Vitamin D and type 1 diabetes

Maija E. Miettinen

Research output: ThesisDoctoral ThesisCollection of Articles

Abstract

Type 1 diabetes is an autoimmune disease, in which insulin-producing β-cells in the pancreas are destroyed leading to a life-long external insulin-dependency. Finland has the highest incidence of type 1 diabetes in the world, increasing almost 5-fold since the 1950s. The reasons for this increase are not known, therefore it is not possible to delay or prevent the disease. Identifying the factors that can modify the disease risk and interfere with the disease process is highly important, since despite advances in disease management, the life expectancy of patients with type 1 diabetes is estimated as more than 10 years shorter than that of the normal population. Type 1 diabetes develops as a result of complex interactions between genetic and environmental factors. While more than 50 genetic loci associated with type 1 diabetes risk have been identified the strongest risk is conferred by the human leukocyte antigen (HLA) gene region. The environmental factors, however, remain unknown. Epidemiological evidence suggests an association between vitamin D and type 1 diabetes, but information on the actual vitamin D status (serum 25-hydroxyvitamin D (25OHD) concentration) during pregnancy or childhood prior to diagnosis is scarce. Genes in the metabolic pathway of vitamin D are associated with type 1 diabetes, but the interaction between vitamin D status, vitamin D related genetic factors and type 1 diabetes is poorly known. We investigated the association between vitamin D and type 1 diabetes by determining maternal vitamin D status in a retrospectively case control study setting, when it was already known which of the children later developed type 1 diabetes. We utilised a unique sample collection, the Finnish Maternity Cohort (FMC) that collects serum samples of almost every pregnancy in Finland. We evaluated the association between single nucleotide polymorphisms (SNPs) in the metabolic pathway of vitamin D and type 1 diabetes. Furthermore, we investigated the relationship between vitamin D status and the HLA gene region. No difference in maternal serum 25OHD concentrations emerged between mothers of diabetic and non-diabetic children (43.9 nmol/l and 43.5 nmol/l; n=686). Around 70% of all pregnant women were vitamin D deficient (serum 25OHD concentration <50 nmol/l). We found novel proof of a relationship between maternal genetic factors in the metabolic pathway of vitamin D and type 1 diabetes risk in the child. The genotypes of two SNPs located in the vitamin D receptor (VDR) gene showed different genotype distribution between mothers whose children later developed type 1 diabetes and those whose did not. The VDR regulates the transcription of hundreds of vitamin D target genes. We also found for the first time that associations between serum 25OHD concentration and SNPs in the VDR and the group-specific component (GC) were stronger during pregnancy in mothers whose children later developed type 1 diabetes than in mothers whose children did not. The GC gene encodes vitamin D binding protein to which vitamin D is attached during circulation. Furthermore, we found a novel association between serum 25OHD concentration and the HLA gene region. A group of HLA alleles (HLA-B44 supertype) associated with low serum 25OHD concentration. Our results do not support a direct association between maternal vitamin D status and type 1 diabetes risk in the child. It may be, however, that we were not able to detect a possible protective effect of vitamin D in this population since a considerable proportion of all mothers were vitamin D deficient. Our results demonstrate novel differences in genetic factors related to the metabolic pathway of vitamin D during pregnancy between mothers whose children later developed type 1 diabetes and whose did not. The found relationship between the HLA gene region and vitamin D status indicates an even stronger role for vitamin D in the immune system than previously thought. Our results suggest that more attention should be paid to the mother and pregnancy, when investigating the early programming of type 1 diabetes.
Original languageEnglish
Place of PublicationHelsinki
Publisher
Print ISBNs978-951-51-3137-9
Electronic ISBNs978-951-51-3138-6
Publication statusPublished - 2017
MoE publication typeG5 Doctoral dissertation (article)

Fields of Science

  • 3121 Internal medicine
  • 3142 Public health care science, environmental and occupational health

Cite this

Miettinen, M. E. (2017). Vitamin D and type 1 diabetes. Helsinki: Helsingin yliopisto.
Miettinen, Maija E.. / Vitamin D and type 1 diabetes. Helsinki : Helsingin yliopisto, 2017. 98 p.
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title = "Vitamin D and type 1 diabetes",
abstract = "Type 1 diabetes is an autoimmune disease, in which insulin-producing β-cells in the pancreas are destroyed leading to a life-long external insulin-dependency. Finland has the highest incidence of type 1 diabetes in the world, increasing almost 5-fold since the 1950s. The reasons for this increase are not known, therefore it is not possible to delay or prevent the disease. Identifying the factors that can modify the disease risk and interfere with the disease process is highly important, since despite advances in disease management, the life expectancy of patients with type 1 diabetes is estimated as more than 10 years shorter than that of the normal population. Type 1 diabetes develops as a result of complex interactions between genetic and environmental factors. While more than 50 genetic loci associated with type 1 diabetes risk have been identified the strongest risk is conferred by the human leukocyte antigen (HLA) gene region. The environmental factors, however, remain unknown. Epidemiological evidence suggests an association between vitamin D and type 1 diabetes, but information on the actual vitamin D status (serum 25-hydroxyvitamin D (25OHD) concentration) during pregnancy or childhood prior to diagnosis is scarce. Genes in the metabolic pathway of vitamin D are associated with type 1 diabetes, but the interaction between vitamin D status, vitamin D related genetic factors and type 1 diabetes is poorly known. We investigated the association between vitamin D and type 1 diabetes by determining maternal vitamin D status in a retrospectively case control study setting, when it was already known which of the children later developed type 1 diabetes. We utilised a unique sample collection, the Finnish Maternity Cohort (FMC) that collects serum samples of almost every pregnancy in Finland. We evaluated the association between single nucleotide polymorphisms (SNPs) in the metabolic pathway of vitamin D and type 1 diabetes. Furthermore, we investigated the relationship between vitamin D status and the HLA gene region. No difference in maternal serum 25OHD concentrations emerged between mothers of diabetic and non-diabetic children (43.9 nmol/l and 43.5 nmol/l; n=686). Around 70{\%} of all pregnant women were vitamin D deficient (serum 25OHD concentration <50 nmol/l). We found novel proof of a relationship between maternal genetic factors in the metabolic pathway of vitamin D and type 1 diabetes risk in the child. The genotypes of two SNPs located in the vitamin D receptor (VDR) gene showed different genotype distribution between mothers whose children later developed type 1 diabetes and those whose did not. The VDR regulates the transcription of hundreds of vitamin D target genes. We also found for the first time that associations between serum 25OHD concentration and SNPs in the VDR and the group-specific component (GC) were stronger during pregnancy in mothers whose children later developed type 1 diabetes than in mothers whose children did not. The GC gene encodes vitamin D binding protein to which vitamin D is attached during circulation. Furthermore, we found a novel association between serum 25OHD concentration and the HLA gene region. A group of HLA alleles (HLA-B44 supertype) associated with low serum 25OHD concentration. Our results do not support a direct association between maternal vitamin D status and type 1 diabetes risk in the child. It may be, however, that we were not able to detect a possible protective effect of vitamin D in this population since a considerable proportion of all mothers were vitamin D deficient. Our results demonstrate novel differences in genetic factors related to the metabolic pathway of vitamin D during pregnancy between mothers whose children later developed type 1 diabetes and whose did not. The found relationship between the HLA gene region and vitamin D status indicates an even stronger role for vitamin D in the immune system than previously thought. Our results suggest that more attention should be paid to the mother and pregnancy, when investigating the early programming of type 1 diabetes.",
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Miettinen, ME 2017, 'Vitamin D and type 1 diabetes', Helsinki.

Vitamin D and type 1 diabetes. / Miettinen, Maija E.

Helsinki : Helsingin yliopisto, 2017. 98 p.

Research output: ThesisDoctoral ThesisCollection of Articles

TY - THES

T1 - Vitamin D and type 1 diabetes

AU - Miettinen, Maija E.

N1 - M1 - 98 s. + liitteet Volume: Proceeding volume:

PY - 2017

Y1 - 2017

N2 - Type 1 diabetes is an autoimmune disease, in which insulin-producing β-cells in the pancreas are destroyed leading to a life-long external insulin-dependency. Finland has the highest incidence of type 1 diabetes in the world, increasing almost 5-fold since the 1950s. The reasons for this increase are not known, therefore it is not possible to delay or prevent the disease. Identifying the factors that can modify the disease risk and interfere with the disease process is highly important, since despite advances in disease management, the life expectancy of patients with type 1 diabetes is estimated as more than 10 years shorter than that of the normal population. Type 1 diabetes develops as a result of complex interactions between genetic and environmental factors. While more than 50 genetic loci associated with type 1 diabetes risk have been identified the strongest risk is conferred by the human leukocyte antigen (HLA) gene region. The environmental factors, however, remain unknown. Epidemiological evidence suggests an association between vitamin D and type 1 diabetes, but information on the actual vitamin D status (serum 25-hydroxyvitamin D (25OHD) concentration) during pregnancy or childhood prior to diagnosis is scarce. Genes in the metabolic pathway of vitamin D are associated with type 1 diabetes, but the interaction between vitamin D status, vitamin D related genetic factors and type 1 diabetes is poorly known. We investigated the association between vitamin D and type 1 diabetes by determining maternal vitamin D status in a retrospectively case control study setting, when it was already known which of the children later developed type 1 diabetes. We utilised a unique sample collection, the Finnish Maternity Cohort (FMC) that collects serum samples of almost every pregnancy in Finland. We evaluated the association between single nucleotide polymorphisms (SNPs) in the metabolic pathway of vitamin D and type 1 diabetes. Furthermore, we investigated the relationship between vitamin D status and the HLA gene region. No difference in maternal serum 25OHD concentrations emerged between mothers of diabetic and non-diabetic children (43.9 nmol/l and 43.5 nmol/l; n=686). Around 70% of all pregnant women were vitamin D deficient (serum 25OHD concentration <50 nmol/l). We found novel proof of a relationship between maternal genetic factors in the metabolic pathway of vitamin D and type 1 diabetes risk in the child. The genotypes of two SNPs located in the vitamin D receptor (VDR) gene showed different genotype distribution between mothers whose children later developed type 1 diabetes and those whose did not. The VDR regulates the transcription of hundreds of vitamin D target genes. We also found for the first time that associations between serum 25OHD concentration and SNPs in the VDR and the group-specific component (GC) were stronger during pregnancy in mothers whose children later developed type 1 diabetes than in mothers whose children did not. The GC gene encodes vitamin D binding protein to which vitamin D is attached during circulation. Furthermore, we found a novel association between serum 25OHD concentration and the HLA gene region. A group of HLA alleles (HLA-B44 supertype) associated with low serum 25OHD concentration. Our results do not support a direct association between maternal vitamin D status and type 1 diabetes risk in the child. It may be, however, that we were not able to detect a possible protective effect of vitamin D in this population since a considerable proportion of all mothers were vitamin D deficient. Our results demonstrate novel differences in genetic factors related to the metabolic pathway of vitamin D during pregnancy between mothers whose children later developed type 1 diabetes and whose did not. The found relationship between the HLA gene region and vitamin D status indicates an even stronger role for vitamin D in the immune system than previously thought. Our results suggest that more attention should be paid to the mother and pregnancy, when investigating the early programming of type 1 diabetes.

AB - Type 1 diabetes is an autoimmune disease, in which insulin-producing β-cells in the pancreas are destroyed leading to a life-long external insulin-dependency. Finland has the highest incidence of type 1 diabetes in the world, increasing almost 5-fold since the 1950s. The reasons for this increase are not known, therefore it is not possible to delay or prevent the disease. Identifying the factors that can modify the disease risk and interfere with the disease process is highly important, since despite advances in disease management, the life expectancy of patients with type 1 diabetes is estimated as more than 10 years shorter than that of the normal population. Type 1 diabetes develops as a result of complex interactions between genetic and environmental factors. While more than 50 genetic loci associated with type 1 diabetes risk have been identified the strongest risk is conferred by the human leukocyte antigen (HLA) gene region. The environmental factors, however, remain unknown. Epidemiological evidence suggests an association between vitamin D and type 1 diabetes, but information on the actual vitamin D status (serum 25-hydroxyvitamin D (25OHD) concentration) during pregnancy or childhood prior to diagnosis is scarce. Genes in the metabolic pathway of vitamin D are associated with type 1 diabetes, but the interaction between vitamin D status, vitamin D related genetic factors and type 1 diabetes is poorly known. We investigated the association between vitamin D and type 1 diabetes by determining maternal vitamin D status in a retrospectively case control study setting, when it was already known which of the children later developed type 1 diabetes. We utilised a unique sample collection, the Finnish Maternity Cohort (FMC) that collects serum samples of almost every pregnancy in Finland. We evaluated the association between single nucleotide polymorphisms (SNPs) in the metabolic pathway of vitamin D and type 1 diabetes. Furthermore, we investigated the relationship between vitamin D status and the HLA gene region. No difference in maternal serum 25OHD concentrations emerged between mothers of diabetic and non-diabetic children (43.9 nmol/l and 43.5 nmol/l; n=686). Around 70% of all pregnant women were vitamin D deficient (serum 25OHD concentration <50 nmol/l). We found novel proof of a relationship between maternal genetic factors in the metabolic pathway of vitamin D and type 1 diabetes risk in the child. The genotypes of two SNPs located in the vitamin D receptor (VDR) gene showed different genotype distribution between mothers whose children later developed type 1 diabetes and those whose did not. The VDR regulates the transcription of hundreds of vitamin D target genes. We also found for the first time that associations between serum 25OHD concentration and SNPs in the VDR and the group-specific component (GC) were stronger during pregnancy in mothers whose children later developed type 1 diabetes than in mothers whose children did not. The GC gene encodes vitamin D binding protein to which vitamin D is attached during circulation. Furthermore, we found a novel association between serum 25OHD concentration and the HLA gene region. A group of HLA alleles (HLA-B44 supertype) associated with low serum 25OHD concentration. Our results do not support a direct association between maternal vitamin D status and type 1 diabetes risk in the child. It may be, however, that we were not able to detect a possible protective effect of vitamin D in this population since a considerable proportion of all mothers were vitamin D deficient. Our results demonstrate novel differences in genetic factors related to the metabolic pathway of vitamin D during pregnancy between mothers whose children later developed type 1 diabetes and whose did not. The found relationship between the HLA gene region and vitamin D status indicates an even stronger role for vitamin D in the immune system than previously thought. Our results suggest that more attention should be paid to the mother and pregnancy, when investigating the early programming of type 1 diabetes.

KW - Child

KW - Child, Preschool

KW - Diabetes Mellitus, Type 1

KW - +etiology

KW - +genetics

KW - Genetic Predisposition to Disease

KW - HLA Antigens

KW - Infant

KW - Polymorphism, Single Nucleotide

KW - Pregnancy

KW - +blood

KW - Receptors, Calcitriol

KW - Vitamin D

KW - +analogs & derivatives

KW - Vitamin D Deficiency

KW - +epidemiology

KW - 3121 Internal medicine

KW - 3142 Public health care science, environmental and occupational health

M3 - Doctoral Thesis

SN - 978-951-51-3137-9

T3 - Dissertationes scholae doctoralis ad sanitatem investigandam Universitatis Helsinkiensis

PB - Helsingin yliopisto

CY - Helsinki

ER -

Miettinen ME. Vitamin D and type 1 diabetes. Helsinki: Helsingin yliopisto, 2017. 98 p. (Dissertationes scholae doctoralis ad sanitatem investigandam Universitatis Helsinkiensis; 33/2017).