Young-Onset Lean Diabetes in Asian Indians — Lower Measured AND Genetically Determined Beta-Cell Function

Key finding

Lean young-onset diabetes prevalence was **24–39% in Asian Indians** versus **9.3% in white Europeans** — a 2–4x excess that cannot be attributed to lifestyle or BMI. Two independent lines of evidence explain this gap: 1. **Biochemical**: Stimulated C-peptide was 492 pmol/mL lower in lean versus obese Indians with young-onset diabetes (p<0.0001), confirming that lean SA diabetics have markedly reduced beta-cell secretory capacity even relative to obese SA peers. 2. **Genetic**: Asian Indians carry significantly more beta-cell function risk alleles than white Europeans (p<0.0001). The partitioned polygenic score (pPS) for beta-cell dysfunction was higher in SA and was associated with earlier age of diabetes onset — a relationship that was completely absent in white Europeans. The genetic architecture of beta-cell risk is fundamentally different between the two populations. Together, these

Framework connections: The Fragile Engine

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