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.