Serum Leptin Is Low and Linked to Obesity and Insulin Resistance in Bangladeshi Youth-Onset Type 2 Diabetes Patients: A Cross-Sectional Study

Background Youth-onset type 2 diabetes mellitus (T2DM) is an escalating global public health concern, mostly driven by increasing obesity and insulin resistance. Leptin, a key adipokine regulating appetite, energy balance, and metabolism, has been implicated in the pathogenesis of diabetes. However, its role in youth-onset T2DM remains unclear, with conflicting findings. Objective This study aimed to measure and compare circulating leptin levels between Bangladeshi young individuals with a clinical diagnosis of new-onset T2DM and normal glucose tolerance (NGT), and to investigate the associations of leptin with obesity markers, glycemic parameters, and insulin resistance. Methods This cross-sectional study involved 36 youth (aged 13-30 years) with a clinical diagnosis of new-onset T2DM and 36 age-matched individuals with NGT attending the young diabetes clinic of Bangladesh Medical University (BMU), Bangladesh, during 2017-2018. Anthropometric measurements were recorded, and fasting blood samples were analyzed for glucose, insulin, and leptin levels by glucose-oxidase, chemiluminescent immunoassay, and enzyme-linked immunosorbent assay, respectively. Insulin resistance was assessed by the homeostasis model assessment-insulin resistance (HOMA-IR). Body mass index (BMI) was calculated and both the T2DM and NGT groups were dichotomized to non-obese (including normal weight and underweight; for adults, BMI <23 kg/m², for children <85^th percentile) and obese (including overweight and obesity; for adults, BMI ≥23 kg/m², for children ≥85^th percentile) for subgroup analysis. Results Leptin levels were significantly lower in the T2DM group compared to the NGT group (median (IQR): 1.6 (0.2-6.6) vs. 11.0 (3.5-18.4) ng/mL; p < 0.001). Within subgroups, non-obese individuals with T2DM had lower leptin levels than both non-obese and obese NGT individuals, while obese individuals with T2DM had lower leptin levels than obese NGT individuals. Leptin levels positively correlated with BMI (ρ = 0.45, p < 0.001) and waist circumference (ρ = 0.28, p = 0.019) but negatively with glycemic parameters and HOMA-IR. In multivariate analysis, higher BMI and normoglycemic status were independent predictors of elevated leptin levels. Conclusions Despite a positive correlation with obesity markers, leptin levels were significantly lower in newly diagnosed youth-onset T2DM compared to NGT and had a negative correlation with insulin resistance.