Low-Grade Chronic Inflammation in the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) Population

doi:10.2337/dc08-1795

Low-Grade Chronic Inflammation in the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) Population

Associations with insulin resistance and cardiometabolic risk profile

Susanne R. de Rooij, PHD¹,
Giel Nijpels, MD, PHD¹,
Peter M. Nilsson, MD, PHD²,
John J. Nolan, MD³,
Rafael Gabriel, MD, PHD⁴,
Elisabetta Bobbioni-Harsch, PHD⁵,
Geltrude Mingrone, MD, PHD⁶,
Jacqueline M. Dekker, PHD¹ and
for the Relationship Between Insulin Sensitivity and Cardiovascular Disease (RISC) Investigators*

¹Institute for Research in Extramural Medicine, VU University Medical Center, Amsterdam, the Netherlands;
²Department of Clinical Sciences, Lund University, University Hospital, Malmö, Sweden;
³Metabolic Research Unit, St. James' Hospital, Trinity College, Dublin, Ireland;
⁴Unidad de Investigacion, Hospital Universitario La Paz, Madrid, Spain;
⁵Division of Therapeutical Teaching for Chronic Diseases, University Hospital, Geneva, Switzerland;
⁶Department of Internal Medicine, Catholic University, Rome, Italy.

Corresponding author: Susanne R. de Rooij, s.r.derooij{at}amc.uva.nl.

Abstract

OBJECTIVE Low-grade chronic inflammation has been hypothesized to underlie the constellation of cardiometabolic risk factors, possibly by inducing insulin resistance. In the present study, we investigated associations between inflammation markers, insulin sensitivity (expressed as the ratio of the M value to the mean plasma insulin concentrations measured during the final 40 min of the clamp [M/I]), and a range of cardiometabolic risk factors in a large, healthy population.

RESEARCH DESIGN AND METHODS The Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) cohort includes 1,326 nondiabetic European men and women, aged between 30 and 60 years. We measured cardiometabolic risk factors and performed a hyperinsulinemic-euglycemic clamp. We determined total white blood cell count (WBC) and erythrocyte sedimentation rate (ESR) as markers of chronic inflammation.

RESULTS WBC and ESR were both strongly associated with M/I. WBC and ESR were further associated with a range of cardiometabolic risk factors. Associations between WBC and HDL cholesterol, triglycerides, heart rate, fasting C-peptide, and insulin and 2-h insulin in men and women and between WBC and 2-h glucose in women remained significant after adjustment for both M/I and waist circumference. Associations between ESR and HDL cholesterol, heart rate, fasting, and 2-h insulin in men and women and between ESR and fat mass in women remained significant after adjustment for M/I and waist circumference.

CONCLUSIONS This study showed that low-grade chronic inflammation is associated with the cardiometabolic risk profile of a healthy population. Insulin resistance, although strongly associated with inflammation, does not seem to play a large intermediary role.

Footnotes

↵*A complete list of the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) investigators and recruiting centers is available in an online appendix.
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- Received September 30, 2008.
- Accepted March 28, 2009.
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