Basics of DM

1. DIABETIS
Dr Sravan Kumar M.D Medicine
Assistant Professor
MRIMS

4. • Fulminat Diabetis – Type 1, viral infection of
islets
• Type 3c DM – Pancreatic exocrine deficiency

5. Diagnosis

6. Screening
• Age > 45 Years – every 3 years
• Age < 45 Years if BMI > 25 kg/m2/ 23 kg/m2, with 1 risk factor

7. B Cell – Amylin(IAPP)islet amyloid polypeptide

8. Glucose Threshold for insulin synthesis - 70 mg/dl

9. Type 1 DM
• 80 % Beta cell destruction
• HLA – DQB1
– Type 1 DM(HLA – DQB1-0302/DQB1-0201)
– Celiac disease
– Narcolepsy (HLA – DQB1-0602 – protective type 1 DM)
• Other than beta cells are spared
• Auto antibodies – GAD, Insulin, IA-2(Islet antigen
2) /ICA-512, Zn T8
• Viruses – coxsackie, rubella, enterovirus

10. Type 2 DM
• Genetic
• Type 2> type1
• 50 % beta cell destruction
• Insulin resistance (Muscle, liver, fat)(PPBS)
• Increased hepatic glucose(FBS)
• Adiponectin – insulin sensitising peptide,
decresed in obesity
• Glucose toxicity & lipotoxicity to islet cells

11. liver
• Insulin resistance
• Gluconeogenesis (FBS)
• Decresed glycogen storage (PPBS)
• Lipolysis – FFAs-liver- VLDL triglyceride
• Elevated triglycerides, decreased HDL,
elevated small dense LDL Particles

12. Insulin resistance syndrome
• Hyperinsulinemia, hyperandrogenism
– Type A – young women, obesity
– Type B – middle aged, autoimmune disordoers
(autoantibodies directed against insulin receptors)
• PCOD- chronic anovulation with polycystic
ovarian morphology, hyperandrogenism
(hirsutism, acne, oligomenorrhea)
• Acanthosis nigricans

13. MODY/MONOGENIC DIABETIS
• MODY 2 – HEXOKINASE
• MODY 3 (HNF 1 α) - Responds to sulfonyl urea
• Transient or permanent neonatal Diabetis –
onset < 6 months
– ATP sensitive K+ Channel mutation
• MIDYs: Mutant Ins gene induced Diabetis of
Youth

14. LADA- Age <50, thin, no absolute insulin
deficiency, antibodies GAD, ICA
Type 1 DM
• Age < 30
• Lean
• Insulin requirement initially
• DKA
• Autoimmune disorders
– Hpothyroid,
– Adrenal insufficiency
– Perinicious anemia
– Celiac disease
– vitiligo
Type 2 DM
• Age > 30
• Obese
• May not require initially
• Insulin resistance,
hypetension, CVDs,
Dyslipidemia, PCOS

15. Treatment goals

18. hba1c
Falsely elevated
• Anemia(iron, folate, vit b12)
• Severe hypertriglyceridemia
when level >1,750 mg/dL
• Severe hyperbilirubinemia
when bilurubin > 20 mg/dL
• Uremia
Falsely reduced
• pregnancy

19. Parenteral drugs
Dulaglutide: GLP-1 agonist linked to human Ig G4 Fc
heavy chain – 0.75 mg once a week

21. Biguanides (metformin)
Inhibition of fructose 1,6 bisphosphatase – in
Inhibition of Acetyl CoA Carboxylase – inhibi
Enterocytes: increaes anerobic metabolism – delivers lactate to liver
Insulin sensitiser

22. Metformin – Vitamin B 12 deficiency
• Contraindication:
– GFR < 45 mL/min
– Any acidosis
– Congestive heart failure
– Liver disease
– Severe hypoxemia
– Stop metformin before radiographic contrast
studies
90 % Excreted unchanged in urine , not metabolised in liver

23. Insulin secretagogues – ATP sensitive K Channel
sulfonylureas
• 30 % beta cell required for action
• Most potent
– Glibenclamide (glyburide) – highest incidence of
hypoglycemia
• Least potent
– Tolbutamide
• Glimepride - 100 % absorption

24. Insulin secretagogues – ATP sensitive K Channel
Non sulfonylureas
• Repaglinide
• Nateglinide
• Mitiglinide

25. Thiazolidinediones
rosiglitazone, pioglitazone

26. Thiazolidinediones keep fat where it belongs

27. Thiazolidinediones
• Weight gain, peripheral edema
• Fractures in postmenopausal women
• CHF
• Worsens macular edema
• Pioglitazone – bladder cancer

28. α Glucosidase Inhibitors

29. α Glucosidase Inhibitors
• Intestinal α Glucosidase
• Pancreatic α amylase
• Contraindications : Sr > 2 mg/dL
• Adverse effects:
• Flatulence, diarrhea, abdominal distension

30. DPP-4 Inhibitors

32. SGLT 2 Inhibitors

35. Type 2 DM- bile acid binding resin-
Colesevelamin

36. • BROMOCRIPTINE

38. INSULIN

40. • PANCREAS TRANSPLANTATION (Along with
renal transplant)
• PANCREATIC ISLET TRANSPLANTATION
• Bariatic surgery – BMI > 30 Kg/m2

41. DKA

42. Acetyl coA + oxaloacetate
krebs cycle
Oxaloacetate diverted to
gluconeogenesis

43. DKA the amylase is usually of salivary origin.
Serum lipase should be obtained if
pancreatitis is suspected.

48. Lipodystrophic DM
Recombinant human leptin

49. Metabolic syndrome

50. Metabolic syndrome

51. Pathophysiology of the metabolic syndrome

52. • Insulin resistance – postprandial
hyperinsulinemia, followed by fasting
hyperinsulinemia and ultimately by
hyperglycemia