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 occasional nausea and fatigue. On examination, she appears lean (BMI 22 kg/m²) with no acanthosis nigricans. Fasting blood glucose is 280 mg/dL, and urinalysis shows 3+ glycosuria and 2+ ketonuria. C-peptide level is 0.3 ng/mL (normal 0.8–3.1). Anti-GAD and anti-islet cell antibodies are positive. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: Type 1 Diabetes Mellitus ### Key Diagnostic Features **Key Point:** This patient presents with the classic triad of acute-onset Type 1 diabetes: polyuria, polydipsia, and weight loss in a lean young adult. ### Supporting Evidence | Feature | Finding | Significance | |---------|---------|---------------| | **Age & BMI** | 28 years, BMI 22 | Lean phenotype; T1DM typically presents in youth | | **Symptom onset** | 3 weeks (acute) | T1DM onset is rapid; T2DM is insidious | | **Glycosuria & ketonuria** | Both present | Indicates severe hyperglycemia + metabolic derangement | | **C-peptide** | 0.3 ng/mL (low) | Reflects severe β-cell dysfunction; T1DM shows low C-peptide | | **Autoimmune markers** | Anti-GAD, anti-islet cell positive | Pathognomonic for autoimmune T1DM | | **Absence of acanthosis nigricans** | Not present | Argues against insulin resistance (T2DM) | **High-Yield:** Positive anti-GAD and anti-islet cell antibodies are diagnostic for autoimmune Type 1 diabetes. These are present in ~85–90% of T1DM cases at diagnosis. ### Pathophysiology 1. Autoimmune destruction of pancreatic β-cells (mediated by T cells and B cells) 2. Progressive loss of insulin secretion → hyperglycemia 3. Lipolysis and ketogenesis → ketonuria and risk of DKA 4. Low C-peptide reflects minimal endogenous insulin production **Clinical Pearl:** Young, lean patients with acute hyperglycemic symptoms, ketonuria, and positive autoimmune serology should be treated as Type 1 diabetes and started on insulin immediately to prevent diabetic ketoacidosis (DKA). ### Why C-Peptide Matters **Mnemonic: C-peptide = Connecting peptide = Marker of β-cell function** - Cleaved from proinsulin during insulin secretion - Low C-peptide (< 0.5 ng/mL) = severe β-cell loss → T1DM - Normal/high C-peptide = intact β-cell reserve → T2DM or secondary causes [cite:Harrison 21e Ch 417]