Abstract

Introduction: Given its role in ovarian follicle development, circulating anti-Müllerian hormone (AMH) is correlated with timing of menopause. Accordingly, women with higher AMH levels become menopausal at a higher age. Previous research suggests that a higher age at menopause is associated with a decreased risk of type 2 diabetes (T2D). In contrast, AMH levels are increased in women with polycystic ovary syndrome (PCOS), who have a higher risk of insulin resistance and T2D than women without PCOS. However, it is not clear yet whether AMH actually plays a role in the development of T2D. We aimed to investigate whether plasma AMH levels and age-related AMH trajectories are associated with risk of T2D in women. Hypothesis: Higher age-specific plasma AMH levels are associated with a decreased risk of T2D. Methods: We analyzed longitudinal data from 3104 female participants, aged 20-60 years at recruitment, in the population-based Doetinchem Cohort Study. In total, we analyzed 12460 plasma AMH measurements. We calculated age-specific AMH tertiles, to account for the strong AMH-age correlation. Cox Proportional hazards models adjusted for known risk factors for diabetes were used to assess the relation between age-specific AMH tertiles and T2D. We applied linear mixed models to compare age-related AMH trajectories between T2D cases and non-cases. Results: After a median follow-up of 20 years, 163 incident T2D cases were identified. Higher age-specific AMH levels were associated with a lower risk of T2D (hazard ratio (HR) T2vsT1 = 0.77, 95%CI: 0.53-1.11; HR T3vsT1 =0.62, 95%CI: 0.40-0.94; p for trend = 0.02). These findings were supported by predicted AMH trajectories, which suggested that plasma AMH levels were lower at younger ages and declined at a slower rate in women who were diagnosed with T2D compared to women who were not. However, differences in trajectories between T2D cases and non-cases were not statistically significant. Conclusions: We observed that women with higher age-specific AMH levels were at a lower risk of T2D. In addition, our longitudinal analyses may suggest that AMH is lower in women who develop T2D compared to women who do not. These findings are in line with previous studies that observed that a higher age at menopause was associated with a decreased risk of T2D.

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