Insulin resistance not sole contributor to cardiovascular risk

Insulin exposure, obesity independently contribute to resistance.

Issue: October 2007

AMSTERDAM — Insulin resistance, obesity, central obesity and high insulin response each make an independent but partial contribution to cardiometabolic risk factors, according to data presented at the 43rd Annual Meeting of the European Association for the Study of Diabetes.

Preliminary three-year follow-up data from the Relationship between Insulin Sensitivity and Cardiovascular Risk (RISC) study showed that 25% of participants whose beta cell function was most impaired at baseline had a more than threefold risk of developing diabetes or prediabetes and a twofold risk of developing abdominal diabetes after three years in comparison to the rest of the population.

We also demonstrated that “insulin resistance is not the single, central cause of the onset of cardiometabolic risk,” said Ele Ferrannini, MD, RISC project coordinator and professor at the University of Pisa, Italy. “This sheds light on an untested hypothesis that was often mistaken for an established fact — that insulin resistance is the primary driver of cardiometabolic risk.”

Investigating insulin resistance

Researchers in the European Group for the Study of Insulin Resistance (EGIR) RISC Study recruited more than 1,500 healthy volunteers (55% women, aged 30 to 60 years) from 19 centers in 14 European countries. They used the euglycemic hyperinsulinemic clamp technique to measure insulin resistance among 1,338 participants and used an oral glucose tolerance test to calculate insulin exposure and to model beta cell function. This was a prospective, observational, multicentered cohort study.

At baseline, BMI was positively related to all CVD risk factors. Waist circumference was related to hypertension, serum triglycerides and low HDL cholesterol. Insulin sensitivity was positively associated with postload glucose, free fatty acids, triglycerides and LDL cholesterol, and negatively associated with HDL cholesterol levels. Insulin exposure was associated with a higher heart rate, BP, fasting glucose and adverse levels of all lipid parameters. The researchers found that insulin resistance and hyperinsulinemia are not necessarily dependant on each other.

Effect of physical activity

Findings also showed that although obesity is strongly associated with insulin resistance, physical activity is beneficially associated with insulin sensitivity, even in the more obese participants. Physical activity was inversely and independently related to carotid artery stiffness, and the benefits of physical activity appeared to increase with increased activity.

The researchers quantitatively measured physical activity at baseline in 807 participants using an accelerometer. Insulin sensitivity was negatively associated with the number of sedentary hours per day. This relationship was stronger even in more abdominally obese men and women, according to findings from the study. Additionally, it was the total accumulated activity that was important, and even in the most sedentary there were benefits on insulin activity with increased physical activity.

“The benefits of physical activity include a decrease in age-related arterial stiffness, as well as some compensation for being overweight or obese. It will be interesting to see whether these benefits translate into cardioprotective effect in the RISC long-term follow-up,” said Mark Walker, MD, RISC researcher in the central laboratory for genetic analyses and professor at the University of Newcastle-Upon-Tyne, United Kingdom. – by Tara Grassia

For more information:

Dekker J, Walker, M, Balkau B. Insulin resistance, cardiovascular risk and physical activity in a European population – the RISC study. Symposium.
Mari A, Tura A, Pacini G, et al. Beta cell compensation for insulin resistance involves distinct mechanisms, which are differentially impaired in prediabetes. #49.
Lalic N, Nilsson PM, Nilsson J-A, et al. Body mass index is strongly associated with impaired insulin sensitivity in Europeans from 19 countries, independent of age, sex, social class and smoking habits. #270.
Bonnet F, Patel S, Ibrahim IM, et al. Association between the ACE gene I/D polymorphism and insulin sensitivity and impaired glucose tolerance in healthy subjects. #313.
All presented at: the 43rd Annual Meeting of the European Association for the Study of Diabetes; Sept. 18-21, 2007; Amsterdam, Netherlands.