1. DIABETES MELLITUS
DR HEYAM AWAD
FRCPATH

2. DEFINITION
DM IS A GROUP OF METABOLIC DISORDERS CHARACTERIZED BY HYPERGLYCEMIA.
HYPERGLYCEMIA CAUSED BY… DEFECTS IN INSULIN SECRETION , INSULIN ACTION OR BOTH.
RESULTS IN DAMAGE IN MANY ORGANS.

3. DM IS THE LEADING CAUSE OF :
END STAGE RENAL DISEASE.
ADULT ONSET BLINDNESS.
NON TRAUMATIC LOWER EXTREMITY AMPUTATION.

4. CLASSIFICATION
TYPE 1 DM…ABSOLUTE INSULIN DEFICIENCY DUE TO BETA CELL DESTRUCTION % OF CASES.
TYPE 2 DM… RELATIVE INSULIN DEFICIENCY..DUE TO PERIPHERAL RESISTANCE TO INSULIN ALONG WITH INADEQUATE COMPENSATORY RESPONSE.
MINORITY OF CASES…SECONDARY CAUSES.

5. SECONDARY CAUSES
GENETIC DEFECTS IN BETA CELL FUNCTION OR INSULIN ACTION.
EXOCRINE PANCREATIC DEFECTS: CHRONIC PANCREATITIS, PANCREATECTOMY, NEOPLASIA….
ENDOCRINOPATHIES: ACROMEGALY, CUSHING SYNDROME, HYPERTHYROIDISM.
INFECTIONS: CMV, CONGENITAL RUBELLA, COXSACKIEVIUS B INFECTION.
DRUGS: STEOIDS, THYROID HORMONE.
GESTATIONAL DIABETES.

6. GLUCOSE HOMEOSTASIS REGULATED BY THREE MECHANISMA…
GLUCOSE PRODUCTION IN LIVER
GLUCOSE UPTAKE BY PERIPHERAL TISSUE.
ACTION OF INSULIN AND GLUCAGON.

7. INSULIN EFFECTS
INSULIN INCREASES GLUCOSE TRANSPOT INTO STRIATED MUSCLE AND ADIPOCYTES.
IN MUSCLE …. GLUCOSE IS STORED AS GLYCOGEN OR OXIDISED TO GENERATE ATP.
IN ADIPOCYTES GLUCOSE IS STORED AS LIPID.
ALSO.. INSULIN HAS ANABOLIC EFFECT: INCREASED SYNTHESIS AND DECREASED DEGRADATION OF GLYCOGEN, LIPID AND PROTEIN

8. INSULIN REDUCES GLUCOSE PRODUCTION BY LIVER.
THE MOST IMPORTANT STIMULUS OF INSULIN IS GLUCOSE.

9. TYPE 1 DM AUTOIMMUNE DISEASE. ISLET DESTRUCTION.
CLINICAL DISEASE WHEN 90% OF ISLET CELLS DESTROYED.
DEVELOPS IN CHILDHOOD, MANIFEST AT PUBERTY, PROGRESS WITH AGE.
NEED EXOGENOUS INSULIN.

10. TYPE 2 DM GENETIC AND ENVIRONMENTAL FACTORS. TWO METABOLIC DEFECTS:
* INSULIN RESISTANCE.
* BETA CELL DYSFUNCTION.

11. INSULIN RESISTANCE FAILURE OF TARGET TISSUES TO RESPOND TO INSULIN.
ASSOCIATED WITH OBESITY.
RISK OF DM INCREASES WITH INCREAING BMI.

12. BETA CELL DYSFUNCTION
INABILITY OF BETA CELLS TO ADAPT THEMSELVES TO THE DEMANDS OF PERIPHERAL INSULIN RESISTANCE.

13. MORPHOLOGICAL CHANGES IN DIABETIC PANCREAS
REDUCTION IN NUMBER AND SIZE OF THE ISLETS.
LEUKOCYTIC INFILTRATION OF THE ISLETS.
AMYLOID REPLACEMENT OF ISLETS.
FIBROSIS.

14. COMPLICATIONS OF DM ALL BODY ORGANS AND TISSUES CAN BE AFFECTED.
MAINLY… ARTERIES, KIDNEY, RETINA, NERVES.

15. VASCULAR DISEASE MACROVASCULAR DISEASE:
ACCELERATED ATHEROSCLROSIS AFFECTING AORTA AND LARGE AND MEDIUM SIZED ARTERIES.
MI IS THE MOST COMMON CAUSE OF DEATH IN DM.
GANGRENE OF THE LOWER LEGS DUE TO ADVANSED VASCULAR DISEASE.

16. VASCULAR DISEASE
HYALINE ARTERIOLOSCLEROSIS IN SMALL BLOOD VESSELES.

17. DIABETIC NEPHROPATHY
RENAL FAILURE IS THE SECOND MOST COMMON CAUSE OF DEATH IN DIABETICS.
THREE LESIONS CAN BE SEEN: GLUMERULAR LESIONS, RENAL VASCULAR LESIONS AND PYELONEPHRITIS.

18. OCULAR COMPLICATIONS RETINOPATHY. CATARCT. GLAUCOMA.
RETINOPTHY IS THE MOST COMMON PATTERN

19. DIABETIC NEUROPATHY
PERIPHERAL SYMMETRIC NEUROPATHY OF LOWER EXTREMITIES.
AUTONOMIC NEUROPATHY… DISTURBANCES IN BOWEL AND BLADDER FUNCTION.
CAUSED BY: MICROANGIOPATHY OR DIRECT AXONAL DAMAGE

20. CLINICAL FEATURES
POLYURIA.
POLYDIPSIA
POLYPHAGIA
HOW THESE HAPPEN?

21. CLINICAL FEATURES
WEIGHT LOSS ESPECIALLY IN TYPE 1….. WHY?

22. TREATMENT TYPE 1:INSULIN.
TYPE 2: DIET AND EXERCISE, ORAL DRUGS THAT DECREASE GLUCOSE LEVELS.

23. ACTIVITY
TYPE 1 AND 2 COMPARISON