Investigating Etiological Heterogeneity in a Bangladeshi Young-Onset Diabetes Cohort Through Clinical, Biochemical, Imaging, and Genetic Profiling

Abstract

Background: In South Asian populations, overlapping clinical features often complicate etiological diagnosis of young-onset diabetes, leading to potential misclassification and suboptimal management.

Objective: To investigate the etiological landscape of hyperglycemia in a Bangladeshi young-onset diabetes cohort through integrated clinical, biochemical, imaging, and genetic profiling.

Methods: This study involved 284 participants (aged 10-34 years) recruited at Bangladesh Medical University (2023-24) through hospital-based and community-based screening. Assessments included fasting C-peptide, islet autoantibodies (GAD65, ZnT8, IA2), and pancreatic imaging. Targeted gene panel sequencing for maturity-onset diabetes of the young (MODY) was performed in cases with suggestive features.

Results: Low C-peptide (<0.6 ng/mL) was identified in 9.5% (n=27) of the cohort. Among them, only 5 were antibody-positive for one or more islet antibodies [Type 1 Diabetes (T1D)], and the rest were antibody-negative (Hybrid/Idiopathic type 1). Among the 90.5% (n=257) with preserved C-peptide, multi-modal screening identified 6.0% (n=17) with positive islet antibody (LADA), 0.7% (n=2) with pancreatic calcification [fibrocalculous pancreatic diabetes (FCPD)], and 3.5% (n=10) with MODY variants. Further BMI-based categorization revealed 4.9% (n=14) with a 'Type 5' phenotype. Type 2 Diabetes (T2D) was the predominant etiology, representing 75.3% (n=214) of the cohort, including obese, overweight, and normal-weight phenotypes.

Conclusion: Young-onset diabetes in Bangladesh is highly heterogeneous, with T2D being the most prevalent form. The identification of different proportions of T1D, LADA, MODY, FCPD, hybrid form, and T5D subgroups demonstrates that the etiology of DM in young people is heterogeneous. Incorporating C-peptide, imaging, and genetic testing is essential to achieve diagnostic precision and optimize therapy.

Bangladesh J Medicine 2026; Vol. 37, No. 2(1) Supplementation: 230.