Differential sex effects of systolic blood pressure and low‐density lipoprotein cholesterol on type 2 diabetes: Life course data from the Bogalusa Heart Study

Background There may be sex‐specific cardiometabolic mechanisms early in life that affect the development of type 2 diabetes mellitus (T2DM) through mid‐adulthood. However, few studies have examined whether early life course interactions between cardiometabolic risk factors and sex are associated with incident T2DM. Methods This study followed 7725 children (3834 [49.6%] females, 3891 [50.4%] males) from the Bogalusa Heart Study through mid‐adulthood to examine whether low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), body mass index (BMI), or systolic blood pressure (SBP) differentially affect the risk of T2DM for females versus males. Potential sex interactions were tested after adjusting for age, race, triglycerides, smoking, follow‐up time, puberty stage, use of birth control, and enrollment year. Results Mean (± SD) age at baseline was 9.4 ± 3.5 years. There were 176 cases of T2DM (cumulative incidence = 2.3%) during a median follow‐up of 9.1 years. In females versus males, LDL‐C and SBP were differentially associated with T2DM (P ≤ 0.001 and P = 0.017, respectively). The relationships of BMI and HDL‐C with T2DM were non‐differential between females and males (P = 0.79 and P = 0.27, respectively). Conclusions This study is the first to show evidence of sex‐specific differential effects of LDL‐C and SBP on the risk of T2DM from childhood to adulthood. Greater LDL‐C places girls at disproportionally higher risk of T2DM as women, whereas greater SBP differentially exposes boys to a greater risk of T2DM as men. Additional studies within existing child cohorts are needed to confirm and investigate the mechanisms underlying these differential effects. 摘要 背景 在生命的早期以至成年中期不同性别之间不同的心血管代谢机制可能会对2型糖尿病的发生具有影响。然而, 目前在早期生命历程中调查心血管危险因素与性别之间的交互作用是否与2型糖尿病的发生具有相关性的研究还很少。 方法 这项研究随访了7725名来自博加卢萨心血管研究的儿童(3834名[49.6%]女性, 3891名[50.4%]男性)至成年中期, 调查低密度脂蛋白胆固醇(LDL‐C)、高密度脂蛋白胆固醇(HDL‐C)、体重指数(BMI)或者收缩压(SBP)的性别差异是否会影响男性与女性的2型糖尿病风险。校正年龄、种族、三酰甘油、吸烟、随访时间、青春期、避孕药的使用以及登记年份后对潜在的性别导致的交互作用进行了检验。 结果 基线时的平均年龄(±SD)为9.4 ± 3.5岁。在中位数为9.1年的随访期间共有176名2型糖尿病患者(累积发病率= 2.3%)。女性与男性之间的LDL‐C以及SBP的差异与2型糖尿病相关(分别P ≤ 0.001与P = 0.017)。女性与男性之间的BMI以及HDL‐C的差异与2型糖尿病没有相关性(分别P = 0.79与P = 0.27)。 结论 这项研究第一次证实了从儿童期至成年期的LDL‐C以及SBP性别特异性的差异可以影响2型糖尿病的风险。LDL‐C升高可导致女孩成年后发生2型糖尿病的风险明显增高, 而SBP升高可导致男孩成年后发生2型糖尿病的风险增高。还需要在目前的儿童队列中进行更多的研究来调查与证实这些差异效应的潜在机制。 Highlights From childhood to adulthood, an increase in low‐density lipoprotein cholesterol (LDL‐C) imposes a differentially greater risk