Carbohydrates(CHO)

EMADELDEEN MAHMOUD KHALIL

AL-NEELAIN UNIVERSITY
MLS-CLINICAL CHEMISTRY

Are chemical substances that contain only carbon,

hydrogen, and oxygen that constitute a major food
class.
The general formula for a carbohydrates in C x (H2O)
y`

. all carbohydrates contain C = O and OH

functional purposes. There are some derivatives

can be formed by
.groups

the addition of other chemical

such as phosphates, sulfates and amines

Carbohydrates, including sugar and starch, are widely

distributed in plants and animals. They perform multiple
functions ranging from structural components or RNA and
DNA (ribose and deoxy ribose sugars) to a source of energy
(glucose).
Classification of carbohydrates is based on four different
properties:
the size of the base carbon chain,
the location of the CD function group
the number of sugar unit, and
the stereochemistry of the compound

Monosaccharides - simple
carbohydrates that cannot be broken down to further sugars by hydrolysis Monosaccharides are the units that make up more
.complex carbohydrates. Glucose, fructose , ribose, and galactose are common monosaccharides of living organisms

O
C H
OH C H
H C OH
OH C H
OH C H
CH2O
H
L. Glucose

O
C H
H C OH
OH C H
H C OH
H C OH
CH2O
H
D. Glucose

Disaccharides
Two monosaccharides bind together covalently through
glycosidic bond with the loss of a molecule of water
.Lactose, maltose, and sucrose are common
. disaccharides of living cells

Oligosaccharides
More than two monosaccharides bind together
covalently through glycosidic bond with the loss of a
. molecule of water

polysaccharides - complex
carbohydrates composed of more than 20
monosaccharides (large polymers of
monosaccharides).Starch, cellulose, and
glycogen are common polysaccharides of
living cells. Plants store glucose as starch and
cellulose. Animals store glucose as long,
.branching polymers called glycogen

Fructosamine.
Many integral membrane proteins have
oligosaccharides covalently attached to the
intracellular region, forming glycoprotein. In
addition, most proteins that are secreted such an
antibodies, hormones, and coagulation factors, are
glycoproteins. The number of attached
carbohydrates residues varies among proteins and
constitutes 1% to 70% of the weight of the
.glycoprotein

The oligosaccharides are attached by oglucosidic linkages to the side chain oxygen of
serine or threonine residues. Alternatively,
attachment is by N-glucosidic linkages to the
.side chain nitrogen of asparagine residues

One biological function of the carbohydrate chains

is to regulate the life span of proteins. For
example, loss of sialic acid residues from the end
of oligosaccharide chains on erythrocytes results in
the removal of red blood cells from the circulation.
Carbohydrates also have been implicated in cell
recognition and secretion and targeting of proteins
. to specific subcellular domains

Metabolism of Carbohydrates:
Glucose is the primary energy source for the human
body. After digestion of carbohydrate and absorption of
the glucose the blood glucose concentration
. controlled by the action of several hormones

Digestion and Absorption

Most of our ingested carbohydrates are polymers such
as starch and glycogen salivary amylase and pancreatic
amylase are responsible for the digestion of these non
absorbable polymers to dextrin and disaccharide,
which are further hydrolyzed to monosaccharide by
.disaccharidase enzymes

Sucrose and lactase are two other important gut

derived enzymes that hydrolyze sucrose to glucose
and fructose, and lactose to glucose and galactose.
Once disaccharides are converted into
monosaccharides, they are absorbed by the gut and
.transported to the liver by the hepatic portal venous

Intermediary Metabolism
All hexoses proceeds according to the bodys requirements.
This metabolism results in

(1) Energy production by conversion to carbon dioxide

and water,
(2) Storage as glycogen in the liver or triglyceride in
adipose tissue, or
(3) Conversion to ketoacids, amino acids, or protein.
Glucose is the only carbohydrate to be either directly
used for energy or stored as glycogen

After glucose enters the cell, it is quickly shunted into

one of three possible metabolic pathways, depending
on the availability of substrates or the nutritional
states of the cell. The ultimate goal of the cell is to
convert glucose to carbon dioxide and water or the
. Embden-Meyerhof metabolic pathway

During this process, the cell obtains the high energy

molecule adenosine triphosphate (ATP) from inorganic
phosphate and adenosine diphosphate (ADP).
The cell requires oxygen for the final steps in the electron
transport chain (ETC). Nicotinamide adenine dinucleotide
(NAD) in its reduced form (NADH) will act as intermediate to
couple glucose oxidation to the ETC in the mitochondria
where much of the ATP is gained

The first step for all three pathways requires glucose to be

converted to glucose.-6- Phosphate using the high energy
molecule ATP. This reaction is catalyzed by the enzyme
hexokinase. Glucose 6 phosphate can enter the Embden.
Myorhof pathway or the hexose monophosohate pathway, or
can be converted to glycogen. The first two pathways are
important for the generation of energy from glucose; the
conversion to glycogen pathway is important for the storage
. of glucose

In the Embden- myerhof pathway, glucose is broken

down into two three - carbon molecules of pyruvic acid
that can enter the tricarboxylic acid cycle (TCA cycle) on
conversion to acetyl coenzyme A (acetyl CoA). This
pathway requires oxygen and is called the aerobic
pathway. Other substrates have the opportunity to enter
the pathway at several points. Glycerol released from
the hydrolysis of triglycerides can enter at 3phosphoglycerate, and fatty acids and ketones and
some amino acids are converted or catabolized to acetyl
. CoA, which is part of the TCA cycle

Other amino acids enter the pathway as pyruvate or as

deaminated - ketoacid and oxoacids. The conversion
of amino acids by the liver, and other specialized
tissues such as the kidney, to substrates that can be
converted to glucose is called gluconeogenesis.
Gluconeogenesis also encompasses
the conversion of glycerol, lactate, and pyruvate to
. glucose

Anaerobic glycolysis is important for tissues such as muscle,

which often have important energy requirements without an
adequate oxygen supply.
These tissues can derived ATP from glucose in oxygen
deficient environment by converting pyruvic acid into lactic
acid. The lactic acid diffuses from the muscle cell, enters the
. systemic circulation then taken up and used by the liver

For anaerobic glycolysis to occur, 2 moles of ATP must

be consumed for each mole of glucose; however, 4
moles of ATP are directly produced, resulting in a net
gain of 2 moles of ATP.
Further gains of ATP result from the introduction of
.pyruvate into the TCA cycle and NADH into the ETC

Regulation of blood glucose concentration

The concentration of glucose in blood is regulated by
complex of interplay of multiple pathways, modulated by
number of enzymes and hormones

Glycolysis

Metabolism of glucose molecule to pyruvate

or lactate for production of energy

Gluconeogenesis Formation of glucose-6-phosphate from

noncarbohydrate source

Glycogenolysis

Breakdown of glycogen to glucose for use as energy

Glycogenesis

Conversion of glucose to glycogen for storage

Lipogenesis

Conversion of carbohydrates to fatty acids

Lipolysis

Decomposition of fat

The reducing power of NADPH is required for the

protection of the cell form oxidative and free radical
damage. Without NADPH, the lipid bilayer membrane of
the cell and critical enzymes would eventually be
destroyed, resulting in cell death. The HMP shunt also
permits pentoses, such as ribose, to enter the glycolytic
. pathway

When the cells energy requirements are being met,

glucose can be stored as glycogen. This third pathway,
which is called glycogenesis, is relatively
straightforward. Glucose -6- phosphate is converted to
glucose -1- phosphate, which is then converted to
uridine diphosphoglucose and then to glycogen by
glycogen synthase. Several tissues are capable of the
synthesis of glycogen, especially the liver and muscles.
Hepatocytes are capable of releasing glucose from
glycogen or other sources to maintain the blood glucose
. concentration

This is because the liver synthesizes the enzyme

glucose-6-phosphatase. Without this enzyme, glucose is
trapped in the glycolytic pathway. Muscle cells do not
synthesize glucose -6-pphosohatase, and therefore they
are incapable of dephosphorylating glucose. Once
glucose enters a muscle cell , it remains as glycogen
unless it is catabolized .Glycogenolysis is the process by
which glycogen is converted back to glucose -6. phosphate for entry into the glycolytic pathway

The second energy pathway is the hexose

monophosphate shunt (HMP shunt), which is
actually a resource of glucose - 6 -phosphate
from the glycolytic pathway to become 6phosphogluconic acid. This oxidized product
permits the formation of ribose -5- phosphate
and nicotinamide dinucleotide phosphate in its
reduced form (NADPH) , NADPH is important
to erythrocytes that lack mitochondria and are
. therefore incapable of the TCA cycle

glycolysis and gluconeogenesis

Hormones that regulate blood glucose concentration

Hormones that regulate blood glucose concentration

The concentration of glucose in the blood is normally
maintained within narrow range by hormone that modulate the
movement of glucose into and out of the circulation. These
include insulin, which decreases blood glucose , and the
counterregulatory hormones which increase blood glucose
. concentration

Insulin
A peptide hormone, produced by beta cells of the pancreas, and is central to
regulating carbohydrate and fat metabolism in the body. Insulin causes cells
in the liver, skeletal muscles, and fat tissue to take up glucose from the blood.
In the liver and skeletal muscles, glucose is stored as glycogen, and in
adipocytes it is stored as triglycerides.
Insulin stops the use of fat as an energy source by inhibiting the release of
. glucagon

is provided within the body in a constant proportion to

remove excess glucose from the blood, which otherwise
would be toxic. As a central metabolic control
mechanism, its status is also used as a control signal to
other body systems (such as amino acid uptake by body
cells

The human insulin protein is composed of 51 amino

acids, and has a molecular weight of 5808 Da. It is a
dimer of an A-chain and a B-chain, which are linked
together by disulfide bonds.
When control of insulin levels fails, diabetes mellitus
can result. As a consequence, insulin is used medically
to treat some forms of diabetes mellitus

Regulation
Several regulatory sequences in the promoter region of the human
insulin gene bind to transcription factors

Glucose transport
Into the cell is modulated by two families of proteins facilitative glucose
transporter -the sodium-glucose cotransport as the mechanism for intestinal
glucose absorption

Glucose transport:
Glucose transporters are a wide group of membrane proteins that
facilitate the transport of glucose over a plasma membrane.
Into the cell is modulated by two families of proteins facilitative
glucose transporter(GLUT) and the sodium-glucose cotransport as
the mechanism for Sodium-dependent glucose cotransporters (or
.sodium-glucose linked transporter, SGLT)
.

These families of glucose transporter found in the intestinal

mucosa of the small intestine (SGLT1) And the proximal tubule
of the nephron (SGLT2 and SGLT1). They contribute to renal
glucose reabsorption. In the kidneys, 100% of the filtered
glucose in the glomerulus has to be reabsorbed along the
. nephron (98% in PCT, via SGLT2)

Glucose transporters are a wide group of membrane proteins

that facilitate the transport of glucose over a plasma membrane.
Because glucose is a vital source of energy for all life these
transporters are present in main two families .
The GLUT or SLC2A family are a protein family that is found in
most mammalian cells

Formation of glycated hemoglobin

Is essential irreversible , the concentration in
the blood depends on both the life span of the
red blood cell and the blood glucose
concentration

Haemoglobin in the blood (red, rectangle) combines

with glucose in the blood (green, circle) to form
.glycosylated haemoglobin

Controlled diabetes,
not much glucose, not
much glycosylated
haemoglobin

Uncontrolled diabetes, more

glucose, much more glycosylated
haemoglobin

synthesis

starts many
protein
activation
cascades

glycolysis

synthesis

Insulin binds to its receptor (1), which starts many

protein activation cascades (2). These include
translocation of Glut-4 transporter to the plasma
membrane and influx of glucose (3), glycogen
.synthesis (4), glycolysis (5) and fatty acid synthesis (6)

Insulin-like growth factor 1 (IGF-1) and (IGF-2)

Also called somatomedin C, is a protein that in humans is

encoded by the IGF1 gene. Exhibit metabolic and growth
promoting effects similar to those of insulin
Its effects were termed "nonsuppressible insulin-like activity"
(NSILA).
IGF-1 is a hormone similar in molecular structure to insulin. It
plays an important role in anabolic effects in adults

A counterregulatory hormone
Is a hormone that opposite the action of another hormone.
The action of insulin is counterregulated by glucagon,
adrenaline (epinephrine), noradrenaline (norepinephrine),
cortisol, and growth hormone.
raise the level of glucose in the blood by promoting
glycogenolysis , gluconeogenesis, ketosis, and other catabolic
.processes
In healthy people, counterregulatory hormones constitute a
principal defense against hypoglycemia, and levels are expected
to rise as the glucose falls

Glucagon
A peptide hormone secreted by alpha cells of the pancreas, raises
blood glucose levels. Its effect is opposite that of insulin.
The pancreas releases glucagon when blood sugar (glucose)
levels fall too low. Glucagon causes the liver to convert stored
. glycogen into glucose, which is released into the bloodstream

High blood glucose levels stimulate the release of

insulin. Insulin allows glucose to be taken up and used
by insulin-dependent tissues. Thus, glucagon and
insulin are part of a feedback system that keeps blood
glucose levels at a stable level. Glucagon belongs to a
family of several other related hormones

Epinephrine (also known as adrenaline)

Is a hormone and a neurotransmitter.
Epinephrine has many functions in the
body, regulating heart rate, blood vessel
and air passage diameters, and metabolic
shifts

Growth hormone (GH)

Is a peptide hormone that stimulates growth, cell reproduction and
regeneration in humans and other animals. Its role as an anabolic agent

Cortisol
Is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal
gland. It is released in response to stress and a low level of blood glucocorticoids. Its
primary functions are to increase blood sugar through gluconeogenesis; suppress the
..immune system; and aid in fat, protein and carbohydrate metabolism

Thyroxine or T4

A synthetic form of thyroid hormone (or Thyroxine), the

hormone normally secreted by the follicular cells of the
thyroid gland.Is used to treat thyroid hormone deficiency, and
occasionally to prevent the hypoglasemia

Somatostatin (also known as growth hormone-inhibiting

hormone (GHIH) or somatotropin release-inhibiting factor
(SRIF)) is a peptide hormone that regulates the endocrine system
and affects neurotransmission and cell proliferation

Ketone bodies
Are three water-soluble compounds that are produced as byproducts when fatty acids are broken down for energy in the
liver. Two of the three are used as a source of energy in the heart
and brain while the third is a waste product excreted from the
body. In the brain, they are a vital source of energy during
fasting. The three endogenous ketone bodies are acetone,
.acetoacetic acid, and beta-hydroxybutyric acid

Diabetes mellitus

Alteration in CHO metabolism: Humans can have hyper or

hypoglycemia state , hyperglycemia (elevation of blood
glucose) can be caused by physiologic or endocrine changes.
Diabetes mellitus is a group of metabolic disorders of
carbohydrates
metabolism in which glucose is underutilized, producing
. hyperglycemia

Diabetes mellitus is a chronic disorder of carbohydrate, fat and protein metabolism

. It characterized by an absolute or relative insulin deficiency, resulting from
defects in insulin secretion, insulin action, or both to hyperglycemia and possible risk
for development of complications .
The WHO export committee (1980) defined diabetes mellitus as a state of chronic
hyperglycemia in which plasma glucose concentration is 126 mg/dL. (7.8
mmol/L) in the fasting state or 200mg/dL (11.1 mmol/L) two hours after
. administration of standardized oral glucose load

Diabetes Mellitus is one of the most common chronic disease in the world, with a
prevalence that approaches 8% of the adult populations of the USA and with more
than 100 million cases world wide . It is a common disease in Africa. It affects more
than 7.7 million people in 1997. Those with type 1 were 84.3 thousands and 7.6
million with type 2.
Diabetes Mellitus is common among adult populations of northern Sudan and is
associated mostly with poor metabolic control. High prevalence of complications and
. low quality of life

Type 2 is a common type of diabetes in diabetic clinics. Patients show

severe complications and morbidity due to poor metabolic control. The
prediction is that in2025 there will be more than 450 million adult with
diabetes , greater than 75 % of whom will live in the developing
countries these statistics have led diabetes being described as one of
the main threats to human health in the twentyfirst century

Etiologic Classification of Diabetes Mellitus

1-Type 1 diabetes : InsulinDependent Diabetes Mellitus
IDDM
Patients have insulinopenia

-(beta cell destruction, usually leading to absolute insulin

deficiency)

-Immune mediated autoimmunity

-Triggering factors, such as rubella, mumps , and
other viral infection,

-Idiopathic

Type 2 diabetes: NonInsulinDependent Diabetes Mellitus -2

(NIDDM) (may range from predominantly insulin resistance
with relative insulin deficiency to a predominantly secretory
defect with insulin resistance)
3- Gestational diabetes mellitus (GDM)
4- Other specific types : Associated with secondary conditions
- Genetic defects of beta cell function
- Drug- or chemical-induced

Infections- Uncommon forms of immune-mediated diabetes

Impaired Glucose Tolerance (IGT): The fasting blood glucose is
less than required for diagnosis of DM, but have a plasma
glucose response during OGTT between normal and diabetic
states.
Impaired Fasting Glucose (IFG) : is analogous to IGT, but is
diagnosed by fasting glucose between of normal and diabetic
. individuals

The disorders of diabetes differ in their presentation as well

as their etiology. Approximately 10% of diabetics are of the
type 1 variety. The type 1 disease state usually occurs as
acute illness, glucose blood levels are usually more severe
than type 2 and are more likely to develop ketoacidosis .
Of disease, type 1 diabetics are insulin dependent , younger
.(less than 30 years old when diagnosed) and thinner

Approximately 90% of diabetics are of the type 2 .

type 2 diabetes progresses slowly over time.
the most type 2 diabetics are not insulin dependent. type 2
diabetics are usually older (40 years old when diagnosed) and
.more likely to be obese

However, these characteristics of presentation are not

uniform to all type 1 and type 2 diabetics. Type 1 diabetes
may be diagnosed after the age of 18-30 years. Type 2
diabetes may develop in obese children. Type 2 diabetics may
need insulin if glycemia cannot be controlled by other
.measures

Former name

Preferred name

: Type I

Type 1 diabetes

Juvenile diabetes insulin dependent

diabetes mellitus IDDM

: Type II
Adult onset diabetes
Non insulin dependent diabetes
mellitus (NIDDM)

Type 2 diabetes

Gestational diabetes is similar in etiology to type 2 diabetes;

however, it is defined as diabetes that is diagnosed in
pregnancy. Pregnancy is associated with increased tissue cell
resistance to insulin due to metallic and hormonal changes.
Most pregnant women will compensate with increased
secretion of insulin; those individuals who are unable to
. compensate may develop gestational diabetes

The hyperglycemia of gestational diabetes diminishes after

delivery; however, the individual who has developed
gestational diabetes is at higher risk for the development of
.type 2 diabetes there after

Pathophysiology of Diabetes Mellitus:

In both type 1 and 2 diabetes the individual will be
hyperglycemic, which can be severe glucosuria can also occur
after the renal tubular transporter system for glucose become
saturated. This happens when the glucose concentration of
plasma exceed roughly 180 mg/dL in an individual with normal
renal function and urine output

Pathophysiology of Diabetes Mellitus:

In both type 1 and 2 diabetes the individual will be
- hyperglycemic
- glucosuria(when the glucose concentration of plasma exceed
roughly 180 mg/dL)

As hepatic glucose overproduction continues, the plasma

glucose concentration reaches a plateau around 300 mg/dL to
500 mg/dL (17 mmol/L to 28 mmol/L). Provided renal output in
maintained glucose excretion will match the overproduction
causing the plateau. The individual with type 1 has a higher
tendency to produce ketones.

As hepatic glucose overproduction continues, the plasma

glucose concentration reaches a plateau around 300 mg/dL to
500 mg/dL (17 mmol/L to 28 mmol/L). Provided renal output in
maintained glucose excretion will match the overproduction
causing the plateau. The individual with type 1 has a higher
tendency to produce ketones.

The individual with type 1 has a higher tendency to produce

ketones.
Type 2 patients seldom generate ketones,
but in stead have a greater tendency to develop hyperosmolar
non ketotic states. The difference in glucagon and insulin
concentrations in these two groups appears to be responsible
for the generation of ketones through increased oxidation.
In type 1, there is an absence of insulin with an excess of
glucagon. This permits gluconeogenesis and lipolysis to occur.

ketones.
Type 2 patients seldom generate ketones( tendency to develop
hyperosmolar non ketotic states).
Due to the difference in glucagon and insulin concentrations in
these two groups appears to be responsible for the generation
of ketones through increased oxidation.
In type 1, there is an absence of insulin with an excess of
glucagon.
This permits gluconeogenesis and lipolysis to occur.

In type 2
- Insulin is present as -sometimes- hyperinsulinaemia
- Glucagon is attenuated.
Fatty acid oxidation is inhibited in type 2.

disturbance and acidosis. Acetoacetic acid, hydroxybutyrate and acetone are produced from the
oxidation of fatty acids. The two former ketones
bodies contribute to the acidosis. Lactate, fatty
acids and other organic acids can also contribute to
a lesser degree. Bicarbonate and total carbon
dioxide are usually decreased due to kussmaulkien
respiration (deep respiration). This is a
compensatory mechanism to blow off carbon dioxide
and remove hydrogen ions in the process.

and in part to a shift of water from cell because of the

hyperglycemia. Care must be taken not to falsely
underestimate the sodium value because of
hypertriglyceridemia.
Grossly elevated triglycerides will displace plasma volume and
give the appearance of decreased electrolytes when flame
photometry or pre diluted ion specific electrodes are used
for sodium determination. Hyperkalemia is almost always
present due to the displacement of potassium from cells in
acidosis. This is somewhat misleading because the patients
total body potassium is usually decreased.

More typical of the untreated type 2 patient is the non ketotic

hyperosmolar state. The individual presenting with this syndrome has
an overproduction of glucose; however, there appears to be an
imbalance between production and elimination in urine. Often, this
state is precipitated by heart disease, stroke or pancreatitis.
Glucose concentrations exceed 300mg/dL to 500 mg/dL (17 mmol/L to
28 mmol/L) and severe dehydration is present, the severe
dehydration contributes to the inability to excrete glucose in the
urine. Mortality is high with this condition.

Slightly decreased bicarbonate, elevated blood urea

nitrogen (BUN) and creatinine and an elevated
osmolality. The gross elevation in glucose and
osmolality, the elevation in BUN and the absence of
ketones distinguish this condition from diabetic
ketoacidosis.

Lactate, fatty acids and other organic acids can also contribute
to a lesser degree. Bicarbonate and total carbon dioxide are
usually decreased due to kussmaulkien respiration (deep
respiration). This is a compensatory mechanism to blow off
carbon dioxide and remove hydrogen ions in the process.

osmolality is high due to hyperglycemia; sodium

concentrations tend to be lower due in part losses (polyuria)
and in part to a shift of water from cell because of the
hyperglycemia. Care must be taken not to falsely
underestimate the sodium value because of
hypertriglyceridemia.

Grossly elevated triglycerides will displace plasma volume and

give the appearance of decreased electrolytes when flame
photometry or pre diluted ion specific electrodes are used
for sodium determination. Hyperkalemia is almost always
present due to the displacement of potassium from cells in
acidosis. This is somewhat misleading because the patients
total body potassium is usually decreased.

More typical of the untreated type 2 patient is the non

ketotic hyperosmolar state. The individual presenting with this
syndrome has an overproduction of glucose; however, there
appears to be an imbalance between production and
elimination in urine. Often, this state is precipitated by heart
disease, stroke or pancreatitis.

Glucose concentrations exceed 300mg/dL to 500 mg/dL (17

mmol/L to 28 mmol/L) and severe dehydration is present, the
severe dehydration contributes to the inability to excrete
glucose in the urine. Mortality is high with this condition.

Keton are not observed, because the severe hyperosmolar

state inhibits the ability of glucagon to stimulate lipolysis. The
laboratory findings of non ketotic hyperosmolar coma include
plasma glucose values exceeding 1000 mg/dL (55 mmol/L),
normal or elevated plasma sodium and potassium.

Slightly decreased bicarbonate, elevated blood urea

nitrogen (BUN) and creatinine and an elevated
osmolality. The gross elevation in glucose and
osmolality, the elevation in BUN and the absence of
ketones distinguish this condition from diabetic
ketoacidosis.

Pathogenesis of Type I:
In the vast majority of patients the destruction of B- cells is
mediated by T cell.
1- Antibodies: circulating antibodies can be detected before the
onset of the disease as a marker of B-cells autoimmunity
1-Islet cell cytoplasmic antibodies (ICAs)
2-Insulin autoantibodies (IAAs)
3-Antibodies to the 65-Kd isoform og glutamic acid
decarboxylase(GAD65)
4- Insulinoma-associated antigen(IA-2A and IA2BA)

2- Genetics: the inheritance is multigenic trait, and the major locus is

the major histocompatibility complex (HLA-DR3 or DR4) on
chromosome 6, the concordance rate between identical twins is
30%.
3- Environment : environmental factors are involved in initiating
diabetes , like viruses (mumps, rubella) and chemicals

Pathogenesis of Type 2:
There are at least two major identifiable pathological defect
1-Loss of B-cells function: the major defects is a loss of
glucose- induced insulin release, hyperglycemia render Bcell increasingly unresponsive to glucose (called
glucotoxicity) .
2- Insulin resistance: is a decreased in biological response
to normal concentration of circulating insulin( action) also
known as syndrome X or the metabolic syndrome .

The metabolic syndrome diagnosis if an individual has three

or more of the following criteria such as:
Abdominal obesity
High triglycerides
Low HDL (good) cholesterol
High LDL (bad) cholesterol
Blood pressure greater than 130/85 mm Hg
Fasting plasma glucose 110 mg/dl

3- Environmental factors: Such as diet (obesity) and exercise are

important pathogenesis in type 2 .There is inverse relation
between physical activities and prevalence of type 2
4- Diabetogenes: Genetic factors play greater role in NIDDM than in
IDDM , the concordance rate for type 2 in identical twin is 100%
5- candidate Insulin-Resistance Gene
6- candidate Body Weight Gene
7- Other factors amylin (also called islet amyloid polypeptideIAPP)

Complication of Diabetes Mellitus:

In both IDDM & NIDDM the patient will be hyperglycemic.

1- A cute complication:
A- Diabetic Ketoacidosis: is the increase production of
ketone bodies, commonly presents in IDDM , the liver shift
to fatty acid oxidation as energy sources because of the
insulin absence .

-Clinical features: Thirst- polyuria- dehydrationhypotension ketosis- hyperventilation- vomitingabdominal pain , drowsness and coma.
- Metabolic Feature: hyperglycemia, glycosuria , nonrespiratory acidosis, ketonaemia, uraemia, hyperkalemia ,
hypertriglyceridaemia and haemoconcentration

b) Non ketotic hyperosmolar coma : occurs in NIDDM.

Clinical feature: is an acute complication sharing many symptoms
with DKA, elevated blood glucose, high plasma osmolality,
dehydration, Electrolyte imbalances
c) Hypoglycaemia :abnormally low blood glucose(< 45 mg/dl), is an
acute complication of several diabetes treatments .The patient become
agitated, sweaty, and have many symptoms of sympathetic disorders
leading to coma, and death.

Chronic complications :
1- Over time, hyperglycemia can damage large blood vessels,
leading to stroke, Cardiovascular disease
(atherosclerosis)leading to heart attack, gangrene and loss of
circulation in the arms and legs.
2- Hyperglycemia, often acting in concert with hypertension,
can lead to small blood vessel damage.
A- Microvascular complications include:
1-Diabetic retinopathy (a term for disorders of the retina
associated with diabetes) is the leading cause of blindness .
diabetes are twice as likely to develop glaucoma and cataracts
as those without diabetes..
2- Nephropathy (kidney damage), and diabetes is the leading
cause of end-stage renal disease.

B-Hyperglycemia can lead to nerve damage.

1-Peripheral neuropathy. Peripheral neuropathy of the sensory
nerves contributes to the development of foot ulcers, which
can lead to amputation.
2-Neuropathy also can affect the hands and arms.
3- Diabetes-related damage to nerves that supply internal
body organs (autonomic neuropathy).

4- Other complications (not shown) include dental disease,

complications of pregnancy, and sexual dysfunction including
erectile dysfunction in men and a number of female sexual
problems
Untreated diabetes can cause serious complications even if a
person feels fine. Type 2 diabetes has been called a silent
killer because many people are not aware they have the
disease until they develop serious complications.

Hyperglycemia Can Cause Serious

Long-Term Problems

Glucose Challenge Test and Other Diagnostic Tests

The hallmarks of the laboratorys role in diagnosis of type 1
and type 2 diabetes are
the fasting glucose test and the glucose challenge test.
For 3 days before the challenge test, the patient should
consume at least the minimum daily requirement of
carbohydrates and exercise normally. An overnight fast of 10
to 16 hours is required the night before the test.

period. Blood is drawn before the ingestion of glucose liquid

and at 2 hours after ingestion.
The time period starts when the patient begins to drink the
glucose liquid; all the
liquid should be consumed within 5 minutes. Seventy-five
grams of glucose are
given to adults; children are given 1.75 g/kg of weight, but not
more than 75 g.

blood is collected without anticoagulant and serum is tested.

Blood may be collected into vacuum tube, which contains
sodium fluoride and sodium or potassium oxalate,the
preservative sodium fluoride will reduce glycolysis for up to 24
hours at room temperature. Several methods for testing for
blood glucose are available.

glucose challenge. As the first step in the two-step challenge,

the patient is given a
50-g glucose load. The patient need not be fasting for the test.
Blood is drawn for
glucose testing at 1 hour after ingestion of the glucose
solution.
A 1-hour glucose level of less than 140 mg/dL rules out a frank
diagnosis of gestational diabetes.

Patients who have 1-hour levels of greater than or equal to

140 mg/dL are challenged 100g . Diagnosis of gestational
diabetes is made if any two of the following results are
observed: Fasting blood glucose: 95 mg/dL

1 hour blood glucose: 180 mg/dL

2 hour blood glucose: 155 mg/dL
3 hour blood glucose: 140 mg/dL

Alternatively, the patient may be given 75g of glucose for the

tolerance test. Criteria for fasting, 1-hour, and 2-hour glucose
levels are the same as the 100-g glucose tolerance test;
however, a 3-hour blood test is not drawn.
For the one-step approach, the glucose tolerance test is
performed directly without the 50-g glucose screening test.
This approach is best used for women who are at high risk for
development of gestational diabetes based on personal and
family history and examination findings.

Reference Ranges for Blood Glucose Levels

Indication
Normal

Impaired

of

Diabetes
Fasting blood glucose (mg/dL)

7099

100125

126
2-Hour postprandial blood glucose (mg/dL)
200

< 140

140199

concentration 200
mg/dL (11.1 mmol/L). Random is defined as any time of day
without regard to time
since last meal. The classic symptoms of diabetes include
polyuria, polydipsia,
polyphagia, and unexplained weight loss. OR
2. Fasting plasma glucose (FPG) 126 mg/dL (7.0 mmol/L).
Fasting is defined as no
caloric intake for at least 8 hours. OR

3. 2-Hour postload glucose 200 mg/dL (11.1 mmol/L) during

an oral glucose tolerance test, using a glucose load containing
the equivalent of 75 g anhydrous glucose dissolved in water.
These criteria should be confirmed by repeat testing on a
different day.
The 3-hour oral glucose tolerance test (OGTT) is not
recommended for routine clinical use.

Reference intervals
Plasma/serum
Adults
Children
Premature neonates
Term neonates
Whole blood
CSF
URINE 24hr

Sample fasting glucose

mg/dl
74-106 (4.5-5.9 mmol/L)
60-100 (3.5-5.6 mmol/L)
20-60 (1.1-3.3 mmol/L)
30-60(1.7-3.3 mmol/L)
65-95(3.5-5.3 mmol/L)
40-70(2.2-3.9 mmol/L)
(60% of plasma value )
1 15mg/dl (0.10.8mmol/L)

Curves of OGTT

NORMAL-1
2-DIABETIC
3-GLUCOSURIA
4-SEVERE DIABETIC
5-FLAT CURVE
LAG CURVE -6
7-GESTATIONAL

Sugar isnt such a sweet

!Deal

Hypoglycemia

Definition of hypoglycemia
blood glucose concentration below the fasting level or
a low plasma glucose (PG) level (<4.0 mmol/L) 2 hours
after meal or for patients treated with insulin
the development of autonomic or neuroglycopenic
symptoms
symptoms responding to the administration of
carbohydrates

: Hypoglycemic Syndromes
key features for diagnosis of hypoglycemia ( Whipple
triad).(1) symptoms consistent with hypoglycemia, (2)
a low plasma glucose concentration, and (3) relief of
symptoms after the plasma glucose
level is raised

Neurogenic (autonomic)
Trembling
Palpitations
Sweating
Anxiety
Hunger
Nausea
Tingling

Neuroglycopenic (severe CNS dysfunction)

weakness
confusion
drowsiness
vision changes
difficulty speaking
difficulty concentrating
headache , dizziness and even death
Gradual onset of hypoglycemia may not produce symptoms

Hypoglycemia in Neonates and Infants

The neonatal blood concentration are much lower
than adult ( mean 35 mg/dl)
In most cases it is multifactorial, transient and
easily supported usually develops after fasting or
febrile illness.
1- Prematurity
2- Intrauterine growth retardation
3- Maternal hyperglycemia due to diabetes or
iatrogenic glucose administration
4- GDM.

5- Sepsis
6- Prolonged fasting (e.g., due to inadequate breast
milk or condition interfering with feeding)67-Congenital hypopituitarism
8-Congenital hyperinsulinism, several types, both
transient and persistent
9- Inborn errors of carbohydrate metabolism such as
glycogen storage disease

Fasting hypoglycemia
Decrease rate of hepatic glucose production
or an increase rate of glucose use .
symptoms suggestive of hypoglycemia are
fairly common but hypoglycemic disorders
are rare Fasting hypoglycemia: due to
hepatic and renal disease, endocrine
disease, inherited metabolic disorders eg
glycogen storage disease

Older adults
The incidence of hypoglycemia due to complex drug
interactions, especially involving oral hypoglycemic agents
and insulin for diabetes, rises with age. Though much rarer,
the incidence of insulin-producing tumors also rises with
advancing age. Most tumors causing hypoglycemia by
mechanisms other than insulin excess occur in adults.

Reactive hypoglycemia: Is mostly due to druginduced hypoglycemia, gastric surgery ,alcohol,

hereditary fructose intolerance

Alcohol induced hypoglycemia

Often linked with ketoacidosis (depletion of NAD+
leads to a block of gluconeogenesis) ethanol
inhibiting gluconeogenesis low glucogen storage

Insulin-induced hypoglycemia
Insulin injected for diabetes
Factitious insulin injection (Munchausen syndrome)
Excessive effects of oral .Anti-diabetic medication, betablockers, or drug interactions
Insulin-secreting neuroendocrine tumor (insulinoma) of
the pancreas

demonstration of a low plasma glucose

concentration in the presence of an
abnormally high plasma insulin value is
highly suggestive of insulin producing
pancreatic islet cell tumor below the fasting
level

Nonpancreatic neoplasma that cause hypoglycemia

are often exteremly large mesenchymal neoplasms
that appear to overuse glucose .Tumor of epithelial
may cause hypoglycemia frequently producing IGF.

Depleted glycogen stores , impaired

gluconeogenesis and increased peripheral use of
glucose may all be contributing factors .

appreciates study for evaluating a patient

suspected of having hypoglycemia . The classic
diagnostic test is 72-hour fast conducted in the
hospital during the fast the patient allowed a liberal
intake of calorie free fluids and should be active
when awake
samples should be drawn for analysis of plasma
glucose ,insulin , C- peptide ,and proinsulin every 6
hours when reach 60 mg/dl performed every 1 to 2
hours.

The fast should be concluded when plasma glucose

concentration falls to less than or equal to 45 mg/dl
and the patient exhibits sign or symptoms of
hypoglycemia . if this does not occur the fast should
be terminated after 72 hour plasma glucose
,insulin , C- peptide ,and proinsulin B-Hydroxy
butrate , sulfonylurea for analysis then inject 1
mg/dl of glucagon intravenously and measure
plasma glucose

at 10, 20,30,minutes

Reactive hypoglycemia was defined as a clinical

disorder in which the patient has the postprandial
symptoms suggesting hypoglycemia that occur in
everyday life and are accompanied by blood glucose
concentration less than 45 to 50 mg/dl as
determinated by specific glucose measurement on
arterialized venous or capillary respectively.
patients complains of autonomic symptoms
occurring approximately 1 to 3 hours after eating
and seem to obtain relief , lasting 30 -45 minutes by
food intake .

These symptoms are rarely due to low blood glucose

concentration
(DM, gastrointestinal dysfunction or hormonal
deficiency).Must of these individuals have
postprandial autonomic symptoms without
neuroglycopenia in the postprandial state.
The oral glucose tolerance test (OGTT) should not
be used in the diagnosis of reactive hypoglycemia

A group of disorders may produce hypoglycemia in

the postprandial these include drugs , antibodies to
insulin or insulin receptor and inborn errors .Also
included reactive hypoglycemia which referred to as
functional hypoglycemia ( describes a collection of
clinical signs and symptoms similar to medical
hypoglycemia but without the demonstrably low
blood glucose).
People with this condition suffer from recurrent
episodes of altered mood and cognitive efficiency,
often accompanied by weakness and adrenergic
symptoms

that certain people may be more sensitive to the

bodys normal release of the hormone epinephrine,
which causes many of the symptoms of
hypoglycemia. Others believe deficiencies in
glucagon secretion might lead to reactive
hypoglycemia .
Stomach surgery or hereditary fructose intolerance
are both believed to be causes, of reactive
hypoglycemia.
Preferred terminology should be Idiopathic
reactive hypoglycemia or Idiopathic postprandial
syndrome,

Hypoglycemia in diabetes mellitus

In both type 1 and type 2 diabetes the
patients using insulin experience
approximately one to two episodes of
symptoms hypoglycemia per week and severe
and in type 2 diabetes hypoglycemia caused
by oral hypoglycemia agents or insulin but it
less frequent than type 1 diabetes two
pathophysiological mechanisms contribute to
hypoglycemia in patients with diabetes.

Antibodies detected in certain patients with type 1

diabetes
antiinsulin antibodies causing hypoglycemia have
been reported in Graves disease , multiple myeloma
, systemic lupus erythematosus , and rheumatoid
arthritis.

Defective glucose counterregulation

Counterregulation responses become impaired in type1 in type 1
diabetes patients increase the risk of hypoglycemia . The
responses of glucagon to hypoglycemia is impaired by
unknown mechanism early in the course of type1 diabetes
epinephrine secretory response to hypoglycemia becomes
deficient later in the course of the disease .Glucose
counterregulation does not appear to be notably defective in
patients with type 2 diabetes

than 30 years) type 1 diabetes do not experience

neurogenic warning symptoms and are prone to
more severe hypoglycemia. The mechanism is
thought to be associated with a decreased
epinephrine response to hypoglycemia ..in type 1
diabetes is a marker of an attenuated autonomic,
sympathetic neural as well as a drenomedullary,
response that causes the clinical syndrome of
hypoglycemia unawareness loss of the warning,
largely neurogenic symptoms of developing
hypoglycemia.

The tolbutamide test

Ketone bodies
Primary substrate for ketone bodies formation
are free fatty acids from adipose stores are
broken down for energy in the liver. Two of the
three are used as a source of energy in the heart
and brain while the third is a waste product
excreted from the body. In the brain, they are a
vital source of energy during fasting . In
uncontrolled diabetes the low insulin
concentration result in increase lipolysis and
decreased reesterification

The increase glucagon : insulin ratio enhances

fatty acid oxidation in the liver , increase
counterregulatory hormones these increase
lipolysis and ketogenesis in fat and liver
.Thus increase hepatic ketone production and
decrease peripheral tissue metabolism lead to
acetoacetate accumulation in the blood and
small fraction under goes spontaneous
decarboxylation to form acetone ,but the
majority is converted to beta hydroxybutrate.

Lactate and Pyruvate

The production of lactate is a beneficial process
because it regenerates NAD+ which is used up in the
creation of pyruvate from glucose, and this ensures
that energy production is maintained but when
lactate concentration exceeding 5mmol/l and the PH
less than 7.25 indicate significant lactic acidosis .

MANAGEMENT OF DIABETES
MELLITUS

Management of type 1
1. Diet:
Total energy intake should be tailored to a achieve
and maintain ideal body weight and allow for growth
in children and adolescents.
Fat and free sugar intake must be limited.

2. Exercise:
Regular exercise is important and indolence should be discouraged.
3. Objectives of treatment:
improvement of general well being
Prevention of short term hyperglycaemic/ hypoglycaemic
complications.
Prevention of long term microvascular / macrovascular
complications.
Insulin:
At least two subcutaneous injections per day are required if
acceptable metabolic control is to be achieved.

physical exercise)
It is the first treatment step in patients with only
moderate hyperglycaemia. Although difficult ot
achieve, modest weight loss and increased exercise
have bebeficial effects on glucose values, lipids and
blood pressure. When the fasting blood glucose
target is not achieved within 3 months, drug
treatment should by considered.
2- Oral drug therapy:Sulfonylureas, metformin and acarbose act similarly
in lowering blood glucose. The clinicians should be
aware of side effect and drug interactions,
particularly in the elderly.

.
3- Combination of two oral drugs: Often required achieving good blood glucose control
4- Insulin Therapy:Is indicated when oral agents fail to establish
glycaemic target values.

Monitoring and control of Diabetes Mellitus

2 ways to monitor the adequacy of blood glucose

control
1-Regular visit to the doctor
The visits should be regular, at least once every 3
months and more if the diabetes is not well controlled.
Checking blood glucose is important but will tell the
level at the very moment of checking . It will not tell
what the blood glucose level has been over the last few
months.

2-Home blood glucose monitoring

A person with diabetes cannot always be in the care
of a d doctor or nurse every hour and every day.
This is especially if the person is independent,
active and has to work. Therefore, learning to test
blood glucose levels by him/herself is essential.
Blood glucose level can be measured 1-8 times a
day.
1-Before each meal and at bed time.

2- Fasting and 1 hours after each meal.

3-Before and 2 hours after each meal.
4-Once a day at a different time every day.
5-Twice a day, one fasting and one more at different
times of the day.
6-Fasting only
The targeted range of blood glucose depends on the
age, type of diabetes and the duration of the
diabetes.
A rough guideline would be: Grading of blood
glucose levels

1- Glycosylate HbA1c: Protein in blood reacts with

glucose to form glycated derivatives, the
concentration of glycated protein is measured as
marker for fluctuation of blood glucose during 8-12
weeks, glycated HbA1c is longer life protein fraction
2- Microalbuminamia: Is diagnosed when the urine
albumin level is > 30 mg/dl , (> 20 g/min) or as a
concentration (> 20 mg/L urine). ,reflect the
progress to diabetic nephropathy, and predictive of
cardiovascular risk factors
- microalbumin:creatinine ratio (MACR).

Grading of blood glucose levels

Gradings

Very Good

Good

Fair

Poor

Fasting (mmol/L)

4.4-5.5

5.5-7.7

7.8-10.0

More than 10.0

hours after a meal 1

6.6-7.7

7.8-10.0

10.0-12.0

More than 12.0

(mmol/L)

Fructosamine
Fructosamine is an alternative to glycated haemoglobin. It
tells about the glucose level over the preceding 20 days, the
life span of albumin.
Reference Intervals
values in a nondiabetic population range from 205 to 285
micro molperliter . The reference interval corrected for
albumin is 191 to 265 micro molperliter

A man with a watch knows what time it is.

A man with two watches is never sure

Inborn Errors of Carbohydrate

Metabolism
It is deficiency or absence of an enzyme that
participates in carbohydrate metabolism may
result in accumulation of monosaccharides due
to inherited autosomal recessive traits. Which
can be measured in urine.

Disorder of galactose
metabolism(Galactosaemia)
It is an inherited autosomal recessive
enzymes deficiency resulting in the
inability to digest galactose . Lactose
from milk is hydrolysed by intestinal
lactase to produce glucose and galactose.
1-Galactose-1-phosphate
uridyltransferase (Gal-1-PUT) deficiency.

Infants with this deficiency fail to thrive on

milk because half of the milk sugar (lactose )
is galactose neonate manifest vomiting,
diarrhea , failure to thrive , liver disease
lethargy, jaundice, hepatomegaly , cataracts
and renal tubular disease is often associated
with E. coli septicemia and mental
retardation develop later.

2- Uridine diphosphate-galactose 4-epimerase

deficiency
This is extremely rare disorder exhibits clinical
findings similar to uridyltransferase (Gal-1-PUT)
deficiency.
3- Galactokinase deficiency
Milder condition manifested by cataracts caused by
galactitol deposits in the lens.

Disorder of fructose
metabolism(fructosuria)
fructose may appear in urine after
eating fruits , honey , syrups inherited
as autosomal recessive trait , produced
fructosuria

Essential fructosuria
This rare and harmless defect is due to the a
lack of fructokinase

Hereditary Fructose Intolerance

A deficiency of the enzyme Fructose -1Phosphtealdolase ,this is rare leading to liver
disease ,hypoglycaemia is attributed to inhibition of
glycogenolysis and glyconeogenesis. Early
detection is important because this condition is
responds to a diet devoid to sucrose and fructose

Hereditary Fructose -1,6 diphosphatase

deficiency
Patients with this deficiency have episodes of
hyperventilation and hypoglycaemia , ketosis and
lactic acidosis caused by severe impairment of
glyconeogenesis. Diagnosis is by demonstrating the
enzyme defect in liver biopsy specimens.

Disorder of pentose
metabolism(Pentosuria)
Alimentary pentosuria
Pentose may be present in urine after eating large
quantities of fruits such as cherries , plums, or prunes .

Essential pentosuria
This is a harmless inborn error metabolism an
asymptomatic autosomal recessive caused by
deficiency of hepatic L-xylulose reductase which
involved in glucuronic acid pathway metabolism .

OTHER URINARY SUGARS

LACTOSE
is sometimes detected in the urine of
women during lactation and occasionally
toward the end of pregnancy.

OTHER URINARY SUGARS.

Glycogen storage disease (GSD)

A glycogen storage disease (GSD) is the result of
an enzyme defect. These enzymes normally
catalyze reactions that ultimately convert
glycogen compounds to glucose. Enzyme
deficiency results in glycogen accumulation in
tissues. The specific diagnosis of each type is
made directly by demonstrating the enzyme defect
in tissue

phosphatase deficiency )

Most common and severe form called( Von Gierk

disease):
The patients have accumulation of glycogen of
normal chemical structure in the liver the most
frequent first symptoms include massive
hepatomegaly , growth retardation fasting
hypoglycemia).

There are two different subtypes of Type I Glycogen

Storage Disease Type Ia and type Ib.
GSD Ia is caused by a deficiency of the glucose-6phosphatase (G6Pase) enzyme in liver, kidney and
other organs of the body.
GSD Ib is caused by a deficiency in glucose-6phosphate translocase, or transporter (G6PT)
enzyme, that helps in transporting G-6-Pase enzyme
from one point to another.

Increase Levels of hormones lactic acid,

triglycerides, lipids (fats), uric acid and other byproducts of metabolism increase in the blood as
the body tries to raise blood sugar , but glucagon
and epinephrine do not produce hyperglycemia
but result in increase lactate concentration
The failure of blood glucose to increase in
response to galactose
administration (oral or intravenous ) is diagnostic

Glycogen storage disease type II(Acid alpha-glucosidase deficiency )

GSD type II, affects predominantly the heart and skeletal
muscle producing muscle weakness and cardiomegaly .
liver function is normal and patients do not have
hypoglycemia .
Two forms are identified
Infantile-onset form (Pompe disease) : With this form,
infants usually present during early infancy (4-8 months
of life) with weakness and breathing muscles are also
weak. Without treatment, infants usually die before 12
months of age due to heart failure and respiratory
difficulties.

juvenile and adults : With this form, the disease has

a later onset, usually at second or third decade of life ,
Due to muscle weakness, walking/climbing stairs
becomes difficult. The involvement of the muscle
weakness progresses slowly over the years. Some adults
with Type II GSD use a wheelchair or other assistance
with mobility

Glycogen storage disease type III

(Amylo-1,6

Glucosidase deficiency)

Type III is also known as Forbes-Cori disease or deficiency

of glycogen debranching enzyme result in storage
abnormal form of glycogen
( limit dextrinosis).
In contrast to GSD type both the liver and muscles are
usually affected (type IIIA), producing hepatomegaly
and muscle weakness .

Approximately 15%of paients have only liver

involvement without apparent muscle disease (type
IIIB) .
Glycogen deposited in these organs has an
abnormal structure. Differentiation patients with
GSD type III from those with GSD type I by
hyperglycemia response to galactose ,lower
concentration of urate and lactate in blood.

Glycogen storage disease type IV

(Branching

Enzyme Deficiency )

GSD type IV, also known as Andersen disease, is an

extremely rare disorder manifested by production of
an abnormal form of unbranched glycogen in all
tissue . Patients exhibit hepatosplenomegaly with
ascites and liver failure .

GSD Type V

(Muscle phosphorylase deficiency )

Also called McArdles disease, usually develop in

adolescents or adults in second or third decade .People
with GSDV typically experience fatigue, muscle pain, and
cramps during the first few minutes of exercise (exercise
intolerance).If individuals rest after brief exercise and wait
for their pain to go away, they can usually resume
exercising with little or no discomfort "second
wind.patients respond to oral glucose administration or
injection of glucagon

Glycogen storage disease type VI

(liver phosphorylase or phosphorylase kinase deficiency )
Also known as Hers disease, is heterogeneous group
of diseases arising from liver phosphorylase or
phosphorylase kinase deficiency it is rare and
manifested as hepatomegaly .

Glycogen storage disease type VII

(muscles phosphofructokinase (PFK) deficiency)
Also known as Tarui disease. Patients with this type
have deposits abnormal glycogen accumulation in
erythrocytes causes hyperbilirubinemia and
reticullocytosis .

Methods for measuring individual

sugars
1- Qualitative test (Clini test )for
1- Glucose (specific for glucose) may provide a clue to
the diagnosis but is not specific
2- Galactose
3- Selivanoffs test
4- Bials test.
5- Urine sugars can be identified by Thin Layer
Chromatography (TLC).
2- Quantitative test (Enzymatic method).

IF WE CAN SAFE SOMEONE, THEN

EVERYTHING ELSE IS OF SECONDARY
IMPORTANCE