Enhanced Excretion of Vitamin D Binding Protein in Type 1 Diabetes: A Role in Vitamin D Deficiency?

Context: Vitamin D deficiency is an increasingly recognized comorbidity in patients with both type 1 (T1D) and type 2 diabetes, particularly associated with the presence of diabetic nephropathy. Objective: Because we have previously reported enhanced excretion of megalin in the urine of T1D patients with microalbuminuria, we hypothesized that concurrent urinary loss of the megalin ligand, vitamin D binding protein, might contribute mechanistically to vitamin D deficiency. Design and Participants: Examining a study cohort of 115 subjects with T1D, aged 14-40 yr, along with 55 age-matched healthy control subjects, we measured plasma and urine concentrations of vitamin D binding protein (VDBP) along with serum concentrations of total calcium, parathyroid hormone, 25-hydroxyvitamin D, and 1, 25-dihydroxyvitamin D; these results were compared between groups and investigated for relationships with metabolic control status or with albuminuria. Main Outcome Measure: Between-group differences in urinary VDBP concentration were the main outcome measures. Results: A marked increase in the urinary excretion of VDBP was apparent in subjects with T1D, compared with control subjects. Using multivariate regression modeling, significant correlates of urinary VDBP excretion included microalbuminuria (P = 0.004), glycosylated hemoglobin (P = 0.010), continuous glucose monitoring system average capillary glucose (P = 0.047), and serum 1,25(OH)(2)D concentrations (P = 0.037). Vitamin D deficiency or insufficiency was slightly more prevalent in diabetic subjects with albuminuria, coincident with the increase in urine VDBP excretion. Conclusions: These findings suggest that, theoretically, exaggerated urinary loss of VDBP in T1D, particularly in persons with albuminuria, could contribute mechanistically to vitamin D deficiency in this disease. (J Clin Endocrinol Metab 96: 142-149, 2011)