Lean, Non‐Autoimmune Young‐Onset Diabetes in Bangladesh: A Metabolically Obese Phenotype With Disproportionate Insulin Secretory Defect

BACKGROUND: Young-onset diabetes in South Asians frequently manifests in lean individuals, but the metabolic drivers of this phenotype remain poorlycharacterised. OBJECTIVE: This study aimed to evaluate the clinical, biochemical, and insulin-related indices of lean, non-autoimmune young-onset diabetes mellitus (DM) among Bangladeshi young adults. METHODS: This comparative cross-sectional study (2023-2024) enrolled 373 participants (aged 18-34 years) categorised into four groups based on glycemic status and body mass index (BMI): Lean DM (n = 53), obese DM (n = 125), lean non-DM (n = 78), and obese non-DM (n = 117) from the Young-diabetes Clinic of the Department of Endocrinology, Bangladesh Medical University, Dhaka after excluding those with positive islet autoantibodies, low C-peptide, pancreatic pathology, and monogenic variants. β-cell function (HOMA2-B) and insulin resistance (HOMA2-IR) were quantified using the HOMA2 C-peptide calculator. RESULTS: Lean DM participants were comparable to other groups in age, sex, and family history, though smoking was more prevalent than in lean controls (p < 0.05). Prevalence of central obesity and blood pressure levels of lean DM were similar to those of lean controls, but the lipid profile was comparable to that of obese DM. The median HbA1c was higher in lean DM than in obese DM (11.6% vs. 8.5%; p < 0.001), while their median HOMA2-B was the lowest across all other groups (p < 0.01). The HOMA2 - IR in lean DM was lower than in obese DM but significantly higher than in lean controls and mirrored the resistance seen in the obese non-DM group (p < 0.001). CONCLUSION: Lean young-onset diabetes in Bangladesh appears to be a phenotype of disproportionate insulin secretory defect with only modest insulin resistance and metabolic dysfunction. These features highlight the need for targeted screening and individualised management.