Unlike in Western countries, diagnosis of MODY has been limited in the South Asian region. It is uncertain if this reflects a genuine low prevalence of diagnostic limitations. This study aims to determine the prevalence, clinical characteristics, and genetic profile of individuals with young-onset diabetes in a resource-poor setup.
This cross-sectional study was conducted by recruiting patients with young-onset diabetes with a family history and clinical suspicions of MODY. A targeted next-generation sequencing-based diagnostic test for MODY, including a selected set of syndromic diabetes-associated genes, was designed.
Among 51 patients recruited, 29 (56.9%) were females. These non-obese patients (mean BMI 21.2 ± 4.06 kg/m²) were diagnosed young (mean age 17 ± 5.49 years) with hyperglycemia (mean HbA1C 9.7% ± 3.28). Aligning with diagnostic criteria, the majority of the participants had detectable C-peptide levels (median: 1.97 ng/mL), indicating preserved insulin production. Most had a strong family history, no history of diabetic ketoacidosis, and absent pancreatic autoantibodies. Currently, participants are predominantly on oral medication or a combination of insulin and oral medication, with some achieving glycemic control without any medication. Mutations were detected in 51% (n=26), with the most common being HNF1A, associated with MODY 3 (15.7%), followed by KLF11 (5.9%). GCK, NEUROD1, and PAX4 were detected in 3.4% each. 2 patients had mutations identified as WFS1 (c.1967G>A). 11 patients with an Exeter probability score below 20% had a genetic change associated with MODY, suggesting the tool may have limited predictive value in South Asians.
High incidence of variant detection, including variants of uncertain significance, emphasizes the importance of identification and characterization of genetic heterogeneity in improving treatment outcome and quality of life. Larger population-based studies are warranted to understand the MODY burden in Sri Lanka and the South Asian region.