Insulin Resistance Moderates the Association Between BMI and Metabolic Syndrome Severity in Women 4–10 Years After Pregnancy, Independent of Gestational Diabetes Status

Objective: Obesity and gestational diabetes mellitus (GDM) increase the risk for metabolic syndrome (MetS). Insulin resistance (IR) is associated with obesity, contributes to risk for GDM, and persists after pregnancy even when glucose tolerance returns. Further, IR may enhance the risk of MetS associated with obesity and GDM. The purpose of this study was to test the hypothesis that IR moderates the relationship between BMI and MetS severity 4–10 years after pregnancy, independent of prior GDM, such that the positive association between BMI and MetS severity is stronger among women with greater IR. Methods: This hypothesis was tested in a secondary analysis of data collected from women enrolled in a study of the intergenerational transmission of obesity, 4–10 years after the index pregnancy. Recruitment in the parent study was stratified to include women with normal weight without GDM (NW), overweight or obesity without GDM (OwOB), and women with GDM during the index pregnancy. Standard clinical procedures were used to measure height, weight, waist circumference and blood pressure, and a fasting blood draw was obtained with which to measure glucose, insulin, triglycerides, and HDL-cholesterol. MetS was evaluated as a continuous outcome, reflecting severity, using the method of Gurka and DeBoer.(1) IR was calculated with the homeostatic model assessment (HOMA-IR) and modeled as a continuous variable. An OLS regression model predicting MetS as a function of HOMA-IR, BMI, and their interaction, along with key covariates was used to test whether HOMA-IR moderates the relationship between BMI and MetS severity, independent of GDM. Results: The association between BMI and MetS severity was significantly modified by HOMA-IR (b=0.008, p<0.001), independent of GDM status during pregnancy, such that the positive association between BMI and MetS severity was stronger among individuals with higher HOMA-IR. For example, among women with HOMA-IR values 1-standard deviation below the mean, the estimated association between BMI and MetS severity was (b=0.0394, p<0.001); however, among women with a HOMA-IR value 1-standard deviation above the mean, the association between BMI and MetS severity was (b=0.0745, p<0.001). Conclusion: IR after pregnancy was a significant moderator of the association between BMI and MetS severity. Future studies should explore whether interventions to improve IR can reduce MetS severity independent of BMI and prior GDM. References: 1.Gurka MJ, Lilly CL, Oliver MN, DeBoer MD. An examination of sex and racial/ethnic differences in the metabolic syndrome among adults: a confirmatory factor analysis and a resulting continuous severity score. Metabolism. 2014;63(2):218–225.