Diabetes Mellitus - Medicine - ATOT

Topic: Diabetes Mellitus
Faculty: General Medicine
Course: BSc ATOT - 2nd year

1. Diabetes Mellitus Dr. Salman Ahmad Ansari(MBBS) Kanachur Institute of Medical Sciences

2. Contents Definition of DM Types of DM Causes Clinical features Diagnosis Treatment Complications

3. Diabetes Mellitus Definition : Metabolic disease in which there is hyperglycemia due to insulin deficiency or insulin resistance or both Most common endocrine disease Becoming more common due to sedentary lifestyle India and China: highest prevalence of diabetes

4. Normal fasting glucose levels <100 mg/dl Pre-diabetes(impaired) fasting glucose levels 100-125 mg/dl Diabetes glucose levels: >125 mg/dl

5. Types of DM Type 1 DM Type 2 DM

6. Other types of diabetes Gestational diabetes mellitus(GDM): in pregnancy Maturity-onset diabetes of the young(MODY) Latent autoimmune diabetes in adults(LADA)

7. Etiology and pathogenesis of Type 1 DM(T1DM) 5-10% of all cases Most common in childhood(<20 years of age) Etiology : Autoimmune destruction of beta cells of pancreas Absolute deficiency of insulin

8. Pathogenesis of Type 1 DM Autoimmune disease Genetic risk factors : human leukocyte antigen HLA-DR3. HLA-DR4 Environmental risk factors : viral infection Phases of development : P hase of normal glucose tolerance Phase of impaired glucose tolerance Phase of frank diabetes

9. Etiology and pathogenesis of T2DM Multiple factors 4 major factors: Increasing age Obesity Ethnicity Family history

10. Environmental risk factors: Sedentary lifestyle Dietary habits and associated obesity: over-eating, obesity and less exercise Genetic risk factors: more chances if parents are diabetic

11. Insulin resistance Decreased response of target tissues to stimulation by insulin Due to genetic susceptibility and obesity

12. Clinical features of Diabetes Mellitus Type 1 DM : Age: usually before 30 years of age Weight is normal to lean(wasted) C lassical triad of diabetes : sudden onset of Polyuria(increased urination) Polydipsia(increased thirst) polyphagia(increased hunger) Severe cases: diabetic ketoacidosis Low plasma insulin level

13. Type 2 DM : Age: usually above 40 years of age Weight: obese Sedentary lifestyle Gradual onset of polyuria, polydipsia, weight loss Lack of energy, blurring of vision Severe cases: diabetic ketoacidosis Insulin levels: normal to high

14. Investigations RBS FBS PPBS OGTT HbA1C Others: RFT, Fundoscopy

15. Diagnosis of DM Symptoms of diabetes plus RBS>200 mg/dL or FBS ≥125 mg/dl on 2 occasions or 2-hour plasma glucose ≥200 mg/dl during an oral glucose tolerance test (OGTT) or Glycated haemoglobin (HbA1c): ≥6.5%

16. Oral glucose tolerance test(OGTT) Indication : not done routinely Done when: Fasting glucose is in the impaired range(100-125 mg/dl) Diagnosis of gestational DM Uncertainty about diagnosis of diabetes

17. Preparation : Patient should take carbohydrates without restriction for 3 days or more before the test OGTT is performed in the morning after patient has fasted overnight(at least 8 hours) Patient should rest for half an hour before the test

18. Test : A fasting venous sample of blood is taken to measure glucose level Patient is given 75 g of anhydrous glucose dissolved in 300 ml of water over orally over 5 minutes Venous sample of blood is taken 2 hours after giving glucose and glucose level is measured Result : Plasma glucose between 140 and 200 mg/dl 2 hours after oral glucose load is called Impaired Glucose Tolerance

19. Management of diabetes mellitus Diet and lifestyle(‘Medical Nutrition Therapy’) Medical therapy

20. Diet and lifestyle Aim is to achieve good glycemic control, reduce hyperglycemia and avoid hypoglycemia, and reduce risk of diabetic complications Dietary management is also called ‘Medical Nutrition Therapy’(MNT) Regular pattern of meals and snacks Aim for BMI of 22

21. Calorie recommendation: 36 kcal/kg for male and 34 for females Protein requirement : at least 0.9 g/kg of body weight per day and it should be 15% of total calorie intake Fat : 30% or less of total calories - it should be Carbohydrates : 55% of total calorie intake

22. Carbs with higher fiber content(brown rice, oats) Alcohol: best to avoid 4 meals: breakfast, lunch, evening snack, dinner Lunch and dinner should be heaviest

23. Exercise: 30-60 minutes of aerobic activity 3-4 times a week Brisk walking, swimming, cycling

24. Medical therapy When lifestyle and dietary measures fail to control blood glucose Use of oral anti-diabetic drugs ( hypoglycemic agents ) and insulin

25. Oral antidiabetic drugs (previously called hypoglycaemic drugs): • Sulphonylureas • Biguanides • Meglitinide • Thiazolidinediones • ⍺ -glucosidase inhibitors • Incretin-based therapy • Other drugs:

26. Sulfonylureas Mechanism of action : insulin secretagogues - they i ncrease insulin secretion Example : Glimepiride g lyburide Side-effects : Hypoglycemia Weight gain Drug interactions

27. Glinides Mechanism of action: act on ATP-sensitive potassium channel to increase insulin secretion. Examples : Nateglinide Repaglinide Side-effects : Hypoglycemia Weight gain

28. Biguanide Example: Metformin Mechanism of action: reduces hepatic glucose productio. Avoid in renal failure Side effects : Nausea, vomiting Diarrhoea initially weight loss Risk of lactic acidosis

29. Thiazolidinediones Mechanism of action : binds to PPAR-Ɣ receptor and reduces insulin resistance Example : Pioglitazone Rosiglitazone Side effects : Weight gain Fluid retention(edema) hepato-toxicity

30. ⍺-glucosidase inhibitors Mechanism of action: decreases absorption of carbohydrates in intestine Example: Acarbose Voglibose Side-effects: Abdominal cramps Bloating flatulence diarrhoea

31. Sodium-glucose cotransporter 2( SGLT2 ) inhibitors Mechanism of action : inhibit glucose absorption from renal tubules Examples : Canagliflozin Dapagliflozin Side effects : Thirst Urination Increased risk of UTI

32. Dipeptidyl peptidase 4( DPP4) inhibitors Mechanism of action: block action of DPP4 which acts on incretin and increase effects of incretin(it potentiates insulin effects) Examples : vildagliptin sitagliptin Weight neutral Side effects : Nausea, diarrhoea Headache Risk of pancreatitis

33. Treatment guidelines Lifestyle modification (exercise, diet, weight loss) ↓ Follow up in 3 months - check HbA1C level If not controlled, start metformin ↓ Follow up in 3 months - check HbA1C level If not controlled, add a 2nd anti-diabetic drug(e.g: sulfonylurea)(dual therapy) ↓F ollow up in 3 months - check HbA1C level If not controlled, add 3rd drug to regimen(triple therapy) ↓ Follow up in 3 months - check HbA1C level Start insulin

34. Insulin therapy Indications to start insulin : If oral antidiabetic therapy has not worked If patient has HbA1C>9% Types of insulin (check next slide) Guidelines : Start long acting insulin, 0.1 unit/kg Check morning sugar, adjust dose accordingly If not controlled, add a rapid acting insulin to the biggest meal of the day

35. Insulin(...continued) Types of insulin Ultra short - acting (lispro, aspart, glulisine) short-acting(regular, semi-lente) intermediate -acting (NPH, lente) Long -acting (detemir, glargine, degludec) Side-effects : Hypoglycemia lipodystrophy(changes in skin due to repeated s.c injections)

36. Complications of diabetes Acute complications Long-term complications

37. Acute complications Diabetic ketoacidosis(DKA) Hyperosmolar hyperglycemic state Lactic acidosis Hypoglycemia

38. Long-term complications Vascular Non-vascular : infections, skin changes Microvascular : Diabetic retinopathy, cataract Diabetic nephropathy Diabetic neuropathy Diabetic foot Macrovascular : stroke, HTN

39. References: Archith Boloor, Ramadas Nayak - Prep Manual for Undergraduates K. George Mathews - Prep Manual Questions: [email protected] For notes, click here Or scan: For PPT, scan: