Insulin resistance and insufficient insulin secretion are well-recognized contributors to
type 2 diabetes. A potential role of reduced
insulin clearance has been suggested, but few studies have investigated the contribution of
insulin clearance while simultaneously examining decreased
insulin sensitivity and secretion. The goal of this study was to conduct such an investigation in a cohort of 353 non-Hispanic White and African American individuals recruited in the Microbiome and
Insulin Longitudinal Evaluation Study (MILES). Participants underwent oral
glucose tolerance tests from which
insulin sensitivity, insulin secretion,
insulin clearance, and disposition index were calculated. Regression models examined the individual and joint contributions of these traits to early dysglycemia (
prediabetes or newly diagnosed diabetes). In separate models, reduced
insulin sensitivity, reduced disposition index, and reduced
insulin clearance were associated with dysglycemia. In a joint model, only
insulin resistance and reduced insulin secretion were associated with dysglycemia. Models with
insulin sensitivity, disposition index, or three
insulin traits had the highest discriminative value for dysglycemia (area under the receiver operating characteristics curve of 0.82 to 0.89). These results suggest that in the race groups studied,
insulin resistance and compromised insulin secretion are the main independent underlying defects leading to early dysglycemia.