Sex Differences in Insulin Resistance and Cardiovascular Disease Risk

Context: The possibility that differences in insulin sensitivity explain why women, especially younger women, have a lower cardiovascular disease (CVD) risk than men remains an unsettled issue. Objective: The objective of this study was to evaluate whether sex disparities in CVD risk are associated with differences in insulin resistance. Design/Setting/Participants: This was a cross-sectional study of women(n = 468) and men(n = 354) who had the measurement of CVD risk factors and steady-state plasma glucose (SSPG) concentration (insulin resistance) using the insulin suppression test. The population was also divided by median age (51 y) to evaluate the effect of age on sex differences. Main Outcome Measures/Results: In general, the SSPG concentration was similar between sexes. At higher BMI (>= 30 kg/m(2)), women had significantly lower SSPG concentration than men (sex x BMI interaction, P = .001). However, sex differences in CVD risk factors were not due to differences in SSPG but accentuated by a higher degree of insulin resistance in younger (age < 51 y) but not older (> 51 y) individuals. In younger individuals, women had significantly (P < .007) lower diastolic blood pressure and fasting glucose and triglyceride concentration compared with men in SSPG tertile 3 (most insulin resistant) but not in tertile 1 (least insulin resistant). Older women had lower diastolic blood pressure compared with men, regardless of SSPG. High-density lipoprotein cholesterol remained higher in women, regardless of age or SSPG. Conclusions: The female advantage is not due to a difference in insulin action but results from an attenuation of the relationship between insulin resistance and CVD risk, especially in younger individuals.