Circulating vitamin D metabolites and kidney disease in type 1 diabetes

Ian H. De Boer, Michael C. Sachs, Patricia A. Cleary, Andrew N. Hoofnagle, John M. Lachin, Mark E. Molitch, Michael W. Steffes, Wanjie Sun, Bernard Zinman, John D. Brunzell

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Abstract

Context: Impaired vitamin D metabolism may contribute to the development and progression of diabetic kidney disease. Objective: The aim of the study was to test associations of circulating vitamin D metabolites with risks of incident microalbuminuria, impaired glomerular filtration rate (GFR), and hypertension in type 1 diabetes. Design: We performed a cohort study of 1193 participants in the Diabetes Control and Complications Trial (DCCT), a randomized clinical trial of intensive diabetes therapy, and its observational follow-up, the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. We measured plasma concentrations of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D by mass spectrometry at the end of the DCCT and tested associations with incident microalbuminuria, impaired GFR, and hypertension over up to 16 yr of EDIC follow-up. Results: At the time metabolites were measured, mean age was 32.4 yr; mean duration of diabetes, 7.5 yr; mean iothalamate GFR, 132.9 ml/min/1.73m2; and geometric mean albumin excretion rate, 11.8 mg/24 h. Over follow-up, 166 cases of microalbuminuria, 54 cases of impaired GFR, and 541 cases of hypertension were observed. Compared with 25(OH)D of at least 30 ng/ml, 25(OH)D below 20 ng/ml was associated with a 65% higher risk of microalbuminuria (95% confidence interval, 7 to 154%) in adjusted analyses. Low concentrations of 24,25-dihydroxyvitamin D, but not 1,25- dihydroxyvitamin D, were also associated with increased risk of microalbuminuria. No circulating vitamin D metabolite was associated with risk of impaired GFR or hypertension. Conclusions: Low plasma concentrations of 25(OH)D and 24,25-dihydroxyvitamin D are associated with increased risk of microalbuminuria in type 1 diabetes. In contrast, we did not find evidence linking impaired vitamin D metabolism to early GFR loss or the development of hypertension.

Original languageEnglish (US)
Pages (from-to)4780-4788
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume97
Issue number12
DOIs
StatePublished - Dec 1 2012

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    De Boer, I. H., Sachs, M. C., Cleary, P. A., Hoofnagle, A. N., Lachin, J. M., Molitch, M. E., Steffes, M. W., Sun, W., Zinman, B., & Brunzell, J. D. (2012). Circulating vitamin D metabolites and kidney disease in type 1 diabetes. Journal of Clinical Endocrinology and Metabolism, 97(12), 4780-4788. https://doi.org/10.1210/jc.2012-2852