The association between age at menarche and later risk of gestational diabetes is mediated by insulin resistance

Aims: Associations have been reported between age at menarche and the later risk of gestational diabetes. However, it is not known whether these associations reflect differences in insulin sensitivity and/or pancreatic β-cell function in pregnancy. Methods: We examined this question in women enrolled in the prospective Cambridge Baby Growth Study who recalled their age at menarche in questionnaires during pregnancy. Polynomial logistic and linear regression models were used to relate menarche timing to the risk of gestational diabetes, both unadjusted and adjusted for the Homeostasis Model Assessments of insulin resistance (HOMA IR) and pancreatic β-cell function (HOMA B) at week 28 of pregnancy. Results: Age at menarche showed a U-shaped association with gestational diabetes risk (linear term: p = 9.5 × 10; quadratic term: p = 1.0 × 10; n = 889; overall model p = 8.1 × 10). Age at menarche showed a negative linear association with insulin resistance (HOMA IR: β = −0.13, p = 5.2 × 10, n = 771), which explained the relationship between age at menarche and gestational diabetes risk (adjusted linear term going from p = 0.03–0.08; adjusted quadratic term going from p = 0.04–0.08; n = 771). Age at menarche also showed a negative linear association with β-cell function (HOMA B: β = −0.11, p = 2.8 × 10, n = 771) but this did not attenuate the relationship between age at menarche and gestational diabetes (adjusted linear term p = 0.02; adjusted quadratic term p = 0.03, n = 771). Conclusions: These results suggest that the associations between age at menarche and risk of gestational diabetes and raised pregnancy glucose concentrations may be mediated by insulin resistance.