Context 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.Objective To determine whether breastfeeding duration, food supplementation, or age at introduction of gluten-containing foods influences the risk of developing islet autoantibodies. Design and SettingProspective natural history cohort study conducted from 1989 to 2003 in inpatient/outpatient clinics in Germany.Participants 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).Main Outcome Measure Development of islet autoantibodies (insulin, glutamic acid decarboxylase, or IA-2 antibodies) in 2 consecutive blood samples.Results 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 glutencontaining 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. Conclusion Ensuring compliance to infant feeding guidelines is a possible way to reduce the risk of development of type 1 DM autoantibodies.

Childhood autoimmune diabetes is associated with autoimmunity that starts before 2 years of age.

OBJECTIVE -Children of affected probands are at increased risk for type 1 diabetes. The objective of this study was to determine and stratify the risk for islet autoimmunity and childhood diabetes in newborn offspring of affected parents using family history and HLA genetic markers.RESEARCH DESIGN AND METHODS -Antibodies to islet autoantigens were measured at ages 9 months, 2 years, 5 years, and 8 years in 1,610 offspring of parents with type 1 diabetes participating in the German BABYDIAB study. HLA DR and DQ genetic typing was performed. Family history of type 1 diabetes was obtained from questionnaires.RESULTS -Extensive family history of type 1 diabetes and HLA DR/DQ genotyping were associated with islet autoantibody and diabetes risks. Significant contributions to the child's risk for developing islet autoantibodies and type 1 diabetes were conferred by a multiple first-degree family history of type 1 diabetes (two parents or one parent and a sibling; adjusted hazard [HR] ratio, 6.2 for multiple islet autoantibodies and 7.8 for type 1 diabetes), high-risk HLA genotypes (adjusted HR, 11 and 10.9), and moderate-risk HLA genotypes (adjusted HR, 6.3 and 4.3) in a multivariate analysis. Combining these factors stratified the risk for islet autoantibodies from 1 to 46% and for type 1 diabetes from 0 to 19.5% by 5 years of age.CONCLUSIONS -Risk of childhood diabetes in affected families can be stratified using a combination of genetic and family history markers very early in life. Diabetes Care 27:2695-2700, 2004T ype 1 diabetes is preceded by autoimmunity against the insulinproducing islet ␤-cells (1,2). The development of islet autoantibodies and type 1 diabetes is influenced by both genetic and environmental factors, and the detection of islet autoantibodies in members of affected families identifies a minority of individuals who have a markedly elevated risk of type 1 diabetes (3). On this principle, two large-scale intervention trials to delay onset of type 1 diabetes in islet autoantibody-positive first-degree relatives of patients with type 1 diabetes have recently been completed in North America and Europe (4,5). Despite promising pilot studies, both trials reported no delay in onset of type 1 diabetes in the treatment group. Successful prevention may, therefore, require alternative therapies and/or strategies that treat diabetes very early in the autoimmune process or before its appearance.Primary prevention requires an ability to identify children who will develop autoimmunity. The German BABYDIAB study prospectively followed islet autoantibody and diabetes development in newborn offspring of parents with type 1 diabetes with the prospect of designing early intervention trials (6). The risk of developing islet autoantibodies in BABY-DIAB children is strongly linked to HLA genes (7). Nevertheless, several children developed multiple antibodies and diabetes in the absence of established type 1 diabetes genetic markers, implying the presence of other strong familial genetic or environmental risk factors. In...

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These data are consistent with a reduced capacity to make IL-4 promoted antibody responses to exogenous antigen in early pre-diabetes.

Plasma glucagon levels decrease significantly during night-time sleep in healthy control subjects. This nocturnal decrease is preserved in T1DM patients regardless of the duration of diabetes. These observations point to distinct nocturnal regulation of spontaneous glucagon release that does not depend on circulating glucose and insulin levels and is unaltered in T1DM patients.

OBJECTIVE-The modulatory influence of nocturnal sleep on neuroendocrine secretory activity is increasingly recognized as a factor critical to health. Disturbances of sleep may arise from and contribute to the disease process in chronically ill patients with type 1 diabetes. RESEARCH DESIGN AND METHODS-Using standard polysomnography and repetitive blood sampling, neuroendocrine sleep architecture was assessed under well-controlled nonhypoglycemic conditions in 14 type 1 diabetic patients and 14 healthy control subjects matched for age, sex, and BMI. RESULTS-As expected, plasma glucose (P ϭ 0.02) and serum insulin (P Ͻ 0.001) levels were constantly higher in type 1 diabetic patients than in healthy subjects throughout the night. Beside these characteristic alterations of glucose metabolism, type 1 diabetic patients displayed higher blood levels of growth hormone (P ϭ 0.001) and epinephrine (P ϭ 0.02) during the entire night and higher levels of ACTH (P ϭ 0.01) as well as a tendency toward higher cortisol levels (P ϭ 0.072) during the first night-half, compared with healthy control subjects. Patients spent slightly less time in slow wave sleep (P ϭ 0.09) during the first night-half (where this sleep stage predominates), and overall exhibited an increased proportion of stage 2 sleep (P ϭ 0.01). Correspondingly, assessment of mood and symptoms after sleep revealed that subjective sleep was less restorative in type 1 diabetic patients than in healthy subjects. CONCLUSIONS-Our data indicate distinct alterations in the neuroendocrine sleep architecture of patients with type 1 diabetes, which add to the generally adverse impact of the disease on the patients' health.