Insulin Resistance Linked To Increased Risk of Cardiovascular Disease

Michelle Schmiegelow MD, PhD Student Gentofte Hospital Copenhagen Area, Capital Region, Interview with:
Michelle Schmiegelow MD, PhD Student
Gentofte Hospital
Copenhagen Area, Capital Region, Denmark

Medical Research: What is the background for this study?

Dr. Schmiegelow: Use of cardiovascular risk stratification models is highly encouraged by U.S. and European guidelines in order to prevent cardiovascular disease (CVD). Individuals with insulin resistance are likely to progress to type 2 diabetes, but measures of insulin resistance are not included in current risk stratification models, although this might improve prediction of CVD in patients without diabetes. The aim of this study was to evaluate whether measures of insulin resistance would improve CVD risk predictions based solely on traditional CVD risk factors in postmenopausal women without existing CVD or diabetes. The main outcome was risk of developing CVD, defined as non-fatal and fatal coronary heart disease and ischemic stroke, within ten years, and the measures of insulin resistance considered were fasting serum glucose, fasting serum insulin, “homeostasis model assessment-insulin resistance“ (HOMA-IR) and the ratio of triglycerides and high-density lipoprotein-cholesterol (TG/HDL-C).

From the Women’s Health Initiative Biomarkers studies we identified 15,288 postmenopausal women with no history of CVD, atrial fibrillation, or diabetes at baseline (included 1993–1998), who over a mean follow-up of 9.2 years (standard deviation 1.9 years) had 894 first CVD events (5.8%).

Medical Research: What are the main findings?

Dr. Schmiegelow: The main findings of our study were that measures of insulin resistance were significantly associated with increased risk of CVD after adjusting for age and race/ethnicity, but measures of insulin resistance did not provide additional prognostic information beyond traditional cardiovascular risk factors. Particularly, measures of insulin resistance appeared to add little prognostic information once HDL-C levels were considered.

Medical Research: What should clinicians and patients take away from your report?

Dr. Schmiegelow: Insulin resistance is suggested as the pathophysiological link between obesity and CVD risk, but the information insulin resistance measures provides regarding risk seems to be adequately captured by traditional cardiovascular risk factors, primarily HDL-cholesterol. Put differently, although measures of insulin resistance were associated with CVD risk when considered alone, these associations were greatly attenuated after adjusting for traditional risk factors, particularly HDL-C.

Recent studies suggest that HDL-C per se may not be causally related to cardiovascular disease risk, but HDL-C is still a key risk factor because of its strong association with coronary heart disease. Several explanations for the associations between HDL-C and coronary heart disease has been suggested including confounding by apolipoprotein and atherogenic lipoprotein concentrations, modified by insulin resistance, or that HDL-C simply just be a reliable marker of a harmful risk profile.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Schmiegelow: Due to the observational nature of our study, we can only explore associations, not causality. Other types of studies are thus needed to disentangle the effects of insulin resistance and factors correlated with it; for assessment of causality, Mendelian randomization studies could be useful, and it could be tested if interventions that directly target insulin resistance reduce the incidence of CVD.


Insulin Resistance and Risk of Cardiovascular Disease in Postmenopausal Women: A Cohort Study From the Women’s Health Initiative

Michelle D. Schmiegelow, Haley Hedlin, Marcia L. Stefanick, Rachel H. Mackey, Matthew Allison, Lisa W. Martin, Jennifer G. Robinson, and Mark A. Hlatky

Circ Cardiovasc Qual Outcomes. 2015;CIRCOUTCOMES.114.001563published online before print May 5 2015, doi:10.1161/CIRCOUTCOMES.114.001563


[wysija_form id=”1″] Interview with:, Michelle Schmiegelow MD, PhD Student, Gentofte Hospital, & Copenhagen Area, Capital Region, Denmark (2015). Insulin Resistance Linked To Increased Risk of Cardiovascular Disease