Subtypes of pre-diabetes in rural adolescent girls from India (DERVAN-11)

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.

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.

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/m²), no central obesity and adiposity, and the lowest fasting insulin concentration, HOMA-IR, and HOMA-β compared with remaining subgroups.

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.