Administering 25-hydroxyvitamin D3 in vitamin D-deficient young type 1A diabetic patients reduces reactivity against islet autoantigens

• Published in: Clinical nutrition (Edinburgh, Scotland) Vol. 33; no. 6; pp. 1153 - 1156
• Main Authors: Federico, G, Focosi, D, Marchi, B, Randazzo, E, De Donno, M, Vierucci, F, Bugliani, M, Campi, F, Scatena, F, Saggese, G, Mathieu, C, Marchetti, P
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.12.2014; Elsevier
• Subjects: 25-Hydroxyvitamin D; Adolescent; Autoantigens - metabolism; Biological and medical sciences; C-Peptide - metabolism; Calcifediol - administration & dosage; Calcifediol - blood; Child; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - drug therapy; Diabetes. Impaired glucose tolerance; ELISpot; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology and Hepatology; Glutamate Decarboxylase - metabolism; Humans; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Interferon-gamma - metabolism; Interferon-γ; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Male; Medical sciences; Proinsulin - metabolism; Type 1A diabetes mellitus; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vitamin D; Vitamin D Deficiency - blood; Vitamin D Deficiency - drug therapy; Type 1A diabetes mellitus; tyrosine phosphatase-like protein IA-2; PBMC; ELISpot; IFN-γ; Vitamin D; Interferon-γ; 1,25-dihydroxyvitamin D; glycated hemoglobin; 25(OH)D; GAD-65; glutamic acid decarboxylase 65-kD isoform; HbA1c; peripheral blood mononuclear cell; 25-Hydroxyvitamin D; IA-2; 1,25(OH) 2D; 1,25(OH)2D; Endocrinopathy; Autoimmunity; Human; Steroid hormone; Diabetes mellitus; Deficiency; Langerhans islet; Metabolic diseases; Autoantigen; Reactivity; Cholecalciferol(25-hydroxy); Endocrine pancreas
• ISSN: 0261-5614; 1532-1983
• DOI: 10.1016/j.clnu.2014.01.001

Summary Background & aims We investigated whether improving 25-hydroxyvitamin D status in young type 1A diabetic patients reduces reactivity of peripheral blood mononuclear cells against islet autoantigens and associates with beta-cell functional changes. Methods Eight patients with 25-hydroxyvitamin D deficiency (<20 ng/ml), out of 15 consecutive young type 1A diabetic subjects received 25-hydroxyvitamin D3 to achieve and maintain levels above 50 ng/ml for up to one year. Peripheral blood mononuclear cell reactivity (Interferon-γ spots) against beta-cell autoantigens (glutamic acid decarboxylase 65-kD isoform, proinsulin and tyrosine phosphatase-like protein IA-2) and C-peptide during mixed meal were assessed before and after 25-hydroxyvitamin D3 replenishment. Results Target 25-hydroxyvitamin D blood levels were safely reached and maintained. Peripheral blood mononuclear cell reactivity against glutamic acid decarboxylase 65-kD isoform (3.8 ± 4.0 vs. 45 ± 16) and proinsulin (3.5 ± 3.2 vs. 75 ± 51) decreased significantly ( p  < 0.001 and p  < 0.02) upon 25-hydroxyvitamin D3 replenishment, which was correlated with 25-hydroxyvitamin D concentrations. C-peptide values remained stable after one year of treatment. Conclusions Safely restored and maintained 25-hydroxyvitamin D levels associated with reduced peripheral blood mononuclear cell reactivity against beta-cell autoantigens with no significant decrease of beta-cell function in this cohort of patients.