an advanced renal derangement, mostly
leading to diabetic nephritic syndrome (Solomon and De Wayne, 1977).
Much controversy has been reported to the evidence of proteinuria and the
aetiology of nephropathy in diabetes. Oakley et al., 1978, suggested that diabetic
patients never develop clinical evidence of nephropathy and the renal lesion may
be evident only at postmortem. (Mogensen, 1976) and (Solomon et al., 1977),
reported that, proteinuria is an important parameter in measuring renal function
and clinical sign of nephropathy among diabetics.

Attalah et al., (2004), reported that although heavy proteinuria was

demonstrated in only two cases of juvenile diabetics, yet, the degree of non
selectivity was lesser than those detected in adult diabetics.
Other studies, suggested that, proteinuria may be increased at the onset of
diabetes, and the frequency of nephropathy in younger ages is greater, which is
opposite to our findings. In contrast to our results, Ditzel et al., (1972) reported
insignificant difference in urinary protein excretion between sexes of adult
diabetics. In our diabetic females with non selectivity (63% of all non-selective
group), the abnormal protein pattern, α1 acidglycoprotein, α1- antitrypsin,
ceruloplasmin, haemopexin, are excreted as an inflammatory response which
exceeded that present in urine of male diabetic patients. Furthermore, such

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II=======================================================Chapter IV

increment in urinary proteins seemed to be parallel with the advancement of age

as well as duration of disease.
In all adult female patients with age exceeding 50 years and with duration
of the diabetic condition of more than 10 years, the occurrence of heavy non-
selective proteinuria, suggested that, the nephropathic ailment reached the
advanced deteriorating condition described as diabetic nephrosis. No
relationship was found between the nature of proteinuria and type of treatment
in our advanced cases. Wathins (1972) related the poor prognosis of the
nephrotic syndrome in diabetes to the early development of azotemia.

In conclusion, (Attalah et al., 2004), it can be suggested that, in spite of

the clinical significance of a trace protein reading on urine analysis is unclear,
such a result is often ignored by the clinician (Sam et al., 2003). Selective
proteinuria was most common among young male and female patients of the
same age below 25 years, while the non-selectivity was more common in
females than in males at older ages. Diabetics of either sexes with duration of
more than 5 years and proteinuria of more than 100 mg/dl may suffer from
remarkable degree of lesions as evidenced by augmented degree of non-
selectivity and our findings are consistent with (Oakley et al., 1978) who
reported that, as the duration of diabetes increased an increasing number of
patients will exhibit clinical and laboratory manifestations of diabetic
nephropathy without the evidence of progressive renal failure.

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II=======================================================Chapter IV

RECOMMENDATION

As little is known on the exact mechanism by which type 1 diabetes

develops, there are no preventive measures available for that form of diabetes.
Some studies have attributed a protective effect of breastfeeding on the
development of type 1 diabetes.

Type 2 diabetes can be prevented in many cases by making changes in

diet and increasing physical activity (Lindström et al., 2006) (Knowler et al.,
2002). A review article by the (American Diabetes Association, 2006)
recommends maintaining a healthy weight, getting at least 2½ hours of exercise
per week, not too much fat intake, and eating a good amount of fiber and whole
grains. Although they do not recommend alcohol consumption as a preventative,
they note that moderate alcohol intake may reduce the risk. They state that there
is not enough consistent evidence that eating foods of low glycemic index is
helpful, but nutritious, low glycemic-index foods are encouraged. (It should be
noted that many low-GI foods are not recommended, for various reasons.)

Some studies have shown delayed progression to diabetes in predisposed

patients through the use of metformin, (Knowler et al., 2002) rosiglitazone
(Gerstein et al., 2006), or valsartan (Kjeldsen, 2006). Breastfeeding might also
be correlated with the prevention of type 2 of the disease in mothers (Stuebe et
al., 2005).

As of late 2006, although there are many claims of nutritional cures, there
is no reliable proof of their effectiveness. In addition, despite claims by some
that vaccinations may cause diabetes, there are no studies proving any such
connection.

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II=======================================================Chapter IV

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Balistreri,W.F. and raj, R. (1994): Liver function In : Tietz text book of clinical
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- 129 -
APPENDIX
Table (16): glucose level, liver function, and kidney function testes, total protein, albumin, globulin fractions and A/G ratio in
non-insulin dependent diabetic patients (NIDD) with either non-ketosis or ketosis.

NIDDM with non-ketosis

Total
Serial Age sex glucose Urea Creat. GOT GPT ALK.ph Amylase Lipase Protein Album. α1-glob α2-glob ß-glob. γ-glob. A/G-
No years mg/dl mg/dl mg/dl IU/L IU/L IU/L IU/L µµmol/FFA/ml g/dl g/dl g/dl g/dl g/dl g/dl ratio

1 36 F 128 62 0.9 17 13 291 134 33.7 6.38 3.2 0.48 0.52 1.12 1.06 1.00
2 67 F 202 49 0.61 13 6 209 89 26.1 5.85 3.2 0.32 0.69 0.63 1.01 1.2
3 77 F 301 42 0.9 35 30 177 144 28.0 6.1 3.5 0.41 0.56 0.71 0.92 1.34
4 32 M 413 34 0.7 14 7 320 49 24.0 7.15 4.3 0.36 0.49 0.79 1.21 1.5
5 31 M 195 40 1.0 13 11 176 65 21.1 6.04 3.1 0.14 0.379 0.89 1.53 1.05
6 40 M 322 42 0.9 21 30 182 166 54.0 7.0 3.6 0.27 0.48 0.95 1.71 1.05
7 28 M 182 49 12 10 19 215 65 33.7 5.63 2.9 0.23 0.38 0.71 1.41 1.10
8 32 M 151 94 1.4 22 16 153 95 36.3 7.42 4.2 0.28 0.45 0.71 1.78 1.30

M 42.87 236.75 51.5 0.95 18.1 16.5 215.37 100.87 32.1 6.44 3.5 0.31 0.49 0.81 1.32 1.19

S.E± 6.54 34.74 6.74 0.089 2.82 3.31 21.02 15.02 3.6 0.23 0.18 0.04 0.035 0.06 0.11 0.06
NIDDM with ketosis
Lipase Total α1- α2- ß- γ-
Serial Age sex glucos Urea Creat. GOT GPT ALK.ph Amylase µmol\ Protein Album glob glob glob. glob. A/G-
No years mg/dl mg/dl mg/dl IU/L IU/L IU/L IU/L FFA/ml g/dl g/dl g/dl g/dl g/dl g/dl Ratio

1 40 F 329 30 11 22 14 374 124 60.5 6.99 4.4 0.18 0.61 0.387 1.41 1.69
2 60 F 369 28 0.8 85 39 246 198 86.2 5.54 3.4 0.12 0.37 0.69 0.96 1.58
3 88 F 256 60 1.1 41 31 92.1 143 79.0 5.27 2.9 0.12 0.71 1.2 1.42 0.83
4 30 F 320 25 0.9 22 15 223 203 92.0 6.47 3.3 0.13 0.812 0.91 1.32 1.04
5 40 F 443 40 0.7 23 27 513 129 67.0 6.12 3.1 0.24 0.75 0.862 1.17 1.02
6 49 M 381 30 1.1 36 29 211 150 51.0 8.23 4.4 0.22 0.79 1.01 1.81 1.15
7 42 M 290 65 1.3 27 27 422 140 66.0 6.12 3.3 0.26 0.33 0.91 1.31 1.17
8 50 M 284 56 0.9 8 17 320 143 58.0 6.24 3.5 0.37 0.47 0.69 1.21 1.27

M 49.87 334.0 41.75 0.99 33.0 24.9 300.13 153.75 69.9 6.37 3.54 0.21 0.605 0.71 1.33 1.22

S.E± 6.28 21.57 5.71 0.07 8.21 3.11 47.45 10.62 5.1 0.32 0.19 0.03 0.067 0.11 0.09 0.10

T 2.38 1.10 0.35 1.71 1.84 1.63 2.87 6.1 0.81 0.15 2.0 1.52 0.79 0.035 0.25

P <0.025 >0.1 >0.4 <0.05 <0.05 <0.05 <0.01 <0.01 >0.4 >0.4 <0.025 >0.1 >0.05 >0.4 >0.4
m.s.i n.s n.s s.s.i s.s.i s.s.i h.s.i v.h.s.i n.s n.s m.s.d n.s n.s n.s n.s
Table (17): glucose level, liver function tests, kidney function testes, total protein, albumin, globulin fractions and A/G ratio in
insulin dependent diabetic patients with either non-ketosis or ketosis.

IDDM with non-ketosis

Lipase Total α1- α2- ß- γ-
Serial Age sex glucose Urea Creat. GOT GPT ALK.ph Amylase µmol\ Protein Alb. glob glob glob. glob. A/G-
No Years mg/dl mg/dl mg/dl IU/L IU/L IU/L IU/L FFA\ml g/dl g/dl g/dl g/dl g/dl g/dl ratio

1 23 M 171 31 1.5 19 13 201 35 20.0 7.14 4.4 0.21 0.51 1.01 1.01 1.0
2 21 M 159 154 3.1 14 19 410 21 17.0 6.99 3.9 0.18 0.52 1.11 1.28 1.26
3 28 M 137 68 2.0 74 27 480 32 21.3 8.59 4.6 0.77 0.86 0.91 1.46 1.15
4 20 M 340 19 3.0 34 33 220 43 35.0 7.82 4.0 0.52 0.91 0.75 1.60 1.04
5 27 M 295 23 1.1 20 34 240 190 17.0 7.67 3.9 0.37 0.48 0.98 1.94 1.41
6 21 F 95 34 0.9 15 22 98 52 26.1 6.88 3.0 0.21 1.26 0.72 1.69 0.77
7 25 F 90 36 1.3 25 18 132 86 24.0 7.96 4.1 0.48 0.51 1.01 1.86 1.06
8 36 F 250 24 1.2 34 29 285 60 12.7 7.34 3.5 0.521 0.48 0.92 1.91 0.91
9 27 F 143 30 0.9 12 20 219 31 35.6 5.86 3.5 0.21 0.9 1.3 1.12 0.99
10 49 F 103 40 2.4 26 11 559 45 17.0 6.93 3.3 0.32 0.71 0.75 1.85 0.91
11 47 F 122 46 1.1 23 19 151 122 18.1 7.79 4.5 0.48 0.51 1.1 1.2 1.37

M 29.5 173.27 45.91 1.68 26.91 22.27 271.91 65.18 22.16 7.36 3.88 0.38 0.69 0.96 1.54 1.13

S.E 3.07 25.80 11.54 0.24 5.2 2.29 44.81 15.22 2.25 0.22 0.15 0.05 0.08 0.05 0.10 0.07
Table (16) continue
IDDM with ketosis
Lipase Total Alb. α1- α2- ß- γ- A/G-
Serial Age sex glucose Urea Creatin. GOT GPT ALK.ph Amylase µmol\ Protein g/dl glob glob glob. glob. Ratio
No years mg/dl mg/dl mg/dl IU/L IU/L IU/L IU/L FFA\ml g/dl g/dl g/dl g/dl g/dl

1 24 M 335 126 1.3 16 14 157 34 27.2 6.04 3.5 0.34 0.4 0.7 1.11 1.37
2 27 M 425 28 0.99 26 13 212 99 30.4 7.34 3.9 0.51 1.01 0.95 0.97 1.13
3 20 M 437 168 2.2 25 240 300 43 24.0 6.57 3.4 0.35 0.48 0.72 1.62 1.07
4 29 M 304 40 1.9 27 169 221 65 36.3 6.65 3.5 0.52 0.59 0.92 1.12 1.11
5 29 M 482 50 1.2 34 22 448 39 40.0 7.01 3.2 0.21 1.26 0.72 1.62 0.84
6 57 F 448 84 0.9 28 14 413 68 18.1 6.05 2.8 0.31 0.43 0.87 1.64 0.86
7 31 F 361 29 1.2 28 29 133 35 17.8 8.03 4.0 0.36 0.76 0.89 2.01 0.99
8 50 F 570 30 1.3 42 22 99.6 75 23.0 7.12 3.7 0.34 0.68 0.78 1.62 1.08
9 23 F 365 30 1.2 29 19 213 84 17.0 7.36 4.2 0.24 0.51 0.77 1.64 1.33
10 52 F 491 28 1.2 17 19 435 66 16.0 7.7 3.8 0.52 0.67 0.89 1.82 0.97
11 50 F 515 42 1.2 23 19 415 62 35.0 6.3 2.99 0.36 1.01 1.01 0.93 0.9
12 56 F 308 55 1.3 16 13 356 96 18.5 6.41 3.1 0.35 0.68 0.68 1.6 0.93
13 85 F 422 94 1.4 18 17 443 95 28.0 6.25 2.9 0.41 0.62 0.88 1.44 0.86

M 41.0 420.23 61.84 2.02 25.31 46.92 296 66.23 25.48 6.83 3.45 0.37 0.70 0.83 1.47 1.03

S.E± 5.27 22.82 12.24 0.66 2.09 19.84 35.76 6.45 2.24 0.18 0.12 0.03 0.07 0.03 0.09 0.05

T 7.19 0.94 0.46 0.28 1.23 0.42 0.06 1.04 1.86 2.24 0.29 0.1 2.23 0.51 1.16

P <0.001 >0.1 >0.4 >0.4 >0.1 >0.4 >0.4 >0.1 <0.05 <0.025 >0.4 >0.4 <0.025 >0.4 >0.1
v.h.s.i n.s n.s n.s n.s n.s n.s n.s s.s.d m.s.d n.s n.s m.s.d n.s n.s
Table (18): shows glucose level, liver function and kidney function testes, total protein, albumin, globulin fractions and A/G ratio
in juvenile diabetic patients with either non-ketosis or ketosis.

Juvenile diabetic patients with non-ketosis

Lipase. Total α1- α2- ß- γ-
Serial Age sex glucose Urea Creat. GOT GPT ALK. Amylase µmol Protein Alb. glob glob glob. glob. A/G-
No years mg/dl mg/dl mg/dl IU/L IU/L IU/L IU/L \FFA\ml g/dl g/dl g/dl g/dl g/dl g/dl ratio

1 9 F 295 37 0.1 18 25 185 145 21.7 6.42 3.1 0.25 0.65 0.88 1.54 0.93
2 8 F 220 39 1.1 14 16 122 132 58.6 7.44 4.4 0.41 0.62 0.70 1.31 1.44
3 8 F 220 39 1.1 14 16 122 132 33.7 7.44 4.4 0.41 0.62 0.70 1.31 1.44
4 16 F 214 39 1.1 18 24 201 55 27.0 7.19 3.8 0.43 0.61 1.01 1.34 1.12
5 9 M 279 30 0.7 27 25 211 66 51.0 7.78 4.5 0.27 1.53 1.04 0.44 1.37
6 6 M 215 40 0.8 21 20 199 69 33.0 9.46 6.5 0.21 0.61 0.93 1.21 2.19
7 4 M 170 27 0.8 15 19 95 98 31.0 7.03 4.4 0.13 0.35 0.93 1.21 1.67
8 10 M 188 30 0.8 25 22 120 166 24.0 8.86 5.6 0.22 0.6.9 1.14 1.21 1.71
9 14 M 145 27 1.1 16 22 95 44 34.0 8.48 4.5 0.13 1.12 1.04 1.69 1.13
10 9 M 122 14 1.5 16 22 111 45 35.0 6.62 4.0 0.133 0.72 0.57 1.19 1.52

M 9.30 206.8 32.2 1.0 18.4 21.1 146.1 95.2 34.9 7.67 4.52 0.26 0.75 0.89 1.25 1.45

S.E± 1.11 17.05 2.62 0.07 1.44 1.05 14.84 14.34 3.65 0.31 0.29 0.04 0.1 0.05 0.1 0.11
Table (18) continue
Juvenile diabetic patients with ketosis
Lipase Total α1- α2- ß- γ- A/G-
Serial Age sex glucose Urea Creat. GOT GPT ALK.ph Amylase µmol\ Protein Alb. glob glob glob. glob. ratio
No years mg/dl mg/dl mg/dl IU/L IU/L IU/L IU/L FFA\ml g/dl g/dl g/dl g/dl g/dl g/dl

1 4 F 279 30 0.7 16 21 181 172 21.5 7.83 3.8 0.13 0.27 1.42 2.21 0.94
2 6 F 273 59 1.3 17 20 95 238 76.0 6.63 3.7 0.422 0.53 0.69 1.29 1.26
3 11 F 235 59 14 22 25 212 192 66.0 6.66 3.3 0.21 1.31 0.93 0.91 0.98
4 15 F 420 29 0.9 16 15 111 349 85.0 7.58 3.8 0.91 1.22 0.93 0.72 1.23
5 20 F 302 37 1.2 19 22 92 133 28.0 7.64 4.3 0.13 1.29 0.69 1.23 1.28
6 7 F 422 40 1.1 18 19 84 391 97.0 6.95 4.2 0.12 1.09 0.42 1.12 1.52
7 4 M 387 23 0.4 40 24 210 184 31.0 5.77 3.5 0.19 0.66 0.59 0.83 1.54
8 16 M 411 30 1.0 39 30 299 284 70.0 5.82 3.2 0.29 0.59 0.72 1.01 1.22
9 11 M 302 72 1.4 12 7 281 198 42.0 7.85 4.6 0.29 0.64 1.01 1.31 1.41
10 16 M 398 30 1.1 18 19 211 340 83.0 8.34 4.4 0.21 1.21 0.73 1.79 1.11

M 11.0 342.9 40.9 1.05 21.7 20.2 177.6 248.1 59.95 7.11 3.88 0.292 0.88 0.81 1.24 1.25

S.E± 1.78 22.55 5.22 0.1 3.07 1.94 24.97 27.74 8.55 0.28 0.15 0.075 0.12 0.09 0.14 0.06

t 4.81 1.49 0.41 0.97 0.41 1.08 4.89 2.69 1.34 1.96 0.37 0.84 0.82 0.06 1.6

P <0.001 >0.1 >0.4 >0.4 >0.4 >0.1 <0.001 <0.01 >0.1 <0.05 >0.4 >0.1 >0.1 >0.4 <0.05
v.h.s.i n.s n.s n.s n.s n.s v.h.s.i h.s.i n.s s.s.d n.s n.s n.s n.s s.s.d
Table (19): Serum glucose (mg/dl), lipid components (mg/dl) (FFA/µmol ml/hr) in normal subjects.

Male Female

Group Number Glucose Total Total Phospho- Tri- Free Glucose Total Total Phosph Tri- Free
Age Of cases lipids Cholesterol lipids glycerides fatty lipids cholesterol lipids glycerides fatty
acids acids

1 120 533 148 164 107 11 87 541 175 176 -- 15

2 111 538 150 106 118 9.0 92 617 164 188 110 15
3 73 417 -- 135 150 10 110 460 170 111 127 --
4 88 683 173 115 184 15 95 642 244 269 90 12
<25
5 80 383 139 152 -- 10 90 580 163 186 110 14
years 6 120 533 150 106 120 9.0 116 615 126 139 128 17
7 110 418 120 135 60 12 114 717 182 265 184 8.0
8 113 583 152 231 143 -- 104 610 125 138 127 16
9 80 590 174 156 115 17 -- -- -- -- -- --

Mean 99 520 151 144 125 12 101 598 169 184 125 14
SE. 6.0 32 6.0 13 13 1.0 4.0 27 13 20 11 1.0

1 88 593 221 166 67 11 116 505 148 202 125 9.0

2 88 407 146 113 162 15 100 531 204 218 85 --
3 88 591 190 186 124 -- 107 587 179 208 62 12
4 113 634 190 257 92 9.0 110 546 157 206 55 19
>25 5 110 609 200 225197 142 10 80 614 195 -- 75 10
Years 6 110 449 137 194 87 17 119 396 110 114 67 16
7 110 556 189 211 112 19 100 440 127 208 58 11
8 121 551 189 194 112 13 100 539 138 223 77 14
9 100 520 146 190 159 -- 116 600 148 207 100 15
10 90 590 194 125 125 -- 120 745 279 244 115 --
11 109 686 220 142 10 -- -- -- -- -- --

Mean 102.0 562 184.0 187 120.0 13.0 107.0 550 169 203 82.0 13.0
SE. 4.0 24 9.0 12 9.0 1.0 4.0 31 15 12 8.0 1.0
All Mean 101.0 543 170.0 168 122.0 12.0 104.0 571 169 194 100.0 14.0
SE 3.0 20 7.0 10 7.0 1.0 3.0 21 10 11 8.0 1.0
Table (20): Serum glucose (mg/dl), in different class of diabetes.

Groups Diabetic males Diabetic females

Number Non- Duration of diabetes Well- Moerat Poorly- Non- Duration of Well- Moder Poorly-
of ketotic ketotic IDDM NIDDM-I contro ly Contro ketotic ketotic IDDM NIDDM-I diabetes Contro atly- contro
cases lled Contro lled lled contr lled
lled olled
<3 3-6 >6 <3 3-6 >6

1 287 217 217 268 287 418 417 157 211 311 343 195 195 229 482 253 357 161 217 306
2 169 294 294 295 169 350 255 157 217 314 482 370 370 226 200 130 583 174 226 314
3 211 504 504 255 211 349 311 161 228 322 459 357 357 235 386 130 297 180 229 340
4 527 148 148 311 241 527 360 165 241 339 200 357 357 297 293 229 261 109 229
5 360 342 342 374 195 360 504 169 255 342 250 583 383 180 217 265 200 130 235
357
6 418 322 322 270 171 200 400 171 264 349 386 442 442 161 161 174 287 130 243 357
7 350 339 339 360 113 314 120 164 268 360 504 200 200 109 314 200 188 135 253 370
8 349 417 417 146 228 200 264 120 270 360 293 340 340 283 182 340 442 182 261 386
9 400 429 429 448 273 148 165 113 273 374 217 229 443 217 229 235 109 188 265 442
10 200 161 161 273 193 322 374 148 287 400 161 226 482 161 226 267 443 200 267 443
11 273 417 417 120 217 295 270 193 294 417 130 235 459 130 180 357 459 200 283 459
12 120 165 165 264 294 339 146 195 295 417 200 297 200 200 195 203 504 200 287 482
13 264 550 550 157 550 417 448 200 -- 418 287 180 253 287 370 -- 305 -- 293
496
14 157 286 287 157 268 429 157 200 -- 429 305 161 386 305 -- -- 496 -- 297
15 157 295 169 241 342 161 157 -- -- 448 496 109 504 496 -- -- 243 -- --
504
16 241 255 211 195 -- -- -- -- -- 504 243 283 293 243 -- -- -- -- -- 583
17 195 311 527 171 -- -- -- -- -- 550 182 -- -- 182 -- -- -- -- -- --
18 171 374 360 113 -- -- -- -- -- 527 314 -- -- 314 -- -- -- -- -- --
19 113 270 418 228 -- -- -- -- -- 350 130 -- -- 130 -- -- -- -- -- --
20 228 360 350 314 -- -- -- -- -- -- 229 -- -- 229 -- -- -- -- -- --
21 314 148 349 200 -- -- -- -- -- -- 265 -- -- 265 -- -- -- -- -- --
22 200 448 400 193 -- -- -- -- -- -- 174 -- -- 174 -- -- -- -- -- --
23 193 -- 200 -- -- -- -- -- -- -- 267 -- -- 267 -- -- -- -- --
--
24 -- -- -- -- -- -- -- -- -- -- 188 -- -- 189 -- -- -- -- --
--
--
--
Mean 256 320 329 243 250 322 290 146 259 396 284 292 367 234 264 239 345 171 256 417
SE. 22 24 25 18 26 28 32 7.0 8.0 16 24 29 29 16 27 21 35 9.0 7.0 22
Table (21): Serum total lipids (mg/dl), in different class of diabetes.

Groups Diabetic males Diabetic females

Number Non- Duration of diabetes Well- Moerat Poorly Non- Duration of diabetes Well- Moder Poorly
of ketoti ketoti IDDM NIDDM Contr ly - ketotic ketotic IDDM NIDDM-I Contr atly Contr
cases c c -I olled Contr Contr olled Contr olled
<3 3-6 >6 olled olled <3 3-6 >6 olled

1 592 634 634 944 592 633 765 620 742 500 921 531 531 769 562 421 619 744 577 705
2 500 839 839 583 500 461 500 612 634 539 562 580 580 582 425 705 913 769 582 78 5
3 742 718 718 500 742 665 500 650 659 500 534 529 529 857 491 633 725 492 769 554
4 607 789 789 500 550 607 571 718 550 520 425 619 619 725 375 769 551 635 769 619
5 581 677 677 571 981 581 718 500 500 677 421 913 913 492 380 661 731 705 857 529
6 633 500 500 704 1077 513 327 1077 613 665 491 585 585 551 744 769 577 633 711 560
7 461 520 520 571 714 539 474 403 944 581 628 820 820 635 785 820 1120 531 421 491
8 665 714 714 403 659 461 613 474 704 571 577 554 554 600 535 554 585 535 551 585
9 513 827 827 637 478 789 718 714 478 571 744 769 921 577 769 857 635 820 661 921
10 476 650 650 478 513 500 571 789 592 765 705 582 562 744 582 596 921 731 596 534
11 474 765 765 474 634 583 704 513 839 714 731 857 534 705 492 629 534 425 600 562
12 613 718 718 613 839 520 403 981 583 633 577 725 425 731 531 600 628 -- 577 756
13 620 615 615 620 615 714 637 461 -- 827 705 492 421 577 580 -- 705 -- 725 628
14 612 944 592 612 944 827 620 513 -- 637 756 551 491 705 -- -- 756 -- -- 913
15 550 583 500 550 677 650 612 -- -- 718 711 635 628 756 -- -- 711 -- -- --
16 981 500 742 981 -- -- -- -- -- 615 535 600 375 711 -- -- -- -- -- --
17 1077 500 607 1077 -- -- -- -- -- 607 785 -- -- 535 -- -- -- -- -- --
18 714 571 581 714 -- -- -- -- -- 461 633 -- -- 785 -- -- -- -- -- --
19 659 704 633 659 -- -- -- -- -- -- 769 -- -- 633 -- -- -- -- -- --
20 539 571 461 539 -- -- -- -- -- -- 661 -- -- 769 -- -- -- -- -- --
21 461 403 665 461 -- -- -- -- -- -- 769 -- -- 661 -- -- -- -- -- --
22 513 637 327 513 -- -- -- -- -- -- 596 -- -- 769 -- -- -- -- -- --
23 -- -- 513 -- -- -- -- -- -- -- 1120 -- -- 596 -- -- -- -- -- --
24 -- -- -- -- -- -- -- -- -- -- -- -- 1120 -- -- -- -- --

Mean 618 654 634 623 701 603 582 645 653 617 668 646 593 691 558 660 714 638 648 654
SE. 33 28 26 37 48 29 32 53 39 23 33 32 40 27 38 37 41 39 32 37
Table (22): Serum total cholesterol (mg/dl), in different class of diabetes.

Groups Diabetic males Diabetic females

Number Non- Well- Moder Poorly- Non- Poorly Modera Poorly-

of Ketoti ketotic IDDM NIDDM- Duration of diabetes controll atly Contro ketoti ketotic IDDM NIDDM Duration of diabetes - Tly Contr
cases c I ed Contro lled c -I Contr contro Olled
lled olled lled
<3 3-6 >6 <3 3-6 >6
705
1 167 171 171 208 167 212 263 196 189 127 184 192 192 78 5 183 142 204 200 192 228
2 155 268 168 211 155 191 192 229 171 191 183 211 211 554 154 220 254 212 183 209
3 189 152 152 192 189 207 127 128 200 171 206 188 188 619 125 288 216 147 200 204
4 184 233 233 127 102 184 250 212 102 150 154 204 204 529 142 200 192 200 204 204
5 181 130 130 250 253 181 152 155 192 130 142 254 254 560 192 188 232 220 179 188
6 212 171 171 242 261 191 104 261 167 207 125 169 169 491 200 212 152 192 196 211
7 191 150 150 250 167 196 192 121 208 181 175 211 211 585 209 211 306 194 142 125
8 207 196 196 121 200 122 167 192 242 250 142 204 204 921 194 204 169 211 192 169
9 104 147 147 175 159 233 212 167 159 250 192 204 184 534 204 179 200 232 188 184
10 131 128 128 159 161 171 250 233 167 104 200 183 163 562 183 151 184 154 151 206
11 159 263 263 192 171 111 242 161 268 263 220 179 206 756 147 188 206 -- 162 183
12 192 212 212 167 268 150 121 253 111 196 232 216 154 628 192 162 175 -- 152 236
13 167 158 159 196 158 196 175 122 -- 212 152 147 142 913 211 -- 228 -- 142 175
14 169 208 167 229 208 147 196 191 -- 147 228 192 125 -- -- -- 236 -- 116 251
15 229 111 155 102 130 128 129 -- -- 148 236 200 175 -- - -- 136 -- -- --
16 102 192 189 253 -- -- -- -- -- 152 196 162 142 -- -- -- -- -- -- --
17 253 127 184 261 -- -- -- -- -- 158 194 -- -- -- -- -- -- -- -- --
18 261 250 181 167 -- -- -- -- -- 184 209 -- -- -- -- -- -- -- -- --
19 167 242 211 200 -- -- -- -- -- 191 288 -- -- -- -- -- -- -- -- --
20 200 250 191 196 -- -- -- -- -- -- 200 -- -- -- -- -- -- -- -- --
21 196 121 207 122 -- -- -- -- -- -- 188 -- -- -- -- -- -- -- -- --
22 122 175 104 161 -- -- -- -- -- -- 212 -- -- -- -- -- -- -- -- --
23 161 -- 191 -- -- -- -- -- -- -- 151 -- -- - -- -- -- -- -- --
24 -- -- -- -- -- -- -- -- -- -- 306 -- -- - -- -- -- -- -- --

Mean 162 184 181 190 183 175 191 187 181 180 196 195 184 654 180 195 210 196 179 198
SE. 8.0 11 8.0 10 12 9.0 13 13 14 10 9.0 6.0 8.0 37 8.0 11 10 9.0 7.0 8.0
Table (23): Serum phospholipids (mg/dl), in different class of diabetes.

Groups Diabetic males Diabetic females

Number Non- Duration of diabetes Well- Moeratly Poorly- Non- Duration of diabetes Well- Moeratly Poorly-
of ketoti ketotic IDDM NIDDM- Contro Contro Contro ketotic ketotic IDDM NIDDM- Contr Contro contro
cases c I lled lled lled I o lled lled
<3 3-6 >6 <3 3-6 >6 lled

1 202 299 299 133 202 140 108 231 373 115 466 159 159 300 144 130 143 250 234 258
2 148 167 167 209 148 154 210 132 299 119 144 230 230 135 130 243 221 206 135 344
3 173 141 141 210 373 394 115 169 210 313 114 138 138 176 138 169 143 138 260 140
4 144 313 313 115 337 144 150 216 337 163 130 143 143 143 98 260 250 155 300 143
5 186 163 163 149 373 186 167 148 210 141 130 221 221 138 234 274 258 234 176 138
6 140 183 183 107 192 192 169 118 136 394 183 125 125 250 250 206 226 169 130 230
7 154 394 394 150 210 119 214 214 133 186 182 258 258 155 344 258 280 159 250 183
8 394 169 169 118 173 115 136 192 107 150 98 140 140 173 296 140 125 296 274 125
9 169 108 108 230 299 313 216 173 115 149 234 300 144 234 300 176 155 280 173 114
10 192 216 216 115 133 209 149 115 202 169 250 135 114 250 135 394 114 258 225 144
11 115 115 115 214 141 163 107 192 209 108 234 176 130 234 138 138 182 258 89 174
12 214 133 202 136 -- 183 118 -- -- 183 258 143 130 258 159 173 258 130 143 162
13 136 209 148 231 -- 395 230 -- -- 140 226 138 183 226 230 -- 174 -- -- 221
14 231 210 373 132 -- 169 132 -- -- 394 258 250 182 258 -- -- -- -- -- --
15 132 115 144 337 -- -- 231 -- -- 230 174 155 98 176 -- -- -- -- -- --
16 337 149 186 373 -- -- -- -- -- 167 490 173 -- 296 -- -- -- -- -- --
17 373 107 140 192 -- -- -- -- -- 115 296 -- -- 344 -- -- -- -- -- --
18 452 150 154 210 -- -- -- -- -- 144 344 -- -- 169 -- -- -- -- -- --
19 192 118 394 119 -- -- -- -- -- 154 169 -- -- 260 -- -- -- -- -- --
20 210 230 169 115 -- -- -- -- -- -- 260 -- -- 274 -- -- -- -- -- --
21 119 -- 192 173 -- -- -- -- -- -- 274 -- -- 206 -- -- -- -- -- --
22 155 -- -- -- -- -- -- - -- -- 206 -- -- 394 -- -- -- -- -- --
23 173 -- -- -- -- -- -- -- -- -- 394 -- -- 280 -- -- -- - -- --
24 -- -- -- -- -- -- -- -- -- -- 280 -- -- -- -- -- -- -- -- --

Mean 215 184 208 179 235 205 163 173 212 186 241 180 160 232 203 213 195 211 200 184
SE. 21 17 20 16 28 25 12 12 27 20 21 13 12 14 22 22 16 17 19 18
Table (24): Serum triglycerides (mg/dl), in different class of diabetes.

Groups Diabetic males Diabetic females

Number Non- Duration of diabetes Well- Moeratly Poorly- Non- Duration of diabetes Well- Moeratly Poorly-
of ketoti ketotic IDDM NIDDM- Contro Contro Contro ketotic ketotic IDDM NIDDM- Contro Contro Contro
cases c I lled lled lled I lled lled lled
<3 3-6 >6 <3 3-6 >6

1 132 60 60 204 132 60 77 67 194 105 170 204 204 115 125 182 172 115 75 142
2 90 249 249 163 90 60 56 97 160 77 125 206 206 175 69 75 147 75 175 171
3 194 294 294 77 194 117 203 180 199 167 125 140 140 299 105 172 294 165 115 180
4 110 179 179 56 64 110 67 105 64 180 69 172 172 294 80 52 140 75 98 172
5 112 180 180 204 255 112 75 90 77 117 182 147 147 75 75 47 115 172 182 140
6 60 77 77 264 154 85 60 154 60 112 105 143 143 140 115 305 62 204 140 206
7 60 167 167 203 112 105 105 72 204 203 152 274 274 165 171 274 143 82 66 105
8 117 222 222 72 199 77 204 75 264 204 80 180 180 132 82 180 165 115 132 142
9 67 152 152 181 249 179 72 112 132 67 75 115 170 75 115 299 190 69 62 170
10 85 180 180 55 194 76 181 179 249 222 115 175 125 115 175 66 125 -- 80 125
11 55 105 105 75 204 163 67 62 163 152 75 299 125 75 75 140 152 -- -- 125
12 75 194 184 60 180 167 187 76 -- 181 115 294 180 115 204 132 142 -- -- 157
13 60 132 132 67 -- 222 -- 85 -- 294 62 75 105 62 206 -- 142 -- -- 147
14 67 90 90 97 -- 152 -- -- -- 194 142 140 152 141 -- -- 98 -- -- --
15 96 194 194 64 -- 180 -- -- -- 110 142 165 -- 142 -- -- -- -- -- --
16 64 110 110 255 -- -- -- -- -- -- 98 132 -- 98 -- -- -- -- -- --
17 255 112 112 154 -- -- -- -- -- -- 82 -- -- 82 -- -- -- -- -- --
18 154 60 60 112 -- -- -- -- -- -- 171 -- -- 171 -- -- -- -- -- --
19 112 60 60 199 -- -- -- -- -- -- 172 -- -- 172 -- -- -- -- -- --
20 199 117 117 105 -- -- -- -- -- -- 52 -- -- 52 -- -- -- -- -- --
21 105 67 67 77 -- -- - -- -- -- 47 -- -- 47 -- -- -- -- -- --
22 76 86 85 62 -- -- -- -- -- -- 66 -- -- 305 -- -- -- -- -- --
23 62 -- -- -- - -- -- -- -- -- -- - -- 66 -- -- -- -- -- --
24 -- -- -- -- -- -- -- -- -- -- -- -- -- 312 -- -- -- -- -- --

Mean 105 166 140 128 169 124 113 104 161 159 110 179 166 143 123 160 148 119 113 152
SE. 11 15 14 15 17 13 18 11 21 16 9.0 16 11 17 14 27 14 17 14 7.5
Table (25): Serum free fatty acids (mg/dl), in different class of diabetes.

Groups Diabetic males Diabetic females

Number Non- Duration of diabetes Well- Moeratly Poorly Non- Duration of diabetes Well- Moera Poorly
of keto ketotic IDDM NIDDM- Contro Contro - ketoti ketotic IDDM NIDDM Contro tly -
cases tic I lled lled Contro c -I lled Contro Contro
<3 3-6 >6 lled <3 3-6 >6 lled lled

1 19 15 15 55 19 44 30 18 38 23 9.0 37 37 41 29 22 14 18 44 38
2 17 23 23 30 17 38 23 38 15 65 29 14 14 18 20 30 47 36 18 42
3 38 31 31 23 38 22 23 31 15 34 40 14 14 60 35 52 24 24 24 16
4 32 39 39 65 30 22 30 17 30 29 20 47 47 24 34 24 44 53 41 14
5 9.0 34 34 20 37 9.0 20 26 30 39 22 49 49 24 44 20 49 30 60 14
6 44 29 29 65 26 21 32 21 23 22 35 16 16 53 18 36 53 52 20 35
7 38 22 22 31 21 40 18 31 20 65 31 41 29 40 42 16 40 37 22 49
8 22 48 48 59 15 31 7.0 32 19 65 34 18 40 44 43 60 31 43 20 40
9 5.0 39 39 23 59 34 -- 37 23 22 44 60 20 18 41 20 39 20 26 29
10 21 30 30 18 32 29 -- 40 -- 44 18 24 22 30 18 40 24 -- 40 24
11 3.0 26 26 30 15 22 -- 21 -- 48 30 24 35 44 24 -- 20 -- 44 31
12 23 55 19 34 23 48 -- -- -- 31 3.0 53 31 38 37 -- -- -- 34 47
13 18 30 17 26 26 38 -- -- -- 26 44 40 34 24 14 -- -- -- 24 --
14 7.0 23 38 20 55 -- -- -- -- 32 38 -- -- 20 -- -- -- -- -- -
15 30 65 32 65 39 -- -- -- -- 38 24 -- -- 43 -- -- -- -- -- --
16 34 20 9.0 40 -- -- -- -- -- -- 20 -- -- 42 -- -- -- -- -- --
17 26 65 44 32 -- -- -- -- -- -- 43 -- -- 52 -- -- -- -- -- --
18 21 31 38 -- -- -- -- -- -- -- 42 -- -- 24 -- -- -- -- -- --
19 15 -- 22 -- -- -- -- -- -- -- 52 -- -- 21 -- -- -- -- -- --
20 40 -- 21 -- -- -- -- -- -- -- 24 -- -- 36 -- -- -- -- -- --
21 32 -- -- -- -- -- -- -- -- -- 21 -- -- 26 -- -- -- -- -- --
22 -- -- -- -- -- -- -- -- -- -- 36 -- -- -- -- - -- -- -- --
23 - -- -- -- -- -- -- -- -- -- 26 -- -- - -- -- -- -- -- --
24 -- -- -- -- -- -- -- -- 9.0 -- -- -- -- -- -- -- --

Mean 24 35 29 37 30 31 23 28 24 39 29 34 30 34 31 32 35 35 32 32
SE. 3.0 3.0 2.0 4.0 3.0 3.0 3.0 2.0 3.0 4.0 3.0 4.0 3.0 3.0 3.0 4.6 4.0 4.0 4.0 4.0
 ABSTRACT

Diabetes mellitus is a common metabolic disorder affecting the

metabolism of carbohydrate, lipids, proteins and enzymes activities. The
purpose of this study is to determine if the pancreatic or liver and kidney
function tests are changed in diabetic patients with or without ketosis and
whether ketosis show any evidence of pancreatitis in juvenile or adult diabetic
patients. For this reason three groups of diabetic patients associated with either
ketotic or non-ketotic condition were selected and investigated.
60 diabetic patients were chosen for investigations on liver and pancreatic
function tests for serum GOT, GPT, ALP, lipase, and amylase enzymes. Kidney
function tests were also assed for blood urea, and serum creatinine. Serum total
protein and protein fractions were also studied. In addition, correlation of such
finding with age, sex, ketotic state and type of diabetics have been investigated.
Although the serum pancreatic enzymes showed normal level in ketotic
cases with IDDM, they significantly increased with the degree of diabetic
disequilibrium in ketotic cases with NIDDM and in cases with juvenile diabetic
ketosis. In cases with either IDDM or NIDDM, the pancreas is properly
functioning through treatment with insulin or the pancreas still secretes minimal
concentrations of insulin required for diminished lipolysis.
Although many biochemical parameters are now available, investigations
of diabetic patients with pancreatic disease, yet any one of them alone was found
unsatisfactory.
From our data, we concluded, the increased lipase and amylase activities
are good indicators for the diagnostic of tissue injury (pancreatitis), particularly
in juvenile diabetic patients associated with ketosis as compared to diabetic
patients without ketosis.
 Other 85 diabetic patients were also chosen for serum total lipids,
triglycerides, free fatty acids, cholesterol and phospholipids.
In all diabetics, the mean value of serum total lipids was significantly
increased as compared to the control. This elevation of serum total lipids was
explicable in terms of significant increase in serum triglycerides, cholesterol,
phospholipids and free fatty acids. The risk of the disease and aggravated data
obtained from our diabetics was nearly parallel to that recorded from other
previous published data. In diabetic male and female groups with long duration,
the level of serum total lipids was significantly decreased and increased
respectively than in corresponding group with less duration. In diabetic females,
a relation has been found between the level of serum total lipids and the age
range as well as with the duration of the disease, while this relation was not
detected in male diabetics.
The observed high level of serum cholesterol in diabetics may be due to
increased synthesis or due to the increased of biliary secretion and synthesis of
bile acids which enhance the absorption of cholesterol. In both ketotic and non-
ketotic females, the level of serum cholesterol was significantly increased while
in males the level was insignificantly increased as compared to control subjects.
In females with NIDDM-I, the level of cholesterol was significantly increased as
compared to females with IDDM and control.
In diabetic females, a relation has been found between serum cholesterol and
duration of the disease while this relation was not detected in male patients.
The observed high concentration of serum triglycerides was more
detected in female patients either with IDDM or NIDDM-I, than in male patients
and this may explain the high risk of arteriosclerosis among the diabetic females
than in males. Furthermore, serum triglyceride level was significantly increased
in both sexes of the ketotic than in the non-ketotic and the control. In both sexes
the serum triglyceride level, which showed high value in poorly-controlled
patients, revealed normal value with the proper control of blood glucose level by
insulin treatment. In addition, a relation was found between serum triglyceride
concentrations and blood glucose level in both male and female diabetic.
Thus, our results showed increased level of free fatty acids in all groups
as compared to the corresponding control. Serum free fatty acids in ketotic
patients were higher than in non-ketotic group of both sexes but the level was
significantly increased only in male patients. In well-and moderately- controlled
diabetic males, the serum free fatty acids were significantly decreased as
compared to poorly- controlled although still higher than in normal subjects. A
relation was found between serum free fatty acids and blood glucose level in
male diabetics.
Also, we concluded that the elevation of individual lipid components is very
important to be analyzed regularly in order to follow the modulation of risk
condition in diabetic patients. A great interest, also, to follow up the abnormal
lipid metabolism to avoid any metabolic complication that may associate most
of the diabetic patients.

115 Juvenile and adult diabetic patients were also subjected for urine
protein investigation by gel electrophoresis and the immunoelectrophoresis. The
obtained results were correlated with age, disease duration, sex and treatment
type.
In patients with diabetes for less than 5 years and proteinuria not more
than 100 mg/dl, albumin, transferrin and ceruloplasmin were the protein
components mostly excreted in urine and the proteinuria in such cases was
described as selective.
In patients with diabetes of more than 5 years and proteinuria exceeding
100 mg/dl, additional relatively high molecular weight proteins including IgA
and IgG were detected and the proteinuria in such cases can be considered as
non selective.
 From the previous results, it can be concluded that, selective proteinuria
was encountered in young males as well as the same number of young females
at the same age, whereas the non-selective proteinuria seems to be of higher
frequency among adult females than adult males, and it can be considered as a
sign of advanced nephritic status that would require much more intensive
medical care.
 RESUME

Le diabète sucré est un désordre métabolique commun affectant le

métabolisme des glucides, lipides, protéines et les activités enzymatiques.
Le but de cette étude est de déterminer si les fonctions du pancréas, foie et rein
changent chez les patients diabétiques avec ou sans cétose et si les
concentrations de corps cétoniques augmentent, une pancréatite peut se révéler
chez les jeunes et adultes diabétiques. Pour cette raison trois groupes de
diabétiques ont été choisis et étudiés selon la présence ou l`absence de cétose.
60 diabétiques ont été choisis pour des explorations de la fonction
hépatique et pancréatique, dosage des enzymes sérique, GOT, GPT, ALP,
lipase, et amylase. L`exploration de la fonction rénale a été réalisée aussi pour
l'urée sanguine, et la créatinine sérique. Les protéines totales et leurs fractions
ont été également étudiées. En outre, la corrélation d'une telle conclusion avec
l'âge, le sexe, l'état cétonique et le type de diabète ont été étudiés. Bien que
beaucoup de paramètres biochimiques soient maintenant disponibles, des
investigations sur les patients diabétiques présentant la pancréatite, restent
insuffisants.
De nos données, nous avons conclu, que les augmentations des activités
enzymatiques de la lipase et de l'amylase sont de bons indicateurs du diagnostic
des dommages de tissu pancréatique (pancréatite), en particulier chez les jeunes
patients diabétiques liés au cétoses par rapport aux patients diabétiques sans
cétoses.

85 autres patients diabétiques ont été également choisis pour les lipides
totaux, triglycérides, acides gras libres, cholestérol et les phospholipides. Chez
tous les diabétiques, le taux moyen des lipides totaux sérique a été sensiblement
augmenté par rapport aux sujets témoins. Chez les femmes diabétiques selon la
présence ou l`absence de cétose, le taux du cholestérol sérique a sensiblement
augmenté tandis que chez les hommes le taux était très peu augmenté par
rapport aux sujets témoins. En outre, le taux de triglycéride sérique a été
sensiblement augmenté chez les deux sexes ont présence de cétose par rapport
aux sujets qui non pas de cétose et aux sujet témoins. Ainsi, nos résultats montre
une augmentation de taux des acides gras libres chez tous les groupes par
rapport aux sujets témoins.
En outre, nous avons conclu que les seuils de différents composants
lipidiques sont très importants pour être analysés régulièrement afin de suivre la
modulation du risque dans les patients diabétiques. Un grand intérêt, aussi est de
poursuivre le métabolisme de lipide pour éviter toute complication métabolique
qui peut survenir chez la plupart des patients diabétiques.

115 diabétiques jeunes et adultes ont été également soumis pour la

recherche des protéines urinaires par l'électrophorèse et l'immunoélectrophorèse.
Les résultats obtenus ont été corrélés avec l'âge, la durée de la maladie, le sexe
et le type de traitement. Chez les malades présentant le diabète pour moins
de 5 années et protéinurie inférieure à 100 mg/dl, l’albumine, la transferrine et la
ceruloplasmine étaient les éléments protéiques les plus excrétés dans les urines,
et la protéinurie a été décrite dans ces cas-ci comme sélective. Chez les malades
présentant le diabète de plus de 5 ans et une protéinurie excédant 100 mg/dl,
relativement des protéines additionnelles de haut poids moléculaire comprenant
l’IgA et l'IgG ont été détectés et la protéinurie peut être considéré dans ces cas-ci
comme non sélective.
A partir des résultats précédents, on peut conclure que, le protéinurie
sélective a été produite dans les hommes jeunes aussi bien que le même nombre
de femmes jeunes du même âge, tandis que la protéinurie non sélective semble
être d'une fréquence plus élevée parmi les adultes hommes et femmes, et on peut
considérer comme signe de syndrome néphrétique avancé qui exigerait un soin
médical beaucoup plus intensif.
 ‫ﺍﻟﻤﻠﺨـــﺹ‬

‫ﻤﺭﺽ ﺍﻟﺒﻭل ﺍﻟﺴﻜﺭﻱ ﻋﺒﺎﺭﺓ ﻋﻥ ﻤﺠﻤﻭﻋﺔ ﻤﺘﺯﺍﻤﻨﺔ ﻤﻥ ﺍﻷﻋﺭﺍﺽ ﺍﻟﻨﺎﺘﺠﺔ ﻋـﻥ ﻨﻘـﺹ ﺇﻓـﺭﺍﺯ‬
‫ﻫﺭﻤﻭﻥ ﺍﻷﻨﺴﻭﻟﻴﻥ ﻤﻤﺎ ﻴﺘﺴﺒﺏ ﻓﻲ ﺃﻀﻁﺭﺍﺏ ﺍﻟﺘﻤﺜﻴل ﺍﻟﻐﺫﺍﺌﻲ ﻟﻠﻜﺭﺒﻭﻫﻴـﺩﺭﺍﺕ‪ ،‬ﺍﻟﻠﻴﺒﻴـﺩﺍﺕ‪ ،‬ﺍﻟﺒﺭﻭﺘﻴﻨـﺎﺕ‬
‫ﻭ ﻨﺸﺎﻁ ﺍﻷﻨﺯﻴﻤﺎﺕ‪ .‬ﺍﻟﻬﺩﻑ ﻤﻥ ﻫﺫﻩ ﺍﻟﺩﺭﺍﺴﺔ ﻫﻭ ﻤﺤﺎﻭﻟﺔ ﻗﻴﺎﺱ ﻭﻅﺎﺌﻑ ﺍﻟﺒﻨﻜﺭﻴﺎﺱ‪ ،‬ﺍﻟﻜﺒﺩ ﻭﺍﻟﻜﻠﻰ ﻭﺫﻟـﻙ‬
‫ﻟﻠﺘﻌﺭﻑ ﻋﻠﻰ ﺍﻟﺘﻐﻴﺭﺍﺕ ﺍﻟﺘﻲ ﻗﺩ ﺘﺤﺩﺙ ﻓﻲ ﻤﺭﻀﻰ ﺍﻟﺒﻭل ﺍﻟﺴﻜﺭﻱ ﺍﻟﻤﺼﺎﺤﺒﺔ ﺃﻭ ﻏﻴﺭ ﺍﻟﻤﺼـﺎﺤﺒﺔ ﺒﻤـﻭﺍﺩ‬
‫ﻜﻴﺘﻭﻨﻴﺔ ﻓﻲ ﺍﻟﺒﻭل‪ ،‬ﻭﻋﻤﺎ ﺇﺫﺍ ﻜﺎﻨﺕ ﻫﺫﻩ ﺍﻟﻤﻭﺍﺩ ﻟﻬﺎ ﺘﺄﺜﻴﺭ ﻀﺎﺭ ﻋﻠﻰ ﺒﻨﻜﺭﻴـﺎﺱ ﺼـﻐﺎﺭ ﺃﻭ ﻜﺒـﺎﺭ ﺍﻟﺴـﻥ‬
‫ﻟﻤﺭﻀﻰ ﺍﻟﺒﻭل ﺍﻟﺴﻜﺭﻱ‪ ،‬ﻭﻟﻬﺫﻩ ﺍﻷﺴﺒﺎﺏ ﺘﻡ ﺃﺨﺘﻴﺎﺭ ﺜﻼﺜﺔ ﻤﺠﻤﻭﻋـﺎﺕ ﻤـﻥ ﻤﺭﻀـﻰ ﺍﻟﺒـﻭل ﺍﻟﺴـﻜﺭﻱ‬
‫ﺍﻟﻤﺼﺎﺤﺒﺔ ﺃﻭ ﻏﻴﺭ ﺍﻟﻤﺼﺎﺤﺒﺔ ﺒﺄﺠﺴﺎﻡ ﻜﻴﺘﻭﻨﻴﺔ ﻟﻠﻔﺤﺹ ﻭﺍﻟﺩﺭﺍﺴﺔ‪.‬‬
‫ﺘﻤﺕ ﺍﻟﺩﺭﺍﺴﺔ ﻋﻠﻰ ‪ 60‬ﺤﺎﻟﺔ ﻤﻥ ﻤﺭﻀﻰ ﺍﻟﺒﻭل ﺍﻟﺴﻜﺭﻱ ﻟﻔﺤﺹ ﻭﻅـﺎﺌﻑ ﺍﻟﻜﺒـﺩ ﻭﺍﻟﺒﻨﻜﺭﻴـﺎﺱ‬
‫ﻷﻨﺯﻴﻤﺎﺕ ﺍﻷﺴﺒﺎﺭﺘﺎﺕ‪،‬ﺍﻷﻻﻨﻴﻥ ﺃﻤﻴﻨﻭﺘﺭﺍﻨﺴﻔﺭﻴﺯ‪ ،‬ﺍﻟﻔﻭﺴﻔﺎﺘﻴﺯ ﺍﻟﻘـﻠﻭﻱ‪ ،‬ﺍﻷﻤﻴﻠﻴﺯ ﻭﺍﻟﻠﻴﺒﻴﺯ ﻓﻲ ﻤﺼل ﺍﻟـﺩﻡ‪،‬‬
‫ﻜﻤﺎ ﺘﻡ ﻓﺤﺹ ﺍﺨﺘﺒﺎﺭ ﻭﻅﺎﺌﻑ ﺍﻟﻜﻠﻰ ﻟﻜل ﻤﻥ ﺍﻟﻴﻭﺭﻴﺎ ﻭﺍﻟﻜﺭﻴﺎﺘﻴﻨﻴﻥ ﻭﺘﻘﺩﻴﺭ ﻤﺴـﺘﻭﻯ ﺍﻟﺒﺭﻭﺘﻴﻨـﺎﺕ ﺍﻟﻜﻠﻴـﺔ‬
‫ﻭ ﺃﺠﺯﺍﺌﻬﺎ ﻓﻲ ﻤﺼل ﺍﻟﺩﻡ‪ .‬ﻭﻗﺩ ﺃﻤﻜﻥ ﻤﻥ ﺨﻼل ﻫﺫﻩ ﺍﻟﺩﺭﺍﺴﺔ ﺇﻴﺠﺎﺩ ﺍﻟﻌﻼﻗﺔ ﺒﻴﻥ ﻜل ﻤﻥ ﻫـﺫﻩ ﺍﻟﻤﺅﺸـﺭﺍﺕ‬
‫ﺍﻟﺒﻴﻭﻜﻤﻴﺎﺌﻴﺔ ﻤﻊ ﻜل ﻤﻥ ﻋﻤﺭ ﺍﻟﻤﺭﻴﺽ ﻭﺍﻟﺠﻨﺱ ﻭﻨﻭﻉ ﺍﻟﻤﺭﺽ ﺃﻭ ﺍﻟﺤﺎﻟﺔ ﺍﻟﻜﻴﺘﻭﻨﻴﺔ‪ ،‬ﻭﻋﻠﻰ ﺍﻟﺭﻏﻡ ﻤـﻥ ﺃﻥ‬
‫ﻫﺫﻩ ﺍﻟﻤﺅﺸﺭﺍﺕ ﺍﻟﺒﻴﻭﻜﻤﻴﺎﺌﻴﺔ ﻤﺘﻭﻓﺭﺓ ﻓﻲ ﺍﻟﻭﻗﺕ ﺍﻟﺤﺎﻟﻲ ﻓﺈﻥ ﺃﺴﺘﺨﺩﺍﻡ ﺃﻱ ﻤﻨﻬﺎ ﺒﻤﻔﺭﺩﻫﺎ ﻭﺠﺩ ﺃﻨﻬﺎ ﻏﻴﺭ ﻜﺎﻓﻴﺔ‬
‫ﻋﻨﺩ ﻓﺤﺹ ﺍﻟﻤﺭﻀﻰ ﺒﺎﻷﺨﺹ ﺒﺄﻟﺘﻬﺎﺏ ﺍﻟﺒﻨﻜﺭﻴﺎﺱ‪.‬‬
‫ﻭﻗﺩ ﺩﻟﺕ ﺍﻟﻨﺘﺎﺌﺞ ﻋﻠﻰ ﺃﻥ ﺍﻟﺯﻴﺎﺩﺓ ﻓﻲ ﻨﺸﺎﻁ ﺃﻨﺯﻴﻤﺎﺕ ﺍﻷﻤﻴﻼﺯ ﻭ ﺍﻟﻠﻴﺒﻴﺯﻜﺎﻥ ﻟـﻪ ﺩﻭﺭ ﻫـﺎﻡ ﻓـﻲ‬
‫ﺘﺸﺨﻴﺹ ﺘﻠﻑ ﺃﻨﺴﺠﺔ ﺍﻟﺒﻨﻜﺭﻴﺎﺱ‪ ،‬ﺒﺎﻷﺨﺹ ﻓﻲ ﺼﻐﺎﺭ ﻤﺭﻀﻰ ﺍﻟﺒﻭل ﺍﻟﺴﻜﺭﻱ ﺍﻟﻤﺼـﺤﻭﺒﺔ ﺒﺎﻟﻜﻴﺘﻭﻨـﺎﺕ‬
‫ﻤﻘﺎﺭﻨﺔ ﻤﻊ ﻤﺭﻀﻰ ﺍﻟﺒﻭل ﺍﻟﺴﻜﺭﻱ ﻏﻴﺭ ﺍﻟﻤﺼﺎﺤﺒﺔ ﺒﻅﻬﻭﺭﺍﻟﻜﻴﺘﻭﻨﺎﺕ ﻓﻲ ﺍﻟﺒﻭل‪.‬‬

‫ﺘﻡ ﺃﺨﺘﻴﺎﺭ‪ 85‬ﺤﺎﻟﺔ ﻤﻥ ﻤﻥ ﺍﻟﺤﺎﻻﺕ ﺍﻟﻤﺼﺎﺒﺔ ﺒﻤـﺭﺽ ﺍﻟﺒـﻭل ﻟﺩﺭﺍﺴـﺔ ﻤﺴـﺘﻭﻯ ﺍﻟﺘﻐﻴـﺭﺍﺕ‬
‫ﺍﻟﺒﻴﻭﻜﻤﻴﺎﺌﻴﺔ ﻟﻠﺩﻫﻭﻥ ﺍﻟﻜﻠﻴﺔ ﻭﻤﻜﻭﻨﺎﺘﻬﺎ ﺍﻟﻤﺨﺘﻠﻔﺔ‪.‬‬
‫ﻜﻤﺎ ﺃﻅﻬﺭﺕ ﺍﻟﻨﺘﺎﺌﺞ ﺃﻥ ﻤﺴﺘﻭﻯ ﺍﻟﺩﻫﻭﻥ ﺍﻟﻜﻠﻴﺔ ﻜﺎﻥ ﻤﺭﺘﻔﻌﺎ ﺃﺭﺘﻔﺎﻋﺎ ﻤﻠﺤﻭﻅﺎ ﻓﻲ ﺠﻤﻴـﻊ ﺤـﺎﻻﺕ‬
‫ﻤﺭﻀﻰ ﺍﻟﺒﻭل ﺍﻟﺴﻜﺭﻱ ﺒﻤﻘﺎﺭﻨﺘﻬﺎ ﺒﻤﺠﻤﻭﻋﺔ ﺍﻷﺼﺤﺎﺀ‪.‬‬
‫ﻅﻬﺭ ﺃﻥ ﻤﺴﺘﻭﻯ ﺍﻟﻜﻭﻟﺴﺘﺭﻭل ﻜﺎﻥ ﻤﺭﺘﻔﻌﺎ ﻓﻲ ﻤﺼل ﺩﻡ ﻤﺭﻀﻰ ﺍﻟﺒﻭل ﺍﻟﺴﻜﺭﻱ ﻤـﻥ ﺍﻹﻨـﺎﺙ‬
‫ﺴﻭﺍﺀ ﺍﻟﻤﺼﺎﺤﺒﺔ ﺃﻭ ﻏﻴﺭ ﻤﺼﺎﺤﺒﺔ ﻟﻸﺠﺴﺎﻡ ﺍﻟﻜﻴﺘﻭﻨﻴﺔ‪ .‬ﺃﻤﺎ ﻓﻲ ﻤﺭﻀﻰ ﺍﻟﺒﻭل ﺍﻟﺴﻜﺭﻱ ﻤﻥ ﺍﻟـﺫﻜﻭﺭ ﻓـﺈﻥ‬
‫ﻤﺴﺘﻭﻯ ﺍﻟﻜﻭﻟﺴﺘﺭﻭل ﻟﻡ ﻴﺘﻐﻴﺭ ﻓﻲ ﺍﻟﺩﻡ ﻋﻨﺩ ﻤﻘﺎﺭﻨﺘﻬﺎ ﺒﺎﻷﺼﺤﺎﺀ‪.‬‬
‫ﺘﻡ ﺍﻷﺴﺘﺩﻻل ﻜﺫﻟﻙ ﻋﻠﻰ ﻭﺠﻭﺩ ﺃﺭﺘﻔﺎﻉ ﻭﺍﻀﺢ ﻓﻲ ﻤﺴﺘﻭﻯ ﺜﻼﺜﻲ ﺍﻟﺠﻠﺴﺭﻴﺩﺍﺕ ﺒﺎﻷﺨﺹ ﻓـﻲ ﺩﻡ‬
‫ﺍﻟﻤﺼﺎﺒﻴﻥ ﺒﺈﺭﺘﻔﺎﻉ ﻓﻲ ﻤﺴﺘﻭﻯ ﺍﻟﻜﻴﺘﻭﻨﺎﺕ ﺒﻜل ﻤﻥ ﺍﻟﺫﻜﻭﺭ ﻭﺍﻹﻨﺎﺙ ﺒﺎﻟﻤﻘﺎﺭﻨﺔ ﻤﻊ ﻤﺭﻀﻰ ﺍﻟﺒﻭل ﺍﻟﺴـﻜﺭﻱ‬
‫ﺍﻟﻐﻴﺭ ﻤﺼﺎﺤﺒﺔ ﺒﺎﻟﻜﻴﺘﻭﻨﺎﺕ ﻭﺒﺎﻟﻤﺜل ﺘﻡ ﺍﻟﺤﺼﻭل ﻋﻠﻰ ﻤﺜل ﻫﺫﻩ ﺍﻟﻨﺘﺎﺌﺞ ﻋﻨﺩ ﻤﻘﺎﺭﻨﺘﻬﺎ ﻤـﻊ ﻤﺜﻴﻼﺘﻬـﺎ ﻓـﻲ‬
‫ﻤﺼل ﺩﻡ ﻤﺠﻤﻭﻋﺔ ﻤﻥ ﺍﻷﺼﺤﺎﺀ‪.‬‬
‫ﻅﻬـﺭ ﻜﺫﻟﻙ ﺃﻥ ﻤﺴﺘﻭﻯ ﺜﻼﺜﻲ ﺍﻟﺠﻠﺴﺭﻴﺩﺍﺕ ﻓﻲ ﻤﺼل ﺩﻡ ﻜل ﻤﻥ ﺍﻟﺫﻜﻭﺭ ﻭﺍﻹﻨﺎﺙ ﻜﺎﻥ ﻤﺭﺘﻔﻌـﺎ‬
‫ﺃﺭﺘﻔﺎﻋﺎ ﻤﻠﺤﻭﻅﺎ ﻓﻲ ﺒﻌﺽ ﻤﺭﻀﻰ ﺍﻟﺒﻭل ﺍﻟﺴﻜﺭﻯ ﻀﻌﻴﻔﺔ ﺍﻷﺴﺘﺠﺎﺒﺔ ﻟﻠﻌﻼﺝ‪ .‬ﻜﻤﺎ ﺃﻤﻜﻥ ﻜﺫﻟﻙ ﺍﻷﺴـﺘﺩﻻل‬
‫ﻋﻠﻰ ﺃﻥ ﻁﺭﻴﻘﺔ ﺇﺘﺒﺎﻉ ﻨﻅﺎﻡ ﺠﻴﺩ ﻟﻠﻌﻼﺝ ﺒﺎﻷﻨﺴﻭﻟﻴﻥ ﻗﺩ ﻴﺅﺩﻱ ﺒﺎﻟﺘﺎﻟﻲ ﺇﻟﻰ ﺍﻷﻨﺨﻔﺎﺽ ﻓﻲ ﺯﻴـﺎﺩﺓ ﻤﺴـﺘﻭﻯ‬
‫ﺜﻼﺜﻲ ﺍﻟﺠﻠﺴﺭﻴﺩﺍﺕ ﻓﻲ ﺒﻌﺽ ﺍﻷﺤﻴﺎﻥ ﺇﻟﻰ ﺍﻟﻤﺴﺘﻭﻯ ﺍﻟﻁﺒﻴﻌﻲ‪.‬‬
‫ﺘﻡ ﺃﺴﻨﺘﺎﺝ ﺃﻥ ﻤﺴﺘﻭﻯ ﺍﻷﺤﻤﺎﺽ ﺍﻟﺩﻫﻨﻴﺔ ﺍﻟﺤﺭﺓ ﻜﺎﻥ ﻤﺭﺘﻔﻌﺎ ﻓﻲ ﻤﺼل ﺩﻡ ﺠﻤﻴﻊ ﺤﺎﻻﺕ ﻤﺭﻀـﻰ‬
‫ﺍﻟﺒﻭل ﺍﻟﺴﻜﺭﻱ ﻭﻜﺫﻟﻙ ﻓﻲ ﺍﻟﻤﺠﻤﻭﻋﺎﺕ ﺍﻟﻤﺨﺘﻠﻔﺔ ﻜل ﻋﻠﻰ ﺤﺩﻯ ﻋﻨﺩ ﻤﻘﺎﺭﻨﺘﻬﺎ ﺒﺎﻷﺼﺤﺎﺀ‬
‫ﻭﻋﻤﻭﻤﺎ ﻓﺈﻥ ﻜﺜﻴﺭﺍ ﻤﻥ ﺍﻷﻫﺘﻤﺎﻡ ﻴﺠﺏ ﺃﺨﺫﻫﺎ ﻓﻲ ﺍﻷﻋﺘﺒﺎﺭ ﻋﻨﺩ ﻤﺘﺎﺒﻌﺔ ﻤﺴﺘﻭﻯ ﺍﻟـﺩﻫﻭﻥ ﺍﻟﻤﺨﺘﻠﻔـﺔ ﻓـﻲ‬
‫ﺍﻟﺤﺎﻻﺕ ﺍﻟﻤﺭﻀﻴﺔ ﺍﻟﻤﺼﺎﺤﺒﺔ ﻟﻸﺠﺴﺎﻡ ﺍﻟﻜﻴﺘﻭﻨﻴﺔ ﻓﻲ ﺍﻟﺩﻡ ﻭ ﺒﺎﻷﺨﺹ ﻓﻲ ﺍﻟﻤﺭﻀﻰ ﺫﺍﺕ ﺍﻟﻤﺴﺘﻭﻯ ﺍﻟﻤﺭﺘﻔﻊ‬
‫ﻟﻠﺠﻠﻭﻜﻭﺯ ﻓﻲ ﺍﻟﺩﻡ ﺒﻜل ﻤﻥ ﺍﻹﻨﺎﺙ ﻭﺍﻟﺫﻜﻭﺭ‪ .‬ﻜﻤﺎ ﺃﻨﻪ ﻤﻥ ﺍﻷﻓﻀل ﻤﺘﺎﺒﻌﺔ ﺍﻟﺘﻘﺩﻴﺭ ﺍﻟﻜﻤﻲ ﻟﻠـﺩﻫﻭﻥ ﺍﻟﻜﻠﻴـﺔ‬
‫ﺒﺎﺴﺘﻤﺭﺍﺭ ﻓﻲ ﻤﺼل ﺍﻟﺩﻡ ﻭﺘﺤﻠﻴل ﻤﻜﻭﻨﺎﺘﻬﺎ ﺒﺄﻨﺘﻅﺎﻡ ﻓﻲ ﻤﺭﻀﻰ ﺍﻟﺒﻭل ﺍﻟﺴﻜﺭﻱ ﻟﻤﺤﺎﻭﻟﺔ ﻤﺘﺎﺒﻌـﺔ ﺘﺄﺜﻴﺭﻫـﺎ‬
‫ﻭﻤﺩﻯ ﺨﻁﻭﺭﺘﻬﺎ ﻋﻠﻰ ﺘﺼﻠﺏ ﺍﻟﺸﺭﺍﻴﻴﻥ ﻓﻲ ﺍﻟﺠﺴﻡ ﻭﻤﺤﺎﻭﻟﺔ ﻋﻼﺠﻬﺎ ﻭﻤﻨﻊ ﺤﺩﻭﺙ ﺒﻌـﺽ ﺍﻟﻤﻀـﺎﻋﻔﺎﺕ‬
‫ﻭﺘﺠﻨﺏ ﺴﻭﺀ ﺍﻟﺤﺎﻟﺔ ﺍﻟﻤﺭﻀﻴﺔ‪.‬‬

‫ﺘﻡ ﻜﺫﻟﻙ ﻓﺤﺹ ﺇﻓﺭﺍﺯ ﺍﻟﺒﺭﻭﺘﻴﻨﺎﺕ ﻓﻲ ﺒﻭل ‪ 115‬ﺤﺎﻟﺔ ﻤﻥ ﺼـﻐﺎﺭ ﻭ ﻜﺒـﺎﺭ ﻤﺭﻀـﻰ ﺍﻟﺒـﻭل‬
‫ﺍﻟﺴﻜﺭﻱ ﺒﻁﺭﻴﻘﺔ ﺍﻟﻔﺼل ﺒﻭﺍﺴﻁﺔ ﺍﻹﻟﻜﺘﺭﻭﻓﻭﺭﻴﺴﻴﺱ ﻭﺍﻷﻤﻴﻨﻭﺇﻟﻜﺘﻭﻓﻭﺭﻴﺴﻴﺱ‪ .‬ﻜﻤﺎ ﺘـﻡ ﻤﻘﺎﺭﻨـﺔ ﺍﻟﻨﺘـﺎﺌﺞ‬
‫ﻭ ﻋﻼﻗﺘﻬﺎ ﺒﻌﻤﺭ ﺍﻟﻤﺭﻀﻰ ﻭ ﺩﻭﺭﺓ ﺍﻟﻤﺭﺽ ﻭ ﺍﻟﺠﻨﺱ ﻭ ﻨﻭﻉ ﺍﻟﻌﻼﺝ ﺍﻟﻤﺴﺘﺨﺩﻡ‪.‬‬
‫ﻭﻟﻘﺩ ﺃﻅﻬﺭﺕ ﺍﻟﻨﺘﺎﺌﺞ ﺃﻥ ﺩﻭﺭﺓ ﺍﻟﻤﺭﺽ ﻋﻨﺩﻤﺎ ﻜﺎﻨﺕ ﺃﻗل ﻤﻥ ﺨﻤﺱ ﺴﻨﻭﺍﺕ ﻓـﺈﻥ ﻜﻤﻴـﺔ ﺇﻓـﺭﺍﺯ‬
‫ﺍﻟﺒﺭﻭﺘﻴﻨﺎﺕ ﺍﻷﺨﺘﻴﺎﺭﻴﺔ ﻓﻲ ﺍﻟﺒﻭل ﻻ ﺘﺘﻌﺩﻯ ‪100‬ﻤﻠـ ﻎ‪100/‬ﻤـل‪ ،‬ﻭﺃﻥ ﻤﺴـﺘﻭﻯ ﻤﻜﻭﻨـﺎﺕ ﺍﻻﻟﺒﻴـﻭﻤﻴﻥ‬
‫ﻭﺍﻟﺘﺭﺍﻨﺴﻔﺭﻴﻥ ﻭ ﺍﻟﺴﺭﻴﻭﺒﻼﺯﻤﻴﻥ ﻜﺎﻨﺕ ﺃﻜﺜﺭ ﻭﻀﻭﺤﺎ ﻓﻲ ﺒﻭل ﻤﻌﻅﻡ ﻤﺭﻀﻰ ﺍﻟﺴﻜﺭ‪.‬‬
‫ﻟﻤﺎ ﻜﺎﻨﺕ ﺩﻭﺭﺓ ﺍﻟﻤﺭﺽ ﺘﺯﻴﺩ ﻋﻥ ﺨﻤﺱ ﺴﻨﻭﺍﺕ ﻓﻲ ﺒﻭل ﺒﻌﺽ ﺍﻟﻤﺭﻀﻰ‪ ،‬ﻓـﺈﻥ ﻜﻤﻴـﺔ ﺇﻓـﺭﺍﺯ‬
‫ﺍﻟﺒﺭﻭﺘﻴﻥ ﺍﻟﻼﺃﺨﺘﻴﺎﺭﻴﺔ ﻜﺎﻨﺕ ﻤﺭﺘﻔﻌﺔ ﻋﻥ ‪100‬ﻤﻠﻎ‪100 /‬ﻤل ﻤﻊ ﻅﻬﻭﺭ ﺒﻌـﺽ ﺍﻟﻤﻜﻭﻨـﺎﺕ ﺫﺍﺕ ﺍﻷﻭﺯﺍﻥ‬
‫ﺍﻟﺠﺯﺌﻴﺔ ﺍﻟﻌﺎﻟﻴﺔ ﻤﺜل ﺍﻷﻤﻴﻨ ﻭﺠﻠﻭﺒﻴﻭﻟﻴﻥ ﺃ‪ ،‬ﺝ‪ ،‬ﻓﻲ ﺤﻴﻥ ﺍﻟﻤﻜﻭﻨﺎﺕ ﺍﻟﺒﺭﻭﺘﻴﻨﻴﺔ ﺫﺍﺕ ﺍﻟﻨﻔﺎﺫﻴـﺔ ﺍﻟﻼﺍﺨﺘﻴﺎﺭﻴـﺔ‬
‫ﻜﺎﻨﺕ ﻤﺭﺘﻔﻌﺔ ﻓﻲ ﺒﻭل ﻋﺩﺩ ﻜﺒﻴﺭ ﻤﻥ ﻜﺒﺎﺭ ﺇﻨﺎﺙ ﺍﻟﻤﺭﻀﻰ ﺃﻜﺜﺭ ﻤﻥ ﺍﻟﺫﻜﻭﺭ‪ ،‬ﻤﻤﺎ ﻴﺩل ﻋﻠﻰ ﺸـﺩﺓ ﺍﻟﺤﺎﻟـﺔ‬
‫ﺍﻟﻤﺭﻀﻴﺔ ﻤﺼﺤﻭﺒﺔ ﺒﻅﻬﻭﺭ ﺍﻟﺘﻬﺎﺒﺎﺕ ﻜﻠﻭﻴﺔ‪ ،‬ﻤﻤﺎ ﻴﺅﻜﺩ ﺍﻟﺤﺎﺠﺔ ﺇﻟﻰ ﺴﺭﻋﺔ ﻋﻼﺝ ﻫﺅﻻﺀ ﺍﻟﻤﺭﻀﻰ‪.‬‬