Free fatty acids are associated with pulse pressure in women, but not men, with type 1 diabetes mellitus

Abstract

Cardiovascular disease (CVD) is the leading cause of death in type 1 diabetes mellitus (T1D). Pulse pressure, a measure of arterial stiffness, is elevated in T1D and associated with CVD. Free fatty acids (FFAs), elevated in women and abdominal adiposity, are also elevated in T1D and CVD. We thus examined the association of fasting FFAs with pulse pressure and coronary artery calcification (CAC, a marker of coronary atherosclerotic burden) in an adult population (n = 150) of childhood-onset T1D and whether any such associations varied by abdominal adiposity and sex. Mean age and diabetes duration were 42 and 33 years, respectively, when CAC, visceral abdominal adiposity (VAT), and subcutaneous abdominal adiposity (SAT) were determined by electron beam tomography. Free fatty acids were determined by in vitro colorimetry. Pulse pressure was calculated as systolic blood pressure minus diastolic blood pressure. Free fatty acids were log transformed before analyses, and all analyses were controlled for serum albumin. Free fatty acids were associated with pulse pressure in women (r = 0.24, P = .04), but not in men (r = 0.07, P = .55). An interaction for the prediction of pulse pressure was noted between FFAs and both VAT (P = .03) and SAT (P = .008) in women, but only a marginal interaction with SAT (P = .09) and no interaction for VAT (P = .40) with FFAs were observed in men. In multivariable linear regression analysis allowing for serum albumin, age, height, heart rate, albumin excretion rate, hemoglobin A1c, high-density lipoprotein cholesterol, hypertension medication use, FFAs, SAT, and the interaction between FFAs and SAT, the interaction between FFAs and SAT remained associated with pulse pressure in women (FFAs, P = .04; interaction term, P = .03), but not men (FFAs, P = .32; interaction term, P = .32). FFAs showed no association with log-transformed CAC. Although FFAs were not associated with CAC in either sex, they were associated with pulse pressure in women and their effect appeared to vary by abdominal adiposity, particularly SAT. This finding might help explain the loss of the sex difference in CVD in T1D.