Abstract
Insulin resistance and insufficient insulin secretion lead to type 2 diabetes. A role of reduced insulin clearance has been suggested, but few studies have investigated the contribution of insulin clearance while simultaneously examining insulin sensitivity and secretion. The goal of this study was to conduct such an investigation in 224 non-Hispanic White and 129 African Americans individuals from MILES (mean age 59, 62% female). Participants underwent oral glucose tolerance tests from which insulin sensitivity, insulin secretion, insulin clearance, and disposition index were calculated. Logistic regression models (controlling for age, sex, race, and BMI) examined the individual contributions of these traits separately, as well as the joint contribution of insulin sensitivity, clearance, and secretion, to early dysglycemia (prediabetes plus newly diagnosed diabetes; 46% of cohort). Models used standardized predictors such that odds ratios (OR) represent the change in odds of dysglycemia per standard deviation change. Model performance was assessed via Akaike’s Information Criterion (AIC) and area under the receiver operator characteristic curves (AUROC). In separate models, dysglycemia was associated with insulin sensitivity (OR 0.2; 0.14-0.30; P<.001), disposition index (OR 0.13; 0.08-0.20; P<.001) and insulin clearance (OR 0.66; 0.51-0.87; P<.001). In a joint model, only reduced insulin sensitivity (OR 0.04; 0.02-0.08; P<.001) and secretion (OR 0.15; 0.08-0.27; P<.001) were associated with dysglycemia. Models with insulin sensitivity (AIC=376.7; AUROC=0.82), disposition index (AIC=324.8; AUROC=0.87), or three insulin traits (AIC=303.4; AUROC=0.89) had the highest discriminative value. These results suggest that in the race groups studied, insulin resistance and compromised insulin secretion are the main independent defects leading to dysglycemia, while reduced insulin clearance may have a minor contributory role. Disclosure A. Wood: None. E. T. Jensen: None. G. Ramesh: None. Z. Arzumanyan: None. K. Lam: None. A. Bertoni: None. J. I. Rotter: None. Y. Chen: None. M. O. Goodarzi: None. Funding National Institutes of Health (R01DK109588)
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