Department of Family Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea.
Biostatistics Collaboration Unit, Department of Research Affairs, Yonsei University College of Medicine, Seoul, Republic of Korea.
Maturitas. 2020 Dec;142:31-37. doi: 10.1016/j.maturitas.2020.07.004. Epub 2020 Jul 10.
We hypothesized that reproductive years, a marker of total estrogen exposure, may play an important role in insulin resistance.
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.
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.
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.
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.
我们假设生殖年限（总雌激素暴露的一个标志物）可能在胰岛素抵抗中发挥重要作用。
这项大型前瞻性队列研究共纳入了 3327 名年龄在 40-69 岁的韩国基因组和流行病学研究中的中年及以上女性，平均随访时间为 10.8 年。
使用稳态模型评估的胰岛素抵抗（HOMA-IR）和定量胰岛素敏感性检查指数（QUICKI）计算胰岛素抵抗和敏感性。采用重复测量协方差模式的线性混合模型，协方差在参与者内部为非结构，评估基线生殖年限与 HOMA-IR 和 QUICKI 后续变化之间的纵向关联。采用 Cox 比例风险回归估计根据生殖年限四分位数发生新诊断的胰岛素抵抗的风险比（HR）和 95%置信区间（CI）。
在调整了可能的混杂因素后，与 Q4（生殖年限最长的四分位数）相比，Q1（生殖年限最短的四分位数）的 HOMA-IR 变化明显更大（β[SE] = 0.038[0.016]；p 值 = 0.022），而 Q1 的 QUICKI 变化明显小于 Q4（β[SE] = -0.001[0.000]；p 值 = 0.048）。与 Q1 相比，在调整了可能的混杂因素后，Q2（95%CI：0.807[0.654-0.994]）、Q3（95%CI：0.793[0.645-0.974]）和 Q4（95%CI：0.770[0.622-0.953]）的新诊断胰岛素抵抗发生率的 HR 值较低。
生殖年限较短与 HOMA-IR 水平升高和 QUICKI 水平降低有关。生殖年限最低的四分位数与新诊断的胰岛素抵抗风险显著升高相关。
