This document contains lecture notes from Dr. Kunal on diabetes mellitus. It discusses the pathophysiology of diabetes including hyperglycemia and hypoglycemia. It describes the clinical features of diabetes such as polydipsia, polyuria, and weight loss. It also summarizes the complications of chronic diabetes including retinopathy, nephropathy, neuropathy, infections, and cardiovascular and cerebrovascular diseases. Contact information for Dr. Kunal is provided.

1. Dr Kunal; MBBS, MD
Associate Prof. Physiology
drkunal10@gmail.com
8792873242
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Diabetes

2. Diabetes Mellitus
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3. Blood Glucose
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• Hyperglycemia: concentrations >110 mg/dl
 long term damage of nerves, eyes, blood
vessels, kidney, heart
• Hypoglycemia: concentrations <70 mg/dl
 irritation, confusion, seizure, coma/death
Brain uses 25% of blood glucose!
 free from insulin, depends directly on blood glucose level!
• Plasma level of HbAIc (Glycated Hemoglobin) is
an integrated index of diabetic control for the
4-6-weeks period before measurement
Dr Kunal’s Physiology Notes

4. Impaired Glucose Homeostasis
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6. Diabetes
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Glycated Hb

7. Diabetes
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8. Diabetes
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 Diabetes mellitus (DM): group of metabolic
disorders due to hyperglycemia
 Type 1 DM: near-total insulin deficiency (IDDM)
•  cell destruction
• Immune-mediated (mostly) or Idiopathic
• Features of DM is evident only if 70–80% of
 cells are destroyed
Dr Kunal’s Physiology Notes

9. Diabetes
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 Type 2 DM:
defects in insulin action / insulin resistance,
defects in insulin secretion / relative deficiency
A failure to compensate the insulin resistant
by  insulin secretion, results in
Impaired () fasting glucose (IFG)
Impaired () glucose tolerance (IGT)
Dr Kunal’s Physiology Notes

10. Insulin secretion Vs sensitivity
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11. Causes of Insulin Resistance
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 Visceral / Central Obesity (BMI >25 kg/m2)
 Excess glucocorticoids (Cushing’s synd./ therapy)
 Excess growth hormone (acromegaly)
 Pregnancy, Polycystic ovary disease
 Lipodystrophy (acquired or genetic; lipid
accumulation in liver)
 Autoantibodies to insulin receptor
 Mutations of insulin receptor
 Hemochromatosis (tissue iron accumulation)
Dr Kunal’s Physiology Notes

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Diabetes

13. Risk Factors for Type 2 DM
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 Family history of diabetes
 Visceral / Central Obesity (BMI >25 kg/m2)
 Physical inactivity
 Race/ethnicity (e.g., African, Latino, Asian
 People with IFG, IGT, or an A1C of 5.7–6.4%
 Hypertension (blood pressure >140/90 mmHg)
 HDL cholesterol level <35 mg/dL (0.90 mmol/L)
 Triglyceride level >250 mg/dL (2.82 mmol/L)
 Polycystic ovary syndrome
 History of GDM or delivery of baby >4 kg
Dr Kunal’s Physiology Notes

14. Hyper-glycemia in DM
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•  glucose entry in liver, muscle & fat cells
 Postprandial hyper-glycemia;
 impaired glucose tolerance (IGT)
 plasma glucose even  up to 1200 mg/dl
•  hepatic breakdown of glycogen and cholesterol
 Fasting hyper-glycemia: impaired fasting
glucose (IFG)
  FFA in plasma
•  hepatic utilization of Free fatty acids to produce
phospholipids and cholesterol
Dr Kunal’s Physiology Notes

15. Plasma levels in DM
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16. Pathophysiology of DM
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• Initially, insulin resistance   insulin secretion
•  cells get destroyed (over-use)
  Beta cell mass in long run
  insulin secretion  Hyperglycemia
• Glucose enters, independent of Insulin action, in:
pancreatic  cells, renal tubules, most neurons,
retina, RBC, germinal epithelium of gonads, etc
 depends directly on blood glucose level !!
•  glucose entry   oxidation of glucose 
  formation of free radicals
 Glucose Toxicity
Dr Kunal’s Physiology Notes

17. Pathophysiology of DM
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• Glucose Toxicity: due to  entry of glucose
• Lipotoxicity: due to  entry of FFA to cells
• Complications of chronic DM
 Retinopathy
 Nephropathy
 Neuropathy
 Cardiomyopathy
Dr Kunal’s Physiology Notes

18. Clinical Features of DM
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• rapid weight loss and asthenia (lack of energy)
• despite eating large amounts of food (polyphagia)
• Easy fatigue: Muscles starving for glucose
• Polyphagia
 Feeding center is stimulated, VMN inhibited
•  Weight in spite of excessive eating
  utilization of fats & protein for energy
  body mass of fat & protein
Dr Kunal’s Physiology Notes

19. Clinical Features of DM
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 Glycosurea: DM means “Sweet Urine”
 Renal threshold: 180 mg/dl
 Polyuria: osmotic diuresis
 Glucose osmotically attracts  fluid in urine
 Polydipsia:  thirst
 Easy intracellular and extracellular dehydration
  Glucose in plasma
 osmotically pulls water out of ECF & ICF
Dr Kunal’s Physiology Notes

20. Complications of chronic DM
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• Frequent infection with delayed healing
• Ischemia and gangrene of the limbs
• Micro- vs macro- vascular complications
 End-stage kidney disease,
 Retinopathy and blindness,
 Stroke in heart, brain, kidney etc.
 Hypertension secondary to renal injury
 Atherosclerosis,

21. Complications of chronic DM
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• Arteriosclerosis:  deposition of cholesterol in
arterial walls
• Fruity odor (acetone breath):  acetoacetic acid,
β-hydroxybutyric acid & acetone production
• Kussmaul Respiration (Air Hunger)
 Irregular, effortful, shallow & rapid breathing
• Autonomic & peripheral neuropathy
 Impaired CVS reflexes, bladder control,
 Decreased sensation in extremities,

22. Complications of Diabetes
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23. Complications of Diabetes
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Dr Kunal’s Physiology Notes
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