Young-Onset Diabetes Tied to Beta Cell Deficiency, Not Obesity: PHENOEINDY-2 Study

The study involved 240 GADA-negative young adults (diagnosed with type 2 diabetes before the age of 40) and 252 non-diabetic individuals from similar socio-economic backgrounds as controls. Notably, both groups shared a median BMI of 23 kg/m². Many participants came from economically disadvantaged tea garden communities, a setting that offered critical insights into the interplay between poverty, malnutrition, and metabolic disorders.

The key findings of the study were as follows:

• 53% of young diabetic patients and 61% of control participants exhibited elevated body fat levels despite having a normal BMI, indicating a prevalent "thin–fat" phenotype.
• The "thin–fat" body composition was characterized by relatively high abdominal fat despite a lean outward appearance.
• Over two-thirds of the diabetic patients had a BMI below 25 kg/m², and 14% were underweight (BMI <18.5 kg/m²).
• Stunted growth was observed in 28% of the diabetic individuals.
• 27% of the diabetic participants were anaemic, pointing toward chronic undernutrition.
• Compared to non-Hispanic white Americans in the NHANES study, both Assamese diabetic and non-diabetic participants showed higher waist-to-hip ratios, body roundness indices, and truncal fat content, reinforcing the presence of the "thin–fat" phenotype.
• The metabolic profile of these patients differed from the typical Western pattern of obesity-driven diabetes.
• Patients showed marked beta-cell dysfunction with a median HOMA-B score of 25.7.
• Insulin resistance was only mild among the patients, with a median HOMA-S score of 103.
• Underweight individuals had the most severe hyperglycemia, significant beta-cell deficiency but remained insulin-sensitive.

Further classification revealed that around two-thirds of the participants with diabetes belonged to the "severely insulin-deficient diabetes" (SIDD) subgroup based on the Swedish classification system. These findings point toward beta cell deficiency, rather than insulin resistance, as the primary abnormality in this population.

The authors suggest that multigenerational undernutrition may play a crucial role in the development of diabetes in this setting. The study underscores the need to broaden the understanding of diabetes phenotypes in low- and middle-income countries and tailor interventions accordingly.

"The PHENOEINDY-2 study calls attention to the heterogeneity of young-onset type 2 diabetes in India. In regions like Assam, where undernutrition remains a persistent issue, the conventional obesity-linked model of diabetes may not apply. Instead, chronic nutritional deprivation and associated beta-cell impairment appear to be at the heart of the disease's development," the authors concluded.

Reference:

Dutta, A., Dutta, P.K., Baruah, S.M. et al. Non-autoimmune diabetes in young people from Assam, India: the PHENOEINDY-2 study. Diabetologia (2025). https://doi.org/10.1007/s00125-025-06500-9