Cutaneous signs of insulin resistance with central obesity: insights into adipocentric metabolic dysfunction in South Asians

Aim and objectives To investigate the C utaneous S igns of I nsulin R esistance, namely acanthosis nigricans (AN) and acrochordon (AC), in individuals with C entral O besity (CO-CSIR) as physical predictors of metabolic syndrome (MetS), underlying adipose tissue pathology, and consequent pathophysiological traits in South Asians. Methods In this study, 371 participants were recruited in a tertiary care facility and grouped based on the presence of cutaneous signs (AC and/or AN) and central obesity. Each participant was assessed for MetS, T2D, as well as other demographic, biochemical, and radiological parameters. Additionally, we conducted transcriptome profiling in adipose depots for selected individuals to investigate whether there are modules of co-expressed genes that show a correlation with cutaneous sign(s) and MetS/T2D, in order to decipher the link between these signs and metabolic derangement. Results ANOVA analyses revealed significant differences among groups with varying cutaneous signs and W:H ratios, particularly highlighting the combined predictive capability of these markers. Post hoc tests further confirmed these findings, showing substantial differences in MetS, T2D, and HOMA-IR between these groups. Sensitivity-specificity analyses demonstrated that CO-CSIR provides a more balanced and accurate prediction of MetS status compared to either CO or CSIR alone. Furthermore, in predicting MetS status based on the number of MetS components (from 5 to ≥1), it also performed well. WGCNA analysis in visceral fat revealed modules of co-expressed genes significantly correlated with AC and MetS, indicating a link between the adipose tissue molecular pathology and the cutaneous signs. Conclusion CO-CSIR is a promising physical sign for predicting MetS and the underlying adipose tissue-driven dysmetabolism in South Asians.