Carbohydrates

Are hydrates of aldehyde or ketone derivatives based on the

location of the CO functional grp.
Monosaccharide, disaccharides, oligosaccharides,
polysaccharides- CHOs.
Glycol aldehyde-is the simpliest CHO
Glucose, maltose, fructose, lactose and galactose- reducing
substances/sugars.
The presence of a double bond and a negative charge in the
enol anion makes glucose an active reducing substance.
Sucrose- most common non-reducing sugar
Non-reducing sugar do not contain an active ketone or
aldehyde group.
Glucose is the only CHO to be directly used for energy or
stored as glycogen.

Pancreas

Functions: an endocrine and exocrine organ in the control of

the CHO metabolism
As an exocrine gland, it produces and secretes an amylase
responsible for the breakdown of ingested complex CHO.
As an endocrine gland, it secrets the hormones; insulin,
glucagon and somatostatin from different cells residing in the
islets of langerhans in the pancreas

INSULIN

The primary hormone responsible for the entry of glucose into

the cell.
Synthesized by the beta cells of the islets of langerhans in the
pancreas
It is normally released when glucose levels are high.
It is the only hormone that decreases glucose levels
hyploglycemic agent
Stored from sources such as liver, fat and muscles.
Has a reciprocal relationship with glucagon.
 Promotes glycogenesis, lipogenesis and glycolysis; decreases
glycogenolysis.

GLUCAGON

The primary hormone responsible for increasing glucose

hyperglycemic agent
Synthesized by the alpha cells of the islets of langerhans in the
pancreas
It is released during stress and fasting states.
It enhances catabolic functions during fasting periods;
promotes glycogenolysis and gluconeogenesis

Other hormones that tend to increase glucose concentration

1. Cortisol and corticosteroids (Glucocorticoids)

Secreted by the cells of the zona fasciculata and zona
reticularis of the adrenal cortex
Decreases intestinal entry of glucose into the cell
It promotes gluconeogenesis and lipolysis

2. Cathecolamines
It is released from the chromaffin cells of the adrenal
medulla
Inhibits insulin secretions and promotes glycogenolysis
and lipolysis.
3. Growth hormones(Somatotrophic)
Secreted by the anterior pituitary gland
Decreases entry of glucose into the cell
It promotes glycogenolysis and glycolysis.

4. Thyroid hormones
Secreted by the thyroid gland.
Promotes glycogenolysis, gluconeogenesis and intestinal
absorption of glucose.

5. Adrenocorticotropic hormones (ACTH)

It stimulates release of cortisol from the adrenal cortex
It promotes glycogenolysis and gluconeogenesis.

6. Somatostatin
 Produced by the delta cells of the islets of langerhans of
the pancreas
It is primarily inhibits the action of insulin and glucagon.

CLINICAL CONDITIONS OF CARBOHYDRATE

METABOLISM
1. Hyperglycemia
Increase in blood glucose levels
Causes: stress, severe infection, dehydration or
pregnancy, pancreatectomy, hemochromatosis, insulin
deficiency, abnormal insulin receptor.
FBS level= 126 mg/dL All adults older than 45 yrs.old
should have a measurement of FBS every 3 years unless
the individual is diabetic.

Lab. findings in Hyperlgycemia

1. Increase glucose in plasma and urine
2. Increase urine specific gravity
3. Ketones in serum and urine
4. Decrease blood and urine pH(acidosis)
5. Electrolyte imbalance

2. Hypoglycemia
Involves decreased glucose levels and can have many
causes.
Warning signs and symptoms of hypoglycemia are all
related to CNS.
80 mg/dl to 5mg/dl (2.8-3.0 mmol/L) observable
symptoms of hypoglycemia occur.

CLASSIFICATION:
1. Drug administration- insulin alcohol, salicylates,
sulfonamides, pentamidine. Etc.
2. Critical illnesses- hepatic failure, sepsis, renal failure, cardiac
failure, malnutrition
 3. Hormonal deficiency- epinephrine, glucagons, cortisol,
growth hormone
4. Endogenous hyperinsulinism- pancreatic beta cell disorder
5. Autoimmune hypoglycemia- insulin antibodies
6. Non beta cell tumors- leukemia, hepatoma,
pheochromocytoma, lymphoma etc.
7. Hypoglycemia if infancy and childhood- galactosemia, GSD,
Reyes syndrome
8. Alimentary (reactive) hypoglycemia- post-gastric surgery 9.
Idiopathic (functional) postprandial hypoglycemia

A diagnosis of hypoglycemia should not be mad unless a

patients meets the criteria WHIPPLES TRIAD low blood
glucose concentration with typical symptoms alleviated by
glucose administration.

Diabetes Mellitus(DM)
A group of metabolic disorders characterized by
hyperglycemia resulting from defects in insulin secretion,
insulin or both.
Fasting plasma glucose concentrations > 26 mg/dL on more
than one testing are diagnostic DM.
Glucosuria occurs when the plasma glucose levels exceeds
180 mg/dL (9.99mmol/L) with normal renal function
In severe DM, the ratio of beta-hydroxybutyrate to
acetoacetate is 6:1

Classification of DM:

A. Type 1 DM
Formerly known as:
Insulin Dependent Diabetes Mellitus (IDDM)
Juvenile Onset Diabetes Mellitus
Brittle Diabetes Ketosis-Prone Diabetes
 Is a result of cellular-mediated autoimmune destruction of the
beta cells of the pancreas.
Diabetic individuals have insulinopenia (absolute insulin
deficiency) because of loss of pancreatic beta-cells and depend
on insulin to sustain life and prevent ketosis.
80-90% reduction in the vol. of the beta cell is required to
induce symptomatic type 1 DM
Signs and symptoms: polyuria, polydipsia, polyphagia, rapid
wt. loss, hyperventilation, mental confusion and possible loss
of consciousness.
Complications: nephropathy, neuropathy, and retinopathy
microvascular disorders.
Microalbumin of 50-200 mg/24hrs. diabetic nephropathy
Urine albumin excretion rate of 200 g/minute overt diabetic
nephropathy.

Idiopathic Type 1 DM is a form of type DM that has no

known etiology, is strongly inherited, does not have beta-
cell auto antibodies and have episodic requirements for
insulin replacement.

B. Type 2 DM
Formerly known as:
Non-insulin Dependent Diabetes Mellitus
Adult Type/maturity Onset Diabetes Mellitus
Stable Diabetes
Ketosis- Resistant Diabetes
Receptor-Deficient Diabetes Mellitus

Characterized by hyperglycemia du to an individuals

resistance to insulin; there is relative insulin deficiency.
Associated with strong genetic predisposition and not
related to an autoimmune disease.
It has been described as a geneticists nightmare.
Has a milder symptoms as compared to type 1, however,
untreated type 2 DM will result to nonketotic hyperosmolar
coma- overproduction of glucose (>500mg/dL), severe
 dehydration, electrolyte imbalance, and increased BUN and
creatinine.

Risk factors:
obesity
family history
advanced age
hypertension
lack of exercise
impaired glucose metabolism

C. Other specific types of diabetes

1. Pancreatic disroders
2. Endocrine disorders Cushings syndrome,
pheochromocytoma, accromegaly and thyrotxicosis
3. Drugs or chemical inducers of beta cells dysfunction
(dilantin and pentamidine)and impair insulin action
(thiazides,glucocorticoids)
4. Genetic syndromes- down syndrome, klinefelters
syndrome, leprechaunism etc.

D.Gestational DM(GDM)

Characterized by impaired ability to metabolized CHO

usually caused by a deficiency of insulin,metabolic or
abnormal changes occuring in pregnancy and
disappearing after delivery but in some cases returning
yrs. Later
Glucose intolerance with onset or first recognition
during pregnancy
Screening should be performed between 24 and 23 wks.
Of gestation
A plasma glucose concentration of 140 mg/dL or greater
requires a full diagnostic glucose tolerance test (3hr GTT
with 100g glucose)
 GDM results:
FBS = >105 mg/dL
1 hr. = < 190 mg/dL
2 hrs. = 165 mg/dL
3 hrs. = 145 mg/dL

GDM is diagnosed when any two of the above

mentioned four values are met or exceeded.
After giving birth, woman with GDM should be
evaluated 6-12 wks.
Infants born to diabetic mothers are at increased risk
for respiratory distress syndrome, hypocalcemia and
hyperbilirubinemia.

4. Impaired Fasting Glucose

Characterized by fasting blood glucose concentrations
between normal and diabetic values.

5. Impaired Glucose tolerance

Characterized by fasting blood glucose concentration less
than those required for the diagnosis of DM, but the OGTT
is between normal and diabetic values

Diabetes Insipidus
Deficiency of anti diuretic hormone released by the posterior
gland.

Clinical picture include:

1. Normoglycemia
2. Polyuria with low specific gravity
3. Polydipsia
4. Polyphagia occasional

Glucose Methodologies
 Fasting glucose in whole blood is 15% lower than in serum or
plasma.
Serum or plasma must be separated from the cells within one
hour to prevent losses of glucose.
At rm. Temp. (20-25C), glycolysis decreases glucose by 5-
7%/hour (5-10mg/dL) in normal uncentrifuged coagulated
blood.
At refrigerated temp. (4 C) glucose is metabolized at the rate
of about 1-2 mg/dL/hr.
WBC and RBC metabolize glucose resulting to decrease value
in clotted, uncentrifuge blood.
CSF glucose concentration should be approximately 60% (40-
60 mg/dL) of the plasma concentrations.
Plasma glucose levels increase with age fasting 2
mg/dL/decade; postprandial, 4mg/dL/decade; glucose
challenge, 8-13 mg/dL/decade.

I. CHEMICAL METHODS

A. Oxidation Reduction Methods

1. Alkaline Copper Reduction Methods

Reduction of cupric ions to cuprous oxide in hot alkaline
solution by glucose.

a. FolinWu Method
b. Nelson Somogyi Method
c. Neocuproine method
d. Benedicts method- used for detection and quantitation of
reducing substances in body fluids like blood and urine.
e. Citrate or tartrate as stabilizing agent

2. Alkaline Ferric Reduction Method (Hagedorn Jensen)

Reduction of a yellow ferricyanide to a colorless
ferrocyanide by glucose (inverse colorimetry)
 3. Condensation Method

II. Enzymatic Method

Acts on glucose but not on other sugars and not on other
reducing substances.

1. Glucose oxidase method

> Measures the beta-D glucose

a. Colorimetric Glucose Oxidase Method (saifer Gernstenfield

Method)
b. Polarographic Glucose oxidase

The enzymatic conversion of glucose is quantitated by the

consumption of oxygen
Measure rate of oxygen consumption.

2. Hexokinase Method
Most specific glucose method ; reference method

NOTES TO REMEMBER

Elevated amounts of bilirubin, uric acid and ascorbate false

decreased values of glucose(glucose oxidase method)
Hemolysis affects hexokinase method false low glucose value
The enzymatic conversion of glucose to product is quantitated
by a color change reaction at the last of a series of coupled
chemical reactions (kinetic analysis)

3.Dextrostics
Important in establishing correct insulin amount for next
dose
Effective in reducing the rate of development of diabetic
complications
Samples for Glucose Measurement

1. RBS random Blood Sugar

- requested during insulin shock, hyperglycemic ketonic coma

2. FBS Fasting Blood Sugar

- NPO (Non-Per Orem) 6-8hrs.

3. 2-HR PPBS 2 hour Post Prandial Blood Sugar

- below 110 mg/dL at 2 hours

4. GTT Glucose Tolerance Test

Requirements:
CHO depletion and inactivity or bed rest impair glucose
tolerance
GTT is unnecessary to do for women under 25 yrs. Old who
have normal body wt. no family history of diabetes and are not
member of an ethnic group with high prevalence of diabetes.

1. Patient should be ambulatory

- CHO depletion and inactivity or bed rest impair glucose
tolerance
2. Fasting of 8-16 hrs.
3. Unrestricted diet of 150 gms. CHO/day for 3 days prior to testing.
4. The patient should not smoke and drink alcohol.
5. Glucose Load
- 75 gms (standard glucose load) -100 gms -1.75g of glucose/kg
body wt. (children)

Procedure for GTT

The patient should avoid exercise, eating and drinking (except

water) and smoking during testing
 For nonpregnant women and adults, only the fasting and the 2
hour sample may be measured or accrdg. To the physicians
request
1. Collect the fasting blood sample
2. Instruct the patient to drink the glucose load within 5
mins.
3. Collect blood sample after 30 mins., 1 hour, 2 hours, 3
hours respectively.

Kinds of Glucose Tolerance Test

a. Oral Glucose Tolerance Test

> Janney-Isaacson Method (single dose method)
>Exton Rose Method (divided oral dose or double method)

b. Intravenous GTT
> used for DM patients with GI disorders.
>determine glucose by getting blood samples every 10mins.for
one hour
>0.5 g of glucose/kg body wt. (given within 3mins.)
administered intravenously
>fasting sample is also required.

Indications
a. Those who are unable to tolerate a large CHO load.
b. Those with altered gastric physiology
c. Those who had undergone previous operation or surgery in the
intestine.
d. Those with chronic malabsorption syndrome.

Criteria of Fasting Plasma Glucose (FPG)

1. Non-diabetic = <110mg / dL
2. Impaired PG = 110g/dl but <126 mg / dL
3. DM = 126mg/dl
Categories of Oral Glucose Test
1. Normal GTT = 2hr PG < 200 mg/dl
2. Impaired GTT = 2hr PG 140mg/dl but < 200 mg/dl
3. DM = 2hr PG 200mg/dl

Diagnostic criteria for DM

1. RBS = 200 mg/dl (w/ symptoms of DM)
2. FBS = 126 mg/dl
3. 2-hr post glucose = 200 mg/dl

5.Glycosytated/glycated hemoglobin

Also called glycated hemoglobin

Largest subfraction of normal hemoglobin in both diabetic
and nondiabetic individuals.
A glucose molecule attached to one or both N-terminus
valines of the beta-polyp chains of normal adult hemoglobin
A reliable method in the monitoring of long term glucose
control
It reflects the average blood glucose level over the previous
2-3mos.
3-6% of Hgb is glycosylated; 18-20% is prolonged
hyperglycemia.
For every 1% change in the HbA value, 35mg/dL is added to
plasma glucose.
Older RBCs have higher HbA, iron deficiency anemia high
levels
Not suitable for patients with shortened RBC lifespan
disorders.
Specimen for testing, EDTA whole blood
Preferred method, affinity chromatography

6.Fructosamine
 called glycosylated or glycated albumin/plasma protein
ketoamine.
A reflection of short term glucose control (2-3wks)
May be useful for monitoring diabetes individuals w/ chronic
hemolytic anemias and hemoglobin variants.
It should not be measured in cases of low plasma albumin.

Other clinical Disorders of Carbohydrate Metabolism

1. Galactosemia
> A congenital deficiency; one of three enzymes involved in
galactose metabolism
Cause of failure to thrive syndrome in infants
eficient enzymes: galactose 1-phophate uridyl transferase
galactokinase and uridine diphosphate galastose 4-epimerase
Cllinical features: jauncide, hepatomegally, easy
bruisability,sepsis, cataract, hypotonia and sensory neural
deafness.
Diagnostic test: erythrocyte galactose- 1-PO4 uridyl
transferase activity.

2. Essential fructosuria
An autosomal recessive disorder characterized by
fructokinase deficiency
Diagnostic indicator: (+) fructose in urine

3. Hereditary fructose intolerance

A defect of fructose 1-6-b phosphate aldolase B activity in
the liver, kidney and intestine.
Inability to convert fructose-1-phosphate and fructose-1,6-
phosphate into dihyroxyacetone
phosphate,glyceraldehyde-3-phosphate and
glyceraldehydes.
Clinical features: irritability, seizures, and hepatomegaly
 4. fructose-1,6-biphosphate deficiency
A defect in fructose-1,6-biphosphate results in failure of
hepatic glucose generation by glucoriogenic precursors
such as lactate and glycerol.
Clinical features: +
hypoglycemia, lactic acidosis convulsion and coma.

5. Glycogen Storage Disease (GSD)

Deficiency of a specific enzyme involved in the metabolism
of glycogen
Inherited as autosomal recessive trait
Blood specimen are collected for 2hrs at 15 mins. Interval
Von Gierke disease most common GS

Notes to Remember

1. CSF glucose
It is abt. 60-70% of the blood plasma glucose level
Any changes in blood sugar are reflected in the CSF
approximately one hour later because of the lag in CSF
equilibrium time.
A blood glucose specimen should be collected at least 60
mins. Before the lumbar puncture.
Increased levels: diabetes
Decreased levels: bacterial meningitis, TB, fungal and
amebic meningitis.
Reference value: 40-70 mg/dL (adult)
60-80 mg/dL (child)
Normal CSF to glucose ratio: <0.5

2. C-Peptide test
 Formed during the conversion of pro-insulin to insulin.
The amount of circulating C-peptides provides reliable
indicators for pancreatic and insulin secretionS (beta cells
functions)
Used to monitor individual responses to pancreatic
surgery.
To evaluate hypoglycemia
Specimen: fasting blood

Test for ketone bodies:

1. Gerhards ferric chloride test- reacts only w/ acetoacetate

2. Nitroprusside test- 10x more sensitive to acetoacetate than to
acetone
3. Acetest tablets- detects acetoacetate and acetone
4. ketosux- detects acetoacetate better than acetone
5. Ketosite assay- detects beta hydroxybutyrate; not widely used.