Skip to main content
Top
Published in: Diabetologia 12/2006

01-12-2006 | Article

Lower levels of plasma 25-hydroxyvitamin D among young adults at diagnosis of autoimmune type 1 diabetes compared with control subjects: results from the nationwide Diabetes Incidence Study in Sweden (DISS)

Authors: B. Littorin, P. Blom, A. Schölin, H. J. Arnqvist, G. Blohmé, J. Bolinder, A. Ekbom-Schnell, J. W. Eriksson, S. Gudbjörnsdottir, L. Nyström, J. Östman, G. Sundkvist

Published in: Diabetologia | Issue 12/2006

Login to get access

Abstract

Aims/hypothesis

Low plasma vitamin D concentrations may promote the development of type 1 diabetes. To test this hypothesis, we measured plasma 25-hydroxyvitamin D (25OHD) in young adults with type 1 diabetes.

Methods

The nationwide Diabetes Incidence Study in Sweden (DISS) covers 15- to 34-year-old people with newly diagnosed diabetes. Blood samples at diagnosis were collected during the 2-year period 1987/1988. Patients with islet antibodies (islet cell antibodies, GAD antibodies or tyrosine phosphatase-like protein antibodies) were defined as having autoimmune type 1 diabetes. Plasma 25OHD was measured in samples taken from 459 patients at the time of diagnosis, and in 138 of these subjects 8 years later. The results were compared with age- and sex-matched control subjects (n=208).

Results

At diagnosis, plasma 25OHD levels were significantly lower in patients with type 1 diabetes than in control subjects (82.5±1.3 vs 96.7±2.0 nmol/l; p<0.0001). Eight years later, plasma 25OHD had decreased in patients (81.5±2.6 nmol/l; p=0.04). Plasma 25OHD levels were significantly lower in diabetic men than in diabetic women at diagnosis (77.9±1.4 vs 90.1±2.4 nmol/l; p<0.0001) and at follow-up (77.1±2.8 nmol/l vs 87.2±4.5 nmol/l; p=0.048).

Conclusions/interpretation

The plasma 25OHD level was lower at diagnosis of autoimmune type 1 diabetes than in control subjects, and may have a role in the development of type 1 diabetes. Plasma 25OHD levels were lower in men than in women with type 1 diabetes. This difference may be relevant to the high incidence of type 1 diabetes among young adult men.
Literature
1.
go back to reference Rewers M, Norris J, Dabelea D (2004) Epidemiology of type 1 diabetes mellitus. Adv Exp Med Biol 552:219–246PubMed Rewers M, Norris J, Dabelea D (2004) Epidemiology of type 1 diabetes mellitus. Adv Exp Med Biol 552:219–246PubMed
2.
go back to reference Mathieu C, Gysemans C, Giulietti A, Bouillon R (2005) Vitamin D and diabetes. Diabetologia 48:1247–1257PubMedCrossRef Mathieu C, Gysemans C, Giulietti A, Bouillon R (2005) Vitamin D and diabetes. Diabetologia 48:1247–1257PubMedCrossRef
3.
go back to reference The EURODIAB Substudy 2 Study Group (1999) Vitamin D supplement in early childhood and risk for Type I (insulin-dependent) diabetes mellitus. Diabetologia 42:51–54CrossRef The EURODIAB Substudy 2 Study Group (1999) Vitamin D supplement in early childhood and risk for Type I (insulin-dependent) diabetes mellitus. Diabetologia 42:51–54CrossRef
4.
go back to reference Stene LC, Ulriksen J, Magnus P, Joner G (2000) Use of cod liver oil during pregnancy is associated with lower risk of Type I diabetes in the offspring. Diabetologia 43:1093–1098PubMedCrossRef Stene LC, Ulriksen J, Magnus P, Joner G (2000) Use of cod liver oil during pregnancy is associated with lower risk of Type I diabetes in the offspring. Diabetologia 43:1093–1098PubMedCrossRef
5.
go back to reference Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM (2001) Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 358:1500–1503PubMedCrossRef Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM (2001) Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 358:1500–1503PubMedCrossRef
6.
go back to reference Fronczak CM, Baron AE, Chase HP et al (2003) In utero dietary exposures and risk of islet autoimmunity in children. Diabetes Care 26:3237–3242PubMed Fronczak CM, Baron AE, Chase HP et al (2003) In utero dietary exposures and risk of islet autoimmunity in children. Diabetes Care 26:3237–3242PubMed
7.
go back to reference Strugnell SA, Deluca HF (1997) The vitamin D receptor-structure and transcriptional activation. Proc Soc Exp Biol Med 215:223–228PubMed Strugnell SA, Deluca HF (1997) The vitamin D receptor-structure and transcriptional activation. Proc Soc Exp Biol Med 215:223–228PubMed
8.
go back to reference Zemunik T, Skrabic V, Boraska V et al (2005) FokI polymorphism, vitamin D receptor, and interleukin-1 receptor haplotypes are associated with type 1 diabetes in the Dalmatian population. J Mol Diagn 7:600–604PubMed Zemunik T, Skrabic V, Boraska V et al (2005) FokI polymorphism, vitamin D receptor, and interleukin-1 receptor haplotypes are associated with type 1 diabetes in the Dalmatian population. J Mol Diagn 7:600–604PubMed
10.
go back to reference Kim SH, Cleary MM, Fox HS, Chantry D, Sarvetnick N (2002) CCR4-bearing T cells participate in autoimmune diabetes. J Clin Invest 110:1675–1686PubMedCrossRef Kim SH, Cleary MM, Fox HS, Chantry D, Sarvetnick N (2002) CCR4-bearing T cells participate in autoimmune diabetes. J Clin Invest 110:1675–1686PubMedCrossRef
11.
go back to reference Szanya V, Ermann J, Taylor C, Holness C, Fathman CG (2002) The subpopulation of CD4+CD25+ splenocytes that delays adoptive transfer of diabetes expresses L-selectin and high levels of CCR7. J Immunol 169:2461–2465PubMed Szanya V, Ermann J, Taylor C, Holness C, Fathman CG (2002) The subpopulation of CD4+CD25+ splenocytes that delays adoptive transfer of diabetes expresses L-selectin and high levels of CCR7. J Immunol 169:2461–2465PubMed
12.
go back to reference Giarratana N, Penna G, Amuchastegui S, Mariani R, Daniel KC, Adorini L (2004) A vitamin D analog down-regulates proinflammatory chemokine production by pancreatic islets inhibiting T cell recruitment and type 1 diabetes development. J Immunol 173:2280–2287PubMed Giarratana N, Penna G, Amuchastegui S, Mariani R, Daniel KC, Adorini L (2004) A vitamin D analog down-regulates proinflammatory chemokine production by pancreatic islets inhibiting T cell recruitment and type 1 diabetes development. J Immunol 173:2280–2287PubMed
13.
14.
go back to reference Blohmé G, Nyström L, Arnqvist HJ et al (1992) Male predominance of type 1 (insulin-dependent) diabetes mellitus in young adults: results from a 5-year prospective nationwide study of the 15–34-year age group in Sweden. Diabetologia 35:56–62PubMedCrossRef Blohmé G, Nyström L, Arnqvist HJ et al (1992) Male predominance of type 1 (insulin-dependent) diabetes mellitus in young adults: results from a 5-year prospective nationwide study of the 15–34-year age group in Sweden. Diabetologia 35:56–62PubMedCrossRef
15.
go back to reference Nyström L, Dahlquist G, Östman J et al (1992) Risk of developing insulin-dependent diabetes mellitus (IDDM) before 35 years of age: indications of climatological determinants for age at onset. Int J Epidemiol 21:352–358PubMed Nyström L, Dahlquist G, Östman J et al (1992) Risk of developing insulin-dependent diabetes mellitus (IDDM) before 35 years of age: indications of climatological determinants for age at onset. Int J Epidemiol 21:352–358PubMed
16.
go back to reference Östman, Arnquist HJ, Blohmé G et al (1986) Epidemiology of diabetes mellitus in Sweden. Results of the first year of a prospective study in the population age group 15–34 years. Acta Med Scand 220:437–445PubMedCrossRef Östman, Arnquist HJ, Blohmé G et al (1986) Epidemiology of diabetes mellitus in Sweden. Results of the first year of a prospective study in the population age group 15–34 years. Acta Med Scand 220:437–445PubMedCrossRef
17.
go back to reference Landin-Olsson M, Karlsson FA, Lernmark é , Sundkvist G, and the Diabetes Incidence Study in Sweden Group (1992) Islet cell and thyrogastric antibodies in 633 consecutive 15- to 34-yr-old patients in the Diabetes Incidence Study in Sweden. Diabetes 4:1022–1027 Landin-Olsson M, Karlsson FA, Lernmark é , Sundkvist G, and the Diabetes Incidence Study in Sweden Group (1992) Islet cell and thyrogastric antibodies in 633 consecutive 15- to 34-yr-old patients in the Diabetes Incidence Study in Sweden. Diabetes 4:1022–1027
18.
go back to reference Schölin A, Bjorklund L, Borg H et al (2004) Islet antibodies and remaining beta-cell function 8 years after diagnosis of diabetes in young adults: a prospective follow-up of the nationwide Diabetes Incidence Study in Sweden. J Intern Med 255:384–391PubMedCrossRef Schölin A, Bjorklund L, Borg H et al (2004) Islet antibodies and remaining beta-cell function 8 years after diagnosis of diabetes in young adults: a prospective follow-up of the nationwide Diabetes Incidence Study in Sweden. J Intern Med 255:384–391PubMedCrossRef
19.
go back to reference Landin-Olsson M, Sundkvist G, Lernmark é (1987) Prolonged incubation in the two-colour immunofluorescence test increases the prevalence and titres of islet cell antibodies in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 30:327–332CrossRef Landin-Olsson M, Sundkvist G, Lernmark é (1987) Prolonged incubation in the two-colour immunofluorescence test increases the prevalence and titres of islet cell antibodies in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 30:327–332CrossRef
20.
go back to reference Borg H, Fernlund P, Sundkvist G (1997) Measurements of antibodies against glutamic acid decarboxylase 65 (GADA): two new 125I assays compared with 35SGAD 65-ligand binding assay. Clin Chem 43:779–785PubMed Borg H, Fernlund P, Sundkvist G (1997) Measurements of antibodies against glutamic acid decarboxylase 65 (GADA): two new 125I assays compared with 35SGAD 65-ligand binding assay. Clin Chem 43:779–785PubMed
21.
go back to reference Borg H, Fernlund P, Sundkvist G (1997) Protein tyrosine phosphatase-like protein IA-2-antibodies plus glutamic acid decarboxylase 65 antibodies (GADA) indicates autoimmunity as frequently as islet cell antibodies assay in children with recently diagnosed diabetes mellitus. Clin Chem 43:2358–2363PubMed Borg H, Fernlund P, Sundkvist G (1997) Protein tyrosine phosphatase-like protein IA-2-antibodies plus glutamic acid decarboxylase 65 antibodies (GADA) indicates autoimmunity as frequently as islet cell antibodies assay in children with recently diagnosed diabetes mellitus. Clin Chem 43:2358–2363PubMed
22.
go back to reference Jeppsson JO, Jerntorp P, Sundkvist G, Englund H, Nylund V (1986) Measurement of haemoglobin A1c by a new liquid-chromatographic assay: methodology, clinical utility, and relation to glucose tolerance evaluated. Clin Chem 32:1867–1872PubMed Jeppsson JO, Jerntorp P, Sundkvist G, Englund H, Nylund V (1986) Measurement of haemoglobin A1c by a new liquid-chromatographic assay: methodology, clinical utility, and relation to glucose tolerance evaluated. Clin Chem 32:1867–1872PubMed
23.
go back to reference Binkley N, Krueger D, Cowgill CS, Plum L, Lake E, Hansen KE, DeLuca HF, Drezner MK (2004) Assay variation confounds the diagnosis of hypovitaminosis D: a call for standardization. J Clin Endocrinol Metab 89:3152–3157PubMedCrossRef Binkley N, Krueger D, Cowgill CS, Plum L, Lake E, Hansen KE, DeLuca HF, Drezner MK (2004) Assay variation confounds the diagnosis of hypovitaminosis D: a call for standardization. J Clin Endocrinol Metab 89:3152–3157PubMedCrossRef
24.
go back to reference Product insert 2001. Nichols ADVANTAGE 25-hydroxyvitamin D assay. Nichols Institute Diagnostics, San Clemente, CA Product insert 2001. Nichols ADVANTAGE 25-hydroxyvitamin D assay. Nichols Institute Diagnostics, San Clemente, CA
25.
go back to reference Antoniucci DM, Black DM, Sellmeyer DE (2005) Serum 25-hydroxyvitamin D is unaffected by multiple freeze-thaw cycles. Clin Chem 51:258–260PubMedCrossRef Antoniucci DM, Black DM, Sellmeyer DE (2005) Serum 25-hydroxyvitamin D is unaffected by multiple freeze-thaw cycles. Clin Chem 51:258–260PubMedCrossRef
26.
go back to reference Littorin B, Sundkvist G, Hagopian W et al (1999) Islet cell and glutamic acid decarboxylase antibodies present at diagnosis of diabetes predict the need for insulin treatment. A cohort study in young adults whose disease was initially labelled as type 2 or unclassifiable diabetes. Diabetes Care 22:409–412PubMed Littorin B, Sundkvist G, Hagopian W et al (1999) Islet cell and glutamic acid decarboxylase antibodies present at diagnosis of diabetes predict the need for insulin treatment. A cohort study in young adults whose disease was initially labelled as type 2 or unclassifiable diabetes. Diabetes Care 22:409–412PubMed
27.
go back to reference Borg H, Gottsäter A, Fernlund P, Sundkvist G (2002) A 12-year prospective study of the relationship between islet antibodies and β-cell function at and after the diagnosis in patients with adult onset diabetes. Diabetes 51:1754–1762PubMed Borg H, Gottsäter A, Fernlund P, Sundkvist G (2002) A 12-year prospective study of the relationship between islet antibodies and β-cell function at and after the diagnosis in patients with adult onset diabetes. Diabetes 51:1754–1762PubMed
28.
go back to reference Borg H, Arnqvist HJ, Björk E et al (2003) Evaluation of the new ADA and WHO Criteria for Classification of Diabetes Mellitus in young adult people (15–34 yrs) in the Diabetes Incidence Study in Sweden (DISS). Diabetologia 46:173–181PubMedCrossRef Borg H, Arnqvist HJ, Björk E et al (2003) Evaluation of the new ADA and WHO Criteria for Classification of Diabetes Mellitus in young adult people (15–34 yrs) in the Diabetes Incidence Study in Sweden (DISS). Diabetologia 46:173–181PubMedCrossRef
29.
go back to reference Holick, MF (2004) Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr 80:1678–1688 Holick, MF (2004) Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr 80:1678–1688
31.
go back to reference Kyvik KO, Nyström L, Gorus F et al (2004) The epidemiology of type 1 diabetes mellitus is not the same in young adults as in children. Diabetologia 47:377–384PubMedCrossRef Kyvik KO, Nyström L, Gorus F et al (2004) The epidemiology of type 1 diabetes mellitus is not the same in young adults as in children. Diabetologia 47:377–384PubMedCrossRef
32.
go back to reference Graham J, Kockum I, Sanjeevi CB et al (1999) Negative association between type 1 diabetes and HLA DQB1*0602-DQA1*0102 is attenuated with age at onset. Eur J Immunogenet 26:117–127PubMedCrossRef Graham J, Kockum I, Sanjeevi CB et al (1999) Negative association between type 1 diabetes and HLA DQB1*0602-DQA1*0102 is attenuated with age at onset. Eur J Immunogenet 26:117–127PubMedCrossRef
33.
go back to reference Scragg R, Sowers M, Bell C (2004) Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey. Diabetes Care 27:2813–2818PubMed Scragg R, Sowers M, Bell C (2004) Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey. Diabetes Care 27:2813–2818PubMed
34.
go back to reference Diabetes Prevention Trial-Type 1 Diabetes Study Group (2002) Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med 346:1685–1691CrossRef Diabetes Prevention Trial-Type 1 Diabetes Study Group (2002) Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med 346:1685–1691CrossRef
35.
go back to reference Gale EA, Bingley PJ, Emmett CL, Collier T (2004) European Nicotinamide Diabetes Intervention Trial (ENDIT): a randomised controlled trial of intervention before the onset of type 1 diabetes. Lancet 363:925–931PubMedCrossRef Gale EA, Bingley PJ, Emmett CL, Collier T (2004) European Nicotinamide Diabetes Intervention Trial (ENDIT): a randomised controlled trial of intervention before the onset of type 1 diabetes. Lancet 363:925–931PubMedCrossRef
36.
go back to reference Isaia G, Giorgino R, Adami S (2001) High prevalence of hypovitaminosis D in female type 2 diabetic population. Diabetes Care 24:1496PubMed Isaia G, Giorgino R, Adami S (2001) High prevalence of hypovitaminosis D in female type 2 diabetic population. Diabetes Care 24:1496PubMed
37.
go back to reference Norman AW, Frankel JB, Heldt AM, Grodsky GM (1980) Vitamin D deficiency inhibits pancreatic secretion of insulin. Science 209:823–825PubMedCrossRef Norman AW, Frankel JB, Heldt AM, Grodsky GM (1980) Vitamin D deficiency inhibits pancreatic secretion of insulin. Science 209:823–825PubMedCrossRef
38.
go back to reference Chiu KC, Chu A, Go VL, Saad MF (2004) Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr 79:820–825PubMed Chiu KC, Chu A, Go VL, Saad MF (2004) Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr 79:820–825PubMed
39.
go back to reference Borissova AM, Tankova T, Kirilov G, Dakovska L, Kovacheva R (2003) The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients. Int J Clin Pract 57:258–261PubMed Borissova AM, Tankova T, Kirilov G, Dakovska L, Kovacheva R (2003) The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients. Int J Clin Pract 57:258–261PubMed
40.
go back to reference Petrova NL, Foster AVM, Edmonds ME (2005) Calcaneal bone mineral density in patients with Charcot neuropathic osteoarthropathy: differences between type 1 and type 2 diabetes. Diabet Med 22:756–761PubMedCrossRef Petrova NL, Foster AVM, Edmonds ME (2005) Calcaneal bone mineral density in patients with Charcot neuropathic osteoarthropathy: differences between type 1 and type 2 diabetes. Diabet Med 22:756–761PubMedCrossRef
Metadata
Title
Lower levels of plasma 25-hydroxyvitamin D among young adults at diagnosis of autoimmune type 1 diabetes compared with control subjects: results from the nationwide Diabetes Incidence Study in Sweden (DISS)
Authors
B. Littorin
P. Blom
A. Schölin
H. J. Arnqvist
G. Blohmé
J. Bolinder
A. Ekbom-Schnell
J. W. Eriksson
S. Gudbjörnsdottir
L. Nyström
J. Östman
G. Sundkvist
Publication date
01-12-2006
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 12/2006
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-006-0426-x

Other articles of this Issue 12/2006

Diabetologia 12/2006 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.