Environmental Determinants Of Diabetes Research Articles

Country-specific birth weight and length in type 1 diabetes high-risk HLA genotypes in combination with prenatal characteristics.

Objective:To examine the relationship between high-risk human leukocyte antigen (HLA) genotypes for type 1 diabetes and birth size in combination with prenatal characteristics in different countries.Study Design:Four high-risk HLA genotypes were enrolled in the Environmental determinants of Diabetes in the Young study newborn babies from the general population in Finland, Germany, Sweden and the United States. Stepwise regression analyses were used to adjust for country, parental physical characteristics and environmental factors during pregnancy.Result:Regression analyses did not reveal differences in birth size between the four type 1 diabetes high-risk HLA genotypes. Compared with DQ 4/8 in each country, (1) DQ 2/2 children were heavier in the United States (P=0.028) mostly explained however, by parental weight; (2) DQ 2/8 (P=0.023) and DQ 8/8 (P=0.046) children were longer in Sweden independent of parents height and as well as (3) in the United States for DQ 2/8 (P=0.023), but again dependent on parental height.Conclusion:Children born with type 1 diabetes high-risk HLA genotypes have comparable birth size. Longitudinal follow-up of these children should reveal whether birth size differences between countries contribute to the risk for islet autoimmunity and type 1 diabetes.

Enrollment experiences in a pediatric longitudinal observational study: The Environmental Determinants of Diabetes in the Young (TEDDY) study

Objective Our objective was to identify characteristics of infants and their families who were enrolled, refused to enroll, or were excluded from The Environmental Determinants of Diabetes in the Young (TEDDY) study. Method 16,435 infants screened at birth and identified as at increased genetic risk for type 1 diabetes (T1DM) were placed into one of three categories: enrolled, excluded, or refused to enroll. Enrollment, exclusion and refusal rates were compared across countries and between infants from the general population (GP) and infants with a first degree T1DM relative (FDR). A multivariate logistic model was used to identify factors associated with TEDDY enrollment. Results TEDDY enrollment, exclusion, and refusal rates differed by country and by GP/FDR status but reasons for refusal to enroll were similar across countries and GP/FDR populations. Sweden had the highest enrollment rate, US had the highest exclusion rate, and Finland had the highest refusal rate. FDR infants were more likely to enroll than GP infants. Inability to re-contact the family was the most common reason for exclusion. Primary reasons for refusal to enroll included protocol factors (e.g. blood draws) or family factors (e.g., too busy). Study enrollment was associated with FDR status, European country of origin, older maternal age, a singleton birth, and having another child in TEDDY. Conclusions Findings highlight the importance of country specific estimates for enrollment targets in longitudinal pediatric studies and suggest that enrollment estimates should be lowered when the study involves the general population, painful procedures, or makes multiple demands on families.

Food composition database harmonization for between-country comparisons of nutrient data in the TEDDY Study

The Environmental Determinants of Diabetes in the Young (TEDDY) Study aims at examining the associations between islet autoimmunity and various environmental exposures (e.g. diet) in Finland, Germany, Sweden and the United States (US). In order to produce comparable results from dietary assessments, the national food composition databases (FCDB) must contain mutually comparable food composition data. Systematic comparison (definition, unit of measurement, and method of analysis) of energy, protein, fats, carbohydrates, cholesterol, fiber, 13 vitamins, and 8 minerals was carried out among the FCDB of the four countries. Total fat, cholesterol, vitamin A: retinol equivalents and beta-carotene, thiamin, riboflavin, pyridoxine, vitamin B12, calcium, phosphorus, potassium, magnesium, iron, and zinc are comparable across all four databases. Carbohydrates, fiber, sugars, fatty acids, vitamin D, vitamin E: alpha-tocopherol, vitamin K, vitamin C, pantothenic acid, niacin, manganese, and copper are comparable or can be converted comparable at least across three of the databases. Vitamin E: alpha-tocopherol equivalents, will be comparable across all databases after Finland and Germany subtract tocotrienols from their values. Nitrogen values were added to the Swedish and US databases. After recalculation of protein from nitrogen (Sweden and US), and subtraction of fiber from the total carbohydrate (Finland) followed by recalculations of energy, these values will be comparable across the countries. Starch and folate are not comparable.

The Environmental Determinants of Diabetes in the Young (TEDDY) study: predictors of early study withdrawal among participants with no family history of type 1 diabetes.

The Environmental Determinants of Diabetes in the Young (TEDDY) study seeks to identify environmental triggers of autoimmunity and type 1 diabetes mellitus (T1DM) in children at increased human-leukocyte-antigen conferred genetic risk for this disease. The objective of this study was to identify predictors of early withdrawal from TEDDY among families with no immediate family history of T1DM. Logistic multiple regression was used to discriminate 2994 (83%) families currently active in the TEDDY study for ≥1 yr from 763 (17%) families who withdrew in the first year. Data collected on the screening form at the time of the child's birth and from interview and questionnaire data obtained at the baby's first study visit (at ≤4.5 months of age) were used. Significant and independent predictors of early withdrawal included country of residence, young maternal age, no father participation, and female gender of the study participant. Mothers of children who withdrew were more likely to report smoking during pregnancy, abstaining from alcohol, and reducing their work hours or not working at all during pregnancy. Mothers who withdrew were also more likely to underestimate their child's risk for T1DM and fail to respond to multiple items on the enrollment questionnaires or interview. Among mothers with accurate risk perceptions, those experiencing high anxiety about their child's risk were more likely to be early withdrawals. Identifying families at high risk for study withdrawal at the time of enrollment allows for targeting these families with individually tailored plans to help maintain their participation in the study.

135-P: The Environmental Determinants of Diabetes in the Young ( TEDDY): Denver, CO (An Update)

135-P: The Environmental Determinants of Diabetes in the Young ( TEDDY): Denver, CO (An Update)

Infant and Childhood Diet and Type 1 Diabetes Risk: Recent Advances and Prospects

Type 1 diabetes is a chronic autoimmune disease characterized by a preclinical period of autoimmunity. It is well accepted that both genetic and environmental factors contribute to disease risk. Given that type 1 diabetes, and its preclinical autoimmunity, appear early in life, infant and childhood diet have been implicated as potential initiating exposures in the etiology of the disease. Several publications in the past year have provided further evidence for existing hypotheses regarding the roles of wheat, cow's milk, omega-3 fatty acids, and the maternal diet during pregnancy. However, inconsistencies in findings between studies suggest the need for collaboration and standardization of study methods to move forward in research in this area. One such example of this is the TEDDY (The Environmental Determinants of Diabetes in the Young) study, which is an international, multicenter birth cohort study with standardized recruitment, dietary collection methodologies, and analytic approaches.

Proficiency Testing of Human Leukocyte Antigen-DR and Human Leukocyte Antigen-DQ Genetic Risk Assessment for Type 1 Diabetes Using Dried Blood Spots

The plurality of genetic risk for developing type 1 diabetes mellitus (T1DM) lies within the genes that code for the human leukocyte antigens (HLAs). Many T1DM studies use HLA genetic risk assessment to identify higher risk individuals, and they often conduct these tests on dried blood spots (DBSs) like those used for newborn bloodspot screening. One such study is The Environmental Determinants of Diabetes in the Young (TEDDY), a long-term prospective study of environmental risk factors. To provide quality assurance for T1DM studies that employ HLA genetic risk assessment, the Centers for Disease Control and Prevention (CDC) conducts both a voluntary quarterly proficiency testing (VQPT) program available to any laboratory and a mandatory annual proficiency testing (PT) challenge for TEDDY laboratories. Whole blood and DBS samples with a wide range of validated HLA-DR and HLA-DQ genotypes were sent to the participating laboratories. Results were evaluated on the basis of both the reported haplotypes and the HLA genetic risk assessment. Of the reported results from 24 panels sent out over six years in the VQPT, 94.7% (857/905) were correctly identified with respect to the relevant HLA-DR or HLA-DQ alleles, and 96.4% (241/250) were correctly categorized for risk assessment. Significant improvement was seen over the duration of this program, usually reaching 100% correct categorization during the last three years. Of 1154 reported results in four TEDDY PT challenges, 1153 (99.9%) were correctly identified for TEDDY eligibility. The different analytical methods used by T1DM research centers all provided accurate (>99%) results for genetic risk assessment. The two CDC PT programs documented the validity of the various approaches to screening and contributed to overall quality assurance.

Use of dietary supplements in relation to sociodemographic factors in pregnant women in the TEDDY study

The Environmental Determinants of Diabetes in Youth (TEDDY) is a longitudinal study that aims to identify environmental exposures that may affect islet autoimmunity and the development of type 1 diabetes among children at high genetic risk. Participating mothers recalled dietary supplement use during pregnancy 3‐month postpartum. Descriptive analyses and chi‐square test were used to analyze data from 3,630 mothers in 4 countries. Over 90% of the mothers used at least 1 type of supplement during pregnancy (94% in the US, 85% in Finland, 93% in Germany, and 89% in Sweden, p<0.01). Among users, 48% took multivitamin/mineral (MVM), 16% took single supplements (SS), and others took both. Iron was the mostly taken SS in all TEDDY countries (n=1340), followed by calcium in the US, vitamin D in Finland, and folic acid in Germany and Sweden. Vitamin D‐containing MVM and SS were taken by 2,323 mothers, of them 49% were from the US. Among 456 fatty acid supplement users, 250 took the formulations without other nutrients. Probiotics users were 10‐fold more in the US and Finland than in Germany and Sweden. Overall, dietary supplement use was associated with higher education, non‐smoking, non‐drinking, and 1st‐child delivery (p<0.01). Sociodemographic factors did not notably affected the average duration of supplementation which ranged from 17.5 weeks for single iron product to 37.6 weeks for probiotics‐containing MVM.

The Environmental Determinants of Diabetes in the Young (TEDDY) Study.

The etiology of type 1 diabetes (T1D) remains unknown, but a growing body of evidence points to infectious agents and/or components of early childhood diet. The National Institutes of Health has established the TEDDY Study consortium of six clinical centers in the United States and Europe and a data coordinating center to identify environmental factors predisposing to, or protective against, islet autoimmunity and T1D. From 2004-2009, TEDDY will screen more than 360,000 newborns from both the general population and families already affected by T1D to identify an estimated 17,804 children with high-risk HLA-DR,DQ genotypes. Of those, 7,801 (788 first-degree relatives and 7,013 newborns with no family history of T1D) will be enrolled in prospective follow-up beginning before the age of 4.5 months. As of May 2008, TEDDY has screened more than 250,000 newborns and enrolled nearly 5,000 infants--approximately 70% of the final cohort. Participants are seen every 3 months up to 4 years of age, with subsequent visits every 6 months until the subject is 15 years of age. Blood samples are collected at each visit for detection of candidate infectious agents and nutritional biomarkers; monthly stool samples are collected for infectious agents. These samples are saved in a central repository. Primary endpoints include (1) appearance of one or more islet autoantibodies (to insulin, GAD65 or IA-2) confirmed at two consecutive visits; (2) development of T1D. By age 15, an estimated 800 children will develop islet autoimmunity and 400 will progress to T1D; 67 and 27 children have already reached these endpoints.

40-OR: The environmental determinants of diabetes in the young ( TEDDY): Denver, CO

40-OR: The environmental determinants of diabetes in the young ( TEDDY): Denver, CO

Maternal Feeding Practices among Infants with Genetic Predisposition to Type 1 Diabetes: Results from the Environmental Determinants of Diabetes in the Young Study

Maternal Feeding Practices among Infants with Genetic Predisposition to Type 1 Diabetes: Results from the Environmental Determinants of Diabetes in the Young Study

A High-Throughput Population Screening System for the Estimation of Genetic Risk for Type 1 Diabetes: An Application for the TEDDY (The Environmental Determinants of Diabetes in the Young) Study

In the TEDDY (The Environmental Determinants of Diabetes in the Young) study patient eligibility is based on the presence of some selected type 1 diabetes risk-associated human leukocyte antigen DR-DQ genotypes. A practical screening strategy was needed with efficient exclusion of ineligible patients at an early stage. Also, a simple, low-cost, and fast screening system was essential for the primary step of the risk assessment including thousands of samples. A homogeneous genotyping system utilizing an asymmetric polymerase chain reaction (PCR) and subsequent hybridization of allele-specific probes was designed to be used as the first screening step. This assay was combined with methods further elucidating the genetic risk of type 1 diabetes to screen for high-risk individuals. The homogeneous assay platform allows the typing of hundreds of samples within one working day. The costs of the assay are minimal, and the reduction in hands-on time provides considerable improvements compared to the heterogeneous genotyping methods comprising separate PCR and hybridization steps. The primary selection criteria used in the first step proved to be efficient since the numbers of samples typed in subsequent stages were markedly reduced. The presented assay system provides a practical approach to the rapid screening of thousands of samples at low cost, a general starting point for large-scale screening studies.

The Environmental Determinants of Diabetes in the Young (TEDDY) study: study design

The primary objective of this multicenter, multinational, epidemiological study is the identification of infectious agents, dietary factors, or other environmental exposures that are associated with increased risk of autoimmunity and type 1 diabetes mellitus (T1DM). Factors affecting specific phenotypic manifestations such as early age of onset or rate of progression or with protection from the development of T1DM will also be identified. The Environmental Determinants of Diabetes in the Young (TEDDY) is an observational cohort study in which newborns who are younger than 4 months and have high-risk human leukocyte antigen alleles in the general population or are first-degree relatives (FDRs) of patients affected with T1DM will be enrolled. Six clinical centers in the USA and Europe will screen 361,588 newborns, of which it is anticipated that 17,804 will be eligible for enrollment with just over 7,800 followed. Recruitment will occur over 5 yr, with children being followed to the age of 15 yr. Identification of such factors will lead to a better understanding of disease pathogenesis and result in new strategies to prevent, delay, or reverse T1DM.

TEDDY–The Environmental Determinants of Diabetes in the Young

The aim of the TEDDY study is to identify infectious agents, dietary factors, or other environmental agents, including psychosocial factors, which may either trigger islet autoimmunity, type 1 diabetes mellitus (T1DM), or both. The study has two end points: (a) appearance of islet autoantibodies and (b) clinical diagnosis of T1DM. Six clinical centers screen newborns for high-risk HLA genotypes. As of December 2005 a total of 54,470 newborns have been screened. High-risk HLA genotypes among 53,560 general population (GP) infants were 2576 (4.8%) and among 910 newborns with a first-degree relative (FDR) were 194 (21%). A total of 1061 children have been enrolled. The initial enrollment results demonstrate the feasibility of this complex and demanding a prospective study.

Diabetes in Wallis Polynesians: A comparison of residents of Wallis Island and first generation migrants to Noumea, New Caledonia

A comparative study of diabetes, impaired glucose tolerance and obesity was undertaken in samples of rural Wallisians of Wallis Island and first generation Wallisian migrants in the urban centre of Noumea, New Caledonia. Approximately 20-25% of the adult population of the 2 communities was included in the study. Wallisians in Noumea tended to be more obese than those in Wallis (particularly females). The prevalence of diabetes was 7 and 4 times higher in Noumea compared to Wallis for males and females respectively. Differences in the extent of obesity appeared to account for some of the difference in prevalence of diabetes, but other environmental factors (such as constituents of the diet, and exercise) must be operative as well. The results of this study are consistent with previous findings concerning environmental determinants of diabetes in Pacific populations.