Background: Carotid Intima-Media Thickness (C-IMT) is a reliable predictor of cardiovascular events. We examined if increased C-IMT was associated with defects in glucose metabolism in non-diabetic subjects independently of age. Methods: In 366 Caucasian non-diabetic subjects of the CARAMERIS study, we measured glucose response during a 75g-Oral Glucose Tolerance Test (OGTT), insulin sensitivity index (ISI, by Matsuda Index), Liver Insulin Resistance Index (Liver-IR), insulin secretion by δAUC Ins0-120/Glu0-120 (δI/δG) and beta cell function (Disposition Index, DI). Results: Subjects were divided in two groups according to the median age (AGE1≤45y; AGE2>45y). Only 5 subjects in AGE1 and 32 in AGE2 had C-IMT>0.9mm. Compared to AGE1, AGE2 had a worse cardio-metabolic profile, increased cholesterol, glucose and insulin concentrations, blood pressure and C-IMT. Both δI/δG ratio and DI were significantly reduced in AGE2. By considering tertiles of C-IMT in each AGE group (G1-G3, where G3 comprised the highest C-IMT), we found that G3 showed increased OGTT glucose profiles and Liver IR, decreased ISI and DI, compared to G1 in each AGE group. Conclusions: Increased C-IMT, but within normal ranges, is associated independently of age with altered postprandial glucose profile, increased peripheral and hepatic insulin resistance, decreased b-cell function. C-IMT measurement should become a routine analysis even in younger subjects to predict the risk of cardio-metabolic disease.