Circulating Vitamin D Metabolites and Kidney Disease in Type 1 Diabetes

J Clin Endocrinol Metab. 2012 Dec;97(12):4780-8. doi: 10.1210/jc.2012-2852. Epub 2012 Sep 18.

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/1.73 m(2); 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.

Trial registration: ClinicalTrials.gov NCT00360815 NCT00360893.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albuminuria / blood
  • Albuminuria / complications
  • Albuminuria / epidemiology
  • Albuminuria / metabolism
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetic Nephropathies / blood*
  • Diabetic Nephropathies / complications
  • Diabetic Nephropathies / epidemiology
  • Diabetic Nephropathies / metabolism*
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Humans
  • Hypertension / blood
  • Hypertension / complications
  • Hypertension / epidemiology
  • Hypertension / metabolism
  • Incidence
  • Male
  • Randomized Controlled Trials as Topic
  • Vitamin D / analysis
  • Vitamin D / blood*
  • Vitamin D / metabolism

Substances

  • Vitamin D

Associated data

  • ClinicalTrials.gov/NCT00360815
  • ClinicalTrials.gov/NCT00360893