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author:("jones, gear")
1.  Breast-Feeding and Childhood-Onset Type 1 Diabetes 
Diabetes Care  2012;35(11):2215-2225.
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 (I2 = 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 (I2 = 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.
doi:10.2337/dc12-0438
PMCID: PMC3476923  PMID: 22837371
3.  Maternal Serum Levels of 25-Hydroxy-Vitamin D During Pregnancy and Risk of Type 1 Diabetes in the Offspring 
Diabetes  2011;61(1):175-178.
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.
doi:10.2337/db11-0875
PMCID: PMC3237654  PMID: 22124461
5.  Reduction in BMI z-score and improvement in cardiometabolic risk factors in obese children and adolescents. The Oslo Adiposity Intervention Study - a hospital/public health nurse combined treatment  
BMC Pediatrics  2011;11:47.
Background
Weight loss and increased physical fitness are established approaches to reduce cardiovascular risk factors. We studied the reduction in BMI z-score associated with improvement in cardiometabolic risk factors in overweight and obese children and adolescents treated with a combined hospital/public health nurse model. We also examined how aerobic fitness influenced the results.
Methods
From 2004-2007, 307 overweight and obese children and adolescents aged 7-17 years were referred to an outpatient hospital pediatrics clinic and evaluated by a multidisciplinary team. Together with family members, they were counseled regarding diet and physical activity at biannual clinic visits. Visits with the public health nurse at local schools or at maternal and child health centres were scheduled between the hospital consultations. Fasting blood samples were taken at baseline and after one year, and aerobic fitness (VO2peak) was measured. In the analyses, 230 subjects completing one year of follow-up by December 2008 were divided into four groups according to changes in BMI z-score: Group 1: decrease in BMI z-score≥0.23, Group 2: decrease in BMI z-score≥0.1-< 0.23, Group 3: decrease in/stable BMI z-score≥0.0-< 0.1, Group 4: increase in BMI z-score (>0.00-0.55).
Results
230 participants were included in the analyses (75%). Mean (SD) BMI z-score was reduced from 2.18 (0.30) to 2.05 (0.39) (p < 0.001) in the group as a whole. After adjustment for BMI z-score, waist circumference and gender, the three groups with reduced BMI z-score had a significantly greater reduction in HOMA-IR, insulin, total cholesterol, LDL cholesterol and total/HDL cholesterol ratio than the group with increased BMI z-score. Adding change in aerobic fitness to the model had little influence on the results. Even a very small reduction in BMI z-score (group 3) was associated with significantly lower insulin, total cholesterol, LDL and total/HDL cholesterol ratio. The group with the largest reduction in BMI z-score had improvements in HOMA-IR and aerobic fitness as well. An increase in BMI z-score was associated with worsening of C-peptide and total/HDL cholesterol ratio.
Conclusions
Even a modest reduction in BMI z-score after one year of combined hospital/and public health nurse intervention was associated with improvement in several cardiovascular risk factors.
doi:10.1186/1471-2431-11-47
PMCID: PMC3121603  PMID: 21619652
6.  Maternal Age at Birth and Childhood Type 1 Diabetes: A Pooled Analysis of 30 Observational Studies 
Diabetes  2009;59(2):486-494.
OBJECTIVE
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.
RESEARCH DESIGN AND METHODS
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.
RESULTS
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 I2 = 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.
CONCLUSIONS
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.
doi:10.2337/db09-1166
PMCID: PMC2809958  PMID: 19875616
7.  A CLEC16A variant confers risk for juvenile idiopathic arthritis and anti-cyclic citrullinated peptide antibody negative rheumatoid arthritis 
Annals of the Rheumatic Diseases  2010;69(8):1471-1474.
Objective
Variants in CLEC16A have conferred susceptibility to autoimmune diseases in genome-wide association studies. The present work aimed to investigate the locus' involvements in juvenile idiopathic arthritis (JIA) and further explore the association with rheumatoid arthritis (RA), type 1 diabetes (T1D) and Addison's disease (AD) in the Norwegian population.
Methods
Three single nucleotide polymorphisms (SNPs) were genotyped in patients with RA (n=809), JIA (n=509), T1D (n=1211) and AD (n=414) and in healthy controls (n=2149).
Results
All diseases were associated with CLEC16A, but with different SNPs. The intron 22 SNP, rs6498169, was associated with RA (p=0.006) and JIA (p=0.016) and the intron 19 SNPs, rs12708716/rs12917716, with T1D (p=1×10−5) and AD (p=2×10−4). The RA association was confined to the anti-cyclic citrullinated peptide antibody (anti-CCP) negative subgroup (p=2×10−4).
Conclusion
This is the first report of a CLEC16A association with JIA and a split of the RA association according to anti-CCP status. Different causative variants underlie the rheumatic versus the organ specific diseases.
doi:10.1136/ard.2009.114934
PMCID: PMC2938883  PMID: 19734133
8.  Maternal and paternal age at delivery, birth order, and risk of childhood onset type 1 diabetes: population based cohort study 
BMJ : British Medical Journal  2001;323(7309):369.
Objective
To estimate the associations of maternal and paternal age at delivery and of birth order with the risk of childhood onset type 1 diabetes.
Design
Cohort study by record linkage of the medical birth registry and the national childhood diabetes registry in Norway.
Setting
Norway.
Subjects
All live births in Norway between 1974 and 1998 (1.4 million people) were followed for a maximum of 15 years, contributing 8.2 million person years of observation during 1989-98. 1824 cases of type 1 diabetes diagnosed between 1989 and 1998 were identified.
Main outcome measures
Incidence of type 1 diabetes.
Results
There was no association between maternal age at delivery and type 1 diabetes among firstborn children, but among fourthborn children there was a 43.2% increase in incidence of diabetes for each five year increase in maternal age (95% confidence interval 6.4% to 92.6%). Each increase in birth order was associated with a 17.9% reduction in incidence (3.2% to 30.4%) when maternal age was 20-24 years, but the association was weaker when maternal age was 30 years or more. Paternal age was not associated with type 1 diabetes after maternal age was adjusted for.
Conclusions
Intrauterine factors and early life environment may influence the risk of type 1 diabetes. The relation of maternal age and birth order to risk of type 1 diabetes is complex.
What is already known on this topicMaternal age at birth is positively associated with risk of childhood onset type 1 diabetesStudies of the effect of birth order on risk of type 1 diabetes have given inconsistent resultsWhat does this study add?In a national cohort, risk of diabetes in firstborn children was not associated with maternal ageIncreasing maternal age was a risk factor in children born second or laterThe strength of the association increased with increasing birth order
PMCID: PMC37395  PMID: 11509426
9.  Birth weight and childhood onset type 1 diabetes: population based cohort study 
BMJ : British Medical Journal  2001;322(7291):889-892.
Objective
To assess the associations between birth weight or gestational age and risk of type 1 diabetes.
Design
Population based cohort study by record linkage of the medical birth registry and the National Childhood Diabetes Registry.
Setting
Two national registries in Norway.
Participants
All live births in Norway between 1974 and 1998 (1 382 602 individuals) contributed a maximum of 15 years of observation, a total of 8 184 994 person years of observation in the period 1989 to 1998. 1824 children with type 1 diabetes were diagnosed between 1989 and 1998.
Main outcome measures
Estimates of rate ratios with 95% confidence intervals for type 1 diabetes from Poisson regression analyses.
Results
The incidence rate of type 1 diabetes increased almost linearly with birth weight. The rate ratio for children with birth weights 4500 g or more compared with those with birth weights less than 2000 g was 2.21 (95% confidence interval 1.24 to 3.94), test for trend P=0.0001. There was no significant association between gestational age and type 1 diabetes. The results persisted after adjustment for maternal diabetes and other potential confounders.
Conclusion
There is a relatively weak but significant association between birth weight and increased risk of type 1 diabetes consistent over a wide range of birth weights.
What is already known on this topicResults of case-control studies of birth weight and risk of type 1 diabetes have been inconsistentIt is possible that a relatively weak association exists, and large studies are needed to find out if this is the caseWhat this study addsThis is the largest study of birth weight and type 1 diabetes published to date, and the first one to use a cohort designThe incidence of type 1 diabetes increased almost linearly with increasing birth weight over a wide range of birth weights, independent of gestational age, maternal diabetes, and other potential confoundersThe trend was highly significant, but the increment in risk with increasing birth weight was still relatively low
PMCID: PMC30582  PMID: 11302899

Results 1-9 (9)