Association between targeted inflammatory proteomics and insulin sensitivity as well as beta-cell function in subjects with normal glucose tolerance.

Obese individuals even with normal glucose tolerance (NGT) are at higher risk for developing type 2 diabetes (T2D), and obesity is associated with inflammation. However, mechanisms linking inflammation to beta-cell function and insulin sensitivity in NGT individuals are not fully understood. We aimed to investigate the relationships between inflammation-related proteins (IRPs) and insulin dynamics in NGT subjects. The explorations were conducted using data from 1109 non-diabetes subjects aged 40-44 with normal or excess body weight and 21 Chinese NGT subjects aged 22-32 with accurate metabolic assessment. IRPs were detected with Olink technology. Insulin sensitivity and beta-cell function were evaluated with hyperinsulinemic-euglycemic clamp and hyperglycemic clamp. Eight associators were identified with obesity in NGT subjects, among which MCP-3, IL-6, TWEAK, HGF, and CST5 also showed associations in non-diabetes people. Four IRPs were linked to insulin sensitivity, with IL-24 being a novel finding. Seven IRPs were related to beta-cell function, including novel associators CD244, CD40, and IL-15RA. Moreover, most IRPs were interconnected, with IL-6 as the hub. In conclusion, insulin sensitivity and beta-cell function are related to IRPs involved in chemotaxis, activation of immune cells, and cell proliferation, which might provide valuable information for the understanding of the mechanisms associated with T2D pathogenesis.