Assessment of Circulating Insulin Using Mass Spectrometry During Insulin Glargine Treatment in Type 2 Diabetes: Implications for Estimating Insulin Sensitivity and β-cell Function

Authors

Jesse C. Seegmiller, Department of Laboratory Medicine, Advanced Research and Diagnostic Laboratory, University of Minnesota, Minneapolis, MN, USA.
David J. Schmit, Department of Laboratory Medicine, Advanced Research and Diagnostic Laboratory, University of Minnesota, Minneapolis, MN, USA.
Valerie L. Arends, Department of Laboratory Medicine, Advanced Research and Diagnostic Laboratory, University of Minnesota, Minneapolis, MN, USA.
Michael W. Steffes, Department of Laboratory Medicine, Advanced Research and Diagnostic Laboratory, University of Minnesota, Minneapolis, MN, USA.
Steven E. Kahn, Division of Metabolism, Endocrinology and Nutrition, VA Puget Sound Health Care System and University of Washington, Seattle, WA, USA.
Naji Younes, The Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD, USA.

Document Type

Journal Article

Publication Date

3-30-2023

Journal

Diabetes, obesity & metabolism

DOI

10.1111/dom.15072

Keywords

HOMA; immunoassay; insulin analogs; insulin sensitivity; oral glucose tolerance test; type 2 diabetes; β-cell function

Abstract

AIMS: Given the potential effect of cross-reactivity of insulin glargine U-100 and its metabolites in the insulin immunoassay, we determined the impact on insulin sensitivity and β-cell measures in GRADE participants with type 2 diabetes receiving the analog. MATERIALS AND METHODS: Using liquid chromatography mass spectrometry (LC-MS), we measured concentrations of endogenous insulin, glargine, and its two metabolites (M1 and M2) in fasting and OGTT-stimulated plasma from 19 participants and fasting specimens from another 97 participants 12 months after randomization to receive the insulin glargine. The last dose of glargine was administered before 10:00 pm the night before. Insulin was also measured on these specimens using an immunoassay. We used fasting specimens to calculate insulin sensitivity (HOMA2-S%; QUIKI index, PREDIM index) and β-cell function (HOMA2-B%). Using specimens following glucose ingestion, we calculated insulin sensitivity (Matsuda ISI[comp] index) and β-cell response (insulinogenic index [IGI], and total incremental insulin response [iAUC] / iAUC glucose). RESULTS: In plasma, glargine was metabolized to form the M1 and M2 metabolites that were quantifiable by LC-MS; however, the analog and its metabolites cross-reacted <100% in the insulin immunoassay. This incomplete cross-reactivity resulted in a systematic bias of fasting based measures. In contrast, as M1 and M2 did not change following glucose ingestion, a bias was not observed for IGI and iAUC insulin. CONCLUSIONS: Despite glargine metabolites being detected in the insulin immunoassay, dynamic insulin responses can be used to assess β-cell responsiveness. However, given the cross-reactivity of the glargine metabolites in the insulin immunoassay, fasting-based measures of insulin sensitivity and β-cell function are biased. This article is protected by copyright. All rights reserved.

APA Citation

Seegmiller, Jesse C.; Schmit, David J.; Arends, Valerie L.; Steffes, Michael W.; Kahn, Steven E.; and Younes, Naji, "Assessment of Circulating Insulin Using Mass Spectrometry During Insulin Glargine Treatment in Type 2 Diabetes: Implications for Estimating Insulin Sensitivity and β-cell Function" (2023). GW Authored Works. Paper 2522.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2522

Department

Biostatistics and Bioinformatics