Diabetes mellitus type 1 Study Guide

📖 Core Concepts Type 1 diabetes = autoimmune destruction of pancreatic β‑cells → absolute insulin deficiency. Insulin: hormone that enables glucose uptake into cells; without it, blood glucose stays high (hyperglycemia). Autoantibodies (GAD65, insulin, IA‑2, ZnT8) appear months‑years before symptoms and are the hallmark of the disease. β‑cell loss → loss of intra‑islet insulin → α‑cell dysregulation (post‑prandial hyperglucagonemia, blunted glucagon response to hypoglycemia). DKA = insulin‑deficiency‑driven fat breakdown → ketone production → metabolic acidosis. Hypoglycemia unawareness = repeated low‑glucose episodes blunt autonomic warning signals. --- 📌 Must Remember Diagnostic thresholds (ADA/WHO): Fasting plasma glucose ≥ 126 mg/dL (7.0 mmol/L) or 2‑hr OGTT ≥ 200 mg/dL (11.1 mmol/L) or HbA1c ≥ 6.5 % (48 mmol/mol). Autoantibody panel: GAD65, insulin, IA‑2, ZnT8 – positive in 80 % of patients; ≥ 2 antibodies → rapid progression. C‑peptide: very low/absent in type 1 (distinguishes from type 2). Glucose targets: pre‑meal 80–130 mg/dL (4.4–7.2 mmol/L); post‑meal < 180 mg/dL (< 10.0 mmol/L). HbA1c goal: < 7 % (adults), < 7.5 % (children). DKA mortality: 13–19 % of type 1 deaths; leading cause of death < 58 yr. Severe hypoglycemia: glucose < 70 mg/dL (3.9 mmol/L) with neuroglycopenic symptoms; treat with “15‑15 rule”. --- 🔄 Key Processes Autoimmune β‑cell destruction Autoantigens → autoantibodies → CD8⁺ T‑cell & macrophage attack → necroptosis/apoptosis. Insulin‑deficient metabolism → DKA ↓ insulin → ↑ lipolysis → ↑ free fatty acids → hepatic ketogenesis → ↑ β‑hydroxybutyrate → metabolic acidosis. Basal‑bolus insulin dosing Basal (long‑acting) → maintain fasting glucose. Bolus (rapid‑acting) → given 10–15 min before meals, dose = (carb ÷ ICR) + correction factor. “15‑15” hypoglycemia treatment 15 g fast‑acting carbs → wait 15 min → recheck glucose → repeat if < 70 mg/dL. --- 🔍 Key Comparisons Type 1 vs. Type 2 Diabetes Autoimmunity: present in Type 1, absent in Type 2. C‑peptide: low/absent in Type 1, normal‑high in Type 2. Age of onset: childhood/young adult (Type 1) vs. adult‑onset (Type 2). Rapid‑acting vs. Long‑acting insulin Onset: 10–15 min (rapid) vs. 1–2 h (long). Peak: 1–2 h (rapid) vs. flat/no peak (long). Use: mealtime bolus vs. basal coverage. --- ⚠️ Common Misunderstandings “All diabetics need the same glucose targets.” Targets differ for children (< 7.5 % A1c) and adults; pregnancy has tighter goals. “DKA only occurs in adults.” DKA is the most common presentation in children and can be the first sign of disease. “If blood glucose is high, giving more insulin always fixes it.” Over‑insulination can precipitate hypoglycemia; adjust based on carbohydrate intake and current glucose. --- 🧠 Mental Models / Intuition “Insulin = the key; glucose = the car.” Without the key (insulin), the car (cells) can’t move, so glucose piles up. “Beta‑cell loss = removing the brake on glucagon.” Think of insulin as a brake on α‑cells; when it’s gone, glucagon runs wild, worsening hyperglycemia. “DKA is fuel‑starved fire.” Lack of insulin forces the body to burn fat → ketones (the “fire”) → acidosis. --- 🚩 Exceptions & Edge Cases Idiopathic type 1 (10–30 %): β‑cell loss without detectable autoantibodies – diagnosis relies on low C‑peptide. Protective HLA haplotype: DR15‑DQ6 reduces risk despite other risk factors. Pregnant women: hybrid closed‑loop systems are specifically recommended. --- 📍 When to Use Which Basal‑bolus regimen → most patients needing tight glucose control and flexibility. Fixed‑ratio mixes → when frequent dosing is impractical (e.g., limited self‑monitoring). Insulin pump → patients desiring precise basal adjustments, frequent hypo‑/hyperglycemia, or active lifestyles. Hybrid closed‑loop → pregnant patients, tech‑savvy individuals, or those with frequent nocturnal lows. --- 👀 Patterns to Recognize Polyuria + Polydipsia + Weight loss → classic pediatric triad → suspect type 1. Fruity breath + high glucose + ketones → DKA pattern. Recurrent lows + blunted symptoms → developing hypoglycemia unawareness. Multiple autoantibodies + family history → high‑risk for imminent clinical onset. --- 🗂️ Exam Traps “A fasting glucose of 125 mg/dL diagnoses diabetes.” – Threshold is ≥ 126 mg/dL. “C‑peptide is high in type 1.” – It is low/absent. “All patients with type 1 have detectable autoantibodies.” – Up to 30 % can be idiopathic. “DKA can be treated with oral glucose.” – Insulin, fluids, and electrolytes are required; oral glucose worsens ketosis. “HbA1c < 6 % is always the goal.” – Target is < 7 % for most adults; stricter goals may increase hypoglycemia risk. ---