Early menopause in mothers and the risks of pre-diabetes and type 2 diabetes mellitus in female and male offspring: a population-based cohort study.

Abstract

Background: Genetic factors and an unfavorable intrauterine environment may contribute to the development of metabolic disorders in offspring later in life. The present study aims to investigate and compare the risks of pre-diabetes mellitus (pre-DM), type 2 diabetes mellitus (T2DM) and abnormal glucose tolerance in female and male offspring with early maternal menopausal age versus those with normal maternal menopausal age, later in life.

Methods: In this prospective population-based study, there were 1,516 females and 1,563 males with normal maternal menopausal age, as well as 213 females and 237 males with early maternal menopausal age. Unadjusted and adjusted cox regression models were used to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between early maternal menopausal age with pre-DM, T2DM and abnormal glucose tolerance in offspring. Statistical analysis was performed using the STATA software package; the significance level was set at P < 0.05.

Results: The present study revealed a higher risk of pre-DM in female offspring with early maternal menopausal age compared to females with normal maternal menopausal age (unadjusted HR (95% CI): 1.42 (0.98, 2.05); P = 0.06 (marginal significant) and adjusted HR (95% CI): 1.47 (1.00, 2.16); P = 0.04). Additionally, a higher risk of abnormal glucose tolerance among female offspring with early maternal menopausal age in adjusted model was observed (HR (95% CI): 1.13 (0.99-1.29); P = 0.06, marginal significant). However, no significant differences were observed in the risks of developing pre-DM and abnormal glucose tolerance in male offspring with early maternal menopausal age compared to males with normal maternal menopausal age in both unadjusted and adjusted models. No significant difference was observed in the risk of T2DM in the offspring with early maternal menopausal age compared to offspring with normal maternal menopausal age.

Conclusions: This pioneering study, characterized by a long-term follow-up, demonstrated that early maternal menopausal age is associated with an increased risk of developing pre-DM in female offspring later in life. It may be advisable to implement screening for pre-DM and glucose metabolism disorders in these female offspring.

Clinical trial number: Not applicable.