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: WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); JENSEN, ELIZABETH - Wake Forest School Of Medicine; BERTONI, ALAIN - Wake Forest School Of Medicine; RAMESH, GAUTAM - University Of California; RICH, STEPHEN - University Of Virginia; ROTTER, JEROME - Harbor-Ucla Medical Center; CHEN, YII - Harbor-Ucla Medical Center; GOODZARI, MARK - Cedars-Sinai Medical Center

Submitted to: Metabolites
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/16/2021
Publication Date: 6/26/2021
Citation: Wood, A.C., Jensen, E.T., Bertoni, A.G., Ramesh, G., Rich, S.S., Rotter, J.I., Chen, Y.D., Goodzari, M.O. 2021. 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). Metabolites. 11(7):420. https://doi.org/10.3390/metabo11070420.
DOI: https://doi.org/10.3390/metabo11070420

Interpretive Summary: Insulin resistance and insufficient insulin secretion are well-recognized contributors to type 2 diabetes. It has been suggested that an additional problem underlying type 2 diabetes may also be reduced insulin clearance, but few studies have investigated this. Using data from a 353 multi-ethnic adults, we found that in addition to increased insulin resistance and reduced insulin sensitivity, insulin clearance was reduced in adults with poor glucose control (a risk factor for type 2 diabetes). However, when all the traits were considered together, only insulin resistance and reduced insulin secretion were associated with poor glucose control. These results suggest that insulin resistance and compromised insulin secretion are the main defects leading to early difficulties with glucose control and so the factors clinicians should consider measuring and treating, in order to reduce type 2 diabetes risk.

Technical 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.