2. Objectives
Review of CHO metabolism
Regulation of blood glucose
State the basic criteria for the diagnosis of diabetes
mellitus, including American Diabetes Association
guidelines.
Outline the procedure for administration of an oral
glucose tolerance test and interpret the results.
Lab tests for monitoring long-term glucose control in
people with diabetes mellitus.
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
3. Introduction
Carbohydrates are widely distributed in plants
and animals, their function is ranging from
energy source to structural components.
According to its structure it classified into:
Monosaccharide: It contain 3, 4, 5, 6 or 7
carbon atom. Named tiroses, tetroses,
pentoses. Hexoses or heptoses.
Disaccharides: Two monosaccharide joined by
glycosidic bond.
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
4. Maltose = Glucose – Glucose
Lactose = Glucose – Galactose
Polysaccharides: linkage of multiple
monosaccharide units results in the formation
of polysaccharides.
Starch in plants
Glycogen in animals
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Clinical Chemistry
5. Break down of diet carbohydrates results in
glucose. Which maintained by regulatory
hormones.
When energy intake exceed the need of the body
it converted to fats which stored in the adipose
tissue and glycogen which stored in the liver &
muscle.
When the need of energy exceed the intake
endogenous formation of glucose occur.
Metabolism
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
6. Metabolism…con
The end metabolism of carbohydrates result
in:-
1- production of energy.
2- storage as glycogen and fats.
3- conversion to amino acids and proteins.
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
7. CHO digestion:
CHO digestion started
in the mouth by salivary
amylase (occur little
digestion) then the food
mixed with salivary
amylase pass into
stomach where the acid
pH inhibit the amylase
action gradually.
In the duodenum where
the HCO3 & bile salt of
pancreatic juice make
the pH around 7 which
is suitable for the
pancreatic amylase to
continue the salivary
amylase action in the
hydrolysis of starch to a
maltose molecules.
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
8. Contn....
Then the disaccharide molecules are hydrolyzed by
disaccharides enzymes (found in the small intestine)
into monosaccharide.
CHO absorption:
The absorption of the monosaccharide's occurs by an
active transport process which requires energy. They
are transported to the liver by portal vein of the liver.
Glucose is the only carbohydrate to be directly used
for energy or stored as glycogen. Galactose &
fructose must be converted to glucose before they can
be used. After the glucose enters the cell it will be
processed for production of energy.
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
9. CHO catabolism:
Following absorption, they are transported to the
liver. Depending on the body need, the
monosaccharide are converted to glycogen or
metabolized to energy or they are converted to
triglycerides or proteins.
The raised level of glucose after a meal stimulates the
production of insulin from the pancreas. Insulin
reduce the glucose level by facilitates the entrance of
glucose inside the cells of the body except red cells,
hepatic cells and brain cells.
In the cells there are many processes can be take
place Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
10. 1-Glycolysis: metabolism of glucose to
pyruvate or lactate for production of energy.
2-Glycogenesis: Conversion of glucose to
glycogen for storage, occur in the liver and
muscle.
3-Glycogenolysis: Breakdown of glycogen to
glucose for use as energy.
4-Gluconeogenesis: formation of glucose from
noncarbohydrate substance (fat and protein).
5-Lipogenesis: Conversion of CHO to fatty
acids.
6-Lipolysis: Decomposition of fat.
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
11. Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
12. Regulatory hormones
(A) Insulin secreted by β-cells of the pancreas in
form of proinsulin, converted to active insulin after
removal of peptide chain (C-peptide).
It is anabolic hormone tends to lower the blood
glucose concentration by enhancing glycogenesis.
In the pancreas, insulin is synthesized as pre-
proinsulin (inactive).
This form undergoes first cleavage forming pro-
insulin, then a second cleavage follows result in the
formation of insulin (active form) and a free short
peptide called C-peptide.
Both insulin and C-peptide are secreted in circulation.
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
13. Brain, RBC, Liver, and Intestines are not insulin-
dependent
Muscles are the most important insulin-dependent
tissue.
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
14. Hormones that regulates Plasma glucose Concentration:
1-Insulin:
1.released from pancreas (β-cells)
2.convert excess blood glucose into storage forms
–In liver and muscle:
–Stimulates glucose uptake (muscle)
–Stimulates glucose uptake (liver)
–Stimulates FAT synthesis (liver)
–Stimulates glycogen synthesis
–Inhibits glycogen breakdown
–Stimulates glycolysis, acetyl-CoA production
–In Adipose tissues:
–Stimulates triacylglycerol synthesis
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
15. The action of Insulin
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
17. 2. Glucagon:
Released from α-cells in pancreas;
raises blood glucose level
Mode of action: cAMP-dependent phosphorylations
In the liver: (primary target)
Stimulates glycogen breakdown
Inhibits glycogen synthesis
Inhibits glucose breakdown
Stimulates gluconeogenesis
In adipose tissues:
Stimulates fat mobilization
Dr Isse A, Mohamed/ BSc , MSc
in Clinical Chemistry
18. 3. Epinephrine:
A catecholamine secreted by the adrenal
medulla
Stimulates glycogen breakdown (glycogenolysis)
Stimulates glucagon secretion
Inhibits insulin secretion
Plays a key role in glucose counter regulatory when
glucagon is deficient.
Dr Isse A, Mohamed/ BSc , MSc
in Clinical Chemistry
19. 4. Growth hormone:
A polypeptide hormone secreted by the
anterior pituitary glands
Stimulates gluconeogenesis (During long
fasting)
Enhances lipolysis.
5. Cortisol:
Slow acting hormone, released from adrenal cortex
Counterbalances insulin effects
Stimulates gluconeogenesis (During long fasting)
Increase breakdown of protein & fat.
Dr Isse A, Mohamed/ BSc , MSc
in Clinical Chemistry
20. 6. Thyroxin : secreted by thyroid gland
Increases glucose levels by increasing glycogenolysis,
gluconeogenesis and intestinal absorption of glucose.
7. Somatostatin:
Produced by the δ-cells of the islets of Langerhans of
the pancreas.
Increases plasma glucose levels by the inhibition of
insulin, glucagon, growth hormone and other endocrine
hormones.
Dr Isse A, Mohamed/ BSc , MSc
in Clinical Chemistry
21. Things MUST remember
Normal range of fasting blood glucose: 75-115 mg/dL
Hypoglycemia: in adults: <50 mg/dl, in newborns <40 mg/dl
Serum glucose higher than whole blood glucose by 10-15%
(Plasma glucose = whole blood glucose x 1.15 + 6mg/dL)
Arterial or capillary blood glucose is higher than venous by
2-5 mg/dL
CSF glucose: 70% of FBS
CSF glucose MUST be analyzed immediately
Uncentrifuged whole blood: glucose decreases by 5-7%
each hour
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
22. Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
Carbohydrates metabolism disorders
24. Diabetes Mellitus
A group of metabolic disorders characterized by
hyperglycemia resulting from defect of insulin
secretion, insulin action or both of them.
WHO divides diabetes into:-
Type1 Insulin-dependent-diabetes mellitus (IDDM).
Type2 Noninsulin-dependent-diabetes mellitus
(NIDDM).
Other types a) Specific types of DM.
b) Gestational DM.
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
25. Classification of Diabetes Mellitus
Type 1 Diabetes
This type is also known as Insulin Dependent Diabetes Mellitus
(IDDM). It is characterized as follows:
It occur in young children and young adults (< 35 years of age)
It accounts for 10-20% of all types of diabetes mellitus.
Patients with this disease have deficiency of insulin, and are
dependent on insulin injections.
Insulin deficiency is caused by an autoimmune disorder:
autoantibodies against islet cells, or against insulin itself.
Patients with type of diabetes are commonly prone to
Ketoacidosis.
Occurrence of complications in this type of diabetes mellitus,
are more common than that in type 2.
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
26. Type 2 Diabetes
This type is also known as Non Insulin Dependent Diabetes
Mellitus (NIDDM).
It is the most common, and occur after age 40 years
More commonly seen in obese individuals
It has an inherited pattern
It accounts for 90% of all cases of diabetes mellitus.
It is characterized by either decreased insulin secretion, or
increased resistance to insulin (decreased response to insulin)
Patients with this type are not prone to Ketoacidosis
Complications are les than that in type 1.
Classification of Diabetes Mellitus
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
27. Classification of Diabetes Mellitus
Gestational Diabetes
Occur during pregnancy: (2-5% cases of pregnancy
Caused by inability of pancreas to secrete sufficient amount of
insulin
Women who develop gestational diabetes during pregnancy,
mostly develop diabetes mellitus 20 years later.
Diagnosis: meet with two or more of the following criteria
Fasting plasma glucose >95mg/dL
A 1-hour plasma glucose>180mg/dL
A 2-hour plasma glucose>155mg/dL
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
28. Acute complications
1- Diabetic ketoacidosis.
2- Hyperosmolar nonketotic coma.
3- Hypoglycemia.
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
29. Ketoacidosis
In uncontrolled diabetes the low insulin
concentration result in increase lipolysis and
increase plasma free fatty acids which
converted by liver to ketone bodies. Type I
DM has greater tendency to produce ketone
bodies than type II due to Insulin and
Glucagon concentration imbalance.
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
30. Hyperosmolal non-ketotic coma
Hyperosmolality is due to hyperglycemia but
no detectable ketones or acidosis. Glycosuria
result in severe water and electrolyte depletion
with hypernatremia and uremia. Coma result
from cerebral cells dehydration.
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
31. Hypoglycemia
It is decrease blood glucose below the fasting
value. In diabetics this is due to over dosage of
insulin.
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
33. Signs & symptoms
Polydipsia “excessive thirst”.
polyphagia “increase food intake”.
polyuria “ excessive urine production”.
Weight loss.
hyperventilation.
mental confusion.
loss of consciousness
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
34. Diagnosis of DM
Normal levels
Normal plasma glucose concentration during
fasting ( 55 - 110 ) mg/dl.
And 2 hr post prandial ( 75 - 140) mg/dl.
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
35. Positive findings
Any one of the followings is diagnostic:
– Symptoms of diabetes mellitus plus random
plasma glucose concentration >=200 mg / dL)
***or
– FBG >=126 mg / dL
***or
– 2hr post load BG >=200 mg /dl after 75-g glucose
load.
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
36. Some individuals may not meet with the past
findings but have blood glucose level higher
than normal, those : -
either : Impaired fasting glucose
FBG ( 110 - 126) mg/dl.
Or: Impaired glucose tolerance
2hr after 75 grm g ( 140 - 200) mg/dl.
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
37. GTT
Glucose tolerance test is used to diagnose
GDM or IGT and it is rarely used to
diagnose DM. to perform it : -
I. Patient should take diet rich in
carbohydrates three days before the test.
II. Performed after fasting for 10 to 16 hr.
III. Should not be done in hospital or during
severe illness.
IV. Pt Should not eat or smoke during the test.
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
38. Monitoring DM
Glycosylated Haemoglobin
This test refers to the hemoglobin component formed
by interaction with glucose, since half life of RBCs is
approximately 120 days; a single HbA1c determination
can give information about glycemic control in the last
8-12 weeks.
Reference range:4-6%, effective treatment range<7%.
The levels of HBA1C are affected by:
Hemolytic anemia (falsely decreased)
HbS: falsely decreased
B12 or Macrocytic anemia: falsely increased
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
39. Fructosamine
Is a compound formed by attachment of glucose to
amino groups of proteins other than hemoglobin.
The concentration of glycated serum albumin reflects
glucose control over a period of 2 to 3 weeks.
It is evidence of both deterioration of control and
improvement with therapy, it is evident earlier than
with GHb.
Reference range:205-285 µmol/L
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
40. Microalbuminuria (MAU)
Microalbuminuria is defined as excretion of 30 – 300
mg of albumin /24 h.
MAU is the first warning signal to an impending
“Nephropathy”. Microalbumin is present in 25 per
cent of patients with type I disease and 36 per cent
patients with type II disease. Patients with
microalbuminuria have a greater risk for developing
renal failure, vascular damage and risk for
cardiovascular damage.
Dr Isse A, Mohamed/ BSc , MSc in
Clinical Chemistry
41. Diagnosis:
The types of investigations:
Fasting Blood Glucose (FBG)
2 hr postprandial Blood Glucose (2 hr PP)
Random Blood Glucose
Glucose Tolerance Test
Dr Isse A, Mohamed/ BSc , MSc
in Clinical Chemistry
