Relationship between vitamin D deficiency, post‐challenge hyperglycemia, and endothelial function in healthy older adults

Vitamin D deficiency has been increasingly implicated in the pathogenesis of glucose intolerance and cardiovascular disease (CVD). Mild hyperglycemia in the elderly is often clinically unrecognized, but appears to be particularly associated with an increased risk of CVD, CVD death, and total mortality. Previously, we reported the unfavorable cardiac risk profile of a cohort of community-dwelling older adults with mild post-challenge hyperglycemia (PCH), including enhanced inflammation, impaired fibrinolysis and endothelial dysfunction. 8 In the present study, we sought to evaluate the relationship between vitamin D status and both glucose tolerance and vascular function in this well-characterized cohort. Vitamin D levels were analyzed in subjects with PCH (i.e. fasting plasma glucose <126 mg ⁄dL and 2-h glucose ‡170 mg ⁄dL; n = 28) and a control group with normal glucose tolerance (NGT; n = 27). Detailed inclusion and exclusion criteria have been reported elsewhere. Vitamin D deficiency was defined as serum 25-hydroxy-vitamin D levels <20 ng ⁄mL. Endothelial function was assessed using reactive hyperemia peripheral arterial tonometry (RH-PAT). The PCH and NGT groups were frequency matched for age, sex, and adiposity (body mass index [BMI], waist circumference, and percentage body fat) and were of similar race ⁄ ethnicity. By definition, 2-h glucose levels were higher in the PCH group (193 ± 5 vs 104 ± 3 mg ⁄dL; P < 0.001), as were fasting glucose levels (102 ± 3 vs 93 ± 2 mg ⁄dL; P = 0.02). As reported previously, the PCH group had a more adverse CVD risk profile, including higher levels of plasminogen activator inhibitor (PAI)-1, highly sensitive C-reactive protein (hsCRP), and systolic and diastolic blood pressure and lower adiponectin levels, although lipoprotein levels did not differ between the two groups. Slightly more subjects in the NGT group were recruited during the winter months (December– April) compared with the PCH group (44% vs 32%; P = 0.4). Similar numbers in each group reported taking multivitamins (eight in the NGT group and five in the PCH group) and vitamin D supplements (one in the NGT group and three in the PCH group). Physical activity levels were similar in the two groups, as assessed by an activity questionnaire and 3-day pedometer readings. Median (interquartile range [IQR]) vitamin D levels (ng ⁄dL) in the NGT and PCH groups were 23.8 (21.2–31.3) and 18.8 (11.7–26.7), respectively (P = 0.01) and the prevalence of vitamin D deficiency was significantly higher in the PCH group than the NGT group (53.6% vs 22.2%, respectively; P = 0.01). A significant inverse relationship was found between vitamin D levels and 2-h glucose levels after the oral glucose tolerance test (Spearman’s r = )0.34; P = 0.01). There was also an inverse correlation between vitamin D levels and BMI (Spearman’s r = )0.33; P = 0.01), which was most evident in the PCH group (Spearman’s r = )0.55; P = 0.003). Borderline relationships were found between vitamin D levels and other adiposity measures, namely percentage body fat (r = )0.24; P = 0.08) and waist circumferance (r = )0.29; P = 0.06). There were no significant correlations between Correspondence Seth I. Sokol, Jacobi Medical Center, 1400 Pelham Pkwy, Bld 1, 5W, Bronx, NY 10461, USA. Tel: +1 718 918 5735 Fax: +1 718 918 5733 Email: seth.sokol@nbhn.net Received 1 September 2011; accepted 15 September 2011. doi: 10.1111/j.1753-0407.2011. 00158.x Journal of Diabetes 4 (2012) 102–103