Horm Metab Res 2005; 37(11): 680-683
DOI: 10.1055/s-2005-870578
Original Clinical
© Georg Thieme Verlag KG Stuttgart · New York

Low Levels of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 in Patients with Newly Diagnosed Type 1 Diabetes

P.  Pozzilli1, 3 , S.  Manfrini1 , A.  Crinò2 , A.  Picardi1 , C.  Leomanni1 , V.  Cherubini2 , L.  Valente1 , M.  Khazrai1 , N.  Visalli1 , IMDIAB group4
  • 1Dept Endocrinology and Diabetes, University Campus Bio Medico
  • 2Ospedale Bambino Gesu’, Department of Pediatrics, University of Ancona, Italy
  • 3Institute of Cell and Molecular Science, St. Bartholomew’s Hospital, Queen Mary College, London UK
  • 4IMDIAB group: Paolo Pozzilli, Natalia Visalli, Silvia Manfrini, Elvira Fioriti, Giusy Coppolino, Luciana Valente, Chiara Guglielmi, Giuseppina Beretta Anguissola, Flavia Costanza, Anna Lisa Montemari, Gisella Cavallo, Antonio Picardi, Riccardo Schiaffini, Manon Khazrai, Angelo Lauria, Cesarea Leomanni, Laura Cipolloni, Maria C. Matteoli, Patrizia Patera, Antonio Crinò, Stefania Corbi, Sabrina Spera, Concetta Suraci, Marco Cervoni,, Giancarlo De Mattia, Maria R. Cassone Faldetta, Maria L. Manca Bitti, Carla Bizzarri, Marco Cappa, Dario Pitocco, Giovanni Ghirlanda
Further Information

Publication History

Received 4 January 2005

Accepted after revision 4 May 2005

Publication Date:
25 November 2005 (online)

Abstract

Background and aims: An epidemiological retrospective study and a recent prospective study from Finland have both concluded that vitamin D3 supplementation at birth protects individuals from type 1 diabetes later in life. Moreover, it is thought that vitamin D3 supplementation, in particular its activated form, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], may act as an immunomodulator, facilitating the shift from a Th1 to a Th2 immune response. The aim of this surveillance study was to measure levels of both 25-hydroxyvitamin D3 (25OHD3) and 1,25- dihydroxyvitamin D3 in patients with newly diagnosed type 1 diabetes as compared to normal subjects. Methods: We measured plasma levels of 25-hydroxyvitamin D3 [25OHD3] and 1,25-dihydroxyvitamin D3 by radioimmunoassay in 88 consecutive patients with newly diagnosed type 1 diabetes (mean age 14.6 years; diagnosis within the last week), and in 57 healthy age and sex-matched subjects (mean age 16.5 years) born and residing in the Lazio region of continental Italy. Results: Mean levels of both 25OHD3 and 1,25-(OH)2D3 were significantly lower in patients compared to controls (p < 0.01 and p < 0.03, respectively). There was no correlation between 1,25-(OH)2D3 plasma level and metabolic control status at disease diagnosis, age, gender, or most importantly, seasonality of disease diagnosis. This new observation endorses the findings of the Finnish study, even though Italy is a geographic area with more hours of sunlight than Finland. Conclusions: These findings suggest that vitamin D3 may be an important pathogenic factor in type 1 diabetes independent of geographical latitude, and that its supplementation should be considered not only at birth, but also at diagnosis of type 1 diabetes with the aim of favouring a Th2 immune response and protecting residual beta cells from further destruction.

References

  • 1 The EURODIAB Sub-study Group . Vitamin D supplement in early childhood and risk for type I (insulin-dependent) diabetes mellitus.  Diabetologia. 1999;  42 51-54
  • 2 Hypponen E, Läärä E, Reunanen A, Järvelin M R, Virtanen S M. Intake of vitamin D and risk of type 1 diabetes: a birth cohort study.  The Lancet. 2001;  358 1500-1503
  • 3 Cantorna M T. Vitamin D and Autoimmunity: is vitamin D status an environmental factor affecting autoimmune disease prevalence?.  Proc Soc Exp Biol Med. 2000;  223 230-233
  • 4 Stene L C, Ulrikesen J, Magnus P, Joner G. Use of cod liver oil during pregnancy associated with lower risk of type 1 diabetes in the offspring.  An J Clin Nutr. 2003;  78 1128-1134
  • 5 Mathieu C, Adorini L. The coming of age of 1,25-dihydroxyvitamin D(3) analogs as immunomodulatory agents.  Trends Mol Med. 2002;  8 174-179
  • 6 Lemire J. 1,25 dihydroxyvitamin D3 - a hormone with immunomodulatory properties.  J Rheumatol (Suppl 1). 2000;  59 24-27
  • 7 Cantorna M T, Woodward B, Hayes C E, Deluca H F. 1,25dihydroxyvitamin D3 is a positive regulator for the two antiencephalitogenic cytokines TGF-β1 and IL-4.  J Immunol. 1998;  160 5314-5319
  • 8 Riachy R, Vandewalle B, Kerr Conte J, Moerman E, Sacchetti P, Lukowiak B, Gmyr V, Bouckenooghe T, Dubois M, Pattou F. 1,25-dihydroxyvitamin D3 protects RINm5F and human islet cells against cytokine-induced apoptosis: implication of the antiapoptotic protein A20.  Endocrinology. 2002;  143 4809-4819
  • 9 Casteels K, Waer M, Laureys J, Valckx D, Depovere J, Bouillon R, Mathieu C. Prevention of autoimmune destruction of syngeneic islet grafts in spontaneously diabetic non-obese diabetic mice by a combination of a vitamin D3 analog and cyclosporine.  Transplantation. 1998;  15 1225-1232
  • 10 Mathieu C, Waer M, Casteels K, Laureys J, Bouillon R. Prevention of type 1 diabetes in NOD mice by nonhypercalcemic doses of a new structural analog of 1,25dihydroxyvitamin D3, KH1060.  Endocrinology. 1995;  3 866-872
  • 11 Casteels K M, Mathieu C, Waer M, Valckx D, Overbergh L, Laureys J M, Bouillon R. Prevention of type 1 diabetes in non-obese diabetic mice by late intervention with non hypercalcemic analogs of 1,25dihydroxyvitamin D3 in combination with a short induction course of cyclosporin.  J Endocrinology. 1998;  1 95-102
  • 12 McKinney P A. Seasonality of birth in patients with childhood type 1 diabetes in 19 European regions.  Diabetologia. 2001;  44 Suppl 3 B67-B74
  • 13 Baumgartl H J, Standl E, Schmidt-Gayk H, Kolb H J, Janka H U, Ziegler A G. Changes of vitamin D serum concentrations at the onset of immune-mediated type 1 (insulin-dependent) diabetes mellitus.  Diabetes Res. 1991;  16 145-148
  • 14 Schneider L E, Schedl H P, McCain T, Haussler M R. Experimental diabetes reduces circulating 1,25-dihydroxyvitamin D in the rat.  Science. 1997;  196 1452-1454
  • 15 Ishida H, Seino Y, Tsuda K, Takemura J, Nishi S, Ishizuka S, Imura H. Effects of streptozotocin-induced diabetes on circulating levels of vitamin D metabolites.  Acta Endocrinol (Copenh). 1983;  104 96-102
  • 16 Verhaeghe J, van Bree R, van Herck E, Jans I, Zaman Z, Bouillon R. Calciotrophic hormones during experimental hypocalcaemia and hypercalcaemia in spontaneously diabetic rats.  J Endocrinol. 1999;  162 251-258
  • 17 EURODIAB ACE Study Group . Variation and trends in incidence of childhood diabetes in Europe.  Lancet. 2000;  355 873-876
  • 18 Pani M A, Knapp M, Donner H, Braun J, Baur M P, Usadel K H, Badenhoop K. Vitamin D receptor allele combinations influence genetic susceptibility to type 1 diabetes in Germans.  Diabetes. 2000;  3 504-507
  • 19 Akerblom H K, Vaarala O, Hyoty H, Ilonen J, Knip M. Environmental factors in the etiology of type 1 diabetes.  Am J Med Genet. 2002;  30 18-29
  • 20 Hawa M I, Valorani M G, Buckley L R, Beales P E, Afeltra A, Cacciapaglia F, Leslie R D, Pozzilli P. Lack of effect of vitamin D administration during pregnancy and early life on diabetes incidence in the non-obese diabetic mouse.  Horm Metab Res. 2004;  36 620-624

Prof. Paolo Pozzilli

Dept. of Endocrinology and Diabetes · University Campus Bio-Medico

Via E Longoni, 83 · 00155 Rome · Italy

Phone: +39 (06) 22541 556

Fax: +39 (06) 22541 336

Email: p.pozzilli@unicampus.it