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. 2025 Oct;68(10):2179-2193.
doi: 10.1007/s00125-025-06500-9. Epub 2025 Aug 1.

Non-autoimmune diabetes in young people from Assam, India: the PHENOEINDY-2 study

Anupam Dutta  1 , Pranjal K Dutta  1 , Sreemanta M Baruah  1 , Prasanta Dihingia  1 , Arpita Ray  1 , Dattatrey S Bhat  2 , Sonali W Patki  2 , Pradeep Tiwari  3 , Madhura Deshmukh  4 , Rucha Wagh  2   5 , Rubina Mulchandani  6 , Tanica Lyngdoh  7   8 , Sanjeeb Kakati  9 , Chittaranjan S Yajnik  10
Affiliations

Non-autoimmune diabetes in young people from Assam, India: the PHENOEINDY-2 study

Anupam Dutta et al. Diabetologia. 2025 Oct.

Abstract

Aims/hypothesis: In the Western world, non-autoimmune diabetes in the young is believed to be driven by overweight/obesity and insulin resistance. However, it is increasingly being reported in undernourished people in low- and middle-income countries, including India. We hypothesised that these patients would show markers of chronic undernutrition and a 'thin-fat' phenotype and be predominantly beta cell-deficient.

Methods: We studied young patients (clinically diagnosed with type 2 diabetes at <40 years) who attended the outpatient department of Assam Medical College and Hospital, Dibrugarh (in North-East India). We measured weight, height, waist and hip circumference, haemoglobin, fasting glucose, HbA1c, lipid, GADA and C-peptide levels, and body fat percentage (adiposity, assessed using dual-energy x-ray absorptiometry), and calculated BMI (kg/m2), body roundness index and HOMA indices. Volunteers from similar socioeconomic background with normal glucose tolerance (measured by 75 g OGTT) were assessed as control participants. We also compared the anthropometric characteristics and body composition of our participants with those of non-Hispanic white Americans from the NHANES study.

Results: The study included 252 control participants (136 male participants, median age 30 years, BMI 23.0 kg/m2) and 240 GADA-negative young patients with diabetes (155 male participants, age 36 years, BMI 23.0 kg/m2). The majority of study participants came from a relatively impoverished population of tea garden workers ('tribal' workers). Of the patients with diabetes, 28% had stunted growth (male <161.2 cm, female <149.8 cm), 27% were anaemic, 68% were lean (BMI <25 kg/m2, including 14% who were underweight [BMI <18.5 kg/m2]) and 32% were overweight/obese (BMI ≥25 kg/m2). When assessed using dual-energy x-ray absorptiometry, 61% of control participants and 53% of patients had adiposity (body fat percentage >25% in male participants or >35% in female participants). Compared with a contemporary non-Hispanic white American population, Assamese control participants and diabetic patients had higher WHR, body roundness index, and total and truncal adiposity (assessed using dual-energy x-ray absorptiometry) across the range of BMI, thus conforming to the description of the 'thin-fat' phenotype. The diabetic patients were severely beta cell-deficient (median HOMA-B 25.7) and only moderately insulin-resistant (median HOMA-S 103) with higher triacylglycerol and lower HDL-cholesterol concentrations than control participants. Underweight patients (<18.5 kg/m2) were the most hyperglycaemic (based on fasting plasma glucose and HbA1c), and were severely beta cell-deficient but insulin-sensitive. As previously reported, two-thirds of these patients belonged to the severely insulin-deficient diabetes (SIDD) cluster according to the Swedish diabetes subgroup classification.

Conclusions/interpretation: Diabetes in the young people of this impoverished population is heterogeneous, but the majority of patients are not overweight/obese or insulin-resistant. Overall, these participants conform to the thin-fat phenotype, and their diabetes is predominantly driven by beta cell deficiency. The sociodemographic history and physical characteristics of this population suggest a role for multigenerational undernutrition in the aetiology of non-autoimmune diabetes in these young patients from Assam.

Keywords: Adiposity; Assam; Beta cell deficiency; Body roundness index; India; Lean; Truncal adiposity; Young-onset diabetes.

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Conflict of interest statement

Acknowledgements: We thank all patients and control participants for their support and willingness to participate. We thank H. Kashyap, H. Kaur, A. Gogoi, A. Boruah, D. Boruah, S. Sonowal, P. Boruah, R. Nath, I. Gogoi, P. Gogoi, D. Ahmed (Assam Medical College and Hospital), P. Yajnik and R. Ladkat (Diabetes Unit, Kamalnayan Bajaj Diabetology Research Centre, King Edward Memorial Hospital and Research Centre, Pune, India) and L. Saikia and R. Nath (Multidisciplinary Research Unit, Assam Medical College and Hospital) for their invaluable contributions to this study. We profusely thank M. Thakur, Ministry of Tribal Affairs, Government of India, for providing the socioeconomic background document. We thank N. Gupte, Johns Hopkins India Private Limited, Pune, India, for advice on statistical analysis and Prof E. Gale for useful comments. The graphical abstract was drawn by A. Dutta, based on a concept by C. S. Yajnik. Data availability: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request, subject to necessary administrative permission. Funding: This study was funded by the Indian Council of Medical Research (ICMR study number 55/3/1/Brain Storming Session/Diab./2017-NCD-II, 29 March 2017). The funding agency played no role in the writing of the manuscript. RW is supported by a senior research fellowship from the Council of Scientific and Industrial Research, India. Authors’ relationships and activities: The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: AD, CSY and SK contributed to the conception of the work. AD, PKD, PD, SMB and AR contributed to data collection. DSB, SWP, MD, RM, TL, PT and RW contributed to the data analysis. CSY, AD, RM, TL and RW drafted the article. All authors contributed to the interpretation of data and critical revision of the article. All authors gave final approval of the version to be published. AD, CSY and SK are the guarantors of this work, and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

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