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1.  Infant Exposures and Development of Type 1 Diabetes Mellitus 
JAMA pediatrics  2013;167(9):808-815.
IMPORTANCE
The incidence of type 1 diabetes mellitus (T1DM) is increasing worldwide, with the most rapid increase among children younger than 5 years of age.
OBJECTIVE
To examine the associations between perinatal and infant exposures, especially early infant diet, and the development of T1DM.
DESIGN
The Diabetes Autoimmunity Study in the Young (DAISY) is a longitudinal, observational study.
SETTING
Newborn screening for human leukocyte antigen (HLA) was done at St. Joseph’s Hospital in Denver, Colorado. First-degree relatives of individuals with T1DM were recruited from the Denver metropolitan area.
PARTICIPANTS
A total of 1835 children at increased genetic risk for T1DM followed up from birth with complete prospective assessment of infant diet. Fifty-three children developed T1DM.
EXPOSURES
Early (<4 months of age) and late (≥6 months of age) first exposure to solid foods compared with first exposures at 4 to 5 months of age (referent).
MAIN OUTCOME AND MEASURE
Risk for T1DM diagnosed by a physician.
RESULTS
Both early and late first exposure to any solid food predicted development of T1DM (hazard ratio [HR], 1.91; 95% CI, 1.04–3.51, and HR, 3.02; 95% CI, 1.26–7.24, respectively), adjusting for the HLA-DR genotype, first-degree relative with T1DM, maternal education, and delivery type. Specifically, early exposure to fruit and late exposure to rice/oat predicted T1DM (HR, 2.23; 95% CI, 1.14–4.39, and HR, 2.88; 95% CI, 1.36–6.11, respectively), while breastfeeding at the time of introduction to wheat/barley conferred protection (HR, 0.47; 95% CI, 0.26–0.86). Complicated vaginal delivery was also a predictor of T1DM (HR, 1.93; 95% CI, 1.03–3.61).
CONCLUSIONS AND RELEVANCE
These results suggest the safest age to introduce solid foods in children at increased genetic risk for T1DM is between 4 and 5 months of age. Breastfeeding while introducing new foods may reduce T1DM risk.
doi:10.1001/jamapediatrics.2013.317
PMCID: PMC4038357  PMID: 23836309
2.  The Association between IgG4 Antibodies to Dietary Factors, Islet Autoimmunity and Type 1 Diabetes: The Diabetes Autoimmunity Study in the Young 
PLoS ONE  2013;8(2):e57936.
Background
Infant dietary exposures have been linked to type 1 diabetes (T1D) development. IgG4 antibody responses to food antigens are associated with food intolerances but have not been explored prospectively in the period preceding T1D.
Methods
Using a case-cohort design, IgG4 antibodies to ß-lactoglobulin, gluten, and ovalbumin were measured in plasma collected annually from 260 DAISY participants. Of those, 77 developed islet autoimmunity (IA), defined as positive for either insulin, GAD65 or IA-2 autoantibodies on two consecutive visits, and 22 developed T1D.
Results
In mixed model analysis adjusting for HLA-DR status, T1D family history, age and ethnicity, higher ß-lactoglobulin IgG4 concentrations were associated with shorter breastfeeding duration (beta = −0.03, 95% Confidence Interval: −0.05, −0.006) and earlier first cow’s milk exposure (beta = −0.04, 95% Confidence Interval: −0.08, 0.00). Higher gluten IgG4 was associated with older age at gluten introduction (beta = 0.06, 95% Confidence Interval: 0.00, 0.13). In proportional hazards analysis adjusting for HLA-DR status, T1D family history and ethnicity, IgG4 against individual or multiple dietary antigens throughout childhood were not associated with IA. In addition, mean antigen-specific IgG4 concentrations in infancy (age <2 years) were not associated with risk of IA nor progression to T1D. Higher ovalbumin IgG4 at first IA positive visit was marginally associated with progression to T1D (Hazard Ratio: 1.39, 95% Confidence Interval: 1.00, 1.92).
Conclusion
We found no association between the IgG4 response to β-lactoglobulin, gluten, and the development of either IA or T1D. The association between higher ovalbumin and progression to T1D in children with IA should be explored in other populations.
doi:10.1371/journal.pone.0057936
PMCID: PMC3585253  PMID: 23469110
3.  Erythrocyte membrane omega-3 fatty acid levels and omega-3 fatty acid intake are not associated with conversion to type 1 diabetes in children with islet autoimmunity: The Diabetes Autoimmunity Study in the Young (DAISY) 
Pediatric diabetes  2011;12(8):669-675.
Aim
We investigated whether omega-3 fatty acid intake and erythrocyte membrane omega-3 fatty acid levels are associated with conversion to type 1 diabetes in children with islet autoimmunity (IA).
Methods
The Diabetes Autoimmunity Study in the Young is following children at increased genetic risk for type 1 diabetes for the development of persistent IA, as defined as being positive for glutamic acid decarboxylase 65, i, or insulin autoantibodies on two consecutive visits, and then for the development of type 1 diabetes, as diagnosed by a physician. One hundred and sixty-seven children with persistent IA were followed for a mean of 4.8 yr, and 45 of these developed type 1 diabetes at a mean age of 8.7 yr. Erythrocyte membrane fatty acids (as a percent of total lipid) and dietary fatty acid intake (estimated via food frequency questionnaire) were analyzed as time-varying covariates in proportional hazards survival analysis, with follow-up time starting at detection of the first autoantibody.
Results
Neither dietary intake of omega-3 fatty acids nor omega-6 fatty acids were associated with conversion to type 1 diabetes, adjusting for human leukocyte antigen (HLA)-DR, family history of type 1 diabetes, age at first IA positivity, maternal age, maternal education, and maternal ethnicity. Adjusting for HLA-DR, family history of type 1 diabetes and age at first IA positivity, omega-3 and omega-6 fatty acid levels of erythrocyte membranes were not associated with conversion to type 1 diabetes.
Conclusions
In this observational study, omega-3 fatty acid intake and status are not associated with conversion to type 1 diabetes in children with IA.
doi:10.1111/j.1399-5448.2011.00760.x
PMCID: PMC3475955  PMID: 21435137
dietary intake; IA; omega-3 fatty acids; type 1 diabetes mellitus
4.  Erythrocyte Membrane Fatty Acid Content in Infants Consuming Formulas Supplemented with Docosahexaenoic Acid (DHA) and Arachidonic Acid (ARA): an Observational Study 
Maternal & child nutrition  2010;6(4):338-346.
In this observational study, we compared erythrocyte membrane fatty acids in infants consuming formula supplemented with docosahexaenoic acid (DHA) and arachidonic acid (ARA) with those consuming other types of milks. In 110 infants who were participants in a cohort study of otherwise healthy children at risk for developing type 1 diabetes, erythrocytes were collected at approximately 9 months of age, and fatty acid content was measured as a percent of total lipids. Parents reported the type of milk the infants consumed in the month of and prior to erythrocyte collection – infant formula supplemented with ARA and DHA (supplemented formula), formula with no ARA and DHA supplements (non-supplemented formula), breast-milk, or non-supplemented formula plus breast-milk. Membrane DHA (4.42 versus 1.79, p < 0.001) and omega-3 fatty acid (5.81 versus 3.43, p < 0.001) levels were higher in infants consuming supplemented versus non-supplemented formula. Omega-6 fatty acids were lower in infants consuming supplemented versus non-supplemented formula (26.32 versus 29.68, p = 0.023); ARA did not differ between groups. Infants given supplemented formula had higher DHA (4.42 versus 2.81, p < 0.001) and omega-3 fatty acids (5.81 versus 4.45, p = 0.008) than infants drinking breast-milk. In infants whose mothers did not receive any dietary advice, use of supplemented formula is associated with higher omega-3 and lower omega-6 fatty acid status.
doi:10.1111/j.1740-8709.2009.00230.x
PMCID: PMC2992442  PMID: 21050388
Arachidonic Acid; Docosahexaenoic Acid; Breastfeeding; Infant Feeding; Infant Formula; Infant Feeding Behavior

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