| 1. |
- Knip, Mikael, et al.
(författare)
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Hydrolyzed infant formula and early β-cell autoimmunity : a randomized clinical trial.
- 2014
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 311:22, s. 2279-2287
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The disease process leading to clinical type 1 diabetes often starts during the first years of life. Early exposure to complex dietary proteins may increase the risk of β-cell autoimmunity in children at genetic risk for type 1 diabetes. Extensively hydrolyzed formulas do not contain intact proteins.OBJECTIVE: To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of diabetes-associated autoantibodies in young children.DESIGN, SETTING, AND PARTICIPANTS: A double-blind randomized clinical trial of 2159 infants with HLA-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1078 were randomized to be weaned to the extensively hydrolyzed casein formula and 1081 were randomized to be weaned to a conventional cows' milk-based formula. The participants were observed to April 16, 2013.INTERVENTIONS: The participants received either a casein hydrolysate or a conventional cows' milk formula supplemented with 20% of the casein hydrolysate.MAIN OUTCOMES: AND MEASURES: Primary outcome was positivity for at least 2 diabetes-associated autoantibodies out of 4 analyzed. Autoantibodies to insulin, glutamic acid decarboxylase, and the insulinoma-associated-2 (IA-2) molecule were analyzed using radiobinding assays and islet cell antibodies with immunofluorescence during a median observation period of 7.0 years (mean, 6.3 years).RESULTS: The absolute risk of positivity for 2 or more islet autoantibodies was 13.4% among those randomized to the casein hydrolysate formula (n = 139) vs 11.4% among those randomized to the conventional formula (n = 117). The unadjusted hazard ratio for positivity for 2 or more autoantibodies among those randomized to be weaned to the casein hydrolysate was 1.21 (95% CI, 0.94-1.54), compared with those randomized to the conventional formula, while the hazard ratio adjusted for HLA risk, duration of breastfeeding, vitamin D use, study formula duration and consumption, and region was 1.23 (95% CI, 0.96-1.58). There were no clinically significant differences in the rate of reported adverse events between the 2 groups.CONCLUSIONS AND RELEVANCE: Among infants at risk for type 1 diabetes, the use of a hydrolyzed formula, when compared with a conventional formula, did not reduce the incidence of diabetes-associated autoantibodies after 7 years. These findings do not support a benefit from hydrolyzed formula. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00179777.
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| 2. |
- Juonala, Markus, et al.
(författare)
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Geographic Origin as a Determinant of Carotid Artery Intima-Media Thickness and Brachial Artery Flow-Mediated Dilation. The Cardiovascular Risk in Young Finns Study.
- 2005
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 25:2, s. 392-398
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Tidskriftsartikel (refereegranskat)abstract
- Objective - People living in eastern Finland have approximate to 40% higher coronary heart disease mortality rates than western Finns. Whether this is because of genetic or environmental factors is unknown. We examined the effect of geographic family origin on subclinical atherosclerosis among young Finns. Methods and Results - As part of a longitudinal follow-up study, we measured carotid intima-media thickness (IMT) in 2264 and brachial flow-mediated dilation (FMD) in 2109 white adults, aged 24 to 39 years. Subjects from eastern Finland had greater IMT and lower FMD compared with western subjects. These differences accentuated when the subjects' family origin ( grandparents' birthplace) was taken into account and remained significant after adjusting for several environmental factors. Among subjects with all grandparents born in eastern or western Finland, IMTs were ( mean +/- SEM) 0.592 +/- 0.003 versus 0.565 +/- 0.005 mm ( P < 0.0001), respectively. The corresponding FMD values were 7.61 +/- 0.15% versus 8.75 +/- 0.26%; P < 0.01. The number of grandparents born in eastern Finland was directly related to IMT ( P < 0.0001) and inversely to FMD ( P < 0.05). Conclusions - Young adults originating from eastern Finland have greater carotid IMT and lower brachial FMD than western Finns. Consistent with a hereditable component predisposing to or protecting from atherosclerosis, these differences accentuated when subjects' family origin was taken into account.
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| 3. |
- Laine, Antti-Pekka, et al.
(författare)
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Two insulin gene single nucleotide polymorphisms associated with type 1 diabetes risk in the Finnish and Swedish populations
- 2007
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Ingår i: Disease Markers. - : Hindawi Limited. - 0278-0240 .- 1875-8630. ; 23:3, s. 139-45
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Tidskriftsartikel (refereegranskat)abstract
- We have developed high-throughput tests for the detection of the insulin gene region SNPs -23HphI and -2221MspI. The potential of these markers to enhance the efficiency of type 1 diabetes risk screening was then evaluated by analyzing them in Finnish and Swedish populations. Blood spots on filter paper were analyzed using PCR followed by sequence-specific hybridization and time-resolved fluorometry reading. Distribution of the genotypes at both positions differed significantly among the affected children compared to the controls. The risk genotypes (CC, AA) were significantly more common in Finland than in Sweden, both among patients and controls. The VNTR genotype homozygous for the protective class III alleles showed a significantly stronger protective effect than the heterozygote (p=0.02). Analyzing both SNPs enabled the detection of VNTR class III subclasses IIIA and IIIB. The observed significance between effects of the protective genotypes was due to the strong protective effect of the IIIA/IIIA genotype. IIIA/IIIA was the only genotype with significant discrepancy between protective effects compared to the other class III genotypes. These observations suggest that heterogeneity between the protective IDDM2 lineages could exist, and analyzing both -23HphI and -2221MspI would thus potentially enhance the sensitivity and specificity of type 1 diabetes risk estimation.
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| 4. |
- Luopajärvi, Kristiina, et al.
(författare)
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Reduced expression of CCR4 on cord blood T lymphocytes in neonates at genetic risk of type 1 diabetes
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In type 1 diabetes the T cell polarization and expression of chemokine receptors have been reported to be aberrant. We asked whether these aberrancies are present already at birth in neonates carrying HLA risk haplotypes for type 1 diabetes.Cord blood (CB) samples were obtained from neonates taking part in the Trial to Reduce IDDM in Genetically at Risk (TRIGR) and the Finnish Dietary Intervention Trial for Prevention of Type 1 Diabetes (FINDIA) studies and were screened for type 1 diabetes-associated HLA risk genotypes (HLA DR3-DQ2 and/or DR4-DQ8 without protective alleles). CB lymphocytes were stimulated with phytohemagglutinin (PHA) in type 1 (IL-12, anti-IL4) or type 2 (IL-4, anti-IL12) cytokine environment for 6 days. The expression of chemokine- and cytokine receptors on T cells was determined by flow cytometry, cytokines were analyzed with ELISA, and transcription factors were analyzed using real-time RT-PCR.When compared to the control group, neonates carrying alleles DQ2/DQ8 or DQ8 showed reduced percentage of CD4 T cells expressing CCR4 and lower levels of CCR4 mRNA after culture of CB lymphocytes in type 2 cytokine environment. In addition, these neonates had significantly lower secretion of iL-13 and expression of GATA-3 after culture of CB lymphocytes in type 2 cytok:ine environment in comparison to neonates with no increased genetic risk of type 1 diabetes.These results suggest aberrancies in the in vitro regulation of type 2 immune responses in children with increased genetic risk of type 1 diabetes when compared to neonates without HLA risk haplotypes suggesting that the HLA genotype may affect the T cell polarization already at birth. Aberrant induction ofT cell polarization may contribute to development of autoimmunity later in life.
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| 5. |
- Åkerblom, Hans, et al.
(författare)
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Dietary manipulation of beta cell autoimmunity in infants at increased risk of type 1 diabetes : A pilot study
- 2005
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 48:5, s. 829-837
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: We aimed to assess the feasibility of a dietary intervention trial with weaning to hydrolysed formula in infants at increased risk of type 1 diabetes and to study the effect of the intervention on the emergence of diabetes-associated autoantibodies in early childhood. Methods: We studied 242 newborn infants who had a first-degree relative with type 1 diabetes and carried risk-associated HLA-DQB1 alleles. After exclusive breastfeeding, the infants underwent a double-blind, randomised pilot trial of either casein hydrolysate (Nutramigen, Mead Johnson) or conventional cow's milk-based formula until the age of 6-8 months. During a mean observation period of 4.7 years, autoantibodies to insulin, anti-glutamic acid decarboxylase and insulinoma-associated antigen-2 were measured by radiobinding assays, and islet cell antibodies (ICA) by immunofluorescence. Results: The feasibility of screening and identifying a cohort of first-degree relatives with HLA-conferred disease susceptibility, enrolling them in a dietary intervention trial and following them for seroconversion to autoantibody positivity is established. The cumulative incidence of autoantibodies was somewhat smaller in the casein hydrolysate vs control formula group, suggesting the need for a larger well-powered study. After adjustment for duration of study formula feeding, life-table analysis showed a significant protection by the intervention from positivity for ICA (p=0.02) and at least one autoantibody (p=0.03). Conclusions/interpretation: The present study provides the first evidence ever in man, despite its limited power, that it may be possible to manipulate spontaneous beta cell autoimmunity by dietary intervention in infancy. © Springer-Verlag 2005.
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