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      Weight Gain in Early Life Predicts Risk of Islet Autoimmunity in Children With a First-Degree Relative With Type 1 Diabetes

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          Abstract

          OBJECTIVE—In a prospective birth cohort study, we followed infants who had a first-degree relative with type 1 diabetes to investigate the relationship between early growth and infant feeding and the risk of islet autoimmunity.

          RESEARCH DESIGN AND METHODS—Infants with a first-degree relative with type 1 diabetes were identified during their mother's pregnancy. Dietary intake was recorded prospectively to determine duration of breast-feeding and age at introduction of cow's milk protein, cereals, meat, fruit, and vegetables. At 6-month reviews, length (or height) and weight, antibodies to insulin, GAD65, the tyrosine phosphatase-like insulinoma antigen, and tissue transglutaminase were measured. Islet autoimmunity was defined as persistent elevation of one or more islet antibodies at consecutive 6-month intervals, including the most recent measure, and was the primary outcome measure.

          RESULTS—Follow-up of 548 subjects for 5.7 ± 3.2 years identified 46 children with islet autoimmunity. Weight z score and BMI z score were continuous predictors of risk of islet autoimmunity (adjusted hazard ratios 1.43 [95% CI 1.10–1.84], P = 0.007, and 1.29 [1.01–1.67], P = 0.04, respectively). The risk of islet autoimmunity was greater in subjects with weight z score >0 than in those with weight z score ≤0 over time (2.61 [1.26–5.44], P = 0.01). Weight z score and BMI z score at 2 years and change in weight z score between birth and 2 years, but not dietary intake, also predicted risk of islet autoimmunity.

          CONCLUSIONS—Weight gain in early life predicts risk of islet autoimmunity in children with a first-degree relative with type 1 diabetes.

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          Diabetes

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            Early infant feeding and risk of developing type 1 diabetes-associated autoantibodies.

            Dietary factors modifying type 1 diabetes mellitus (DM) risk have been proposed, but little is known if they trigger the islet autoimmunity that precedes clinical disease. To determine whether breastfeeding duration, food supplementation, or age at introduction of gluten-containing foods influences the risk of developing islet autoantibodies. Prospective natural history cohort study conducted from 1989 to 2003 in inpatient/outpatient clinics in Germany. The BABYDIAB study follows newborn children of parents with type 1 DM. Eligibility requirements were met in 1610 children. Blood samples were obtained at birth, age 9 months, 2, 5, and 8 years. Dropout rate was 14.4% by age 5 years. Breastfeeding data were obtained by prospective questionnaires (91% complete), and food supplementation data were obtained by family interview (72% for food supplementation and 80% for age of gluten introduction). Development of islet autoantibodies (insulin, glutamic acid decarboxylase, or IA-2 antibodies) in 2 consecutive blood samples. Life-table islet autoantibody frequency was 5.8% (SE, 0.6%) by age 5 years. Reduced total or exclusive breastfeeding duration did not significantly increase the risk of developing islet autoantibodies. Food supplementation with gluten-containing foods before age 3 months, however, was associated with significantly increased islet autoantibody risk (adjusted hazard ratio, 4.0; 95% confidence interval, 1.4-11.5; P =.01 vs children who received only breast milk until age 3 months). Four of 17 children who received gluten foods before age 3 months developed islet autoantibodies (life-table 5-year risk, 24%; SE, 10%). All 4 children had the high-risk DRB1*03/04,DQB1*0302 genotype. Early exposure to gluten did not significantly increase the risk of developing celiac disease-associated autoantibodies. Children who first received gluten foods after age 6 months did not have increased risks for islet or celiac disease autoantibodies. Ensuring compliance to infant feeding guidelines is a possible way to reduce the risk of development of type 1 DM autoantibodies.
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              Timing of initial cereal exposure in infancy and risk of islet autoimmunity.

              Dietary exposures in infancy have been implicated, albeit inconsistently, in the etiology of type 1 diabetes mellitus (DM). To examine the association between cereal exposures in the infant diet and appearance of islet autoimmunity (IA). Birth cohort study conducted from 1994 to 2002 with a mean follow-up of 4 years. Newborn screening for HLA was done at St Joseph's Hospital in Denver, Colo. First-degree relatives of type 1 DM individuals were recruited from the Denver metropolitan area. We enrolled 1183 children at increased type 1 DM risk, defined as either HLA genotype or having a first-degree relative with type 1 DM, at birth and followed them prospectively. We obtained exposure and outcome measures for 76% of enrolled children. Participants had variable lengths of follow-up (9 months to 9 years). Blood draws for the detection of insulin autoantibody, glutamic acid decarboxylase autoantibody, or IA-2 autoantibody were performed at 9, 15, and 24 months and annually thereafter. Children with IA (n = 34) were defined as those testing positive for at least 1 of the autoantibodies on 2 or more consecutive visits and who tested positive or had diabetes on their most recent visit. Children initially exposed to cereals between ages 0 and 3 months (hazard ratio [HR], 4.32; 95% confidence interval [CI], 2.0-9.35) and those who were exposed at 7 months or older (HR, 5.36; 95% CI, 2.08-13.8) had increased hazard of IA compared with those who were exposed during the fourth through sixth month, after adjustment for HLA genotype, family history of type 1 DM, ethnicity, and maternal age. In children who were positive for the HLA-DRB1*03/04,DQB8 genotype, adjusted HRs were 5.55 (95% CI, 1.92-16.03) and 12.53 (95% CI, 3.19-49.23) for initial cereal exposure between ages 0 to 3 months and at 7 months or older, respectively. There may be a window of exposure to cereals in infancy outside which initial exposure increases IA risk in susceptible children.
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                Author and article information

                Journal
                Diabetes Care
                diacare
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                January 2009
                : 32
                : 1
                : 94-99
                Affiliations
                [1 ]Department of Diabetes and Endocrinology, Women's and Children's Hospital and Discipline of Paediatrics, University of Adelaide, Adelaide, Australia
                [2 ]Public Health Research Unit, Women's and Children's Hospital, Adelaide, Adelaide, Australia
                [3 ]Discipline of Paediatrics, University of Adelaide, Adelaide, Australia
                [4 ]Royal Melbourne Hospital, Melbourne, Australia
                [5 ]Autoimmunity and Transplantation Division, Walter and Eliza Hall Institute, Melbourne, Australia
                [6 ]Department of Diabetes and Endocrinology and Department of Pathology, Royal Melbourne Hospital, Melbourne, Australia
                Author notes

                Corresponding author: Jennifer Couper, jennifer.couper@ 123456adelaide.edu.au

                Article
                32194
                10.2337/dc08-0821
                2606838
                18835948
                58183b02-20c4-432b-bb08-8a61d6679542
                Copyright © 2009, American Diabetes Association

                Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

                History
                : 30 April 2008
                : 17 September 2008
                Categories
                Pathophysiology/Complications

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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