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Insulin Resistance One of Many Players in Cardiometabolic Risk

Bruce Goldfarb

Insulin resistance is certainly a contributor to—but is not the main cause of—cardiometabolic risk, according to preliminary baseline data from the Relationship Between Insulin Sensitivity and Cardiovascular Risk (RISC) study, reported at the European Association for the Study of Diabetes (EASD) annual meeting, held September 18–21 in Amsterdam.

Obesity, central obesity, high insulin response, and insulin resistance all independently and partially contribute to cardiometabolic risk, say RISC study investigators.

"The RISC study demonstrates that insulin resistance is not the single, central cause of the onset of cardiovascular disease," says study coordinator Ele Ferrannini, MD, professor of internal medicine at University of Pisa in Italy and president of EASD.

Launched in 2001, RISC is a prospective, observational study of 1,338 middle-aged healthy individuals followed by 19 medical centers in 14 countries. Among the physical assessments and exams performed at the beginning of the study, each participant had an oral glucose tolerance test and a euglycemic hyperinsulinemic clamp, which measures insulin resistance.

The researchers' analysis of data from the 3-year follow-up period revealed that 1% of participants developed diabetes, 8% developed impaired fasting glucose, 12% showed impaired glucose tolerance, and 11% developed central obesity—evidence of the multiple factors involved in cardiometabolic risk. The researchers did not report direct measurements of heart or cardiovascular disease functioning, although one of the outcomes RISC is tracking is intima-media thickness, a marker of early atherosclerosis.

Participants with impaired beta-cell function had three times the risk of developing diabetes or pre-diabetes and twice the risk of developing abdominal obesity within 3 years.

The data also indicate that the primary way people can affect their insulin sensitivity is through being active: An increase in total accumulated activity was the main driver of improved insulin sensitivity, and being sedentary was related to worsening insulin sensitivity. Even among men and women with more abdominal obesity, physical activity was associated with better insulin sensitivity. In addition, physical activity appears to reduce age-related stiffening of the arterial wall in young to middle-aged populations.

"Physical activity is the key determinant of insulin sensitivity," says Mark Walker, MD, a professor of molecular diabetes at Newcastle University in England.

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