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24-08-2023 | Prediabetes | Article

Deteriorating beta cell function is the dominant determinant of progression from normal glucose tolerance to prediabetes/diabetes in young women following pregnancy

Authors: Ravi Retnakaran, Chang Ye, Caroline K. Kramer, Anthony J. Hanley, Philip W. Connelly, Mathew Sermer, Bernard Zinman

Published in: Diabetologia | Issue 11/2023

Abstract

Aims/hypothesis

Excess adiposity, insulin resistance and beta cell dysfunction each contribute to the development of prediabetes (impaired glucose tolerance and/or impaired fasting glucose)/diabetes but their comparative impact in relation to one another remains uncertain. We thus ranked their contributions to incident dysglycaemia over the first 5 years postpartum in women reflecting the full spectrum of gestational glucose tolerance (spanning normoglycaemia to gestational diabetes) and hence a range of future diabetic risk.

Methods

In this study, 302 women with normal glucose tolerance (NGT) on OGTT at 3 months postpartum underwent repeat OGTT at 1 year, 3 years and 5 years, enabling serial assessment of glucose tolerance, insulin sensitivity/resistance (Matsuda index, HOMA-IR) and beta cell function (insulin secretion-sensitivity index-2 [ISSI-2], insulinogenic index [IGI]/HOMA-IR). Determinants of prediabetes/diabetes were ranked by change in concordance index (CCI) of Cox proportional hazard regression models.

Results

Over 5 years of follow-up, 89 women progressed from NGT to prediabetes/diabetes (progressors). At 3 months postpartum, though all women were normoglycaemic, future progressors had higher fasting glucose (p=0.03) and 2 h glucose (p<0.0001) than non-progressors, coupled with higher BMI (p=0.001), greater insulin resistance (both Matsuda index and HOMA-IR, p≤0.02) and poorer beta cell function (both ISSI-2 and IGI/HOMA-IR, p≤0.006). Unlike their peers, progressors exhibited deteriorating beta cell function from 1 year to 5 years (both p<0.0001). On regression analyses, the dominant determinants of progression to prediabetes/diabetes were time-varying ISSI-2 (change in CCI 25.2%) and IGI/HOMA-IR (13.0%), in contrast to time-varying Matsuda index (2.9%) and HOMA-IR (0.5%). Neither time-varying BMI nor waist were significant predictors after adjustment for beta cell function and insulin sensitivity/resistance.

Conclusion/interpretation

Declining beta cell function is the dominant determinant of incident prediabetes/diabetes in young women following pregnancy.

Graphical Abstract

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Title: Deteriorating beta cell function is the dominant determinant of progression from normal glucose tolerance to prediabetes/diabetes in young women following pregnancy
Authors: Ravi Retnakaran
Chang Ye
Caroline K. Kramer
Anthony J. Hanley
Philip W. Connelly
Mathew Sermer
Bernard Zinman
Publication date: 24-08-2023
Publisher: Springer Berlin Heidelberg
Keywords: Prediabetes
Insulins
Insulins
Published in: Diabetologia / Issue 11/2023
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-023-05994-5

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