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Ethnic differences in the association between age at natural menopause and risk of type 2 diabetes mellitus among postmenopausal women: a pooled analysis of individual data from 13 cohort studies

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posted on 2023-09-22, 19:30 authored by Hsin-Fang Chung, Annette J Dobson, Kunihiko Hayashi, Rebecca Hardy, Diana Kuh, Debra J. Anderson, Yvonne T van der Schouw, Darren C Greenwood, Janet E. Cade, Panayotes Demakakos, Eric J. Brunner, Sophie V. Eastwood, Sven Sandin, Elisabete Weiderpass, Gita D. Mishra

Objective: To investigate associations between age at natural menopause, particularly premature ovarian insufficiency (POI; natural menopause before 40 years), and incident type 2 diabetes (T2DM) and identify any variations by ethnicity.

Research design and methods: We pooled individual-level data of 338,059 women from 13 cohort studies without T2DM before menopause, with six ethnic groups: White (n=177,674), Chinese (n=146,008), Japanese (n=9,061), South/Southeast Asian (n=2,228), Black (n=1,838), and Mixed/Other (n=1,250). Hazard ratios (HRs) of T2DM associated with age at menopause were estimated in the overall sample and by ethnicity, with study as a random effect. For each ethnic group, we further stratified the association by birth year, education level, and BMI.

Results: Over nine years of follow-up, 20,064 (5.9%) women developed T2DM. Overall, POI (vs menopause at 50-51 years) was associated with an increased risk of T2DM (HR:1.31, 1.20-1.44), while there was an interaction between age at menopause and ethnicity (p<0.0001). T2DM risk associated with POI was higher in White (HR:1.53, 1.36-1.73), Japanese (HR:4.04, 1.97-8.27), and Chinese women born ≥1950 (HR:2.79, 2.11-3.70); while less precise, the risk estimates were consistent in South/Southeast Asian (HR:1.46, 0.89-2.40), Black (HR:1.72, 0.95-3.12), and Mixed/Other (HR:2.16, 0.83-5.57) women. A similar pattern, but smaller increased risk of T2DM was associated with early menopause overall (HR:1.16, 1.10-1.23) and for White, Japanese, and Chinese women born ≥1950.

Conclusions: POI and early menopause are risk factors for T2DM in postmenopausal women, with considerable variation across ethnic groups, and may need to be considered in risk assessments of T2DM among women.

Funding

The InterLACE Consortium is funded by the Australian National Health and Medical Research Council project grant (APP1027196) and Centres of Research Excellence (APP1153420). GDM is supported by the Australian National Health and Medical Research Council Leadership Fellowship (APP2009577). This research is supported in part by the Japan Society for the Promotion of Science (JSPS KAKENHI Fostering Joint International Research B: 19KK023). The study funder had no role in study design, analysis, interpretation of data, and writing of the report or decision to submit the paper for publication.

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