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

Research output: Contribution to journalArticle

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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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Kidney Diseases
Medical problems
Metabolites
Glomerular Filtration Rate
Type 1 Diabetes Mellitus
Vitamin D
Diabetes Complications
Dihydroxycholecalciferols
Hypertension
Epidemiology
Iothalamic Acid
Metabolism
Diabetic Nephropathies
Plasmas
Albumins
Mass Spectrometry
Cohort Studies
Randomized Controlled Trials
Confidence Intervals
Mass spectrometry

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De Boer, I. H., Sachs, M. C., Cleary, P. A., Hoofnagle, A. N., Lachin, J. M., Molitch, M. E., ... 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

Circulating vitamin D metabolites and kidney disease in type 1 diabetes. / De Boer, Ian H.; Sachs, Michael C.; Cleary, Patricia A.; Hoofnagle, Andrew N.; Lachin, John M.; Molitch, Mark E.; Steffes, Michael W.; Sun, Wanjie; Zinman, Bernard; Brunzell, John D.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 97, No. 12, 01.12.2012, p. 4780-4788.

Research output: Contribution to journalArticle

De Boer, IH, Sachs, MC, Cleary, PA, Hoofnagle, AN, Lachin, JM, Molitch, ME, Steffes, MW, Sun, W, Zinman, B & Brunzell, JD 2012, 'Circulating vitamin D metabolites and kidney disease in type 1 diabetes', Journal of Clinical Endocrinology and Metabolism, vol. 97, no. 12, pp. 4780-4788. https://doi.org/10.1210/jc.2012-2852
De Boer IH, Sachs MC, Cleary PA, Hoofnagle AN, Lachin JM, Molitch ME et al. Circulating vitamin D metabolites and kidney disease in type 1 diabetes. Journal of Clinical Endocrinology and Metabolism. 2012 Dec 1;97(12):4780-4788. https://doi.org/10.1210/jc.2012-2852
De Boer, Ian H. ; Sachs, Michael C. ; Cleary, Patricia A. ; Hoofnagle, Andrew N. ; Lachin, John M. ; Molitch, Mark E. ; Steffes, Michael W. ; Sun, Wanjie ; Zinman, Bernard ; Brunzell, John D. / Circulating vitamin D metabolites and kidney disease in type 1 diabetes. In: Journal of Clinical Endocrinology and Metabolism. 2012 ; Vol. 97, No. 12. pp. 4780-4788.
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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.",
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AU - Molitch, Mark E.

AU - Steffes, Michael W.

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N2 - 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.

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