Non-autoimmune, lean diabetes in young people from Assam, India highlights the role of undernutrition in its aetiology – PHEnotypingNOrthEastINDianYoung type 2 diabetes (PHENOEINDY-2)

• DOI: 10.1101/2024.02.02.24302249
• Publication Date: 2024-02-04T17:15:13Z
• Authors: Anupam Dutta; Pranjal Kumar Dutta; Sreemanta Madhab ...; Prasanta Dihingia; Arpita Ray; Dattatrey S Bhat; Sonali Wagle Patki; Pradeep Tiwari; Madhura Deshmukh; Rucha Wagh; Rubina Mulchandani; Tanica Lyngdoh; Sanjeeb Kakati; Chittaranjan S Ya...
• Keywords: Underweight; Etiology

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