| 1. |
- TEDDY study group, The, et al.
(författare)
-
The environmental determinants of diabetes in the young (TEDDY) study: Study design
- 2007
-
Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 8:5, s. 286-298
-
Tidskriftsartikel (refereegranskat)abstract
- 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 7800 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.
|
|
| 2. |
- Larsson, Helena, et al.
(författare)
-
Children developing type 1 diabetes before 6 years of age have increased linear growth independent of HLA genotypes
- 2008
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 51:9, s. 1623-1630
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis High birthweight and increased childhood growth are risk factors for type 1 diabetes. Relative birthweight is associated with HLA genotypes that confer a high risk of diabetes. Our aims were to test whether young children prior to clinical onset of type 1 diabetes have increased: (1) birthweight or birth length standard deviation scores (SDS), (2) height development SDS, or (3) BMI SDS during first 18 months of life and whether these parameters are related to HLA genotypes or mid-parental height (MPH). Methods Birthweight, birth length, weight and height were obtained from 58 type 1 diabetes children and 155 controls matched for HLA or not in the Diabetes Prediction in Skane study. Results Birth length SDS corrected for MPH was increased in children developing diabetes compared with all (p < , 0.048) and with non-HLA- (p < , 0.050) but not with HLA-matched controls. Children developing diabetes had increased height gain at 0 to 18 months of age (p < ; 0.005). Diabetic children were significantly taller from 6 to 18 months of age when correcting for MPH compared with non-HLA-matched as well as HLA-matched controls, but BMI was not increased. Conclusions/interpretation Birth length SDS was associated with diabetes risk HLA. When corrected for MPH, children developing diabetes were taller at birth than non-HLA- but not taller than HLA-matched controls. Diabetic children had increased MPH-corrected height up to 18 months of age compared with both HLA- and non-HLA-matched controls. High-risk HLA affects prenatal growth, but other factors may explain the increased postnatal linear growth in children developing diabetes.
|
|
| 3. |
- Larsson, Helena, et al.
(författare)
-
Diabetes-associated HLA genotypes affect birthweight in the general population.
- 2005
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 48:Jul 1, s. 1484-1491
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesisThe aim of our study was to test the hypothesis that HLA genotypes conferring risk of diabetes, cord blood autoantibodies, or both are associated with increased birthweight. Methods: HLA genotypes were determined in dried blood spots of cord blood from a total of 16,709 children born to healthy mothers in the Diabetes Prediction in Skane (DiPiS) study, a population-based observational clinical investigation of newborn children. Children born to mothers with diabetes or gestational diabetes were excluded. Autoantibodies to glutamic acid decarboxylase (GAD65Ab) and insulinoma-associated protein 2 were determined in standard radioligand binding assays. Birthweight was adjusted for gestational age and divided into quartiles. The upper quartile was defined as high relative birthweight (HrBW) and the lower quartile as low relative birthweight (LrBW). Results: Genotypes conferring risk of type 1 diabetes were strongly associated with relative birthweight (rBW) (p=0.01). The high-risk HLA-DQ2/8, DQ8/0604 and DQ8/X genotypes were associated with HrBW (odds ratio [OR] [95% CI]=1.20 [1.08-1.33], p=0.0006). The HLA-DQB1*0603 allele, which is negatively associated with type 1 diabetes, was also associated with HrBW (p=0.025), confirming a previous report on DQB1*0603-linked HLA-DR13. GAD65Ab were negatively associated with HrBW (OR [95% CI]=0.72 [0.56-0.93], p=0.01). Regression analysis showed that the HLA-associated increase in rBW was independent of confounding factors. Conclusions/Interpreation: HLA genotypes may be associated with intrauterine growth independent of type 1 diabetes risk. The epidemiological observation that high birthweight is a risk factor for type 1 diabetes could possibly result from a moderating effect on intrauterine growth of HLA genotypes conferring a high risk of diabetes.
|
|
| 4. |
- Larsson, Helena, et al.
(författare)
-
Relationship between increased relative birthweight and infections during pregnancy in children with a high-risk diabetes HLA genotype.
- 2007
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 50:6, s. 1161-1169
-
Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Children with high-risk type 1 diabetes HLA genotype have increased risk of high relative birthweight (HrBW), while cord blood islet autoantibodies decrease the risk. As gestational infections may affect offspring type 1 diabetes risk, the aims were to test whether: (1) children of mothers reporting gestational infections have increased HrBW; (2) gestational infections explain islet autoantibody reduction of HrBW; and (3) gestational infections affect the association between HLA and HrBW. Subjects and methods HLA genotypes and autoantibodies to glutamic acid decarboxylase, insulinoma-associated protein 2 and insulin were determined in cord blood of children born to non-diabetic mothers in the Diabetes Prediction in Skane (DiPiS) study. Mothers reported gestational infections when the child was 2 months old. Results Fever or gastroenteritis during pregnancy was reported by 2,848/19,756 mothers (14%); 339 in more than one trimester. Children whose mothers reported infections had increased risk of HrBW (p=0.0003), particularly in the absence of cord blood islet autoantibodies (interaction between HrBW, islet autoantibodies and infections, p=0.0005). The effect on HrBW by high-risk HLA-DQ2/8 was aggravated by infections in more than one trimester (odds ratio [OR]=5.24; p=0.003) (interaction; p=0.022). When infections were reported, cord blood islet autoantibodies decreased HrBW (OR=0.34; p=0.0002). Conclusions/intrepretation This study revealed that: (1) gestational fever, gastroenteritis, or both, increased the risk of HrBW; (2) cord blood islet autoantibodies decreased the risk of HrBW only in combination with infections; and (3) infections aggravated the association between HLA-DQ2/8 and HrBW. These data suggest an interaction between HLA, gestational infections, islet autoantibodies and fetal growth.
|
|
| 5. |
- Rewers, Marian, et al.
(författare)
-
The Environmental Determinants of Diabetes in the Young (TEDDY) Study
- 2008
-
Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1150, s. 1-13
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
