Non-autoimmune, lean diabetes in young people from Assam, India highlights the role of undernutrition in its aetiology – PHEnotypingNOrthEastINDianYoung type 2 diabetes (PHENOEINDY-2)
Authors: Dutta Anupam , Dutta Pranjal Kumar , Baruah Sreemanta Madhab , Dihingia Prasanta , Ray Arpita , Bhat Dattatrey S , Patki Sonali Wagle , Tiwari Pradeep , Deshmukh Madhura , Wagh Rucha , Mulchandani Rubina , Lyngdoh Tanica , Kakati Sanjeeb , Yajnik Chittaranjan S 
Published: February 2024

ABSTRACTAims/hypothesisNon-autoimmune diabetes in the young is believed to be driven by overweight-obesity and insulin resistance. However, it’s increasingly reported in undernourished people in the LMICs, including India. We hypothesized a role for undernutrition in the aetiology of non-autoimmune diabetes in impoverished young patients attending the Assam Medical College Hospital (AMCH), Dibrugarh (North-East India) for treatment.MethodsWe measured socioeconomic status (SES), height and body mass index (BMI, kg/m2), waist and hip circumference, DXA body fat percent (adiposity), GAD antibodies, C-peptide and HOMA indices of β-cell function and insulin sensitivity in young patients (<40 years) with a presumptive diagnosis of T2D. Socio-economically matched volunteers with normal glucose tolerance (NGT, 75 gm OGTT) provided control data.ResultsWe studied 252 NGT controls (136 males, mean age 30 years, mean BMI 23.0 kg/m2) and 240 GAD-negative cases with diabetes (155 males, 36 years, 23.5 kg/m2). The majority of cases came from a relatively impoverished population of tribal people and tea garden employees. Twenty-eight percent of patients were stunted (male <161.2 cm m, female <149.8 cm), 14% were underweight (BMI <18.5 kg/m2) and 32% were overweight-obese (BMI >30 kg/m2). Height and BMI were positively associated with socio-economic status. On DXA, 61% of controls and 53% of cases were adipose (male >25%, female >35% body fat percent), conforming to the thin-fat Indian phenotype. Controls were relatively β-cell deficient (median HOMA-β 68.3) and insulin sensitive (HOMA-S 182.0) while cases were severely β-cell deficient (HOMA-β 25.7) and only moderately insulin resistant (HOMA-S 103). Cases with diabetes showed higher triglyceride and lower HDL-cholesterol concentrations. Thinner cases (lower BMI) were more hyperglycemic (FPG, HbA1c), insulin sensitive but B-cell deficient. As previously reported, two-thirds of these patients belonged to the severely insulin-deficient diabetes (SIDD) cluster of the Swedish diabetes subgroup classification.Conclusions/interpretationDiabetes in the young in this impoverished population is heterogeneous but the majority of patients are not overweight-obese nor insulin-resistant. Diabetes is predominantly driven by β-cell deficiency. Our findings suggest a strong role for life-course undernutrition in the aetiology of non-autoimmune diabetes in this population.Research in contextWhat is already knownNon-autoimmune diabetes in young adult westerners is usually linked to obesity and insulin resistance, associated with ample lifelong nutrition.In poorer parts of the world, young adult diabetes often occurs in lean individuals with evidence of past undernutrition.There is sparse information on this conditionWhat is the key question?Young adult, non-autoimmune diabetes is prevalent in growth-stunted people from a historically impoverished population from Assam, India. Can a detailed study of these patients improve our understanding of this disorder?New FindingsYoung lean adults had ‘type 2’ diabetes in association with evidence of stunted growth and the ‘thin-fat’, centrally obese phenotype, known to be linked with early life undernutrition.Two-thirds belonged to the severely insulin-deficient diabetes (SIDD) subgroup of the Swedish classification, twice as common as in young patients with diabetes from Sweden.Impact on clinical practicePoverty and early-life undernutrition could play an important role in the aetiology of diabetes in many parts of the world.