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DIABETES MELLITUS
Dr. Shashi Pandey
CLINICAL SYNDROME OF HYPERGLYCEMIA
OCCURING DUE TO DEFICIENCY OF INSULIN
Diabetes mellitus
• Type 1 – juvenile diabetes
• (IDDM)
• loss of insulin-producing beta cells
leading to a deficiency of ...
Causes:
• Type 1 appears to be triggered by some
(mainly viral) infections (e.g. Coxackie
virus)
• heredity - stronger inh...
Symptoms:
1) Polyuria (excess
urine production)
2) Polydipsia (excess
drinking of water)
3) Polyphagia
(excessive eating)
...
Cont.
• Hyperglycemia
• Glycosuria
• Ketosis
• Acidosis
• coma
TYPE 1 IDDM
• Develops before the age of 40
• Pt are not obese
• Also called juvenile diabetes
Type I Diabetes Mellitus
• cells of the islets of Langerhans are destroyed
by autoimmune attack which may be provoked by
e...
Consequences of Uncorrected Deficiency in Type I
Diabetes Mellitus
Insert fig. 19.11
Type II Diabetes Mellitus
• Slow to develop.
• Genetic factors are
significant.
• Occurs most often in
people who are
over...
Causes of type 2
Due to identified genes
• Defect in glucokinase (1%)
• Insulin molecule itself (0.5%)
• The insulin recep...
Insert table 19.6
PATHOPHYSIOLOGY
• HYPERGLYCEMIA and its consequences:
• Due to lack of insulin resulting in:
• Decreased periphral utiliza...
HYPERGLYCEMIA
RENAL CAPACITY
FOR GLU REAB
EXCEEDED
EXCRETION OF
OSMOTICALLY
ACTIVE PARTICALS
GLYCOSURIA
EXCRETION OF OSMOTICALLY
ACTIVE PARTICALS
LOSS OF LARGE AMOUNT OF
WATER
DEHYDRATION
STIMULATION OF THIRST
MECHANISM
POLYDI...
1gm of glu loss
=4.1kcal lost
Increasing oral caloric intake
and mobilization of
endogenous protein and fat
store
Weakness...
Effect of Intracellular Glucose
Deficiency
Deficient glucose utilization and
Deficient hormone sensing
In hypothalamus
Fee...
Ketosis
• Excess acetyl –CoA
• Converted to acetoacetyl –CoA
• Then in the liver acetoacetate ,acetone.
• Enter the circul...
Diagnosis
• Urine examination for glycosuria
• Urine examination for ketone bodies
• Fasting and postprandial blood glucos...
Oral Glucose Tolerance Test
• Measurement of
the ability of cells
to secrete insulin.
• Ability of insulin to
lower blood
...
Treatment in Diabetes
• Change in lifestyle:
– Increase exercise:
• Increases the amount of membrane GLUT-4 carriers in th...
1. Diet
2. Insulin -- most patients treated with insulin and diet
3. Oral hypoglycemic agents:
Used when diet control insu...
. Oral hypoglycemic agents (cont.)
a) Sulfonylureas (first generation)
1) Agents - acetohexamide (Dymelor), chlorpropamide...
Treatment of NIDDM
c) Biguanides
Phenformin introduced in 1957
Metformin (Glucophage) available in 1994
Mechanism of actio...
G. Treatment of NIDDM
e) Alpha-glucosidase inhibitors
Acarbose (Precose)
Mechanism of action - reduces intestinal absorpti...
Complications:
• Diabetic cardiomyopathy
• Diabetic nephropathy
• Diabetic neuropathy
• Diabetic foot
• Diabetic retinopat...
Hypoglycemia
• Over secretion of
insulin.
• Reactive
hypoglycemia:
– Caused by an
exaggerated
response to a rise
in blood ...
R
Glucose
transporter
Calcium
channels
Glucose
Glucose
Metabolism
ATP
Closes
Potassium
channel
Insulin
Insulin
granules
Ca...
R
Glycogen
synthetase
Glycogen
Gluconeogenesis
Glucose
Protein
Amino
Acids
Glucagon
Urea
excretion
Lipase Free
Fatty
Acids...
Insulin
R
Decreases
Increases
Glycogen
synthetase
Protein
Amino
Acids
Glucose
Gluconeogenesis
Urea
excretion
Lipase Free
F...
Hyperglycemia
Glycogen
synthetase
Glycogen
Gluco-1-
phosphatase
Energy
utilization
Gluconeogenesis
Protein
Amino
Acids
Ins...
1. Hypoglycemia — insulin requirement reduced, failure to eat,
unaccustomed exercise, or insulin overdose
can all cause hy...
Treatment:
• Diabetes type I:
• artificial insulin – subcutaneous injection
• insulin control, diet, weight control and ex...
• Diabetes type II:
• diet, weight loss
• exercise to increase receptor responsiveness
• sulfonylureas to increase number ...
Diabetes mellitus
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Diabetes mellitus

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Diabetes mellitus

  1. 1. DIABETES MELLITUS Dr. Shashi Pandey
  2. 2. CLINICAL SYNDROME OF HYPERGLYCEMIA OCCURING DUE TO DEFICIENCY OF INSULIN
  3. 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. 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. 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)
  6. 6. Cont. • Hyperglycemia • Glycosuria • Ketosis • Acidosis • coma
  7. 7. TYPE 1 IDDM • Develops before the age of 40 • Pt are not obese • Also called juvenile diabetes
  8. 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.
  9. 9. Consequences of Uncorrected Deficiency in Type I Diabetes Mellitus Insert fig. 19.11
  10. 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. 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%
  12. 12. Insert table 19.6
  13. 13. PATHOPHYSIOLOGY • HYPERGLYCEMIA and its consequences: • Due to lack of insulin resulting in: • Decreased periphral utilization of glucose • Increased hepatic output of glucose
  14. 14. HYPERGLYCEMIA RENAL CAPACITY FOR GLU REAB EXCEEDED EXCRETION OF OSMOTICALLY ACTIVE PARTICALS GLYCOSURIA
  15. 15. EXCRETION OF OSMOTICALLY ACTIVE PARTICALS LOSS OF LARGE AMOUNT OF WATER DEHYDRATION STIMULATION OF THIRST MECHANISM POLYDIPSIA CAUSE OF POLYDIPSIA
  16. 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. 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. 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. 19. Diagnosis • Urine examination for glycosuria • Urine examination for ketone bodies • Fasting and postprandial blood glucose level • Glucose tolerance test (GTT)
  20. 20. 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
  21. 21. 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.
  22. 22. 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
  23. 23. . 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
  24. 24. 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
  25. 25. 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
  26. 26. Complications: • Diabetic cardiomyopathy • Diabetic nephropathy • Diabetic neuropathy • Diabetic foot • Diabetic retinopathy
  27. 27. 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
  28. 28. R Glucose transporter Calcium channels Glucose Glucose Metabolism ATP Closes Potassium channel Insulin Insulin granules Ca+ XIV. PANCREATIC HORMONES B. Mechanism of release Leads to depolarization Decreases potassium conductance
  29. 29. R Glycogen synthetase Glycogen Gluconeogenesis Glucose Protein Amino Acids Glucagon Urea excretion Lipase Free Fatty Acids Ketone Bodies Liver Lipid Energy utilization Gluco-1- phosphatase XIV. PANCREATIC HORMONES C. Role in metabolic processes 1. Review
  30. 30. Insulin R Decreases Increases Glycogen synthetase Protein Amino Acids Glucose Gluconeogenesis Urea excretion Lipase Free Fatty Acids Ketone Bodies Liver Glycogen Lipid Energy utilization Gluco-1- phosphatase XIV. PANCREATIC HORMONES C. Role in metabolic processes 2. Insulin effects
  31. 31. Hyperglycemia Glycogen synthetase Glycogen Gluco-1- phosphatase Energy utilization Gluconeogenesis Protein Amino Acids Insulin R Decreases Increases Urea excretion (Azoturia) Lipase Free Fatty Acids (Ketonemia and Acidosis Liver Lipid Hyperlipemia Ketone Bodies XIV. PANCREATIC HORMONES C. Role in metabolic processes 3. Insulin deficiency
  32. 32. 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
  33. 33. Treatment: • Diabetes type I: • artificial insulin – subcutaneous injection • insulin control, diet, weight control and exercise
  34. 34. • Diabetes type II: • diet, weight loss • exercise to increase receptor responsiveness • sulfonylureas to increase number of receptors

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