Incidence of type 1 diabetes has doubled in Kuwaiti children 0-14 years over the last 20 years

Aims: This study had 2 aims: to report data on the incidence of childhood-onset type 1 diabetes in Kuwaiti children aged 0-14 years during 2011 to 2013 and to compare the recent data with those collected during 1992 to 1997.Methods: All newly diagnosed patients were registered through the Childhood-Onset Diabetes eRegistry (CODeR) in 2011-2013, based on the DiaMond protocol used in 1992-1997.Results: A total of 515 Kuwaiti children (247 boys and 268 girls) aged 0-14 years newly diagnosed with type 1 diabetes were registered from 1 January 2011 to 31 December 2013. Data ascertainment were 96.7%. The mean age ± SD at diagnosis was 8.7 ± 3.4 years in boys and 7.9 ± 3.1 years in girls. The crude incidence rate (95% CI) was 40.9 (37.4-44.6) and the age standardized rate 41.7 (95% 38.1-45.4) per 100,000 per year, 39.3 (34.6-44.4) among boys and 44.1 (39.0-49.7) among girls. A statistically significant increasing trend in incidence was observed as the overall crude incidence rose from 17.7 in 1992-1994 to 40.9 per 100,000 per year in 2011-2013. The Poisson regression model depicting the trend in incidence revealed that, the incidence rates adjusted for age and sex in 2011 to 2013 was 2.3 (95% CI 1.9-2.7) times higher than 1992-1997.Conclusions: The incidence of type 1 diabetes in Kuwaiti children 0-14 years has doubled in the last 2 decades. The reasons for this increase requires further investigation.</p

Molecular epidemiology of enteroviruses in young children at increased risk of type 1 diabetes

Young children are susceptible to enterovirus (EV) infections, which cause significant morbidity in this age group. However, the current knowledge regarding the epidemiology of EVs and the circulating virus strains is mostly based on viruses detected in children with severe diseases leading to contact with the health care system, while the vast reservoir of EVs that circulate in the general population is less characterized

Coeliac disease : what can we learn from prospective studies about disease risk?

Paediatric prospective studies of coeliac disease with longitudinal collection of biological samples and clinical data offer a unique perspective on disease risk. This Review highlights the information now available from international paediatric prospective studies on genetic and environmental risk factors for coeliac disease. In addition, recent omics studies have made it possible to study complex interactions between genetic and environmental factors and thereby further our insight into the causes of the disease. In the future, paediatric prospective studies will be able to provide more detailed risk prediction models combining genes, the environment, and biological corroboration from multiomics. Such studies could also contribute to biomarker development and an improved understanding of disease pathogenesis.Peer reviewe

Cesarean Section on the Risk of Celiac Disease in the Offspring: The Teddy Study

Objective: Cesarean section (C-section) is associated with various immune-mediated diseases in the offspring. We investigated the relationship between mode of delivery and celiac disease (CD) and CD autoimmunity (CDA) in a multinational birth cohort. Methods: From 2004 to 2010, infants from the general population who tested positive for HLADR3-DQ2 or DR4-DQ8 were enrolled in The Environmental Determinants for Diabetes in the Young (TEDDY) study. Children were annually screened for transglutaminase autoantibodies, if positive, they are retested after 3 to 6 months and those persistently positive defined as CDA. Associations of C-section with maternal (age, education level, parity, pre-pregnancy weight, diabetes, smoking, weight gain during pregnancy) and child characteristics (gestational age, birth weight) were examined by Fisher exact test or Wilcoxon rank-sum test. Hazard ratios (HRs) for CDA or CD were calculated by Cox proportional hazard regression models. Results: Of 6087 analyzed singletons, 1600 (26%) were born by C-section (Germany 38%, United States 37%, Finland 18%, Sweden 16%), and the remaining were born vaginally without instrumental support;979 (16%) had developed CDA and 343 (6%) developed CD. C-section was associated with lower risk for CDA (hazard ratio [HR] = 0.85;95% confidence interval [CI] 0.73, 0.99 P = 0.032) and CD (HR = 0.75;95% CI 0.58, 0.98;P = 0.034). After adjusting for country, sex, HLA-genotype, CD in family, maternal education, and breast-feeding duration, significance was lost for CDA (HR = 0.91;95% CI 0.78, 1.06;P = 0.20) and CD (HR = 0.85;95% CI 0.65, 1.11;P = 0.24). Presurgical ruptured membranes had no influence on CDA or CD development. Conclusion: C-section is not associated with increased risk for CDA or CD in the offspring

Participant Experiences in the Environmental Determinants of Diabetes in the Young Study : Common Reasons for Withdrawing

M. Knip on TEDDY Study Grp -työryhmän jäsen.Background. To characterize participant reasons for withdrawing from a diabetes focused longitudinal clinical observational trial (TEDDY) during the first three study years. Methods. 8677 children were recruited into the TEDDY study. At participant withdrawal staff recorded any reason parents provided for withdrawal. Reasons were categorized into (1) family characteristics and (2) protocol reasons. Families who informed staff of their withdrawal were classified as active withdrawals (AW); families without a final contact were considered passive withdrawals (PW). Results. Withdrawal was highest during the first study year (n = 1220). Most families were AW(n = 1549; 73.4%). PW was more common in the United States (n = 1001; 37.8%) and among young mothers (p = 0.001). The most frequent protocol characteristic was blood draw (55%) and the most common family reason was not having enough time (66%). The blood draw was more common among female participants; being too busy was more common among males. Both reasons were associated with study satisfaction. Conclusions. Results suggest that, for families of children genetically at risk for diabetes, procedures that can be painful/frightening should be used with caution. Study procedures must also be considered for the demands placed on participants. Study satisfaction should be regularly assessed as an indicator of risk for withdrawal.Peer reviewe

Neighborhood level risk factors for type 1 diabetes in youth: the SEARCH case-control study

<p>Abstract</p> <p>Background</p> <p>European ecologic studies suggest higher socioeconomic status is associated with higher incidence of type 1 diabetes. Using data from a case-control study of diabetes among racially/ethnically diverse youth in the United States (U.S.), we aimed to evaluate the independent impact of neighborhood characteristics on type 1 diabetes risk. Data were available for 507 youth with type 1 diabetes and 208 healthy controls aged 10-22 years recruited in South Carolina and Colorado in 2003-2006. Home addresses were used to identify Census tracts of residence. Neighborhood-level variables were obtained from 2000 U.S. Census. Multivariate generalized linear mixed models were applied.</p> <p>Results</p> <p>Controlling for individual risk factors (age, gender, race/ethnicity, infant feeding, birth weight, maternal age, number of household residents, parental education, income, state), higher neighborhood household income (p = 0.005), proportion of population in managerial jobs (p = 0.02), with at least high school education (p = 0.005), working outside the county (p = 0.04) and vehicle ownership (p = 0.03) were each independently associated with increased odds of type 1 diabetes. Conversely, higher percent minority population (p = 0.0003), income from social security (p = 0.002), proportion of crowded households (0.0497) and poverty (p = 0.008) were associated with a decreased odds.</p> <p>Conclusions</p> <p>Our study suggests that neighborhood characteristics related to greater affluence, occupation, and education are associated with higher type 1 diabetes risk. Further research is needed to understand mechanisms underlying the influence of neighborhood context.</p

A combined risk score enhances prediction of type 1 diabetes among susceptible children

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this recordType 1 diabetes (T1D)-an autoimmune disease that destroys the pancreatic islets, resulting in insulin deficiency-often begins early in life when islet autoantibody appearance signals high risk1. However, clinical diabetes can follow in weeks or only after decades, and is very difficult to predict. Ketoacidosis at onset remains common2,3 and is most severe in the very young4,5, in whom it can be life threatening and difficult to treat6-9. Autoantibody surveillance programs effectively prevent most ketoacidosis10-12 but require frequent evaluations whose expense limits public health adoption13. Prevention therapies applied before onset, when greater islet mass remains, have rarely been feasible14 because individuals at greatest risk of impending T1D are difficult to identify. To remedy this, we sought accurate, cost-effective estimation of future T1D risk by developing a combined risk score incorporating both fixed and variable factors (genetic, clinical and immunological) in 7,798 high-risk children followed closely from birth for 9.3 years. Compared with autoantibodies alone, the combined model dramatically improves T1D prediction at ≥2 years of age over horizons up to 8 years of age (area under the receiver operating characteristic curve ≥ 0.9), doubles the estimated efficiency of population-based newborn screening to prevent ketoacidosis, and enables individualized risk estimates for better prevention trial selection.National Institutes of Health/National Center for Advancing Translational Sciences Clinical and Translational ScienceDiabetes Research CenterDiabetes UKWellcome TrustJDR

Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study

A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 54-91). Three SNPs within ITGAM were nominally associated (p < 0.05) with IA: rs1143678 [Hazard ratio; HR 0.80; 95% CI 0.66-0.98; p = 0.032], rs1143683 [HR 0.80; 95% CI 0.65-0.98; p = 0.030] and rs4597342 [HR 1.16; 95% CI 1.01-1.32; p = 0.041]. When type 1 diabetes was the outcome, in DR3/4 subjects, there was nominal significance for two SNPs: rs17615 in CD21 [HR 1.52; 95% CI 1.05-2.20; p = 0.025] and rs4844573 in C4BPA [HR 0.63; 95% CI 0.43-0.92; p = 0.017]. Among DR4/4 subjects, rs2230199 in C3 was significantly associated [HR 3.20; 95% CI 1.75-5.85; p = 0.0002, uncorrected] a significance that withstood Bonferroni correction since it was less than 0.000833 (0.05/60) in the HLA-specific analyses. SNPs within the complement genes may contribute to IA, the first step to type 1 diabetes, with at least one SNP in C3 significantly associated with clinically diagnosed type 1 diabetes