Plasma sCD36 is associated with markers of atherosclerosis, insulin resistance and fatty liver in a nondiabetic healthy population

Handberg A, Hojlund K, Gastaldelli A, Flyvbjerg A, Dekker JM, Petrie J, Piatti P, Beck-Nielsen H (Aarhus Hospital and Aalborg Hospital, Aarhus University Hospital, Aarhus, Denmark; Odense University Hospital, Odense, Denmark; Institute of Clinical Physiology, CNR Pisa, Pisa, Italy; Aarhus University Hospital, Aarhus, Denmark; Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; BHF Glasgow Cardiovascular Research Centre, Glasgow, UK; and San Raffaele Institute, Milan, Italy). Plasma sCD36 is associated with markers of atherosclerosis, insulin resistance and fatty liver in a nondiabetic healthy population. J Intern Med 2012; 271: 294304. Objectives. Insulin resistance is associated with increased CD36 expression in a number of tissues. Moreover, excess macrophage CD36 may initiate atherosclerotic lesions. The aim of this study was to determine whether plasma soluble CD36 (sCD36) was associated with insulin resistance, fatty liver and carotid atherosclerosis in nondiabetic subjects. Methods. In 1296 healthy subjects without diabetes or hypertension recruited from 19 centres in 14 European countries (RISC study), we determined the levels of sCD36, adiponectin, lipids and liver enzymes, insulin sensitivity (M/I) by euglycaemic-hyperinsulinaemic clamp, carotid atherosclerosis as intimamediathickness (IMT) andtwo estimates of fatty liver, the fatty liver index (FLI) and liver fat percentage (LF%). Results. IMT, FLI, LF%, presence of the metabolic syndrome, impaired glucose regulation, insulin and triglycerides increased across sCD36 quartiles (Q2-Q4), whereas adiponectin and M/I decreased (P <= 0.01). sCD36 was lower in women than in men (P = 0.045). Log sCD36 showed a bimodal distribution, and amongst subjects with sCD36 within the log-normal distribution (log-normal population, n = 1029), sCD36 was increased in subjects with impaired glucose regulation (P = 0.045), metabolic syndrome (P = 0.006) or increased likelihood of fatty liver (P < 0.001). sCD36 correlated significantly within sulin, triglycerides, M/I and FLI (P < 0.05) after adjustment for study centre, gender, age, glucose tolerance status, smoking habits and alcohol consumption. In the log-normal population, these relationships were stronger than in the total studypopulationand, additionally, sCD36 was significantly associated with LF% and IMT(P < 0.05). Conclusions. In this cross-sectional study of nondiabetic subjects, sCD36 was significantly associated with indices of insulin resistance, carotid atherosclerosis and fatty liver. Prospective studies are needed to further evaluate the role of sCD36 in the inter-relationship between atherosclerosis, fatty liver and insulin resistance.