1. DIABETES MELLTIUS Dr. Ayisha Qureshi Assistant Professor MBBS, MPhil

2. DIABETES MELLITUS Definition: Diabetes mellitus is a syndrome of impaired carbohydrate, protein & fat metabolism caused by either lack of insulin secretion or decreased sensitivity of the tissues to insulin. The word “Diabetes Mellitus” literally means “excessive secretion of sweet urine”

3. DIABETES MELLTIUS In 2000, diabetes affected 150 million people worldwide This number is expected to climb to 220 million by 2010. Third leading cause of death Leading cause of blindness Diabetes is a very prevalent disease, has a huge economic toll, forces individuals to change their lifestyle thus affecting their quality of life & predisposes the affected to a variety of troublesome & even life threatening conditions.

4. Diabetes Mellitus Type I Juvenile onset/ Insulin Dependant Type II Adult onset/ Insulin Independent

5. TYPE I/ Juvenile Onset/ Insulin Dependant It is the more severe from of diabetes. DEFINITION: It is a catabolic disorder in which circulating insulin is virtually absent, plasma glucose is elevated & the pancreatic beta cells fail to produce any insulin in response to all insulinogenic stimuli. Cause: Lack of insulin secretion from the beta cells of the islets of langerhans It is an autoimmune disorder in which there is selective destruction of the pancreatic beta cells by T lymphocytes. Mostly it seems to have an immunological basis & circulating islet cell antibodies & anti-insulin antibodies may be demonstrated. Usually there is a genetic predisposition to this type of diabetes which may be triggered off by: - Viral infections e.g. rota virus, coxsackie virus - Environmental triggers.

7. TYPE II DIABETES/ Non-Insulin Dependant/ Adult Onset Diabetes It is further classified into: 1.Non-obese type II 2.Obese type II It is the most common type of diabetes, accounting for about 90% of all cases of diabetes mellitus. The age of onset is usually after 30, often b/w 50 & 60 years of age. It develops gradually & is the less severe form of diabetes. Cause: Decreased sensitivity of target tissues to the metabolic effects of insulin. This reduced sensitivity to insulin is often called INSULIN RESISTANCE.

9. TYPE II DIABETES Factors that can lead to Insulin resistance include: 1.Anti-insulin antibodies 2.Autoantibodies to the insulin receptor 3.Mutation of insulin receptor 4.Down-regulation of insulin receptors by sustained hyperinsulinism 5.Primary hyperinsulinism (Beta cell adenoma) 6.Secondary hyperinsulinism (Cushing’s syndrome, acromegaly, pregnancy or diabetes mellitus) In both # 5 & 6 Poor response of the target organs is due to reduced numbers of insulin receptors 7. Obesity/overweight especially excess fat deposits around the abdomen

10. PATHOPHYSIOLOGY Diabetes type I is far more rapid in onset occurring over a few days as compared to type II which has a more gradual onset. Type I also shows far more complications as compared to Type II which rarely shows complications Type I requires Insulin while Type II can usually be controlled by simple changes in lifestyle as diet, exercise & weight control Type I insulin is more prone to Ketoacidosis while Type II is not!

12. COMPLICATIONS In long standing diabetes mellitus, following complications may arise: 1.Neuropathies 2.Peripheral vascular disease 3.Gangrene 4.Atherosclerosis 5.Ischemic heart disease 6.Renal disease 7.Early cataract 8.Retinopathy 9.Skin infections 10.Neuropathies affecting the ANS

13. Diabetic foot showing ulcer

14. Gangrene that must be treated with an amputation

15. DIAGNOSIS OF DIABETES 1.Blood sugar random ( 80-120 mg/100ml) 2.Blood sugar fasting (80-90 mg/100ml) 3.GTT or Glucose Tolerance Test: When a normal fasting person is given 1g of glucose /kg body weight, his plasma glucose levels rise to 120-140 but fall back to normal within 2 hours In a prediabetic or diabetic, not only is the fasting plasma glucose on the higher side but also the post meal plasma glucose rises to as high as 140-200 & fails to come back to normal within 2 hours of giving conc. glucose solution. Even after 4-6 hours it rarely comes back to the normal range! NORMAL MEAN BLOOD GLUCOSE IS APP. 110 !

16. POINT TO REMEMBER! WHY IS ORAL GLUCOSE A MORE POWERFUL STIMULANT THAN INJECTABLE GLUCOSE FOR INSULIN SECRETION?

17. Glucose Tolerance Test

20. DIAGNOSIS OF DIABETES 4.Presence of glucose in urine (glucosuria) 5.Acetone breath 6.Lab test for assessing control of diabetes:

21. TREATMENT Type I diabetes WHY CANNOT INSULIN BE GIVEN BY MOUTH? WHY IS ONLY CHO RESTRICTION NOT VERY EFFECTIVE? Administer enough insulin so that metabolism of fat, proteins & CHO proceed as normally as possible! Insulin is available in various forms: 1.Insulin preparations are available with rapid (regular), intermediate & long durations of action: - regular: duration of action is 3-8 hours - Intermediate (NPH) not used during ER - Long: duration of action is 10-48 hours Individualized insulin schedules which consist of one injection of longer acting insulin followed by regular insulin when the glucose level is expected to rise.i.e. at meals. Insulin is administered subcutaneously (s/c) except in the case of emergencies when it is given intravenously (i/v). The less soluble an insulin preparation is, the longer it acts!

22. INSULIN SYRINGES

23. TREATMENT Type II diabetes: Diet Exercise Weight loss The chief goal is to attain patient’s ideal weight! Drugs to increase sensitivity of different organs to insulin - sulfonylureas Insulin injections Portable infusion pump

24. SULFONYLUREAS! NIDDM patients above the age of 40 years & having h/o diabetes of less than 5 years are given Oral Hypoglycemics! Mechanism of Action: 1.Stimulate release of Insulin from beta cells of pancreas 2.Reduction of serum Glucagon! 3.Increased binding of Insulin to target tissues & receptors E.g. Tolbutamide Glyburide Glipizide