Administering 25-hydroxyvitamin D3 in vitamin D-deficient young type 1A diabetic patients reduces reactivity against islet autoantigens.
OBJECTIVE
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.
Sezione di Diabetologia Pediatrica, U.O. Pediatria Universitaria, Dipartimento Materno Infantile, Azienda Ospedaliero-Universitaria Pisana, Italy. Electronic address: giovanni.federico@med.unipi.it.
G
G
Federico
U.O. Medicina Trasfusionale e Biologia dei Trapianti, Dipartimento di Oncologia, dei Trapianti e delle Nuove Tecnologie, Azienda Ospedaliero-Universitaria Pisana, Italy.
D
D
Focosi
Sezione di Diabetologia Pediatrica, U.O. Pediatria Universitaria, Dipartimento Materno Infantile, Azienda Ospedaliero-Universitaria Pisana, Italy.
B
B
Marchi
Sezione di Diabetologia Pediatrica, U.O. Pediatria Universitaria, Dipartimento Materno Infantile, Azienda Ospedaliero-Universitaria Pisana, Italy.
E
E
Randazzo
U.O. Medicina Trasfusionale e Biologia dei Trapianti, Dipartimento di Oncologia, dei Trapianti e delle Nuove Tecnologie, Azienda Ospedaliero-Universitaria Pisana, Italy.
M
M
De Donno
Sezione di Diabetologia Pediatrica, U.O. Pediatria Universitaria, Dipartimento Materno Infantile, Azienda Ospedaliero-Universitaria Pisana, Italy.
F
F
Vierucci
Sezione di Endocrinologia e Metabolismo dei Trapianti d'Organo e Cellulari, Dipartimento di Oncologia, dei Trapianti e delle Nuove tecnologie, Azienda Ospedaliero-Universitaria Pisana, Italy.
M
M
Bugliani
U.O. Malattie Metaboliche e Endocrinologia, Dipartimento di Area Medica, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
F
F
Campi
U.O. Medicina Trasfusionale e Biologia dei Trapianti, Dipartimento di Oncologia, dei Trapianti e delle Nuove Tecnologie, Azienda Ospedaliero-Universitaria Pisana, Italy.
F
F
Scatena
Sezione di Diabetologia Pediatrica, U.O. Pediatria Universitaria, Dipartimento Materno Infantile, Azienda Ospedaliero-Universitaria Pisana, Italy.
G
G
Saggese
Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium.
C
C
Mathieu
Sezione di Endocrinologia e Metabolismo dei Trapianti d'Organo e Cellulari, Dipartimento di Oncologia, dei Trapianti e delle Nuove tecnologie, Azienda Ospedaliero-Universitaria Pisana, Italy.
P
P
Marchetti
D000293:Adolescent; D001324:Autoantigens / Q000378:metabolism*; D002096:C-Peptide / Q000378:metabolism; D002112:Calcifediol / Q000008:administration & dosage* / Q000097:blood; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011384:Proinsulin / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000097:blood / Q000188:drug therapy*
D001324:Autoantigens; D002096:C-Peptide; D007371:Interferon-gamma; D011384:Proinsulin; D005968:Glutamate Decarboxylase; D002112:Calcifediol
25-Hydroxyvitamin D; ELISpot; Interferon-γ; Type 1A diabetes mellitus; Vitamin D