Association of puberty timing with Type 2 diabetes: Systematic review and meta-analysis

OBJECTIVE 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. RESEARCH DESIGN AND METHODS 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. RESULTS 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 higher per year earlier AAM (relative risk (RR)=0.91, 95% confidence interval (CI)=0.89-0.93, 11 estimates, n=833,529, I 2 =85.4%) and for early versus later menarche (RR=1.41, 95% CI=1.28-1.55, 23 estimates, n=1,185,444, I 2 =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, 12 estimates, n=852,268, I 2 =51.8%; early menarche: RR=1.19, 95% CI=1.11-1.28, 21 estimates, n=890,583, I 2 =68.1%). Associations were stronger among Caucasians than Asians, and in populations with earlier average AAM. The estimated population attributable risk of T2D in UK Caucasians 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. CONCLUSIONS A substantial proportion of T2D in women is attributable to early menarche timing. This will increase in light of global secular trends towards earlier puberty timing.