E.J. den Brok1*, P. Brokkelkamp2*, K. Wouters1, C. Dingena1, C. van der Kallen1, M. van Greevenbroek1, S.E. Siegelaar2*, B.E. de Galan1*
1CARIM Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands 2Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
lisa.denbrok@maastrichtuniversity.nl
Background: During menopausal transition, declining oestrogen may lead to metabolic changes that affect glycaemic control. We investigated whether menopausal status and its change over time are associated with glycaemic control independent of glucose tolerance status.
Methods: We used cross-sectional and longitudinal data from The Maastricht Study, a population-based cohort including participants with normal glucose metabolism, prediabetes or type 2 diabetes. At baseline, women were classified as pre- or postmenopausal. For the longitudinal analysis (median follow-up 9 years), women were classified as remaining premenopausal or postmenopausal, or transitioning from premenopausal to postmenopausal. Men served as a reference group. Multivariable linear regression and linear mixed models, with estimated marginal means used for interpretation.
Results: In the cross-sectional analysis, 4477 women (1029 pre- and 2479 post-menopausal women) and 4541 men were included. Postmenopausal women had higher HbA1c than premenopausal women (44.5mmol/mol [95%CI:43.7–45.2] vs. 43.4mmol/mol [95%CI:42.4–44.3], p=0.018), whereas HbA1c in men (44.7mmol/mol [95%CI:44.0–45.5]) was higher than in premenopausal women (p=0.0015) but similar to that in postmenopausal women (p=0.35). A total of 1147 women and 1177 men were included in the longitudinal analysis. Among 243 women transitioning from pre- to postmenopausal status, HbA1c increased from 43.7mmol/mol (95%CI:42.4–45.0) to 46.1mmol/mol (95%CI:44.8-47.3) at follow-up (p<0.0001). In contrast, among 904 women remaining post-menopausal, HbA1c showed a small, non-significant increase from 44.9mmol/mol (95%CI:43.8–46.0) to 45.4mmol/mol (95%CI:44.3–46.5) (p=0.37). Among men, HbA1c increased from 44.7mmol/mol (95%CI:43.6–45.4) to 45.7mmol/mol (95%CI:44.6–46.7) at follow-up (p<0.001). The increase in HbA1c over time was significantly greater in women undergoing menopausal transition compared to postmenopausal women (1.84±0.44mmol/mol, p<0.001) and men (1.36±0.43mmol/mol, p=0.002), independent of age and glucose tolerance status.
Conclusion: Menopausal transition is associated with worsening of glycaemic control over time compared with both postmenopausal women and men, suggesting this period represents a critical window for metabolic deterioration beyond normal ageing.