Temporal sequence of blood lipids and insulin resistance in perimenopausal women: the study of women’s health across the nation

INTRODUCTION: To explore the temporal relationship between blood lipids and insulin resistance in perimenopausal women. RESEARCH DESIGN AND METHODS: The longitudinal cohort consisted of 1386 women (mean age 46.4 years at baseline) in the Study of Women’s Health Across the Nation. Exploratory factor analysis was used to identify appropriate latent factors of lipids (total cholesterol (TC); triglyceride (TG); high-density lipoprotein cholesterol (HDL-C); low-density lipoprotein cholesterol (LDL-C); lipoprotein A-I (LpA-I); apolipoprotein A-I (ApoA-I); apolipoprotein B (ApoB)). Cross-lagged path analysis was used to explore the temporal sequence of blood lipids and homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Three latent lipid factors were defined as: the TG factor, the cholesterol transport factor (CT), including TC, LDL-C, and ApoB; the reverse cholesterol transport factor (RCT), including HDL-C, LpA-I, and ApoA-I. The cumulative variance contribution rate of the three factors was 86.3%. The synchronous correlations between baseline TG, RCT, CT, and baseline HOMA-IR were 0.284, −0.174, and 0.112 (p<0.05 for all). After adjusting for age, race, smoking, drinking, body mass index, and follow-up years, the path coefficients of TG→HOMA-IR (0.073, p=0.004), and HOMA-IR→TG (0.057, p=0.006) suggested a bidirectional relationship between TG and HOMA-IR. The path coefficients of RCT→HOMA-IR (−0.091, P < 0.001) and HOMA-IR→RCT (−0.058, p=0.002) were also significant, but the path coefficients of CT→HOMA-IR (0.031, p=0.206) and HOMA-IR→CT (−0.028, p=0.113) were not. The sensitivity analyses showed consistent results. CONCLUSIONS: These findings provide evidence that TG and the reverse cholesterol transport-related lipids are related with insulin resistance bidirectionally, while there is no temporal relationship between the cholesterol transport factor and insulin resistance.