Reduced IGFBP-1 Is Associated With Thickening of the Carotid Wall in Type 2 Diabetes

Reduced IGFBP-1 Is Associated With Thickening of the Carotid Wall in Type 2 Diabetes Eeva S. Leinonen , MD 1 , Jukka T. Salonen , MD, PHD 4 5 , Riitta M. Salonen , MD, PHD 4 , Riitta A. Koistinen , PHD 2 , Pekka J. Leinonen , MD, PHD 2 , Seppo S. Sarna , PHD 3 and Marja-Riitta Taskinen , MD, PHD 1 1 Department of Internal Medicine, Helsinki University Central Hospital, Helsinki, Finland 2 Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland 3 Department of Public Health, University of Helsinki, Helsinki, Finland 4 Research Institute of Public Health, University of Kuopio, Kuopio, Finland 5 Inner Savo Health Center, Suonenjoki, Finland Abstract OBJECTIVE —The aim of the present study was to assess the role of the insulin-like growth factor (IGF) system and lipids in predicting the carotid intima-media thickness (IMT) in type 2 diabetes. RESEARCH DESIGN AND METHODS —A total of 239 type 2 diabetic participants in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study (76 women) aged 50–75 years were examined before fenofibrate intervention. Patients underwent carotid ultrasonography for determination of IMT. IGF-I, IGF binding protein 1 (IGFBP-1), IGFBP-3, cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoprotein B (apoB), lipoprotein(a) (Lp(a)), glucose, HbA 1c , and C-peptide were measured in fasting samples. Patients were divided in groups without ( n = 168) and with ( n = 71) clinical cardiovascular disease (CVD). RESULTS —Partial correlations adjusted for age, sex, BMI, and diabetes duration showed an inverse association of IGFBP-1 with C-peptide ( r = −0. 24, P = 0.018) and with maximal IMT ( r = −0.42, P < 0.001), whereas IGF I and IGFBP-3 correlated positively with several risk-promoting lipid parameters. In linear regression analysis controlling for age, sex, BMI, diabetes duration, and presence or absence of oral antihyperglycemic or insulin medication, determinants of IMT were age, IGFBP-1, pulse pressure, Lp(a), diabetes duration, and insulin treatment. IGFBP-1 persisted in the model for subjects with CVD. CONCLUSIONS —In summary, a decrease in IGFBP-1 is a marker of carotid IMT thickening in patients with type 2 diabetes. apoB, apolipoprotein B CB, carotid bulb CCA, common carotid artery CVD, cardiovascular disease FIELD, Fenofibrate Intervention and Event Lowering in Diabetes FW, far wall HOMA-IR, homeostasis model assessment of insulin resistance ICA, internal car