| 1. |
- Gullstrand, Camilla, 1977-, et al.
(författare)
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Progression to type 1 diabetes and autoantibody positivity in relation to HLA-risk genotypes in children participating in the ABIS study
- 2008
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 9:3 PART 1, s. 182-190
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Tidskriftsartikel (refereegranskat)abstract
- Background: Autoantibodies against beta-cell antigens together with human leukocyte antigen (HLA)-risk genotypes are used as predictive markers for type 1 diabetes (T1D). In this study, we have investigated the role of HLA-risk and -protective genotypes for development of beta-cell autoantibodies and progression to T1D in healthy children. Methods: T1D-related HLA genotypes and autoantibodies against glutamic acid decarboxylase [glutamic acid decarboxylase antibodies (GADA)] and islet antigen-2 (IA-2A) were studied at 1, 2.5 and 5 yr of age in unselected healthy children and children with T1D participating in the All Babies In Southeast Sweden (ABIS) study. Results: GADA or IA-2A positivity at 5 yr of age was associated with DR4-DQ8 haplotype and DR3-DQ2/DR4-DQ8 genotype. By the age of 6-7 yr, we identified 32 children with T1D among the 17 055 participants in the ABIS study. Eight of 2329 (0.3%) non-diabetic children had permanent autoantibodies, and 143 of 2329 (6%) children had transient autoantibodies. HLA-risk genotypes associated with T1D, whereas protective genotypes were seldom found in children with T1D. Children with permanent autoantibodies had more often risk-associated DR4-DQ8 haplotype than autoantibody-negative children. No associations with HLA-risk or -protective genotypes were found for transient autoantibodies. Conclusions: The strong relation between HLA-risk alleles and T1D once again confirmed that HLA-risk genotypes play an important role for development of T1D. However, HLA genotypes seem not to explain induction of autoantibodies, especially transient autoantibodies, in the general population, emphasizing the role of environmental factors in the initiation of autoimmunity. It seems that HLA-risk genotypes are responsible for maturation of the permanent autoantibody response. © 2008 The Authors Journal compilation © 2008 Blackwell Munksgaard.
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| 2. |
- Holmberg, Hanna, et al.
(författare)
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Short duration of breast-feeding as a risk-factor for beta-cell autoantibodies in 5-year-old children from the general population
- 2007
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Ingår i: British Journal of Nutrition. - : Cambridge University Press. - 0007-1145 .- 1475-2662. ; 97:1, s. 111-116
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Tidskriftsartikel (refereegranskat)abstract
- Breast-feeding has been suggested to have a protective effect against the development of type 1 diabetes. In the present study, we investigated the relation between duration of breast-feeding and beta-cell autoantibodies in 5-year-old non-diabetic children who participated in a prospective population-based follow-up study (the All Babies in Southeast Sweden study). Autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and the protein tryosine phosphatase-like IA-2 (IA-2A) were measured by radiobinding assays. A short duration of total breast-feeding was associated with an increased risk of GADA and/or IAA above the ninety-fifth percentile at 5 years of age (OR 2.09, 95% CI 1.45, 3.02; P<0.000) as well as with an increased risk of IAA above the ninety-fifth percentile at this age (OR 2.89, 95% CI 1.81, 4.62, P<0.000). A short duration of exclusive breast-feeding was associated with an increased risk of GADA, IAA and/or IA-2A above the ninety-ninth percentile (OR 2.01, 95% CI 1.08, 3.73; P=0.028) as well as with an increased risk of IA-2A above the ninety-ninth percentile (OR 3.50, 95% CI 1.38, 8.92, P=0.009) at 5 years of age. An early introduction of formula was associated with an increased risk of GADA, IAA and/or IA-2A above the ninety-ninth percentile (OR 1.84, 95% CI 1.01, 3.37; P=0.047) at 5 years of age. The positive association between a short duration of both total and exclusive breast-feeding, as well as an early introduction of formula, and positivity for beta-cell autoantibodies in children from the general population suggest that breast-feeding modifies the risk of beta-cell autoimmunity, even years after finishing breast-feeding.
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| 3. |
- Holmberg, Hanna, et al.
(författare)
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Short duration of breast-feeding as a risk-factor for β-cell autoantibodies in 5-year-old children from the general population
- 2007
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Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 97:1, s. 111-116
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Tidskriftsartikel (refereegranskat)abstract
- Breast-feeding has been suggested to have a protective effect against the development of type 1 diabetes. In the present study, we investigated the relation between duration of breast-feeding and β-cell autoantibodies in 5-year-old non-diabetic children who participated in a prospective population-based follow-up study (the All Babies in Southeast Sweden study). Autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and the protein tyrosine phosphatase-like IA-2 (IA-2A) were measured by radiobinding assays. A short duration of total breast-feeding was associated with an increased risk of GADA and/or IAA above the ninety-fifth percentile at 5 years of age (OR 2-09, 95% CI 1-45, 3-02; P<0-000) as well as with an increased risk of IAA above the ninety-fifth percentile at this age (OR 2-89, 95% CI 1-81, 4-62; P<0-000). A short duration of exclusive breast-feeding was associated with an increased risk of GADA, IAA and/or IA-2A above the ninety-ninth percentile (OR 2-01, 95% CI 1-08, 3-73; P = 0-028) as well as with an increased risk of IA-2A above the ninety-ninth percentile (OR 3-50, 95% CI 1-38, 8-92; P = 0-009) at 5 years of age. An early introduction of formula was associated with an increased risk of GADA, IAA and/or IA-2A above the ninety-ninth percentile (OR 1-84, 95% CI 1-01, 3-37; P = 0-047) at 5 years of age. The positive association between a short duration of both total and exclusive breast-feeding, as well as an early introduction of formula, and positivity for β-cell autoantibodies in children from the general population suggests that breast-feeding modifies the risk of β-cell autoimmunity, even years after finishing breast-feeding.
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| 4. |
- Landberg, Eva, 1966-, et al.
(författare)
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Detection of molecular variants of prolactin in human serum, evaluation of a method based on ultrafiltration
- 2007
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Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981 .- 1873-3492. ; 376:1-2, s. 220-225
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn human blood, there are several molecular variants of prolactin with different biological effects. There is a need for new methods to detect and quantify these variants in order to fully understand the pathophysiological role of prolactin.MethodsA method based on ultrafiltration was optimized, validated and compared to PEG precipitation. Serum samples from 84 patients were analyzed before and after pre treatment on two immunoassays, Elecsys (Roche) and Access (Beckman). Protein G precipitation was used to confirm presence of macroprolactin.ResultsThe recovery of prolactin after ultrafiltration was lower than after PEG precipitation. A limit of 40% recovery after PEG precipitation corresponded to 27% recovery after ultrafiltration. Using these limits there were total agreement regarding detection of macroprolactin (rs = 0.96). In contrast, recovery of prolactin in samples without macroprolactin showed a considerable disagreement between ultrafiltration and PEG precipitation (rs = 0.48). Within-run CV was 4% for the ultrafiltration method. The correlation coefficient (r) between the immunoassays was 0.96 after ultrafiltration.ConclusionsUltrafiltration can be used to compare different prolactin immunoassays and to detect macroprolactin in assays with interference from PEG. For samples without macroprolactin ultrafiltration may give additional information reflecting individual variations of other molecular variants of prolactin.
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| 5. |
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| 6. |
- Sepa, Anneli, et al.
(författare)
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Psychological stress may induce diabetes-related autoimmunity in infancy
- 2005
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 28:2, s. 290-295
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE— In retrospective studies, a number of disparate environmental factors (including experiences of serious life events) have been proposed as trigger mechanisms for type 1 diabetes or the autoimmune process behind the disease. Psychosocial stress in families may affect children negatively due to a link to hormonal levels and nervous signals that in turn influence both insulin sensitivity/insulin need and the immune system. Our aim was to investigate whether psychological stress, measured as psychosocial strain in families, is associated with diabetes-related autoimmunity during infancy.RESEARCH DESIGN AND METHODS— The first 4,400 consecutive 1-year-old children from a large prospective population-based project participated in the study. Parents completed questionnaires at birth and at 1 year, including various measures of psychosocial stress (e.g., parenting stress) and sociodemographic background. Blood samples drawn from the children at 1 year were analyzed for type 1 diabetes–associated autoantibodies toward tyrosine phosphatase and GAD. Antibodies toward tetanus toxoid were used as non–diabetes-related control antibodies.RESULTS— Psychosocial factors, i.e., high parenting stress (odds ratio 1.8 [95% CI 1.2–2.9], P < 0.01), experiences of a serious life event (2.3 [1.3–4.0], P < 0.01), foreign origin of the mother (2.1 [1.3–3.3], P < 0.001), and low paternal education (1.6 [1.1–2.3], P < 0.01) were associated with diabetes-related autoimmunity in the child, independent of family history of diabetes.CONCLUSIONS— Psychological stress, measured as psychosocial strain in the family, seems to be involved in the induction, or progression, of diabetes-related autoimmunity in the child during the 1st year of life.
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| 7. |
- Wahlberg, Jeanette, 1969-, et al.
(författare)
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Dietary risk factors for the emergence of type 1 diabetes-related autoantibodies in 2½-year-old Swedish children
- 2006
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Ingår i: British Journal of Nutrition. - : Cambridge University Press. - 0007-1145 .- 1475-2662. ; 95:3, s. 603-608
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Tidskriftsartikel (refereegranskat)abstract
- We studied dietary risk factors by analysing a questionnaire administered at birth, 1 year and 2½ years of age, as well as the level of glutamic acid decarboxylase autoantibodies (GADA) and tyrosine phosphatase autoantibodies (IA-2A), in 7208 2½-year-old children from the All Babies in Southeast Sweden cohort, using the 95th percentile cut-off for autoantibodies to identify children at risk of type 1 diabetes. A total of 657 children had either IA-2A (n 360) or GADA (n 335), and thirty-eight children had both GADA and IA-2A. In univariate analysis, male gender and maternal coeliac disease implied a risk of possessing IA-2A. Maternal type 2 diabetes, a high consumption of fresh cows milk at the age of 1 year and a late introduction of gluten were associated with a risk of GADA. Early cessation of breast-feeding (≤2 months of age) was associated with a risk of the simultaneous occurrence of both IA-2A and GADA. In logistic regression analysis, a high consumption of milk at the age of 1 year (odds ratio 2·6) represented a risk for GADA, and maternal coeliac disease (odds ratio 2·9) represented a risk for IA-2A. The combination of an early introduction of cows milk formula and a late introduction of gluten-containing food gave an odds ratio of 6·0 for positivity for at least one autoantibody at 1 and 2½ years of age. The induction of autoantibodies by the age of 2½ years has a male preponderance and is more common in children with maternal type 2 diabetes or maternal coeliac disease. Dietary risk factors for the induction of β-cell autoantibodies in 2½-year-old children are a short duration of breast-feeding, an early introduction of cows milk formula and a late introduction of gluten, as well as a high consumption of milk at the age of 1 year.
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| 8. |
- Wahlberg, Jeanette, 1969-
(författare)
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Environmental determinants associated with Type 1 diabetes-related autoantibodies in children
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Type 1 diabetes is a severe disease, which affects children with potentially severe consequences. The global incidence of Type 1 diabetes is increasing rapidly especially in young children. Second to Finland, Sweden has the highest incidence of Type 1 diabetes in the world.The rapidly increasing incidence cannot be explained by a possible variability of the presence of risk genes in the population, but rather environmental factors.Therefore, environmental factors contributing to ß-cell auto immunity should be of importance for the process leading up to clinical Type I diabetes in genetically predisposed individuals. Those factors should preferably be revealed early in life. The aim of this thesis was to investigate a large population of Swedish children in order to identify environmental factors, which could contribute to the autoimmune reaction towards insulin-producing ß-cells.Material and methodsFamilies from the prospective population-based ABIS-project (All Babies in southeast Sweden) were studied. Blood samples from children were analysed at birth, one year and 2½ years of age for diabetes-related autoantibodies towards Tyrosine phosphatase (IA-2A) and Glutamic Acid Decarboxylase (GAD). The parents completed questionnaires at birth, one year and 2½ years of age.Results Short breast-feeding period, early exposure to cow's milk formula and late introduction of gluten-containing foods as well as large consumption of cow's milk at the age of one year were all risk determinants for development of autoantibodies at 2½ years of age. Combined early introduction of cow's milk formula and late introduction of gluten-containing food increased the risk six times for acquiring persistent autoantibodies at 2½ years of age. Parenting stress and experiences of serious life events were associated with the induction of diabetes-related autoimmunity. Infections during pregnancy are related to diabetes-related autoantibodies in cord blood and at the age of one year.Allergic symptoms such as rash, wheezing, allergy against fur-bearing animals and food allergies implied a risk for development of diabetes-related autoantibodies. Autoantibodies in cord blood had disappeared at the age of one year, and can therefore not be used as a screening method to predict diabetes in the general population.ConclusionsNone of the examined risk factors alone can explain Type 1 diabetes-related autoimmunity; but early nutrition, parental stress and infections can contribute to the development of diabetes-related autoantibodies.Autoantibodies in cord blood cannot be used to predict later diabetes-related autoimmunity. Different aberrances in the immune system seem to co-exist in certain individuals.
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| 9. |
- Wahlberg, Jeanette, 1969-, et al.
(författare)
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Environmental factors related to the induction of beta-cell autoantibodies in 1-yr-old healthy children
- 2005
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Ingår i: Pediatric Diabetes. - : John Wiley & Sons. - 1399-543X .- 1399-5448. ; 6:4, s. 199-205
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Tidskriftsartikel (refereegranskat)abstract
- We studied environmental risk factors which might contribute to the development of beta-cell autoantibodies in healthy children. Here, we investigated 6000 randomly selected children from the large All Babies in Southeast Sweden (ABIS) cohort, including 17 055 newborns recruited between 1997 and 1999. Questionnaires at birth and at 1 yr of age and the levels of autoantibodies to glutamic acid decarboxylase (GADA) and autoantibodies to tyrosine phosphatase (IA-2A) at 1 yr of age were analyzed. The 99th percentile cutoff for autoantibodies was proposed to identify children at risk of type 1 diabetes (T1D) and the 90th percentile cutoff to identify children in whom beta-cell autoimmunity has been induced. Using the 90th percentile cutoff level, 1156 children had either IA-2A (n = 574) or GADA (n = 582), while 126 children had both GADA and IA-2A. When the 99th percentile cutoff level was used, 114 children had either IA-2A (n = 57) or GADA (n = 57), and six children had both GADA and IA-2A. In logistic regression analysis, celiac disease in grandparents [odds ratio (OR) 2.2] and maternal gastrointestinal infection (OR 1.1) represented a risk for simultaneous occurrence of both IA-2A and GADA above the 90th percentile. Birth in spring (March to May) (OR 1.5) and male gender (OR 1.3) were risk factors for induction of IA-2A. Mother's low education represented a risk for induction of IA-2A (OR 1.5) and GADA (OR 1.4). T1D in first-degree relatives increased the risk for beta-cell autoimmunity above the 99th percentile (OR 2.6), whereas type 2 diabetes in grandparents was associated with GADA (OR 2.1). Exposure to cow's milk formulas <2 months of age implied an OR of 2.9 for IA-2A above the 99th percentile.
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