1085-P: Defining the Role of Insulin Clearance in Dysglycemia: The Microbiome and Insulin Longitudinal Evaluation Study (MILES)

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 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)