1. Introduction & Epidemiology

Type 1 Diabetes Mellitus (T1DM) is a chronic autoimmune disease characterized by the destruction of insulin-producing pancreatic \(\beta\)-cells.

2. Pathophysiology

The core mechanism is a T-cell mediated autoimmune attack on the islets of Langerhans.

Genetic Susceptibility

  • HLA Association: Strongest links are with HLA-DR3-DQ2 and HLA-DR4-DQ8.
  • Over 50 non-HLA loci also contribute.

The “Autoimmune Trigger”

The “hygiene hypothesis” and viral triggers (e.g., Coxsackievirus B) are theorized to initiate the response in genetically predisposed individuals.

Staging of T1DM (ADA 2024 Criteria)

Medical students must understand that T1DM is a progressive process, not a sudden “switch.”

Stage Characteristics Clinical Status
Stage 1 Multiple autoantibodies (GAD65, IA-2, ZnT8) Normoglycemic, Asymptomatic
Stage 2 Multiple autoantibodies + Impaired Glucose Tolerance Dysglycemic, Asymptomatic
Stage 3 Clinical Symptoms + Hyperglycemia Overt Diabetes

3. Clinical Presentation: The “3 Ps”

The classic triad results from the osmotic effects of hyperglycemia: 1. Polyuria: Glucose exceeds renal threshold (~180 mg/dL), causing osmotic diuresis. 2. Polydipsia: Dehydration triggers the thirst center. 3. Polyphagia: Negative energy balance as cells “starve” despite high extracellular glucose. 4. Unintentional Weight Loss: Due to lipolysis and muscle proteolysis.

4. Diagnostic Criteria

Diagnosis is confirmed by any of the following:

Clinical Pearl: To differentiate from Type 2, check C-peptide levels (low/absent in T1DM) and Autoantibodies (GAD65, ZnT8).

5. Management: The Basal-Bolus Principle

Exogenous insulin is life-sustaining. The goal is to mimic the healthy pancreas.

Figure 1: Insulin Pharmacokinetics

The graph below demonstrates the difference between “Basal” (background) and “Bolus” (mealtime) insulin.

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Modern Technology

  • CGM (Continuous Glucose Monitor): Sensors measuring interstitial glucose every 5 minutes.
  • AID (Automated Insulin Delivery): “Closed-loop” systems (artificial pancreas) that adjust basal insulin based on CGM readings.

6. Real-Life Clinical Case

Case Study: The “Dehydrated” Athlete

Patient: 19-year-old male college student, previously healthy. Presentation: Brought to the ER after fainting during soccer practice. He reports 3 weeks of “feeling tired,” drinking 6 liters of water a day, and losing 12 lbs despite a high-calorie “bulking” diet. Exam: Tachypneic (30 bpm), fruity breath (acetone), dry mucous membranes. BP 90/60 mmHg. Labs: * Glucose: 540 mg/dL * pH: 7.12 (Metabolic Acidosis) * Bicarbonate: 10 mEq/L * Ketones: Positive in urine and blood.

Diagnosis: Diabetic Ketoacidosis (DKA) - the initial presentation for ~30% of T1DM cases. Immediate Management: 1. Isotonic Fluid Resuscitation (Normal Saline). 2. IV Insulin Infusion (0.1 units/kg/hr). 3. Potassium replacement (critical as insulin shifts K+ into cells).

7. Complications

Acute

  • DKA: Life-threatening emergency.
  • Hypoglycemia: The “limiting factor” in tight control (Blood Glucose < 70 mg/dL).

Chronic (The “Opathies”)

  • Microvascular: Retinopathy (leading cause of blindness), Nephropathy (CKD), Neuropathy.
  • Macrovascular: Coronary Artery Disease, Stroke, Peripheral Artery Disease.

Figure 2: Impact of Glycemic Control

The DCCT trial showed that maintaining HbA1c < 7% significantly delays the onset of microvascular complications (Retinopathy curve shifts significantly to the right/down).

8. Summary for Clinical Rotations