Vitamin D Levels and Mortality in Type 2 Diabetes

Abstract

OBJECTIVE: To evaluate vitamin D as a predictor of all-cause and cardiovascular mortality and risk of progression to micro- or macroalbuminuria in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: In a longitudinal observational follow-up study, 289 type 2 diabetic patients with normoalbuminuria (n = 172), microalbuminuria (n = 73), and macroalbuminuria (n = 44) at baseline were followed for a median (range) of 15.0 (0.2-23) years. Mean ± SD age was 54 ± 9 years. Plasma 25-hydroxyvitamin D(3) levels were determined by high-performance liquid chromatography/tandem mass spectrometry on baseline samples. Severe vitamin D deficiency was defined as the lower 10th percentile (<13.9 nmol/l). RESULTS: Median (range) vitamin D level was 35.7 (5-136.7) nmol/l. Vitamin D levels were not associated with age, sex, estimated glomerular filtration rate, urinary albumin excretion rate (UAER), or A1C at baseline, but low levels were weakly associated with elevated systolic blood pressure (R = 0.13, P = 0.03). During follow-up, 196 (68%) patients died. All-cause mortality was increased in patients with severe vitamin D deficiency (hazard ratio 1.96 [95% CI 1.29-2.98]). The association persisted after adjustment for UAER, A1C, diabetes duration, and conventional cardiovascular risk factors (2.03 [1.31-3.13]). Severe vitamin D deficiency was associated with increased cardiovascular mortality (1.95 [1.11-3.44]), and the association persisted after adjustment (1.90 [1.15-3.10]). Severe vitamin D deficiency at baseline did not predict progression to micro- or macroalbuminuria. CONCLUSIONS: In type 2 diabetic patients, severe vitamin D deficiency predicts increased risk of all-cause and cardiovascular mortality, independent of UAER and conventional cardiovascular risk factors. Whether vitamin D substitution improves prognosis remains to be investigated.