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Fasting insulin has a stronger association with an adverse cardiometabolic risk profile than insulin resistance: the RISC study

Department of Clinical Epidemiology and Biostatistics, Institute for Research in Extramural Medicine, VU University Medical Center, 1081 BT, Amsterdam, The Netherlands¹ Department of Internal Medicine, University of Pisa, Pisa, Italy² Endocrine Unit, Aretaieion Hospital, University of Athens, Athens, Greece³ Hypertension and Cardiovascular Disease, Malmö University Hospital, Lund University, Lund, Sweden⁴ Unidad de Investigacion, Hospital Universitario La Paz, Madrid, Spain⁵ Department of Internal Medicine, Catholic University, Rome, Italy⁶ Department of Endocrinology M, Odense University Hospital, Odense, Denmark⁷ Department of Endocrinology, Trinity College Dublin, St James' Hospital, Dublin, Ireland

(Correspondence should be addressed to S R de Rooij; Email: s.r.derooij{at}amc.uva.nl)

Objective: Fasting insulin concentrations are often used as a surrogate measure of insulin resistance. We investigated the relative contributions of fasting insulin and insulin resistance to cardiometabolic risk and preclinical atherosclerosis.

Design and methods: The Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) cohort consists of 1326 European non-diabetic, overall healthy men and women aged 30–60 years. We performed standard oral glucose tolerance tests and hyperinsulinemic euglycemic clamps. As a general measure of cardiovascular risk, we assessed the prevalence of the metabolic syndrome in 1177 participants. Carotid artery intima media thickness (IMT) was measured by ultrasound to assess preclinical atherosclerosis.

Results: Fasting insulin was correlated with all elements of the metabolic syndrome. Insulin sensitivity (M/I) was correlated with most elements. The odds ratio for the metabolic syndrome of those in the highest quartile of fasting insulin compared with those in the lower quartiles was 5.4 (95% confidence interval (CI) 2.8–10.3, adjusted for insulin sensitivity) in men and 5.1 (2.6–9.9) in women. The odds ratio for metabolic syndrome of those with insulin sensitivity in the lowest quartile of the cohort compared with those in the higher quartiles was 2.4 (95% CI 1.3–4.7, adjusted for fasting insulin) in men and 1.6 (0.8–3.1) in women. Carotid IMT was only statistically significantly associated with fasting insulin in both men and women.

Conclusions: Fasting insulin, a simple and practical measure, may be a stronger and independent contributor to cardiometabolic risk and atherosclerosis in a healthy population than hyperinsulinemic euglycemic clamp-derived insulin sensitivity.