Type 1 diabetes mellitus

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Pathophysiology - Autoimmune Ambush

Pathogenesis of Type 1 Diabetes Mellitus

  • Genetic Predisposition: Strong link to specific HLA genes, particularly HLA-DR3 and HLA-DR4.
  • Mechanism: A trigger (e.g., viral infection) in a susceptible individual initiates a T-cell-mediated autoimmune assault on pancreatic β-cells.
    • CD8+ cytotoxic T-lymphocytes infiltrate islets (insulitis), leading to β-cell destruction.
    • Results in absolute insulin deficiency.
  • Key Markers: Autoantibodies like anti-GAD65, ICA, and IAA serve as markers of autoimmunity.

⭐ Over 90% of individuals with Type 1 Diabetes possess either HLA-DR3 or HLA-DR4 haplotypes.

Clinical Presentation - The Sweet Symptoms

  • Classic Triad (The "3 Ps"):
    • Polyuria: Osmotic diuresis (renal glucose threshold > 180 mg/dL).
    • Polydipsia: Intense thirst from dehydration.
    • Polyphagia: Hunger from cellular starvation.
  • Weight Loss: Unexplained, due to catabolism (muscle, fat breakdown).
  • Diabetic Ketoacidosis (DKA): Often the first sign, with nausea, vomiting, abdominal pain, & Kussmaul respirations.

High-Yield: About 25-30% of children with new-onset T1D first present in Diabetic Ketoacidosis (DKA).

Symptoms of Type 1 Diabetes in Adults and Children

Diagnosis - Cracking the Code

  • Core Criteria: Diagnosis requires one of the following:

    • Fasting Plasma Glucose (FPG) ≥ 126 mg/dL
    • 2-hour OGTT plasma glucose ≥ 200 mg/dL
    • HbA1c ≥ 6.5%
    • Random plasma glucose ≥ 200 mg/dL with classic hyperglycemia symptoms.
  • Antibody Panel: To confirm autoimmune etiology vs. T2DM.

    • Most common: GAD65, Islet antigen-2 (IA-2).

⭐ Low or undetectable C-peptide levels are a hallmark, confirming scant endogenous insulin production, unlike in early T2DM where it can be normal or high.

Pancreatic islet histology: insulitis vs. normal islet

Management - The Insulin Imperative

  • Lifelong insulin replacement is mandatory. The goal is to mimic physiological insulin secretion.
  • Basal-Bolus Regimen (Gold Standard):
    • Basal: Once/twice daily long-acting insulin (Glargine, Detemir) or continuous subcutaneous infusion (insulin pump). Covers ~50% of daily needs.
    • Bolus: Rapid-acting insulin (Lispro, Aspart) before each meal to control postprandial glucose. Covers the remaining ~50%.
  • Initial Dosing: Typically 0.4-1.0 units/kg/day.
  • Monitoring:
    • Self-monitoring of blood glucose (SMBG) or continuous glucose monitoring (CGM).
    • HbA1c target: <7.0%.

Dawn Phenomenon: Early morning hyperglycemia (around 3 AM to 8 AM) due to nocturnal growth hormone spikes. Manage by increasing the evening basal insulin dose or adjusting pump settings.

Insulin action profiles: rapid, short, intermediate, long

Complications - The Highs and Lows

  • Hyperglycemia: Diabetic Ketoacidosis (DKA)

    • Triad: Glucose >250 mg/dL, pH <7.3 (anion gap metabolic acidosis), + ketones.
    • Triggers: Infection, ischemia, infarction, insulin deficit.
    • Symptoms: Fruity breath, Kussmaul respirations, abdominal pain.
  • Hypoglycemia

    • Blood glucose <70 mg/dL.
    • Autonomic symptoms (sweating, tremor) precede neuroglycopenic (confusion, coma).
    • Treatment: Conscious → 15g carbs. Unconscious → IV Dextrose or IM Glucagon.

Dawn Phenomenon vs. Somogyi Effect: To differentiate morning hyperglycemia, check glucose at 3 AM. A low reading suggests Somogyi (rebound), while a normal/high reading indicates Dawn (hormonal surge).

High‑Yield Points - ⚡ Biggest Takeaways

  • Results from T-cell mediated autoimmune destruction of pancreatic β-cells, causing absolute insulin deficiency.
  • Strongest genetic risk is associated with HLA-DR3 and HLA-DR4.
  • Classic triad: polyuria, polydipsia, polyphagia, often with abrupt weight loss.
  • Diabetic Ketoacidosis (DKA) is a frequent and life-threatening initial presentation.
  • Key labs: positive autoantibodies (anti-GAD65, anti-islet cell) and low/absent C-peptide.
  • Management requires lifelong insulin therapy; cannot be managed with oral agents.

Practice Questions: Type 1 diabetes mellitus

Test your understanding with these related questions

A 52-year-old man presents to his primary care physician to discuss laboratory results that were obtained during his annual checkup. He has no symptoms or concerns and denies changes in eating or urination patterns. Specifically, the physician ordered a panel of metabolic laboratory tests to look for signs of diabetes, hyperlipidemia, or other chronic disorders. A spot glucose check from a random blood sample showed a glucose level of 211 mg/dL. A hemoglobin A1c level was obtained at the same time that showed a level of 6.3%. A fasting blood glucose was obtained that showed a blood glucose level of 125 mg/dL. Finally, a 2-hour glucose level was obtained after an oral glucose tolerance test that showed a glucose level of 201 mg/dL. Which of the following statements is most accurate for this patient?

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Flashcards: Type 1 diabetes mellitus

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Etiologies of _____ diabetes insipidus include pituitary tumor, autoimmune, trauma, surgery, and ischemic encephalopathy

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Etiologies of _____ diabetes insipidus include pituitary tumor, autoimmune, trauma, surgery, and ischemic encephalopathy

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