3. Diabetes mellitus
• Type 1 – juvenile diabetes
• (IDDM)
• loss of insulin-producing beta cells
leading to a deficiency of insulin
• Type 2 – maturity onset
(NIDDM)
• insulin resistance - cells fail to use
insulin properly
• the most common type
4. Causes:
• Type 1 appears to be triggered by some
(mainly viral) infections (e.g. Coxackie
virus)
• heredity - stronger inheritance pattern
for type 2
• obesity – type 2
5. Symptoms:
1) Polyuria (excess
urine production)
2) Polydipsia (excess
drinking of water)
3) Polyphagia
(excessive eating)
4) Loss of weight
5) Asthenia (lack of
energy)
7. TYPE 1 IDDM
• Develops before the age of 40
• Pt are not obese
• Also called juvenile diabetes
8. Type I Diabetes Mellitus
• cells of the islets of Langerhans are destroyed
by autoimmune attack which may be provoked by
environmental agent.
– Killer T cells target glutamate decarboxylase in the
cells.
• Glucose cannot enter the adipose cells.
– Rate of fat synthesis lags behind the rate of lipolysis.
• Fatty acids converted to ketone bodies, producing
ketoacidosis.
• Increased blood [glucagon].
– Stimulates glycogenolysis in liver.
10. Type II Diabetes Mellitus
• Slow to develop.
• Genetic factors are
significant.
• Occurs most often in
people who are
overweight.
• Decreased sensitivity to
insulin or an insulin
resistance.
– Obesity.
• Do not usually develop
ketoacidosis.
• May have high blood
[insulin] or normal
[insulin].
Insert fig. 19.12
11. Causes of type 2
Due to identified genes
• Defect in glucokinase (1%)
• Insulin molecule itself (0.5%)
• The insulin receptors (1%)
• GLUT 4 (1%)
• MODY (maturity onset diabetes occuring in
young individual) 1%
13. PATHOPHYSIOLOGY
• HYPERGLYCEMIA and its consequences:
• Due to lack of insulin resulting in:
• Decreased periphral utilization of glucose
• Increased hepatic output of glucose
15. EXCRETION OF OSMOTICALLY
ACTIVE PARTICALS
LOSS OF LARGE AMOUNT OF
WATER
DEHYDRATION
STIMULATION OF THIRST
MECHANISM
POLYDIPSIA
CAUSE OF POLYDIPSIA
16. 1gm of glu loss
=4.1kcal lost
Increasing oral caloric intake
and mobilization of
endogenous protein and fat
store
Weakness and wt loss
17. Effect of Intracellular Glucose
Deficiency
Deficient glucose utilization and
Deficient hormone sensing
In hypothalamus
Feeding area not inhibited
Satiety is not sensed
Food intake increased
18. Ketosis
• Excess acetyl –CoA
• Converted to acetoacetyl –CoA
• Then in the liver acetoacetate ,acetone.
• Enter the circulation
• Circulating ketone body main source of energy
during fasting.
19.
20. Diagnosis
• Urine examination for glycosuria
• Urine examination for ketone bodies
• Fasting and postprandial blood glucose level
• Glucose tolerance test (GTT)
21. Oral Glucose Tolerance Test
• Measurement of
the ability of cells
to secrete insulin.
• Ability of insulin to
lower blood
glucose.
• Normal person’s
rise in blood
[glucose] after
drinking solution is
reversed to normal
in 2 hrs.
Insert fig. 19.8
22. Treatment in Diabetes
• Change in lifestyle:
– Increase exercise:
• Increases the amount of membrane GLUT-4 carriers in the skeletal
muscle cells.
– Weight reduction.
– Increased fiber in diet.
– Reduce saturated fat.
23. 1. Diet
2. Insulin -- most patients treated with insulin and diet
3. Oral hypoglycemic agents:
Used when diet control insufficient
Used with insulin to lower dosage of insulin.
Not when insulin requirements exceed 200 units/day.
Treatment of NIDDM
24. . Oral hypoglycemic agents (cont.)
a) Sulfonylureas (first generation)
1) Agents - acetohexamide (Dymelor), chlorpropamide (Diabinese),
tolazamide (Tolinase), tolbutamide (Orinase)
2) Mechanism of action -- stimulate ß-cells to secrete insulin
3)Adverse effects --associated with cardiovascular disease, hypoglycemia
Effectiveness questioned
b) Sulfonylureas (second generation)
a) Agents - glyburide (Diabeta, Micronase) and glipizide (Glucotrol) and
Glimepride (1996)
b) Mechanism of action:
Stimulate insulin release from ß cells (K channel blockers)
Release glucogon and somatostatin
Inhibit hepatic gluconeogenesis
Enhance insulin receptor sensitivity
c) Adverse effects - less than with first generation
Treatment of NIDDM
25. Treatment of NIDDM
c) Biguanides
Phenformin introduced in 1957
Metformin (Glucophage) available in 1994
Mechanism of action --
increases the utilization of glucose by decreasing
cellular respiration
decreases glucose levels by inhibiting gluconeogenesis
inhibits intestinal absorption of glucose
Adverse effects -- phenformin produced fatal lactic acidosis,
metformin much less so
Contraindications — hepatic disease or past history of lactic
acidosis
26. G. Treatment of NIDDM
e) Alpha-glucosidase inhibitors
Acarbose (Precose)
Mechanism of action - reduces intestinal absorption of starch
dextrin, and disaccharides — postprandial reduction
in plasma glucose
Side effects - malabsorption, flatulence and abdominal
bloating
28. Hypoglycemia
• Over secretion of
insulin.
• Reactive
hypoglycemia:
– Caused by an
exaggerated
response to a rise
in blood glucose.
– Occurs in people
who are
genetically
predisposed to
type II diabetes.
Insert fig. 19.13
33. 1. Hypoglycemia — insulin requirement reduced, failure to eat,
unaccustomed exercise, or insulin overdose
can all cause hypoglycemia
a) A rapid fall in blood glucose
b) A slow fall in blood glucose
Treatment of hypoglycemia is to administer fruit juice or
glucose; if not available, then glucagon
2.Other adverse reactions — mostly allergic reactions, but usually
subside after chronic administration
Insulin side effects
34. Treatment:
• Diabetes type I:
• artificial insulin – subcutaneous injection
• insulin control, diet, weight control and exercise
35. • Diabetes type II:
• diet, weight loss
• exercise to increase receptor responsiveness
• sulfonylureas to increase number of receptors
