Association between reproductive years and insulin resistance in middle-aged and older women: A 10-year prospective cohort study

Abstract

Objectives: We hypothesized that reproductive years, a marker of total estrogen exposure, may play an important role in insulin resistance.

Study design: A total of 3327 middle-aged and older women (age range 40-69 years) from the Korean Genome and Epidemiology Study were included in this large prospective cohort study with a mean follow-up of 10.8 years.

Main outcome measures: Insulin resistance and sensitivity were calculated using the homeostatic model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI). A linear mixed model for a repeated-measures covariance pattern with unstructured covariance within participants was used to assess longitudinal associations between baseline reproductive years and subsequent changes in HOMA-IR and QUICKI. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for new-onset insulin resistance according to quartiles of reproductive years.

Results: Changes in HOMA-IR were significantly greater in Q1 (fewest reproductive years) than in Q4 (most reproductive years) (beta[SE] = 0.038[0.016]; p-value = 0.022), while changes in QUICKI were significantly smaller in Q1 than in Q4 (beta[SE] = -0.001[0.000]; p-value = 0.048) after adjusting for possible confounders over time. Compared with Q1, HRs (95 % CIs) for the incidence of new-onset insulin resistance were 0.807 (0.654-0.994) for Q2, 0.793 (0.645-0.974) for Q3, and 0.770 (0.622-0.953) for Q4 after adjusting for possible confounders.

Conclusion: A short reproductive period is associated with elevated levels on the HOMA-IR and decreased levels on the QUICKI over time. The lowest quartile of reproductive years was significantly associated with a higher risk of new-onset insulin resistance.