Insulin resistance, considered a precursor to diabetes and a contributing risk factor for cardiovascular disease, is a condition in which the body cannot effectively use the hormone insulin.

In the study researchers evaluated 169 male and 126 female adolescents, average age 15, who were part of an ongoing study to determine the influence of weight and insulin resistance on the development of cardiovascular risk and type 2 diabetes in adults.

Researchers found that 62 percent of teens who were both heavy and insulin resistant had two or more cardiovascular disease risk factors, compared with only 8 percent of the teens who were neither heavy nor insulin resistant.

There is general consensus that controlling obesity is a major answer to cardiovascular health, said Alan R. Sinaiko, M.D., professor of pediatrics and nephrology at the University of Minnesota Medical School in Minneapolis. As we followed this group of teenagers, we found that insulin resistance has a significant role in the development of cardiovascular risk factors independent of obesity.

The participants were designated as heavy if their body mass index (BMI) was higher than the median for their age or thin if it was lower. BMI is an index of weight relative to height, and correlates with the amount of body fat in most people. Children and adolescents are not considered overweight until their BMI is at or above the 95th percentile for their age. Between the 85th and 95th percentile, they are considered at risk for overweight. Thus, some of the heavy children in this study would not be considered overweight by these established, stricter criteria.

Teens in the heavy group had a higher percentage of body fat, larger waists, and larger skinfold fat measurements than thin adolescents. The heavy teens also had significantly worse scores on several measures of cardiovascular risk, including:

higher levels of fasting insulin (hormone that removes glucose from the blood so that it can be used for energy); higher triglycerides (a type of fat in the blood); higher systolic blood pressure (the first number in a blood pressure reading, measuring the pressure in arteries when the heart contracts); higher levels of C-reactive protein (a marker of inflammation); higher levels of a marker of oxidative stress (a type of cell damage); lower levels of high-density lipoprotein cholesterol (HDL-C, good cholesterol); lower levels of adiponectin (a protein thought to protect blood vessel walls).

Researchers also tested participants for sensitivity to insulin, using a technique called the insulin clamp. During the test, a small amount of insulin is administered into a vein at a pre-determined rate to keep the circulating insulin levels constant. At the same time, glucose is infused until blood sugar is maintained at a normal level. If the participant is able to maintain normal blood sugar in the presence of only a small amount of glucose, the person is considered insulin resistant. If the person can handle larger amounts of glucose, he or she is insulin sensitive.

Compared with insulin-sensitive teens, those with insulin resistance had higher levels of fasting insulin, triglycerides, and a measure of oxidative stress and lower levels of HDL-C.

Doctors have no practical way to directly test for insulin resistance in the office. The insulin clamp test, considered the gold standard, is complex and expensive and used primarily in research, he said.

Although insulin resistance is related to obesity, some thin teens in the study were insulin resistant and some heavy teens were insulin sensitive. To test the combined effect of obesity and insulin resistance, researchers divided the teens into four groups and compared their scores on a cluster of risk factors, including systolic blood pressure, triglycerides, HDL-C and fasting insulin. All these risk factors are components of the metabolic syndrome, a syndrome that increases risk for cardiovascular disease and diabetes.

Thin insulin-sensitive teens had the healthiest profile: the lowest systolic blood pressure, lowest fasting insulin, lowest triglycerides and the highest HDL. Thin insulin-resistant teens and heavy insulin-sensitive teens ™ risk factor values were in the middle range while the heavy insulin-resistant teens had the highest blood pressure, highest fasting insulin, highest triglyerides and lowest HDL, and thus the highest risk.

The results among the risk groups followed the same pattern when male and female and white and black teens were analyzed separately.

Maintaining a healthy diet, regular physical activity and weight control continue to be important factors in preventing the development of cardiovascular risk, Sinaiko said. However, this study suggests that in addition to losing weight we may need to consider interventions that reduce insulin resistance.

The research was supported by the National Heart, Lung, and Blood Institute.

Co-authors are Julia Steinberger, M.D.; Antoinette Moran, M.D.; Ronald J. Prineas, M.D., Ph.D.; Bengt Vessby, M.D., Ph.D.; Samar Basu, Ph.D.; Russell Tracy, Ph.D.; and David R. Jacobs Jr., Ph.D.

americanheart