Younger women seemed to be less susceptible to the cardiovascular effects of insulin resistance than older people, which may partially explain the "female advantage" in cardiovascular disease (CVD), researchers said.
The clinical impact of insulin resistance appeared to be attenuated in women until the age of 50, with the most insulin-resistant younger women having significantly (P≤0.007) lower diastolic blood pressure, fasting glucose, and triglyceride concentrations than the most insulin-resistant younger men, reported Sun H. Kim, MD, and Gerald Reaven, MD, of Stanford University School of Medicine in Stanford, Calif.
Highly insulin-resistant younger women in the study also had significantly lower fasting glucose and triglyceride concentrations than women over 50 with the same degree of insulin resistance, they wrote in the Journal of Clinical Endocrinology and Metabolism.
However, no difference was seen in the incidence of insulin resistance between men and women regardless of age, the authors pointed out.
"The fact that these younger women were able to compensate for the effects of insulin resistance better than the other groups may help explain why women tend to develop cardiovascular disease about a decade later than men," Kim told MedPage Today.
While some studies have suggested that men are more likely than women to develop insulin resistance, others have found insulin sensitivity to be similar among the two sexes.
It has also been suggested that compared to men, women experience fewer cardiovascular complications related to insulin resistance, which could explain their delayed susceptibility to heart disease, the researchers wrote.
To examine these two possibilities, Kim and Reaven conducted a cross-sectional study to compare insulin resistance among 468 nondiabetic women and 354 nondiabetic men, ages 19 to 79.
The study participants had no history of coronary artery, kidney or liver disease, and insulin sensitivity was assessed by measuring steady-state plasma glucose (SSPG) concentrations.
They compared the relationship between SSPG and five CVD risk factors between sexes:
- Systolic and diastolic blood pressure
- Fasting glucose
- High density lipoprotein cholesterol (HDL-C) concentrations
In addition to sex, researchers divided the study participants by age (<51 and ≥51) and by body mass index (normal BMI of 25 kg/m2, overweight 25-29.9 kg/m2, and obese ≥30 kg/m2).
The analysis revealed that SSPG concentrations increased with BMI regardless of sex or age (P<0.001), and older women and men were generally more insulin resistant than their younger counterparts (P<0.001).
SSPG concentrations did not differ by sex, but a significant interaction was seen between sex and BMI (P=0.001), with obese women of all ages tending to be less insulin resistant than obese men.
All five CVD risk factors examined worsened with increasing insulin resistance, regardless of sex or age. But a significant (P<0.05) interaction between sex and age was seen for glucose, triglyceride and HDL-C levels.
Among participants who were age 50 or younger, women with the highest SSPG concentrations had lower blood pressure, fasting glucose, and triglyceride levels than men with similar SSPG levels.
Younger women with the highest SSPG concentrations were the only group to have mean fasting glucose below the prediabetes cut point (100 mg/dL) and triglyceride concentrations below the cut point to define hypertriglyceridemia (150 mg/dL), the researchers noted.
Among participants with the highest SSPG concentrations, four of the five CVD risk factors were more favorable in younger women than men, but only HDL-C was higher in younger women with the lowest SSPG levels.
Older women had lower diastolic blood pressure compared with men, regardless of SSPG.
"Thus, although the higher degree of insulin resistance can accentuate the female [CVD] advantage, improving insulin resistance can equalize the CVD disparity between the sexes," the researchers wrote.
A major study limitation was a lack of information on the women's menopausal status. But the authors noted that dividing the participants at age 51 -- the median age of menopause -- served as a proxy for this important variable.
The finding that insulin-resistant younger women had fewer CVD risk factors than insulin-resistant younger men appears to add to the evidence that sex steroids are a major play in the female heart disease advantage, Robert M. Carey, MD, told MedPage Today.
Carey is a professor of medicine, endocrinology and metabolism at the University of Virginia School of Medicine in Charlottesville, and he is a past president of The Endocrine Society.
The receptors belong to the renin-angiotensin system, which regulates blood pressure and other CVD risk factors.
"This is the cellular hormonal mechanism that might explain the protection women have in terms of cardiovascular risk factors prior to menopause," he said.
From the American Heart Association:
The Stanford Clinical and Translational Research Unit is supported by an NIH's and Translational Science Award.
The authors reported no conflicts of interest.
- Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
Journal of Clinical Endocrinology & MetabolismSource Reference: Kim SH and Reaven G. "Sex differences in insulin resistance and cardiovascular disease risk" J Clin Endocrinol Metab 2013; DOI: 10.1210/jc.2013-1166.