Defining the Relative Role of Insulin Clearance in Early Dysglycemia in Relation to Insulin Sensitivity and Insulin Secretion: The Microbiome and Insulin Longitudinal Evaluation Study (MILES)

Authors

Alexis C Wood
Elizabeth T Jensen
Alain G Bertoni
Gautam Ramesh
Stephen S Rich
Jerome I Rotter
Yii-Der I Chen
Mark O Goodarzi

Publication Date

6-26-2021

Journal

Metabolites

DOI

10.3390/metabo11070420

PMID

34206745

PMCID

PMC8304591

PubMedCentral® Posted Date

6-26-2021

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

insulin sensitivity, insulin secretion, insulin clearance, disposition index, prediabetes, diabetes

Abstract

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.