DIABETES MELLITUS — COMPLETE MASTER NOTES (BEGINNER → EXAM LEVEL)

🫁 1. WHAT IS DIABETES MELLITUS?

🔹 Simple Definition

Diabetes mellitus is a chronic metabolic disorder characterised by:

👉 Persistent hyperglycaemia (high blood glucose)

🔹 WHY does hyperglycaemia happen?

Because of problems with insulin:

  • ❌ Not enough insulin (Type 1)

  • ❌ Body doesn’t respond to insulin (Type 2)

  • ❌ Or both

🔹 Normal Blood Glucose

  • Fasting: ~4 – 7.8 mmol/L

🧪 2. CLASSIFICATION OF DIABETES

🔹 Based on pathogenesis (cause/mechanism)

1. Type 1 Diabetes Mellitus (T1DM)

  • Absolute insulin deficiency

  • Autoimmune destruction of β-cells

  • Usually younger patients

2. Type 2 Diabetes Mellitus (T2DM)

  • Insulin resistance + relative insulin deficiency

  • Strong link to obesity

3. Gestational Diabetes

  • Occurs during pregnancy

4. Secondary Causes

  • Pancreatitis

  • Pancreatic cancer

  • Endocrine disorders (e.g. Cushing’s)

  • Drugs (e.g. glucocorticoids)

🌍 3. EPIDEMIOLOGY (Australia — Important for exams)

  • ~1.3 million Australians have diabetes

  • Contributes to ~11% of deaths

  • 1 in 6 pregnancies → gestational diabetes

  • Higher risk in:

    • First Nations Australians (×3 risk)

    • Lower socioeconomic groups

🧬 4. NORMAL INSULIN PHYSIOLOGY (FOUNDATION)

🏭 Where is insulin made?

👉 Pancreas → Islets of Langerhans

Cell Type

Hormone

β-cells

Insulin

α-cells

Glucagon

δ-cells

Somatostatin

⚙ HOW INSULIN IS RELEASED (VERY IMPORTANT)

Step-by-step:

  1. 🍞 Blood glucose rises (after eating)

  2. Glucose enters β-cells via GLUT2

  3. → Cell depolarisation

  4. → Ca²⁺ enters cell

  5. → Insulin released

🎯 WHAT DOES INSULIN DO?

👉 It is ANABOLIC (builds & stores energy)

🧈 In Adipose Tissue:

  • ↑ Glucose uptake

  • ↑ Fat storage

  • ↓ Fat breakdown

💪 In Muscle:

  • ↑ Glucose uptake (GLUT4)

  • ↑ Glycogen synthesis

  • ↑ Protein synthesis

🧠 In Liver:

  • ↓ Gluconeogenesis

  • ↑ Glycogen storage

  • ↑ Lipogenesis

🔁 KEY BALANCE

Hormone

Effect

Insulin

↓ Blood glucose

Glucagon

↑ Blood glucose

🔥 5. TYPE 1 DIABETES

🧬 AETIOLOGY (CAUSES)

🔹 1. Genetic Predisposition

  • Associated with:

    • HLA-DR3

    • HLA-DR4

  • Does NOT directly cause → increases risk

🔹 2. Autoimmune Failure (MOST IMPORTANT)

  • Loss of self-tolerance

  • T cells attack β-cells

👉 Type IV hypersensitivity reaction

🔹 3. Environmental Triggers

  • Viral infections (e.g. Coxsackievirus)

  • Possible gut microbiome changes

⚙ PATHOGENESIS (HOW DISEASE DEVELOPS)

Step-by-step:

  1. Genetic susceptibility

  2. Environmental trigger (infection)

  3. Immune system activation

  4. T cells attack β-cells

  5. Progressive β-cell destruction

  6. ↓ Insulin production

  7. → Absolute insulin deficiency

⚠ CRITICAL POINT

By the time symptoms appear:

👉 ~90% of β-cells are destroyed

🔥 WHY SUDDEN ONSET?

  • Infection → ↑ cortisol → ↑ glucose

  • Body cannot compensate → symptoms appear quickly

🚨 CLINICAL MANIFESTATIONS (TYPE 1)

🔹 Classic Symptoms (VERY IMPORTANT)

👉 “3 P’s”

  • Polyuria → frequent urination

  • Polydipsia → excessive thirst

  • Polyphagia → increased hunger

🔹 Other Features

  • Weight loss

  • Fatigue

  • Blurred vision

⚠ LIFE-THREATENING: DKA

Diabetic Ketoacidosis

Why it happens:

  • No insulin → body uses fat

  • → Ketones produced

  • → Metabolic acidosis

Symptoms of DKA:

  • Vomiting

  • Abdominal pain

  • Kussmaul breathing (deep breathing)

  • Fruity breath

  • Confusion/coma

🔥 6. TYPE 2 DIABETES

🧬 AETIOLOGY

🔹 1. Genetic Factors

  • Strong inheritance

  • Twin concordance: 80–90%

🔹 2. Environmental Factors

🚨 Major risk factors:

  • Obesity (especially abdominal)

  • Sedentary lifestyle

  • Poor diet (high fat, high sugar)

⚙ PATHOGENESIS (VERY IMPORTANT — 3 CORE DEFECTS)

🔹 1. INSULIN RESISTANCE

👉 Cells DO NOT respond to insulin

Effects:

  • ↓ Glucose uptake

  • ↑ Gluconeogenesis

  • ↓ Glycogen synthesis

  • ↑ Free fatty acids

WHY does resistance happen?

  • Excess fat → ↑ free fatty acids

  • ↑ triglycerides

  • Adipokines (inflammatory signals)

👉 All impair insulin signalling

🔹 2. BETA CELL DYSFUNCTION

What happens:

  1. Insulin resistance → ↑ glucose

  2. Pancreas compensates → ↑ insulin

  3. Chronic stress on β-cells

  4. Eventually → β-cell failure

👉 Early stage:

  • Hyperinsulinaemia + hyperglycaemia

👉 Late stage:

  • Insulin deficiency

🔹 3. INFLAMMATION

  • Fat tissue releases cytokines (e.g. IL-1)

  • Causes:

    • ↑ insulin resistance

    • ↓ β-cell function

🧠 SUMMARY OF PATHOGENESIS

👉 Obesity → inflammation + fatty acids
→ insulin resistance
→ β-cell stress
→ failure
→ Type 2 Diabetes

🚨 CLINICAL MANIFESTATIONS (TYPE 2)

🔹 Often SILENT initially

🔹 Symptoms (when present)

  • Polyuria

  • Polydipsia

  • Fatigue

  • Blurred vision

🔹 Other Signs

  • Slow wound healing

  • Recurrent infections

  • Acanthosis nigricans (dark skin folds → insulin resistance)

⚠ ACUTE COMPLICATION

Hyperosmolar Hyperglycaemic State (HHS)

  • Severe hyperglycaemia

  • NO ketones

  • Dehydration

  • Confusion/coma

⚠ LONG-TERM COMPLICATIONS (BOTH TYPES)

🔴 Microvascular

  • Retinopathy → blindness

  • Nephropathy → kidney failure

  • Neuropathy → nerve damage

🔵 Macrovascular

  • Coronary artery disease

  • Stroke

  • Peripheral vascular disease

🔁 FINAL BIG PICTURE

TYPE 1

  • Autoimmune

  • No insulin

  • Sudden onset

  • Risk of DKA

TYPE 2

  • Insulin resistance

  • Gradual onset

  • Strong lifestyle link

  • Eventually insulin deficiency

🧠 IF YOU WANT TO ACE EXAMS

Focus on:

✔ Differences (T1 vs T2)
✔ Insulin physiology
✔ Pathogenesis steps
✔ DKA vs HHS
✔ Complications