title: Effects of 12 weeks high dose vitamin D3 treatment on insulin sensitivity, beta cell function, and metabolic markers in patients with type 2 diabetes and vitamin D insufficiency - a double-blind, randomized, placebo-controlled trial.
abstract: OBJECTIVE
  Vitamin D insufficiency is common in subjects with type 2 diabetes. Observational studies suggest that vitamin D plays a role in the pathogenesis of type 2 diabetes. However, results of intervention studies have been inconsistent. We investigated the effects of improving vitamin D status on insulin sensitivity, insulin secretion, and inflammatory markers in patients with type 2 diabetes.
  
  
  METHODS
  A double blind, randomized, placebo controlled trial was conducted. Sixteen patients with type 2 diabetes and hypovitaminosis D were recruited. Eight patients received colecalciferol and (280 μg daily for 2 weeks, 140 μg daily for 10 weeks) and 8 patients received identical placebo tablets for 12 weeks. Before and after intervention, patients underwent IVGTT, hyperinsulinemic euglycemic clamp, assessment of baseline high-frequency insulin pulsatility, glucose-entrained insulin pulsatility, DXA scans, 24-hour-ambulatory blood pressure monitorings, and fasting blood samples.
  
  
  RESULTS
  Serum-25(OH) vitamin D and serum-1,25(OH)₂ vitamin D increased significantly after 12 weeks in the intervention group (p=0.01, p=0.004). Serum-25(OH) vitamin D was also significantly higher in the vitamin D group compared to the placebo group (p=0.02) after intervention. Although no significant changes in insulin sensitivity, inflammation, blood pressure, lipid profile, or HbA1c were found, we observed borderline (p between 0.05 and 0.10) improvements of insulin secretion, in terms of c-peptide levels, first phase incremental AUC insulin and insulin secretory burst mass.
  
  
  CONCLUSIONS
  Improvement in vitamin D status does not improve insulin resistance, blood pressure, inflammation or HbA1c, but might increase insulin secretion in patients with established type 2 diabetes.
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. Electronic address: ulla@opstrup.dk.
authors.forename: Ulla
authors.initials: U
authors.lastname: Kampmann
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Leif
authors.initials: L
authors.lastname: Mosekilde
authors.affiliation: Department of Endocrinology, Sydvestjysk Hospital, Esbjerg, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Juhl
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Moller
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; Section of Sports Science, Institute of Public Health, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Britt
authors.initials: B
authors.lastname: Christensen
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Rejnmark
authors.affiliation: Department of Endocrinology, Sydvestjysk Hospital, Esbjerg, Denmark.
authors.forename: Louise
authors.initials: L
authors.lastname: Wamberg
authors.affiliation: Department of Internal Medicine, Silkeborg Regional Hospital, Silkeborg, Denmark.
authors.forename: Lotte
authors.initials: L
authors.lastname: Orskov
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002096:C-Peptide / Q000097:blood; D002112:Calcifediol / Q000097:blood; D002117:Calcitriol / Q000097:blood; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000276:immunology; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D012621:Seasons; D012720:Severity of Illness Index; D014808:Vitamin D Deficiency / Q000150:complications / Q000178:diet therapy* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D002096:C-Peptide; D018836:Inflammation Mediators; D007328:Insulin; D002762:Cholecalciferol; D002117:Calcitriol; D002112:Calcifediol
keywords: Hyperinsulinemic euglycemic clamp; Inflammation; Insulin pulsatility; Vitamin D deficiency