Anti-M\xfcllerian hormone levels and risk of type 2 diabetes in women

Renée M G Verdiesen,N Charlotte Onland-Moret,W M Monique Verschuren,Frank J M Broekmans,Rebecca K Stellato,Carla H Van Gils,Yvonne T Van Der Schouw,H Susan J Picavet,Annemieke M W Spijkerman

doi:10.1007/s00125-020-05302-5

Abstract

Aims/hypothesisGiven its role in ovarian follicle development, circulating anti-Müllerian hormone (AMH) is considered to be a marker of reproductive ageing. Although accelerated reproductive ageing has been associated with a higher risk of type 2 diabetes, research on the relationship between AMH and type 2 diabetes risk is scarce. Therefore, we aimed to investigate whether age-specific AMH levels and age-related AMH trajectories are associated with type 2 diabetes risk in women.MethodsWe measured AMH in repeated plasma samples from 3293 female participants (12,460 samples in total), aged 20–59 years at recruitment, from the Doetinchem Cohort Study, a longitudinal study with follow-up visits every 5 years. We calculated age-specific AMH tertiles at baseline to account for the strong AMH–age correlation. Cox proportional hazards models adjusted for confounders were used to assess the association between baseline age-specific AMH tertiles and incident type 2 diabetes. We applied linear mixed models to compare age-related AMH trajectories for women who developed type 2 diabetes with trajectories for women who did not develop diabetes.ResultsDuring a median follow-up of 20 years, 163 women developed type 2 diabetes. Lower baseline age-specific AMH levels were associated with a higher type 2 diabetes risk (HRT2vsT3 1.24 [95% CI 0.81, 1.92]; HRT1vsT3 1.62 [95% CI 1.06, 2.48]; ptrend = 0.02). These findings seem to be supported by predicted AMH trajectories, which suggested that plasma AMH levels were lower at younger ages in women who developed type 2 diabetes compared with women who did not. The trajectories also suggested that AMH levels declined at a slower rate in women who developed type 2 diabetes, although differences in trajectories were not statistically significant.Conclusions/interpretationWe observed that lower age-specific AMH levels were associated with a higher risk of type 2 diabetes in women. Longitudinal analyses did not show clear evidence of differing AMH trajectories between women who developed type 2 diabetes compared with women who did not, possibly because these analyses were underpowered. Further research is needed to investigate whether AMH is part of the biological mechanism explaining the association between reproductive ageing and type 2 diabetes.Graphical abstract

Highlights

Female reproductive ageing has been associated with risk of chronic diseases, including type 2 diabetes, in later life [1]
Baseline characteristics and the proportion of incident diabetes cases were mostly comparable between women with and women without a missing anti-Müllerian hormone (AMH) measurement, for each of the five examination rounds (ESM Table 1)
We observed that women with lower age-specific AMH levels had a higher risk of type 2 diabetes (HRT2vsT3 1.24 [95% CI 0.81, 1.92]; HRT1vsT3 1.62 [95% CI 1.06, 2.48]; ptrend across tertiles = 0.02) (Table 2)

Summary

Introduction

Female reproductive ageing has been associated with risk of chronic diseases, including type 2 diabetes, in later life [1]. Women with an earlier menopause have been found to be at a higher risk of postmenopausal type 2 diabetes [2]. This association appears to be independent from the effect of BMI [3, 4]. A potential causal candidate explaining this association is anti-Müllerian hormone (AMH), a gonadal hormone expressed by early-stage ovarian follicles in premenopausal women [5]. The ovarian follicle pool decreases until menopause [6]. AMH can be used as a marker for reproductive ageing in women [7, 8]

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