A 28-year-old woman presents to the outpatient clinic with a 3-week history of polyuria, polydipsia, and weight loss of 4 kg. She reports no prior medical illness and denies any family history of diabetes. On examination, she appears lean (BMI 21 kg/m²), and vital signs are stable. Laboratory investigations show fasting blood glucose 285 mg/dL, venous pH 7.28, HCO₃⁻ 16 mEq/L, and serum ketones positive. Urine dipstick shows 3+ glycosuria and ketonuria. C-peptide level is 0.3 ng/mL (normal >0.8). What is the most likely diagnosis?

Explanation

## Clinical Presentation Analysis **Key Point:** The combination of acute onset, low BMI, rapid symptom progression, and presence of ketoacidosis in a young adult is pathognomonic for Type 1 diabetes mellitus. ### Diagnostic Criteria Met for Type 1 DM | Feature | Finding | Significance | |---------|---------|---------------| | Age of onset | 28 years | Type 1 can present at any age; peak incidence 10–14 years but adult-onset is common | | BMI | 21 kg/m² | Lean phenotype; Type 2 typically obese | | Duration | Acute (3 weeks) | Rapid progression typical of Type 1 autoimmune destruction | | Presentation | DKA with ketonuria | Hallmark of Type 1; indicates absolute insulin deficiency | | C-peptide | 0.3 ng/mL (low) | Indicates severe beta-cell dysfunction; <0.8 suggests Type 1 | | pH & HCO₃⁻ | 7.28, 16 mEq/L | Metabolic acidosis confirms ketoacidosis | **High-Yield:** C-peptide is the gold standard to distinguish Type 1 from Type 2 at presentation: - **Type 1:** C-peptide <0.3 ng/mL (absolute deficiency) - **Type 2:** C-peptide >1.0 ng/mL (preserved or elevated) ### Why Type 1 and Not Type 2 with DKA? **Clinical Pearl:** While Type 2 DM can rarely present with DKA (especially in South Asian populations with "ketosis-prone Type 2"), the lean body habitus, acute onset, low C-peptide, and absence of metabolic syndrome features strongly favor Type 1. Type 2 DKA typically occurs in obese/overweight patients with insulin resistance. ### Pathophysiology Type 1 diabetes results from autoimmune destruction of pancreatic beta cells (mediated by T cells and autoantibodies: GAD-65, IA-2, ZnT8). This leads to: 1. Rapid loss of insulin secretion 2. Uncontrolled lipolysis → free fatty acid mobilization 3. Hepatic ketone body production → metabolic acidosis 4. Hyperglycemia with osmotic diuresis **Mnemonic:** **ACID** — Autoimmune destruction, C-peptide low, Insulin-dependent, Diabetic ketoacidosis ## Management Implications This patient requires: - Immediate insulin therapy (basal-bolus or pump) - Fluid resuscitation and electrolyte monitoring for DKA - Screening for other autoimmune conditions (thyroid, celiac, Addison's) - Diabetes education and psychological support [cite:Harrison 21e Ch 417]