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Chris R Cardwell, Lars C Stene,
Johnny Ludvigsson,
Joachim Rosenbauer,
Ondrej Cinek,
Jannet Svensson,
Francisco Perez-Bravo,
Anjum Memon,
Suely G Gimeno,
Emma J K Wadsworth, [......],
Geir Joner,
Constantin Ionescu-Tirgoviste,
Carine E de Beaufort,
Kirsten Harrild,
Victoria Benson,
Erkki Savilahti,
Anne-Louise Ponsonby,
Mona Salem,
Samira Rabiei,
Chris C Patterson
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Chris R Cardwell, Lars C Stene,
Johnny Ludvigsson,
Joachim Rosenbauer,
Ondrej Cinek,
Jannet Svensson,
Francisco Perez-Bravo,
Anjum Memon,
Suely G Gimeno,
Emma J K Wadsworth, [......],
Geir Joner,
Constantin Ionescu-Tirgoviste,
Carine E de Beaufort,
Kirsten Harrild,
Victoria Benson,
Erkki Savilahti,
Anne-Louise Ponsonby,
Mona Salem,
Samira Rabiei,
Chris C Patterson
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Chris R Cardwell, Lars C Stene,
Johnny Ludvigsson,
Joachim Rosenbauer,
Ondrej Cinek,
Jannet Svensson,
Francisco Perez-Bravo,
Anjum Memon,
Suely G Gimeno,
Emma J K Wadsworth, [......],
Geir Joner,
Constantin Ionescu-Tirgoviste,
Carine E de Beaufort,
Kirsten Harrild,
Victoria Benson,
Erkki Savilahti,
Anne-Louise Ponsonby,
Mona Salem,
Samira Rabiei,
Chris C Patterson
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ABSTRACT: OBJECTIVE To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders. RESEARCH DESIGN AND METHODS Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies. RESULTS Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for >2 weeks (20 studies; OR = 0.75, 95% CI 0.64-0.88), the association after exclusive breast-feeding for >3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75-1.00), and no association was observed after (nonexclusive) breast-feeding for >2 weeks (28 studies; OR = 0.93, 95% CI 0.81-1.07) or >3 months (29 studies; OR = 0.88, 95% CI 0.78-1.00). These associations were all subject to marked heterogeneity (I(2) = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for >2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75-0.99), and heterogeneity was reduced (I(2) = 0%). Adjustments for potential confounders altered these estimates very little. CONCLUSIONS The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies.
Diabetes care 07/2012; 35(11):2215-25. · 8.09 Impact Factor
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Diabetes 07/2012; 61(7):e9. · 8.29 Impact Factor
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ABSTRACT: There is uncertainty as to which intake of vitamin D is needed to suppress PTH and maintain normal bone metabolism throughout winter at northern latitudes. We aimed to investigate whether four weeks' daily supplementation with 10 μg vitamin D3 from fish oil produced a greater change in serum vitamin D metabolites, parathyroid hormone, and bone turnover in healthy adults compared with solid multivitamin tablets. Furthermore, it was studied whether age, gender, ethnic background, body mass index, or serum concentrations at baseline predicted the magnitude of change in these parameters.
Healthy adults aged 19-48 years living in Oslo, Norway (59°N) were randomised to receive a daily dose of 10 μg vitamin D3 given as fish oil capsules or multivitamin tablets during four weeks in late winter. Serum samples from baseline and after 28 days were analysed for 25-hydroxyvitamin D (s-25(OH)D), 1,25-dihydroxyvitamin D (s-1,25(OH)2D), intact parathyroid hormone (s-iPTH), and osteoclast-specific tartrate-resistant acid phosphatase 5b (s-TRACP). Fifty-five eligible participants completed the intervention (74% of those randomised).
S-25(OH)D increased by mean 34.1 (SD 13.1) nmol/l, p < 0.001; s-iPTH decreased by mean 1.2 (SD 2.5) pmol/l, p = 0.001; s-1,25(OH)2D increased by mean 13 (SD 48) pmol/l, p = 0.057; and s-TRACP increased by mean 0.38 (SD 0.33) U/l, p < 0.001. For all these parameters, there was no difference between fish oil and multivitamin formulation. Baseline concentrations were the only independent predictors of changes in biochemical parameters.
Four weeks of daily supplementation with 10 μg vitamin D3 decreased mean s-iPTH and increased s-TRACP concentration, and this did not differ by mode of administration. Our results suggest an increased bone resorption following vitamin D supplementation in young individuals, despite a decrease in parathyroid hormone levels.
ClinicalTrials.gov: NCT01482689.
BMC Endocrine Disorders 06/2012; 12:7. · 2.16 Impact Factor
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ABSTRACT: Enterovirus infections may be involved in the etiology of type 1 diabetes (T1D), which is strongly associated with certain human leukocyte antigen (HLA) class II haplotypes. Our aim was to assess whether HLA genotypes conferring varying degrees of risk for T1D were associated with enterovirus gut infections. From the general Norwegian population, 190 healthy infants at high-risk for T1D (DR4-DQ8/DR3-DQ2), and 383 infants without this genotype were identified. Non-DR4-DQ8/DR3-DQ2 genotypes were further categorized as conferring either an increased-to-moderate risk (DR4-DQ8 or DR3-DQ2), were protective (DQB1*06:02), or were neutral (all other genotypes). A total of 4626 monthly fecal samples taken between age 3 and 12 mo were tested for enterovirus RNA using real-time PCR. Enterovirus prevalence was 11.5% among high-risk children, and 12.2% in other children (adjusted odds ratio: 1.23, p=0.12). The prevalence was 11.3% in those with increased-to-moderate risk, 13.0% in the protective group, and 12.6% in the neutral group (likelihood ratio test, 3 d.f.: p=0.37). In conclusion, there was no statistically significant association between HLA genotype and the occurrence of human enterovirus gut infections.
Viral immunology 06/2012; 25(3):187-92. · 1.78 Impact Factor
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ABSTRACT: OBJECTIVE: Polymorphisms in the IFIH1 (common rs1990760 and four rare rs35667974, rs35337543, rs35744605, rs35732034) have been convincingly associated with type 1 diabetes. The encoded protein (interferon-induced helicase C domain-containing protein 1) senses double-stranded RNA during replication of Picornavirales, including Enterovirus, a genus suspected in the etiology of type 1 diabetes. We therefore investigated whether the polymorphisms are associated with differences in the frequency of enterovirus RNA in blood. RESEARCH DESIGN AND METHODS: The study included 1001 blood samples, each from a child participating in the Norwegian 'Environmental Triggers of Type 1 Diabetes: the MIDIA study'. The enterovirus RNA was tested using qualitative semi-nested real-time reverse transcriptase PCR on RNA extracted from frozen cell packs after removal of plasma. Stool samples previously analyzed for enterovirus RNA were available in 417 children. RESULTS: The genotypes of IFIH1 rs1990760 were associated with different frequencies of enterovirus RNA in blood (7.0%, 14.4% and 9.5% bloods were enterovirus positive among children carrying the Ala/Ala, Ala/Thr and Thr/Thr genotypes, respectively, p = 0.012). This association remained essentially unchanged after adjustment for age and calendar year. The presence of enterovirus in the concomitantly sampled stool further increased the likelihood of enterovirus RNA in blood (odds ratio 2.40, CI 95% 1.13-4.70), but did not affect the association with IFIH1 rs1990760. The rare polymorphisms (individually, or pooled) were not significantly associated with enterovirus RNA in blood. CONCLUSIONS: The common IFIH1 SNP may modify the frequency of enterovirus RNA in blood of healthy children. This effect can help explain the association of IFIH1 with type 1 diabetes.
PLoS ONE 01/2012; 7(11):e48409. · 4.09 Impact Factor
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ABSTRACT: Previous studies indicate reduced risk of type 1 diabetes after intake of vitamin D supplements during pregnancy or early childhood. We aimed to test whether lower maternal serum concentrations of 25-hydroxy-vitamin D (25-OH D) during pregnancy were associated with an increased risk of childhood-onset type 1 diabetes. In this case-control study nested within a cohort of 29,072 women in Norway, 25-OH D levels were measured using a radioimmunoassay on samples from late pregnancy in 109 women delivering a child who developed type 1 diabetes before 15 years of age (case subjects) and from 219 control women. Dividing the levels of maternal 25-OH D into quartiles, there was a trend toward a higher risk of type 1 diabetes with lower levels of vitamin D during pregnancy. The odds of type 1 diabetes was more than twofold higher for the offspring of women with the lowest levels of 25-OH D compared with the offspring of those with levels above the upper quartile. Given future replication in independent cohorts, our findings provide support for the initiation of a randomized intervention trial to prevent type 1 diabetes in children by enhancing maternal 25-OH D status during pregnancy.
Diabetes 11/2011; 61(1):175-8. · 8.29 Impact Factor
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ABSTRACT: To test whether self-reported lower respiratory tract infections in early infancy predicted risk for islet autoimmunity in genetically predisposed children.
The environmental triggers for type 1 diabetes (MIDIA) study recruited newborns in Norway to identify those with the human leukocyte antigen high-risk genotype DR4-DQ8/DR3-DQ2. Of 46 939 newborns genotyped, 1003 (2.1%) carried the high-risk genotype, of whom 885 children were followed longitudinally with questionnaires and blood samples for autoantibody testing at 3, 6, 9 and 12 months of age, and then annually until 4 years of age. The endpoint (autoimmunity) was defined as positivity for at least one of three autoantibodies (to insulin, glutamic acid decarboxylase (GAD) or protein tyrosine phosphatase-like protein (IA2)) on at least two consecutive samples. The parents responded in the questionnaires, whether the child had had 'pneumonia, bronchitis or respiratory syncytial virus'. Cox proportional hazards regression models with time-dependent covariates were used to estimate hazard ratios for autoimmunity using STATA 10.
Forty-two children developed autoimmunity, of whom 15 later developed type 1 diabetes. For 17 of the 42 cases (40%) 'pneumonia, bronchitis or respiratory syncytial virus' was reported (0.5-4 years of age) before or at the onset of autoimmunity. For 187 of the 843 non-cases (22%) 'pneumonia, bronchitis or respiratory syncytial virus' was reported in the same age group. The hazard ratio was 3.4 (p=0.001, 95% confidence interval: 1.6-7.1) for developing autoimmunity. The estimated hazard ratio was only marginally influenced by adjustment for potential confounding factors. No association was found for other infectious self-reported symptoms.
Self-reported lower respiratory tract infections were associated with increased risk of islet autoimmunity in early infancy.
Diabetes/Metabolism Research and Reviews 11/2011; 27(8):834-7. · 3.37 Impact Factor
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ABSTRACT: Maternal age at birth, birth weight, and cesarean section has been associated with a weak but significant increase in risk of type 1 diabetes. The objective was to assess whether the relative risk for type 1 diabetes conferred by established susceptibility loci human leukocyte antigen (HLA)-DQ, INS, and PTPN22 differed depending on these perinatal factors.
We employed a case-control study with 456 cases of type 1 diabetes diagnosed before 15 yr of age and 1377 population-based control children. HLA genotypes were divided into high to moderate risk (DQ8/DQ2, DQ8/DQ8, DQ8/X, DQ2/DQ2) vs. all other genotypes. Case-only analysis using logistic regression was used to test for significant interaction.
There was no significant difference in the relative risks conferred by HLA-DQ, INS, or PTPN22 by maternal age, birth weight, or mode of delivery, except the relative risk conferred by PTPN22 which was 2.11 [95% confidence interval (CI): 1.64-2.72] for those born vaginally and 0.99 (95% CI: 0.50-1.99) for those born by cesarean section [p(interaction) = 0.028].
The relative risks conferred by the three established susceptibility genes investigated here were independent of the perinatal factors, apart from a possible interaction between PTPN22 and mode of delivery.
Pediatric Diabetes 03/2011; 12(2):91-4. · 2.16 Impact Factor
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ABSTRACT: The objective of this study was to investigate a possible association between human parechovirus infections in early infancy, diagnosed in fecal samples, and the development of islet autoimmunity. In the 'Environmental Triggers of Type 1 Diabetes: The MIDIA study', newborns with the highest genetic risk for type 1 diabetes were identified and followed with regular fecal sampling and questionnaires. A nested case-control study, including 27 children who developed islet autoimmunity (repeatedly positive for two or three autoantibodies) and 53 children matched for age and community of residence was used. Monthly stool samples from these children were analyzed for human parechovirus using a semi-quantitative real-time polymerase chain reaction. There was no significant difference in the prevalence of human parechovirus in stool samples when cases and controls were compared: 13.0 and 11.1%, respectively. There was also not any difference as to the number of infection episodes. In analyses restricted to samples collected 3, 6 or 12 months prior to seroconversion for islet autoantibodies, there was a suggestive association in the shortest time window of 3 months (20.8 vs. 8.8%, odds ratio = 3.2, 95% CI 1.2 - 8.5, uncorrected p = 0.022). No symptoms were associated with human parechovirus infection. A subset of the positive samples (n = 31) were sequenced, suggesting that human parechovirus 1 was the dominant genotype. The present study does not support strong associations between human parechovirus infections and the signs of islet autoimmunity. The weak association of parechovirus present in the last 3 months before development of autoimmunity warrants further investigation.
Pediatric Diabetes 02/2011; 12(1):58-62. · 2.16 Impact Factor
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ABSTRACT: Interferon induced with helicase C domain 1 (IFIH1) senses and initiates antiviral activity against enteroviruses. Genetic variants of IFIH1, one common and four rare SNPs have been associated with lower risk for type 1 diabetes. Our aim was to test whether these type 1 diabetes-associated IFIH1 polymorphisms are associated with the occurrence of enterovirus infection in the gut of healthy children, or influence the lack of association between gut enterovirus infection and islet autoimmunity.After testing of 46,939 Norwegian newborns, 421 children carrying the high risk genotype for type 1 diabetes (HLA-DR4-DQ8/DR3-DQ2) as well as 375 children without this genotype were included for monthly fecal collections from 3 to 35 months of age, and genotyped for the IFIH1 polymorphisms. A total of 7,793 fecal samples were tested for presence of enterovirus RNA using real time reverse transcriptase PCR.We found no association with frequency of enterovirus in the gut for the common IFIH1 polymorphism rs1990760, or either of the rare variants of rs35744605, rs35667974, rs35337543, while the enterovirus prevalence marginally differed in samples from the 8 carriers of a rare allele of rs35732034 (26.1%, 18/69 samples) as compared to wild-type homozygotes (12.4%, 955/7724 samples); odds ratio 2.5, p = 0.06. The association was stronger when infections were restricted to those with high viral loads (odds ratio 3.3, 95% CI 1.3-8.4, p = 0.01). The lack of association between enterovirus frequency and islet autoimmunity reported in our previous study was not materially influenced by the IFIH1 SNPs.We conclude that the type 1 diabetes-associated IFIH1 polymorphisms have no, or only minor influence on the occurrence, quantity or duration of enterovirus infection in the gut. Its effect on the risk of diabetes is likely to lie elsewhere in the pathogenic process than in the modification of gut infection.
PLoS ONE 01/2011; 6(11):e27781. · 4.09 Impact Factor
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ABSTRACT: To investigate whether enterovirus infections predict progression to type 1 diabetes in genetically predisposed children repeatedly positive for islet autoantibodies.
Since 1993, the Diabetes and Autoimmunity Study in the Young (DAISY) has followed 2,365 genetically predisposed children for islet autoimmunity and type 1 diabetes. Venous blood and rectal swabs were collected every 3-6 months after seroconversion for islet autoantibodies (against GAD, insulin, or insulinoma-associated antigen-2 [IA-2]) until diagnosis of diabetes. Enteroviral RNA in serum or rectal swabs was detected using reverse transcriptase PCR with primers specific for the conserved 5' noncoding region, detecting essentially all enterovirus serotypes.
Of 140 children who seroconverted to repeated positivity for islet autoantibodies at a median age of 4.0 years, 50 progressed to type 1 diabetes during a median follow-up of 4.2 years. The risk of progression to clinical type 1 diabetes in the sample interval following detection of enteroviral RNA in serum (three diabetes cases diagnosed among 17 intervals) was significantly increased compared with that in intervals following a negative serum enteroviral RNA test (33 cases diagnosed among 1,064 intervals; hazard ratio 7.02 [95% CI 1.95-25.3] after adjusting for number of autoantibodies). Results remained significant after adjustment for ZnT8-autoantibodies and after restriction to various subgroups. Enteroviral RNA in rectal swabs was not predictive of progression to type 1 diabetes. No evidence for viral persistence was found.
This novel observation suggests that progression from islet autoimmunity to type 1 diabetes may increase after an enterovirus infection characterized by the presence of viral RNA in blood.
Diabetes 12/2010; 59(12):3174-80. · 8.29 Impact Factor
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Chris R Cardwell, Lars C Stene,
Geir Joner,
Max K Bulsara,
Ondrej Cinek,
Joachim Rosenbauer,
Johnny Ludvigsson,
Jannet Svensson,
Michael J Goldacre,
Thomas Waldhoer, [......],
Sandra Sipetic,
Edith Schober,
Gabriele Devoti,
Constantin Ionescu-Tirgoviste,
Carine E de Beaufort,
Denka Stoyanov,
Karsten Buschard,
Katja Radon,
Christopher Glatthaar,
Chris C Patterson
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ABSTRACT: The incidence rates of childhood onset type 1 diabetes are almost universally increasing across the globe but the aetiology of the disease remains largely unknown. We investigated whether birth order is associated with the risk of childhood diabetes by performing a pooled analysis of previous studies.
Relevant studies published before January 2010 were identified from MEDLINE, Web of Science and EMBASE. Authors of studies provided individual patient data or conducted pre-specified analyses. Meta-analysis techniques were used to derive combined odds ratios (ORs), before and after adjustment for confounders, and investigate heterogeneity.
Data were available for 6 cohort and 25 case-control studies, including 11,955 cases of type 1 diabetes. Overall, there was no evidence of an association prior to adjustment for confounders. After adjustment for maternal age at birth and other confounders, a reduction in the risk of diabetes in second- or later born children became apparent [fully adjusted OR = 0.90 95% confidence interval (CI) 0.83-0.98; P = 0.02] but this association varied markedly between studies (I² = 67%). An a priori subgroup analysis showed that the association was stronger and more consistent in children < 5 years of age (n = 25 studies, maternal age adjusted OR = 0.84 95% CI 0.75, 0.93; I² = 23%).
Although the association varied between studies, there was some evidence of a lower risk of childhood onset type 1 diabetes with increasing birth order, particularly in children aged < 5 years. This finding could reflect increased exposure to infections in early life in later born children.
International Journal of Epidemiology 12/2010; 40(2):363-74. · 6.41 Impact Factor
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ABSTRACT: To estimate the risk of congenital anomalies in offspring of women with type 1 diabetes in Norway during recent years.
Nationwide population-based study using the Medical Birth Registry of Norway and the Norwegian type 1 Diabetes Registry.
All birth clinics in Norway.
All births in Norway during 1999-2004 (N = 350,961), of which 1,583 were births by a mother registered with pregestational type 1 diabetes.
Congenital anomalies, excluding minor anomalies according to the EUROCAT system.
Anomalies were registered in 5.7% of offspring of women with type 1 diabetes, and in 2.9% among the background population (odds ratio 2.1, 95% CI: 1.7-2.6). Cardiovascular anomalies were registered in 3.2% in the diabetes group and 0.94% in the background population (odds ratio 3.5, 95% CI: 2.7-4.7). Results were similar when restricted to women identified with type 1 diabetes through the Diabetes Registry.
Women in Norway with type 1 diabetes experience a significantly higher risk of congenital anomalies in their babies compared with the background population.
Acta Obstetricia Et Gynecologica Scandinavica 10/2010; 89(11):1403-11. · 1.77 Impact Factor
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ABSTRACT: Established genetic susceptibility loci for type 1 diabetes are important in immune regulation and may play a role also in atopic disorders, potentially explaining the inverse association between childhood eczema and subsequent risk for type 1 diabetes previously reported.
We aimed to directly assess whether HLA-DQ, CTLA4, and PTPN22 genes could explain the putative association between childhood eczema and lower subsequent risk of type 1 diabetes observed in several case-control studies.
We designed a case-control study with 339 incident cases of type 1 diabetes identified in the Norwegian childhood diabetes registry, and 985 population-based control children. DNA was collected, and physician-diagnosed childhood eczema was ascertained by a questionnaire administered to the parents of children with and without type 1 diabetes.
The previously reported association between childhood eczema and lower risk of type 1 diabetes was confirmed (odds ratio,OR, 0.61, 95% confidence interval, CI, 0.40-0.95] and this was consistent in subgroups defined by HLA-DQ, CTLA4, and PTPN22 genotypes. The OR was essentially not influenced by adjustment for genetic variation at these loci (OR simultaneously adjusted for the three genetic loci: 0.55, 95% CI: 0.32-0.92). The ratio of the unadjusted to adjusted OR was 1.12, with a corresponding 95% CI from 0.84 to 1.50.
In this first study of its kind, we demonstrated directly that the observed inverse association between childhood eczema and type 1 diabetes is not likely to be explained by the established diabetes susceptibility genes HLA-DQ, CTLA4, or PTPN22.
Pediatric Diabetes 11/2009; 11(6):386-93. · 2.16 Impact Factor
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Chris R Cardwell, Lars C Stene,
Geir Joner,
Max K Bulsara,
Ondrej Cinek,
Joachim Rosenbauer,
Johnny Ludvigsson,
Mireia Jané,
Jannet Svensson,
Michael J Goldacre, [......],
Girts Brigis,
Brone Urbonaite,
Sandra Sipetic,
Edith Schober,
Gabriele Devoti,
Constantin Ionescu-Tirgoviste,
Carine E de Beaufort,
Denka Stoyanov,
Karsten Buschard,
Chris C Patterson
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ABSTRACT: The aim if the study was to investigate whether children born to older mothers have an increased risk of type 1 diabetes by performing a pooled analysis of previous studies using individual patient data to adjust for recognized confounders.
Relevant studies published before June 2009 were identified from MEDLINE, Web of Science, and EMBASE. Authors of studies were contacted and asked to provide individual patient data or conduct prespecified analyses. Risk estimates of type 1 diabetes by maternal age were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were used to derive combined odds ratios and to investigate heterogeneity among studies.
Data were available for 5 cohort and 25 case-control studies, including 14,724 cases of type 1 diabetes. Overall, there was, on average, a 5% (95% CI 2-9) increase in childhood type 1 diabetes odds per 5-year increase in maternal age (P = 0.006), but there was heterogeneity among studies (heterogeneity I(2) = 70%). In studies with a low risk of bias, there was a more marked increase in diabetes odds of 10% per 5-year increase in maternal age. Adjustments for potential confounders little altered these estimates.
There was evidence of a weak but significant linear increase in the risk of childhood type 1 diabetes across the range of maternal ages, but the magnitude of association varied between studies. A very small percentage of the increase in the incidence of childhood type 1 diabetes in recent years could be explained by increases in maternal age.
Diabetes 10/2009; 59(2):486-94. · 8.29 Impact Factor
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ABSTRACT: To assess whether maternal BMI before pregnancy and weight gain during pregnancy predicted the risk of islet autoimmunity in genetically susceptible children.
Of 46,939 newborns screened for the high-risk HLA genotype DR4-DQ8/DR3-DQ2, 1,003 were positive and 885 were followed with serial blood samples tested for autoantibodies to insulin, GAD, and insulinoma-associated protein 2 (IA2). The end point was defined as repeated positivity for two or three autoantibodies or the onset of type 1 diabetes (islet autoimmunity).
Thirty-six children developed islet autoimmunity, of whom 10 developed type 1 diabetes. Both maternal BMI > or =30 kg/m(2) before pregnancy and maternal weight gain > or =15 kg predicted the increased risk of islet autoimmunity (hazard ratio [HR] 2.5, P = 0.023, and HR 2.5, P = 0.015, respectively), independent of maternal diabetes.
Maternal weight may predict risk of islet autoimmunity in offspring with a high genetic susceptibility for type 1 diabetes.
Diabetes care 07/2009; 32(10):1904-6. · 8.09 Impact Factor
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ABSTRACT: High prevalences of vitamin D deficiency have been reported in non-Western immigrants moving to Western countries, including Norway, but there is limited information on vitamin D status in infants born to immigrant mothers. We aimed to describe the vitamin D status and potentially correlated factors among infants aged 6 weeks and their mothers with Pakistani, Turkish or Somali background attending child health clinics in Norway. Eighty-six healthy infants and their mothers with immigrant background were recruited at the routine 6-week check-up at nine centres between 2004 and 2006. Venous or capillary blood was collected at the clinics from the mother and infant, and serum separated for analysis of 25-hydroxyvitamin D (s-25(OH)D) and intact parathyroid hormone (s-iPTH). The mean maternal s-25(OH)D was 25.8 nmol/l, with 57 % below 25 nmol/l and 15 % below 12.5 nmol/l. Of the mothers, 26 % had s-iPTH>5.7 pmol/l. For infants, mean s-25(OH)D was 41.7 nmol/l, with 47 % below 25 nmol/l and 34 % below 12.5 nmol/l. s-25(OH)D was considerably lower in the thirty-one exclusively breast-fed infants (mean 11.1 nmol/l; P < 0.0001). Use of vitamin D supplements and education showed a positive association with maternal s-25(OH)D. There was no significant association between mother's and child's s-25(OH)D, and no significant ethnic or seasonal variation in s-25(OH)D for mothers or infants. In conclusion, there is widespread vitamin D deficiency in immigrant mothers and their infants living in Norway. Exclusively breast-fed infants who did not receive vitamin D supplements had particularly severe vitamin D deficiency.
The British journal of nutrition 09/2008; 101(7):1052-8. · 3.45 Impact Factor
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ABSTRACT: We have previously described an association between use of cod liver oil (a dietary n-3 fatty acid supplement) and reduced risk of type 1 diabetes. n-3 fatty acids are ligands for the peroxisome proliferator-activated receptor-gamma (PPARG), which has recently been implicated in the control of inflammation and possibly autoimmunity. We aimed to estimate the association between the common Pro12Ala polymorphism of PPARG2 and risk of type 1 diabetes, and to test whether there is gene-environment interaction with use of cod liver oil in the first year of life or gene-gene interaction with the established insulin gene (INS) and human leukocyte antigen DQ (HLA-DQ) genetic susceptibility loci.
We designed a population-based case-control study of childhood-onset type 1 diabetes in Norway with information on use of cod liver oil in the first year of life from questionnaires and PPARG2 genotype data for 483 cases and 1520 control subjects. We used logistic regression for analysis.
The odds ratio for the PPARG2 Ala/Ala or Pro/Ala vs. Pro/Pro genotype and type 1 diabetes was 0.89 (95% CI: 0.69-1.13, p = 0.33). There was no significant interaction with cod liver oil in the first year of life [P (interaction) = 0.35] or with the INS polymorphism [P(interaction) = 0.42].
Although the association between PPARG2 and type 1 diabetes was not significant, the observed odds ratio was almost identical to that observed in two previous studies and can contribute to meta-analysis indicating a weak but significant association. Our hypothesized interaction between cod liver oil and PPARG2 in reducing type 1 diabetes risk was not supported.
Pediatric Diabetes 03/2008; 9(1):40-5. · 2.16 Impact Factor
