Risk Of Childhood Type Research Articles

Is socio-economic status associated with risk of childhood type 1 diabetes? Literature review.

Studies of social inequality and risk of developing type 1 diabetes are inconsistent. The present review aimed to comprehensively review relevant literature and describe what has been reported on socio-economic status or parental occupation and risk of type 1 diabetes in children. We searched for publications between 1 January 1970 and 30 November 2021. We focused on the most recent and/or informative publication in cases of multiple publications from the same data source and referred to these as primary studies. Our search identified 69 publications with relevant data. We identified eight primary cohort studies with individual-level data, which we considered the highest quality of evidence. Furthermore, we identified 13 primary case-control studies and 14 semi-ecological studies with area-level socio-economic status variables which provided a weaker quality of evidence. Four of eight primary cohort studies contained data on maternal education, showing non-linear associations with type 1 diabetes that were not consistent across studies. There was no consistent pattern on the association of parental occupation and childhood-onset type 1 diabetes. There is a need for more high-quality studies, but the existing literature does not suggest a major and consistent role of socio-economic status in the risk of type 1 diabetes.

Higher ultraviolet radiation during early life is associated with lower risk of childhood type 1 diabetes among boys

Population-level ecological studies show type 1 diabetes incidence is inversely correlated with ambient ultraviolet radiation (UVR) levels. We conducted a nested case–control study using administrative datasets to test this association at the individual level. Cases (n = 1819) were children born in Western Australia (WA) from 1980–2014, diagnosed with type 1 diabetes at ≤ 16 years. Controls (n = 27,259) were randomly selected from all live births in WA, matched to cases by sex and date of birth. Total ambient erythemal ultraviolet radiation (UVR) doses for each trimester of pregnancy and first year of life were estimated for each individual, using daily NASA satellite data that were date- and geographically-specific. Conditional logistic regression tested the association between UVR dose and case–control status. Type 1 diabetes risk was 42% lower in boys of mothers with third-trimester UVR dose in the highest (compared to the lowest) quartile (p = 0.04). Higher UVR in the first year of life was associated with lower type 1 diabetes risk among boys (p = 0.01). UVR dose was not associated with type 1 diabetes risk in girls. Higher UVR in late pregnancy and early life appear to interact with sex-specific factors to lower type 1 diabetes risk among boys in Western Australia.

Higher Ultraviolet Radiation During Early Life Reduces Risk of Childhood Type 1 Diabetes in Boys

IntroductionThere is increasing evidence that environmental exposures may be important in the pathogenesis of type 1 diabetes (T1D). Ultraviolet radiation (UVR) is of interest in relation to the development of T1D because of its immunoregulatory actions. Ecological studies testing the correlation between levels of UVR and T1D have shown a significant inverse relationship for both incidence and prevalence.
 Objectives and Approach We used large linked datasets to test ambient UVR during early life against T1D risk at the individual level. We conducted a nested case-control study using linked data from state-wide administrative datasets and NASA satellites. Cases (n=1819) were all children born in Western Australia from 1980-2014 with a diagnosis of T1D on the population-based Western Australian Children’s Diabetes Database between 0-16 years of age. Controls (n=27 259) were randomly selected from all live births in Western Australia and matched to cases on sex and date of birth.
 Daily UVR data from NASA satellites, that were date-and location-specific for each individual, were used to estimate total UVR dose for each trimester of pregnancy and the first year of life.
 ResultsConditional logistic regression showed that T1D risk was 44% lower in boys of mothers with UVR levels in the highest quartile (compared to the lowest quartile) during their third trimester of pregnancy (p=0.04). Higher UVR in the first year of life was also associated with a significantly lower risk of T1D in later childhood among boys. Among girls, there was no evidence of an association between total UVR dose and T1D risk.
 ConclusionHigher UVR in the third trimester and first year of life appears to interact with sex-specific factors to lower T1D risk among boys (but not girls) in Western Australia.

Maternal Level of 25-Hydroxyvitamin D during Pregnancy Associated with Risk of Type 1 Diabetes in the Offspring, a Meta-Analysis.

This aim of this meta-analysis was to evaluate the association between risk of childhood type 1 diabetes and maternal 25-hydroxyvitamin D [25(OH)D] levels during pregnancy. A literature search on databases including PubMed and Embase was conducted up to December 2018. The pooled odds radio weighted mean difference (WMD) and the corresponding 95% confidence intervals (CIs) were calculated using the RevMan 5.3 software. A total of 4 studies were included in this meta-analysis. The overall analysis indicated that the maternal 25(OH)D levels during pregnancy was significantly associated with the risk of type 1 diabetes in offspring (WMD=-2.54, 95% CI=-4.65 to -0.44, p=0.02). The subgroup analyses showed that sample for detection vitamin D (serum/plasma) may not a factor influencing the results of this meta-analysis. However, gestational trimester may be a factor affecting the results. The results showed that no significant association was observed between risk of type 1 diabetes in offspring and 25(OH)D level during first or second gestational trimester (p>0.05). Lower maternal 25(OH)D levels during pregnancy is associated with higher risk of type 1 diabetes in offspring. Gestational trimester may be a factor influencing the results of this meta-analysis.

Maternal and Early Life Iron Intake and Risk of Childhood Type 1 Diabetes: A Danish Case-Cohort Study.

Background: Iron overload has been associated with diabetes. Studies on iron exposure during pregnancy and in early life and risk of childhood type 1 diabetes (T1D) are sparse. We investigated whether iron supplementation during pregnancy and early in life were associated with risk of childhood T1D. Methods: In a case-cohort design, we identified up to 257 children with T1D (prevalence 0.37%) from the Danish National Birth Cohort through linkage with the Danish Childhood Diabetes Register. The primary exposure was maternal pure iron supplementation (yes/no) during pregnancy as reported in interview two at 30 weeks of gestation (n = 68,497 with iron supplement data). We estimated hazard ratios (HRs) using weighted Cox regression adjusting for multiple confounders. We also examined if offspring supplementation during the first 18 months of life was associated with later risk of T1D. Results: Maternal iron supplementation was not associated with later risk of T1D in the offspring HR 1.05 (95% CI: 0.76–1.45). Offspring intake of iron droplets during the first 18 months of life was inversely associated with risk of T1D HR 0.74 (95% CI: 0.55–1.00) (ptrend = 0.03). Conclusions: Our large-scale prospective study demonstrated no harmful effects of iron supplementation during pregnancy and in early life in regard to later risk of childhood T1D in the offspring.

Childhood Vaccinations and the Risk of Childhood Type 1 Diabetes: Results of a Population-Based Case-Control Study

Childhood Vaccinations and the Risk of Childhood Type 1 Diabetes: Results of a Population-Based Case-Control Study

Plasma immunological markers in pregnancy and cord blood: Apossible link between macrophage chemo-attractants and risk of childhood type 1 diabetes.

Previous studies have suggested that immune perturbations during pregnancy can affect offspring type 1 diabetes (T1D) risk. We aimed to identify immunological markers that could predict offspring T1D or that were linked to T1D risk factors. We quantified selected circulating immunological markers in mid-pregnancy (interleukin [IL]-1β, IL-1ra, IL-2Rα, IL-2, -4, -5, -6, -10, -12p70, 13, -17A, GM-CSF, IFN-γ, CXCL10, CCL 2, CCL3, CCL4, TNF) and cord blood plasma (neopterin and kynurenine/tryptophan ratio) in a case-control study with 175 mother/child T1D cases (median age 5.8, range 0.7-13.0years) and 552 controls. Pre-pregnancy obesity was positively associated with CCL4, CXCL10, kynurenine/tryptophan ratio and neopterin (P<.01). The established T1D SNPs rs1159465 (near IL2RA) and rs75352297 (near CCR2 and CCR3) were positively associated with IL-2Rα and CCL4, respectively (P<.01). There was a borderline association of CCL4 and offspring T1D risk, independent of maternal obesity and genotype. When grouping the immunological markers, there was a borderline association (P=.05) with M1 phenotype and no association between M2-, Th1-, Th2- or Th17 phenotypes and offspring T1D risk. Increased mid-pregnancy CCL4 levels showed borderline associations with increased offspring T1D risk, which may indicate a link between environmental factors in pregnancy and offspring T1D risk.

High Neonatal Blood Iron Content Is Associated with the Risk of Childhood Type 1 Diabetes Mellitus.

(1) Background: Iron requirement increases during pregnancy and iron supplementation is therefore recommended in many countries. However, excessive iron intake may lead to destruction of pancreatic β-cells. Therefore, we aim to test if higher neonatal iron content in blood is associated with the risk of developing type 1 diabetes mellitus (T1D) in childhood; (2) Methods: A case-control study was conducted, including 199 children diagnosed with T1D before the age of 16 years from 1991 to 2005 and 199 controls matched on date of birth. Information on confounders was available in 181 cases and 154 controls. Iron was measured on a neonatal single dried blood spot sample and was analyzed by laser ablation inductively coupled plasma mass spectrometry. Multivariate logistic regression was used to evaluate if iron content in whole blood was associated with the risk of T1D; (3) Results: A doubling of iron content increased the odds of developing T1D more than two-fold (odds ratio (95% CI), 2.55 (1.04; 6.24)). Iron content increased with maternal age (p = 0.04) and girls had higher content than boys (p = 0.01); (4) Conclusions: Higher neonatal iron content associates to an increased risk of developing T1D before the age of 16 years. Iron supplementation during early childhood needs further investigation, including the causes of high iron in neonates.

Prelabor Cesarean Section and Risk of Childhood Type 1 Diabetes: A Nationwide Register-based Cohort Study.

Unfavorable conditions associated with cesarean section may influence the risk of type 1 diabetes in offspring, but results from studies are conflicting. We aimed to evaluate the association between prelabor cesarean section and risk of childhood type 1 diabetes. A Danish nationwide cohort study followed all singletons born during 1982-2010. Four national registers provided information on mode of delivery, outcome, and confounders. The risk of childhood type 1 diabetes with onset before the age of 15 years was assessed by Cox regression. A total of 1,760,336 singletons contributed 20,436,684 person-years, during which 4,400 were diagnosed with childhood type 1 diabetes. The hazard ratio (HR) for childhood type 1 diabetes was increased in children delivered by prelabor cesarean section compared with vaginal delivery when adjusted for year of birth, parity, sex, parental age, and education and paternal type 1 diabetes status at childbirth (HR = 1.2; 95% confidence interval [CI] = 1.0, 1.3), but not after additional adjustment for maternal type 1 diabetes status at childbirth (HR = 1.1; 95% CI = 0.95, 1.2). Delivery by intrapartum cesarean section was not associated with childhood type 1 diabetes. Paternal type 1 diabetes was a stronger risk factor for childhood type 1 (HR = 12; 95% CI = 10, 14) than maternal type 1 diabetes (HR = 6.5; 95% CI = 5.2, 8.0). Delivery by prelabor cesarean section was not associated with an increased risk of childhood type 1 diabetes in the offspring.

Vaccinations and childhood type 1 diabetes mellitus: a meta-analysis of observational studies.

Aims/hypothesisThe aim of this study was to investigate the association between routine vaccinations and the risk of childhood type 1 diabetes mellitus by systematically reviewing the published literature and performing meta-analyses where possible.MethodsA comprehensive literature search was performed of MEDLINE and EMBASE to identify all studies that compared vaccination rates in children who subsequently developed type 1 diabetes mellitus and in control children. ORs and 95% CIs were obtained from published reports or derived from individual patient data and then combined using a random effects meta-analysis.ResultsIn total, 23 studies investigating 16 vaccinations met the inclusion criteria. Eleven of these contributed to meta-analyses which included data from between 359 and 11,828 childhood diabetes cases. Overall, there was no evidence to suggest an association between any of the childhood vaccinations investigated and type 1 diabetes mellitus. The pooled ORs ranged from 0.58 (95% CI 0.24, 1.40) for the measles, mumps and rubella (MMR) vaccination in five studies up to 1.04 (95% CI 0.94, 1.14) for the haemophilus influenza B (HiB) vaccination in 11 studies. Significant heterogeneity was present in most of the pooled analyses, but was markedly reduced when analyses were restricted to study reports with high methodology quality scores. Neither this restriction by quality nor the original authors’ adjustments for potential confounding made a substantial difference to the pooled ORs.Conclusions/interpretationThis study provides no evidence of an association between routine vaccinations and childhood type 1 diabetes.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-015-3800-8) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Gestational Age and Birth Weight and the Risk of Childhood Type 1 Diabetes: A Population-Based Cohort and Sibling Design Study.

We investigated the effects of gestational age, birth weight, small for gestational age (SGA), and large for gestational age (LGA) on risk of childhood type 1 diabetes. We conducted a population-based cohort study of all singleton live births in Sweden between 1973 and 2009 and a sibling control study. Perinatal data were extracted from the Swedish Medical Birth Register. Children with type 1 diabetes diagnosis were identified from the Swedish National Patient Register. Log-linear Poisson regression and conditional logistic regression were used for data analysis. The study cohort consisted of 3,624,675 singleton live births (42,411,054 person-years). There were 13,944 type 1 diabetes cases during the study period. The sibling control study consisted of 11,403 children with type 1 diabetes and 17,920 siblings. Gestational age between 33 and 36 weeks (relative risk [RR] 1.18 [95% CI 1.09, 1.28) and 37 and 38 weeks (RR 1.12 [95% CI 1.07, 1.17]) was associated with type 1 diabetes in the cohort study and remained significant in the sibling control study. SGA (RR 0.83 [95% CI 0.75, 0.93]) and LGA (RR 1.14 [95% CI 1.04, 1.24]) were associated with type 1 diabetes in the cohort study. The SGA association remained unchanged in the sibling study, while the LGA association disappeared. Very low birth weight was associated with a reduced risk of type 1 diabetes. The findings suggest a small association between gestational age and type 1 diabetes that is not likely due to familial confounding factors. Gestational age and type 1 diabetes may be related to insulin resistance due to early life growth restriction or altered gut microbiota in preterm babies.

Family psychological stress early in life and development of type 1 diabetes: The ABIS prospective study

AimsThis study investigated whether psychological stress in the family during the child's first year of life are associated with the risk of childhood type 1 diabetes (T1D). According to the beta-cell stress hypothesis all factors that increase the need for, or the resistance to, insulin may be regarded as risk factors for T1D. MethodsAmong 8921 children from the general population with questionnaire data from one parent at child's birth and at 1 year of age, 42 cases of T1D were identified up to 11–13 years of age. Additionally 15 cases with multiple diabetes-related autoantibodies were detected in a sub-sample of 2649 children. ResultsCox regression analyses showed no significant associations between serious life events (hazard ratio 0.7 for yes vs. no [95% CI 0.2–1.9], p=0.47), parenting stress (0.9 per scale score [0.5–1.7], p=0.79), or parental dissatisfaction (0.6 per scale score [0.3–1.2], p=0.13) during the first year of life and later diagnosis of T1D, after controlling for socioeconomic, demographic, and diabetes-related factors. Inclusion of children with multiple autoantibodies did not alter the results. ConclusionsNo association between psychological stress early in life and development of T1D could be confirmed.

Neonatal jaundice is associated with a small increase in the risk of childhood type 1 diabetes: a meta-analysis of observational studies

Published data on the role of neonatal jaundice as a risk factor for childhood type 1 diabetes mellitus is inconsistent. We aimed to review systematically, the evidence for an increased risk of type 1 diabetes in children diagnosed with neonatal jaundice. A comprehensive search of the published literature was performed to identify studies that had recorded the occurrence of neonatal jaundice in a group of children with type 1 diabetes and in a group of control children. Odds ratios (ORs) were extracted from reports or derived from tabulated data and then combined using a random effects meta-analysis. Data were available from 12 case-control studies and one retrospective cohort study. Overall, there was only weak evidence of an increase in the risk of type 1 diabetes in children who had neonatal jaundice (OR 1.14, 95% CI 0.99-1.32; P = 0.07), and there was some evidence of heterogeneity (I(2) = 53%, P = 0.01) mainly attributable to one study. An analysis restricted to studies not relying on parental recall showed a stronger, significant relationship (OR = 1.25, 95% CI 1.03-1.51; P = 0.02), although heterogeneity remained. This analysis found evidence of a small but statistically significant increase in childhood type 1 diabetes risk associated with neonatal jaundice but only for studies which used data from obstetric records. Jaundice caused by blood group incompatibility or requiring phototherapy may be associated with a greater increase in type 1 diabetes risk and deserves further study.

Maternal age at birth and childhood type 1 diabetes: a pooled analysis of 30 observational studies.

OBJECTIVEThe aim if the study was to investigate whether children born to older mothers have an increased risk of type 1 diabetes by performing a pooled analysis of previous studies using individual patient data to adjust for recognized confounders.RESEARCH DESIGN AND METHODSRelevant studies published before June 2009 were identified from MEDLINE, Web of Science, and EMBASE. Authors of studies were contacted and asked to provide individual patient data or conduct prespecified analyses. Risk estimates of type 1 diabetes by maternal age were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were used to derive combined odds ratios and to investigate heterogeneity among studies.RESULTSData were available for 5 cohort and 25 case-control studies, including 14,724 cases of type 1 diabetes. Overall, there was, on average, a 5% (95% CI 2–9) increase in childhood type 1 diabetes odds per 5-year increase in maternal age (P = 0.006), but there was heterogeneity among studies (heterogeneity I2 = 70%). In studies with a low risk of bias, there was a more marked increase in diabetes odds of 10% per 5-year increase in maternal age. Adjustments for potential confounders little altered these estimates.CONCLUSIONSThere was evidence of a weak but significant linear increase in the risk of childhood type 1 diabetes across the range of maternal ages, but the magnitude of association varied between studies. A very small percentage of the increase in the incidence of childhood type 1 diabetes in recent years could be explained by increases in maternal age.

Nitrate in Community Water Supplies and Risk of Childhood Type 1 Diabetes in Sardinia, Italy

We tested the hypothesis of an association between childhood type 1 diabetes (T1D) risk and nitrate concentration in drinking water in Sardinia, Italy, using Poisson regression analysis. Childhood T1D risk showed an inverse trend with increasing quartile of nitrate level in the total population and among men. A nitrate concentration in drinking water below 10 mg/l is unlikely to account for the spatial variation in childhood T1D incidence.

Parental age at delivery, birth order, birth weight and gestational age are associated with the risk of childhood Type 1 diabetes: a UK regional retrospective cohort study

To investigate perinatal risk factors for childhood Type 1 diabetes in a UK population cohort. Perinatal data have been routinely recorded in Northern Ireland for all births in the period 1971-86 (n = 447 663). Diabetes status at the age of 15 years was ascertained in this cohort by identifying 991 children from 1079 registered with Type 1 diabetes diagnosed from 1971 to 2001 and date of birth in the period 1971-86. Increased Type 1 diabetes risk was associated with higher maternal age, paternal age, birth weight and birth weight for gestational and lower gestational age. After adjustment for maternal age, the association between Type 1 diabetes and paternal age remained significant [relative risk (RR) = 1.52 (1.10, 2.09) comparing father's age 35 years or more to less than 25 years] but not vice versa [RR = 1.11 (0.80, 1.54) comparing mother's age 35 years or more to less than 25 years]. Increased birth order was associated with a significant decrease in the risk of Type 1 diabetes [adjusted RR = 0.75 (0.62, 0.90) comparing birth order three or more with firstborn], but this only became apparent when adjustment was made for maternal age. Furthermore this association with birth order was significant only for diabetes diagnosed under the age of 5 years. Our analysis demonstrates, for the first time in a UK regional cohort setting, that maternal age and paternal age at delivery, birth order, birth weight and gestational age are significantly associated with Type 1 diabetes risk.

Zinc and nitrate in the ground water and the incidence of Type 1 diabetes in Finland.

In Finland, the risk of childhood Type 1 diabetes varies geographically. Therefore we investigated the association between spatial variation of Type 1 diabetes and its putative environmental risk factors, zinc and nitrates. The association was evaluated using Bayesian modelling and the geo-referenced data on diabetes cases and population. Neither zinc nor nitrate nor the urban/rural status of the area had a significant effect on the variation in incidence of childhood Type 1 diabetes. The results showed that although there was no significant difference in incidence between rural and urban areas, there was a tendency to increasing risk of Type 1 diabetes with the increasing concentration of NO3 in drinking water. The fact that no significant effect was found may stem from the aggregated data being too crude to detect it.

Decreased prevalence of atopic diseases in children with diabetes

Objective: To test the hypothesis that atopic diseases in early life are associated with a reduced risk (protection) for the development of type 1 diabetes in childhood. Study design: European centers (n = 8) with access to population-based type 1 diabetes registries (>90% degree of ascertainment) participated in a case control study focusing on early exposures and risk factors for type 1 diabetes. Altogether, data from 1028 members of a case group and 2744 members of a control group corresponding to 85.4% eligible members of the case group and 76.1% of the control group were analyzed. Information in this study was collected regarding atopic diseases (atopic eczema, allergic rhinoconjunctivitis, and asthma). Results: Atopic disease and asthma particularly are associated with significant reductions in risk of childhood type 1 diabetes. The risk reduction associated with asthma was observed reasonably consistently among the 8 study centers, which represent a wide range of diabetes incidence. Risk reductions associated with all 3 expressions of atopy were particularly marked in children whose type 1 diabetes was diagnosed in the 10- to 14-year age group. Conclusion: These findings indicate that atopic conditions may be protective against the development of type 1 diabetes and are consistent with the immunologic concept of TH1 (type 1 diabetes) and TH2 (atopy) diseases being mutually exclusive. (J Pediatr 2000;137:470-4)