Association of puberty timing with type 2 diabetes: A systematic review and meta-analysis.
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Cheng, T. S., Day, F., Lakshman, R., & Ong, K. (2020). Association of puberty timing with type 2 diabetes: A systematic review and meta-analysis.. PLoS medicine, 17 (1), e1003017. https://doi.org/10.1371/journal.pmed.1003017
Background Emerging studies have investigated the association between puberty timing, particularly age at menarche, and Type 2 diabetes. However, whether this association is independent of adiposity is unclear. We aimed to systematically review published evidence on the association between puberty timing and Type 2 diabetes or impaired glucose tolerance (T2D/IGT), with and without adjustment for adiposity, and to estimate its potential contribution to the burden of T2D in United Kingdom (UK). Methods and findings We searched PubMed, Medline and Embase databases for publications until February 2019 on the timing of any secondary sexual characteristic in boys or girls in relation to T2D/IGT. Inverse-weighted random-effects meta-analysis was used to pool reported estimates and meta-regression to explore sources of heterogeneity. Twenty eight observational studies were identified. All assessed age at menarche (AAM) in women (combined N=1,228,306); only one study additionally included men. In models without adjustment for adult adiposity, T2D/IGT risk was lower per year later AAM (relative risk (RR)=0.91, 95% confidence interval (CI)=0.89-0.93, p<0.001, 11 estimates, n=833,529, I2=85.4%) and for early versus later menarche (RR=1.39, 95% CI=1.25-1.55, p<0.001, 23 estimates, n=1,185,444, I2=87.8%). Associations were weaker but still evident in models adjusted for adiposity (AAM: RR=0.97 per year, 95% CI=0.95-0.98, p<0.001, 12 estimates, n=852,268, I2=51.8%; early menarche: RR=1.19, 95% CI=1.11-1.28, p<0.001 21 estimates, n=890,583, I2=68.1%). Associations were stronger among white than Asian women, and in populations with earlier average AAM. The estimated population attributable risk of T2D in white UK women due to early menarche, unadjusted and adjusted for adiposity, was 12.6% (95% CI=11.0-14.3) and 5.1% (95% CI=3.6-6.7), respectively. Findings in this study are limited by residual and unmeasured confounding, and self-reported AAM. Conclusions Earlier age at menarche is consistently associated with higher T2D/IGT risk, independent of adiposity. More importantly, this research has identified a substantial proportion of T2D in women is related to early menarche timing, which would be expected to increase in light of global secular trends towards earlier puberty timing. These findings highlight the need to identify underlying mechanisms linking early menarche to T2D/IGT risk.
Humans, Diabetes Mellitus, Type 2, Age Factors, Puberty, Menarche, Female, Male, Adiposity, Observational Studies as Topic
As listed in the Financial Disclosure to the journal: FRD, RL and KKO are supported by the Medical Research Council (Unit programme: MC_UU_12015/2). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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External DOI: https://doi.org/10.1371/journal.pmed.1003017
This record's URL: https://www.repository.cam.ac.uk/handle/1810/300146
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