Low circulating vitamin D levels are associated with increased arterial stiffness in prediabetic subjects identified according to HbA1c

Background and aims: We investigated serum -hydroxyvitamin D levels [25(OH) D] and their correlation with early markers of cardiovascular disease in subjects with pre-diabetes. We particularly focused on individuals identified only by glycated hemoglobin A(1c) (HbA(1c) 5.7-6.4%) according to the American Diabetes Association criteria but who were normotolerant (NT) after oral glucose tolerance test (OGTT) and had normal fasting glucose (NFG). Methods: 25(OH) D levels, HbA(1c), OGTT, arterial stiffness and intima-media thickness (IMT) were evaluated in 286 subjects without history of diabetes. Subjects were stratified into four groups: controls with HbA(1c) <5.7%, NFG and NT; prediabetic patients with pre-diabetes according to only HbA1c (HbA1c 5.7-6.4% and NFG/NT); subjects with impaired fasting glucose and impaired glucose tolerance (IFG/IGT); new onset type 2 diabetes (HbA(1c) >= 6.5%). Results: Subjects with NFG/NT and HbA(1c) 5.7-6.4% (n = 83) showed lower 25(OH) D levels compared with controls (n = 80) (21.7 [15.8-31.1] vs 23.1 [17.1-29.7] ng/mL, P = 0.009); these values were similar to those of the IFG/IGT group and were higher but not significantly different from subjects with new onset type 2 diabetes. After multiple regression analyses, only HbA(1c) and BMI were independently associated with 25(OH) D levels. Age, HbA(1c) and 25(OH) D were the major determinants of Augmentation Index. No independent association between 25(OH) D and IMT was found. Conclusions: Subjects with pre-diabetes (HbA(1c) 5.7-6.4% and NFG/NT) had significantly reduced 25(OH) D levels compared with controls. Reduction of 25(OH) D levels is inversely associated with arterial stiffness independently of classical risk factors and inflammatory markers. Based on these data, subjects with NFG and NT are not a homogeneous population of patients, and they present different cardiovascular and glycometabolic risks. Our data suggest considering HbA(1c) as a reliable marker of cardiovascular and metabolic risk independent of fasting and post-load glycemia. (C) 2015 Elsevier Ireland Ltd. All rights reserved.