title: Low 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 levels are independently associated with macroalbuminuria, but not with retinopathy and macrovascular disease in type 1 diabetes: the EURODIAB prospective complications study.
abstract: BACKGROUND
  Low circulating levels of total vitamin D [25(OH)D] and 25(OH)D3 have been associated with vascular complications in few studies on individuals with type 1 diabetes. However, these measures are affected by UV light exposure. Circulating 25(OH)D2, however, solely represents dietary intake of vitamin D2, but its association with complications of diabetes is currently unknown. We investigated the associations between 25(OH)D2 and 25(OH)D3 and the prevalence of albuminuria, retinopathy and cardiovascular disease (CVD) in individuals with type 1 diabetes.
  
  
  METHODS
  We measured circulating 25(OH)D2 and 25(OH)D3 in 532 individuals (40 ± 10 years old, 51 % men) with type 1 diabetes who participated in the EURODIAB Prospective Complications Study. Cross-sectional associations of 25(OH)D2 and 25(OH)D3 with albuminuria, retinopathy and CVD were assessed with multiple logistic regression analyses adjusted for age, sex, season, BMI, smoking, HbA1c, total-HDL-cholesterol-ratio, systolic blood pressure, antihypertensive medication, eGFR, physical activity, alcohol intake, albuminuria, retinopathy and CVD, as appropriate.
  
  
  RESULTS
  Fully adjusted models revealed that 1 nmol/L higher 25(OH)D2 and 10 nmol/L higher 25(OH)D3 were associated with lower prevalence of macroalbuminuria with ORs (95 % CI) of 0.56 (0.43;0.74) and 0.82 (0.72;0.94), respectively. These vitamin D species were not independently associated with microalbuminuria, non-proliferative and proliferative retinopathy or CVD.
  
  
  CONCLUSIONS
  In individuals with type 1 diabetes, both higher 25(OH)D2 and 25(OH)D3 are associated with a lower prevalence of macroalbuminuria, but not of retinopathy and CVD. Prospective studies are needed to further examine the associations between 25(OH)D2 and 25(OH)D3 and the development of microvascular complications and CVD in type 1 diabetes.
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Centre, Universiteitssingel 50, 6200 MD, Maastricht, The Netherlands. l.engelen@maastrichtuniversity.nl.|CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands. l.engelen@maastrichtuniversity.nl.|Top Institute Food and Nutrition, Wageningen, The Netherlands. l.engelen@maastrichtuniversity.nl.
authors.forename: Lian
authors.initials: L
authors.lastname: Engelen
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Centre, Universiteitssingel 50, 6200 MD, Maastricht, The Netherlands. c.schalkwijk@maastrichtuniversity.nl.|CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands. c.schalkwijk@maastrichtuniversity.nl.|Top Institute Food and Nutrition, Wageningen, The Netherlands. c.schalkwijk@maastrichtuniversity.nl.
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.affiliation: CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, The Netherlands. simone.eussen@maastrichtuniversity.nl.|Department of Epidemiology, Maastricht University, Maastricht, The Netherlands. simone.eussen@maastrichtuniversity.nl.|Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway. simone.eussen@maastrichtuniversity.nl.
authors.forename: Simone J P M
authors.initials: SJ
authors.lastname: Eussen
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Centre, Universiteitssingel 50, 6200 MD, Maastricht, The Netherlands. j.scheijen@maastrichtuniversity.nl.|CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands. j.scheijen@maastrichtuniversity.nl.
authors.forename: Jean L J M
authors.initials: JL
authors.lastname: Scheijen
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands. sabita.soedamah-muthu@wur.nl.
authors.forename: Sabita S
authors.initials: SS
authors.lastname: Soedamah-Muthu
authors.affiliation: International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, UK. n.chaturvedi@ucl.ac.uk.
authors.forename: Nish
authors.initials: N
authors.lastname: Chaturvedi
authors.affiliation: Department of Epidemiology and Public Health, University College, London, UK. johnfuller211@btinternet.com.
authors.forename: John H
authors.initials: JH
authors.lastname: Fuller
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Centre, Universiteitssingel 50, 6200 MD, Maastricht, The Netherlands. cda.stehouwer@mumc.nl.|CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands. cda.stehouwer@mumc.nl.|Top Institute Food and Nutrition, Wageningen, The Netherlands. cda.stehouwer@mumc.nl.
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D015652:25-Hydroxyvitamin D 2 / Q000097:blood* / Q000172:deficiency; D000328:Adult; D000419:Albuminuria / Q000097:blood / Q000453:epidemiology*; D002112:Calcifediol / Q000097:blood* / Q000172:deficiency; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology* / Q000209:etiology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications; D003925:Diabetic Angiopathies / Q000097:blood / Q000453:epidemiology / Q000209:etiology; D003930:Diabetic Retinopathy / Q000097:blood / Q000453:epidemiology* / Q000209:etiology; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D014808:Vitamin D Deficiency / Q000097:blood / Q000453:epidemiology*
chemical_list: D015652:25-Hydroxyvitamin D 2; D002112:Calcifediol