Dnyaneshwar Jadhav

Introduction Pre-diabetes is becoming increasingly prevalent in adolescent populations. We recently reported a high prevalence of pre-diabetes among rural adolescent girls from the DERVAN cohort study established in the predominantly undernourished KONKAN region of India. We aimed to investigate the heterogeneity of pre-diabetes by identification of distinct subtypes. Research design and methods Anthropometry (body mass index (BMI) and waist circumference) and body composition (adiposity), as well as glycemic parameters (glucose, insulin, and glycated hemoglobin), were measured at the recruitment stage. Indices for insulin resistance (homeostatic model assessment (HOMA)-IR), β-cell function (HOMA-β), insulin sensitivity (HOMA-S), and compensatory β-cell response for prevailing insulin insensitivity were calculated using the homeostasis model. Pre-diabetes was diagnosed using the American Diabetes Association criteria. Unsupervised K-means clustering and a subgrouping algorithm were applied to characterize pre-diabetes. We used BMI, waist circumference, and adiposity for characterization. Glycemic parameters and HOMA indices were compared between clusters, as well as subgroups. Results Among 1382 girls, 809 (58.5%) were thin and 550 (39.8%) were pre-diabetic. We identified five clusters based on phenotypic characteristics: Cluster 1: young lean (YL), Cluster 2: old lean (OL), Cluster 3: low BMI-high waist, Cluster 4: normal BMI-low waist, and Cluster 5: obese. The cluster frequencies were 145 (26.4%), 131 (23.8%), 146 (26.5%), 74 (13.5%), and 54 (9.8%). Clusters YL and OL had the lowest fasting insulin concentrations, HOMA-IR, and HOMA-β but high HOMA-S and a compensatory β cell response for prevailing insulin insensitivity. Subgroup analysis further revealed a distinct lean pre-diabetic phenotype (n=314) with the lowest BMI (<18.5 kg/m 2 ), no central obesity and adiposity, and the lowest fasting insulin concentration, HOMA-IR, and HOMA-β compared with remaining subgroups. Conclusions We demonstrated the existence of a distinct lean pre-diabetic phenotype in adolescent girls whose characteristics seem to mirror those of adult type 5 diabetes, which has been recently recognized as a distinct entity. This suggests a need for precise strategies for primordial prevention.

Background The prevalence of diabetes continues to rise in India. The increase in diabetes, which has been previously concentrated in urban areas, is now also occurring in rural India, even though the rural population is predominantly non-obese/lean, undernourished, and physically active. Type 2 diabetes and its pathophysiology (hyperinsulinemia and insulin resistance) among the obese, overnourished, and physically inactive urban populations are very well characterized. However, there is a paucity of such characterization among those non-obese/lean and undernourished. We attempted to characterize type 2 diabetes in the rural Konkan region of India using BMI, body composition, and glycemic parameters. Methods This cross-sectional study was conducted among 508 subjects with type 2 diabetes who visited the rural tertiary care center. They underwent anthropometry, body composition, and glycemic (i.e., glucose, HbA 1C , and C-peptide) measurements. Various homeostatic model assessment (HOMA) indices for insulin resistance (HOMA-IR), β-cell function (HOMA-β), and insulin sensitivity (HOMA-S) were calculated. The subjects were classified into six groups, with the classification system created by combining BMI with the parameters of central obesity and adiposity for comparisons of the glycemic measurements and the HOMA indices. Results The median age, the age at diagnosis, and the duration of type 2 diabetes were 59, 51.5, and 5.2 years, respectively. The BMI distribution showed that 6% were underweight, approximately 46% were normal weight, and 48% were overweight. Central obesity and adiposity were observed in 70% and 56%, respectively. Of those subjects with normal weight, 52% had central obesity, while 29% had excess adipose tissue. The lean group was characterized by a low BMI (mean, 16.7 kg/m 2 ), the absence of central obesity and adiposity, and the lowest C-peptide (median, 463.5 pmol/L) and the lowest insulin resistance. The glycemic characteristics of the overweight, centrally obese, and adipose subjects were similar to those observed in classical type 2 diabetes. Conclusion The use of BMI and simple body composition measures led to the identification of a distinct lean phenotype that is characterized by a low BMI, poor insulin secretion, and the absence of central obesity and adiposity. Further research is warranted to understand the pathophysiology and to develop a personalized therapeutic approach for lean subjects with type 2 diabetes. It is time to reconsider the glucocentric, one-size-fits-all approach for type 2 diabetes treatment.