scholarly journals Use of Antiasthmatic Drugs and the Risk of Type 1 Diabetes in Children: A Nationwide Case-Cohort Study

2020 ◽  
Vol 189 (8) ◽  
pp. 779-787 ◽  
Author(s):  
Johanna Metsälä ◽  
Annamari Lundqvist ◽  
Lauri J Virta ◽  
Minna Kaila ◽  
Mika Gissler ◽  
...  

Abstract Asthma has been reported to be associated with an increased risk of type 1 diabetes mellitus in childhood, but the reasons are unclear. We examined whether the use of antiasthmatic drugs was associated with the development of type 1 diabetes in childhood in a nationwide, register-based case-cohort study. We identified all children who were born January 1, 1995, through December 31, 2008, in Finland and diagnosed with type 1 diabetes by 2010 (n = 3,342). A 10% random sample from each birth-year cohort was selected as a reference cohort (n = 80,909). Information on all dispensed antiasthmatic drugs (Anatomical Therapeutic Chemical classification system code R03) during 1995–2009 was obtained, and associations between the use of antiasthmatic drugs and the development of type 1 diabetes were investigated using time-dependent and time-sequential Cox regression models. Dispensed inhaled corticosteroids and inhaled β-agonists were associated with an increased risk of type 1 diabetes after adjusting for other antiasthmatic drugs, asthma, sex, and birth decade (hazard ratio = 1.29, 95% confidence interval: 1.09, 1.52, and hazard ratio = 1.22, 95% confidence interval: 1.07, 1.41, respectively). These findings suggest that children using inhaled corticosteroids or inhaled β-agonists might be at increased risk of type 1 diabetes.

2019 ◽  
Author(s):  
Nicolai A Lund-Blix ◽  
German Tapia ◽  
Karl Mårild ◽  
Anne Lise Brantsaeter ◽  
Pål R Njølstad ◽  
...  

ABSTRACTOBJECTIVETo examine the association between maternal and child gluten intake and risk of type 1 diabetes in children.DESIGNPregnancy cohortSETTINGPopulation-based, nation-wide study in NorwayPARTICIPANTS86,306 children in The Norwegian Mother and Child Cohort Study born from 1999 through 2009, followed to April 15, 2018.MAIN OUTCOME MEASURESClinical type 1 diabetes, ascertained in a nation-wide childhood diabetes registry. Hazard ratios were estimated using Cox regression for the exposures maternal gluten intake up to week 22 of pregnancy and child’s gluten intake when the child was 18 months old.RESULTSDuring a mean follow-up of 12.3 years (range 0.7-16.0), 346 children (0.4%) developed type 1 diabetes (incidence rate 32.6 per 100,000 person-years). The average gluten intake was 13.6 grams/day for mothers during pregnancy, and 8.8 grams/day for the child at 18 months of age. Maternal gluten intake in mid-pregnancy was not associated with the development of type 1 diabetes in the child (adjusted hazard ratio 1.02 (95% confidence interval 0.73 to 1.43) per 10 grams/day increase in gluten intake). However, the child’s gluten intake at 18 months of age was associated with an increased risk of later developing type 1 diabetes (adjusted hazard ratio 1.46 (95% confidence interval 1.06 to 2.01) per 10 grams/day increase in gluten intake).CONCLUSIONSThis study suggests that the child’s gluten intake at 18 months of age, and not the maternal intake during pregnancy, could increase the risk of type 1 diabetes in the child.WHAT IS ALREADY KNOWN ON THIS TOPICA national prospective cohort study from Denmark found that a high maternal gluten intake during pregnancy could increase the risk of type 1 diabetes in the offspring (adjusted hazard ratio 1.31 (95% confidence interval 1.001 to 1.72) per 10 grams/day increase in gluten intake). No studies have investigated the relation between the amount of gluten intake by both the mother during pregnancy and the child in early life and risk of developing type 1 diabetes in childhood.WHAT THIS STUDY ADDSIn this prospective population-based pregnancy cohort with 86,306 children of whom 346 developed type 1 diabetes we found that the child’s gluten intake at 18 months of age was associated with the risk of type 1 diabetes (adjusted hazard ratio 1.46 (95% confidence interval 1.06 to 2.01) per 10 grams/day increase in gluten intake). This study suggests that the child’s gluten intake at 18 months of age, and not the maternal intake during pregnancy, could increase the child’s risk of type 1 diabetes.


BMJ ◽  
2018 ◽  
pp. k3547 ◽  
Author(s):  
Julie C Antvorskov ◽  
Thorhallur I Halldorsson ◽  
Knud Josefsen ◽  
Jannet Svensson ◽  
Charlotta Granström ◽  
...  

Abstract Objective To examine the association between prenatal gluten exposure and offspring risk of type 1 diabetes in humans. Design National prospective cohort study. Setting National health information registries in Denmark. Participants Pregnant Danish women enrolled into the Danish National Birth Cohort, between January 1996 and October 2002, Main outcome measures Maternal gluten intake, based on maternal consumption of gluten containing foods, was reported in a 360 item food frequency questionnaire at week 25 of pregnancy. Information on type 1 diabetes occurrence in the participants’ children, from 1 January 1996 to 31 May 2016, were obtained through registry linkage to the Danish Registry of Childhood and Adolescent Diabetes. Results The study comprised 101 042 pregnancies in 91 745 women, of whom 70 188 filled out the food frequency questionnaire. After correcting for multiple pregnancies, pregnancies ending in abortions, stillbirths, lack of information regarding the pregnancy, and pregnancies with implausibly high or low energy intake, 67 565 pregnancies (63 529 women) were included. The average gluten intake was 13.0 g/day, ranging from less than 7 g/day to more than 20 g/day. The incidence of type 1 diabetes among children in the cohort was 0.37% (n=247) with a mean follow-up period of 15.6 years (standard deviation 1.4). Risk of type 1 diabetes in offspring increased proportionally with maternal gluten intake during pregnancy (adjusted hazard ratio 1.31 (95% confidence interval 1.001 to 1.72) per 10 g/day increase of gluten). Women with the highest gluten intake versus those with the lowest gluten intake (≥20 v <7 g/day) had double the risk of type 1 diabetes development in their offspring (adjusted hazard ratio 2.00 (95% confidence interval 1.02 to 4.00)). Conclusions High gluten intake by mothers during pregnancy could increase the risk of their children developing type 1 diabetes. However, confirmation of these findings are warranted, preferably in an intervention setting.


2015 ◽  
Vol 100 (8) ◽  
pp. 763-768 ◽  
Author(s):  
Soulmaz Fazeli Farsani ◽  
Patrick C Souverein ◽  
Marja M J van der Vorst ◽  
Catherijne A J Knibbe ◽  
Anthonius de Boer ◽  
...  

ObjectiveTo determine the incidence of chronic comorbidities among children with type 1 diabetes (T1D) and to compare incidences with a group of children without diabetes.DesignPopulation-based cohort study.SettingDutch PHARMO database (1998–2010).PatientsAll patients (<19 years old) with T1D between 1999 and 2009 (T1D cohort) and a group of age- and sex-matched (ratio: 1–4) children without diabetes (reference cohort).Main outcome measureThe incidence of nine common chronic comorbidities was assessed on the basis that they were treated pharmacologically and/or resulted in hospital admission. Cox proportional hazard analysis was used to estimate the strength of the association between T1D and comorbidities, expressed as HRs and 95% CIs.ResultsA total of 915 patients with T1D and 3590 children in the reference cohort (51% boys, mean age of 10.1 (SD 4.5) years) were included. T1D was associated with an increased risk (HR; 95% CI) of hospitalisation for any comorbidity (3.7; 2.5 to 5.5), thyroid disease (14.2; 6.7 to 31.0), non-infectious enteritis and colitis (5.9; 3.0 to 11.5), cardiovascular disorders (3.1; 2.3 to 4.2), mental disorders (2.0; 1.4 to 3.1), epilepsy (2.0; 1.1 to 3.7) and (obstructive) pulmonary disease (1.5; 1.2 to 2.0). There was no significant difference in the incidences of other comorbidities (malignant disorders, anaemia and migraine) between the two cohorts.ConclusionsOur longitudinal study showed that incidences of six chronic diseases were significantly higher in T1D children during the early years of developing this disease compared with the reference children.


BMJ ◽  
2019 ◽  
pp. l4894 ◽  
Author(s):  
Marcus Lind ◽  
Aldina Pivodic ◽  
Ann-Marie Svensson ◽  
Arndis F Ólafsdóttir ◽  
Hans Wedel ◽  
...  

AbstractObjectiveTo evaluate if the lowest target level for glycated haemoglobin (HbA1c) of <6.5% is associated with lower risk for retinopathy and nephropathy than less tight control in children and adults with type 1 diabetes.DesignPopulation based cohort study.SettingSwedish National Diabetes Registry, 1 January 1998 to 31 December 2017.Participants10 398 children and adults with type 1 diabetes followed from diagnosis, or close thereafter, until end of 2017.Main outcome measuresRelative risk (odds ratios) for retinopathy and nephropathy for different mean levels of HbA1c.ResultsMean age of participants was 14.7 years (43.4% female), mean duration of diabetes was 1.3 years, and mean HbA1c level was 8.0% (63.4 mmol/mol). After adjustment for age, sex, duration of diabetes, blood pressure, blood lipid levels, body mass index, and smoking, the odds ratio for mean HbA1c <6.5% (<48 mmol/mol) compared with 6.5-6.9% (48-52 mmol/mol) for any retinopathy (simplex or worse) was 0.77 (95% confidence interval 0.56 to 1.05, P=0.10), for preproliferative diabetic retinopathy or worse was 3.29 (0.99 to 10.96, P=0.05), for proliferative diabetic retinopathy was 2.48 (0.71 to 8.62, P=0.15), for microalbuminuria or worse was 0.98 (0.60 to 1.61, P=0.95), and for macroalbuminuria was 2.47 (0.69 to 8.87, P=0.17). Compared with HbA1c levels 6.5-6.9%, HbA1c levels 7.0-7.4% (53-57 mmol/mol) were associated with an increased risk of any retinopathy (1.31, 1.05 to 1.64, P=0.02) and microalbuminuria (1.55, 1.03 to 2.32, P=0.03). The risk for proliferative retinopathy (5.98, 2.10 to 17.06, P<0.001) and macroalbuminuria (3.43, 1.14 to 10.26, P=0.03) increased at HbA1c levels >8.6% (>70 mmol/mol). The risk for severe hypoglycaemia was increased at mean HbA1c <6.5% compared with 6.5-6.9% (relative risk 1.34, 95% confidence interval 1.09 to 1.64, P=0.005).ConclusionsRisk of retinopathy and nephropathy did not differ at HbA1c levels <6.5% but increased for severe hypoglycaemia compared with HbA1c levels 6.5-6.9%. The risk for severe complications mainly occurred at HbA1c levels >8.6%, but for milder complications was increased at HbA1c levels >7.0%.


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Thomas Inns ◽  
Kate M. Fleming ◽  
Miren Iturriza-Gomara ◽  
Daniel Hungerford

Abstract Background Rotavirus infection has been proposed as a risk factor for coeliac disease (CD) and type 1 diabetes (T1D). The UK introduced infant rotavirus vaccination in 2013. We have previously shown that rotavirus vaccination can have beneficial off-target effects on syndromes, such as hospitalised seizures. We therefore investigated whether rotavirus vaccination prevents CD and T1D in the UK. Methods A cohort study of children born between 2010 and 2015 was conducted using primary care records from the Clinical Practice Research Datalink. Children were followed up from 6 months to 7 years old, with censoring for outcome, death or leaving the practice. CD was defined as diagnosis of CD or the prescription of gluten-free goods. T1D was defined as a T1D diagnosis. The exposure was rotavirus vaccination, defined as one or more doses. Mixed-effects Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CIs). Models were adjusted for potential confounders and included random intercepts for general practices. Results There were 880,629 children in the cohort (48.8% female). A total of 343,113 (39.0%) participants received rotavirus vaccine; among those born after the introduction of rotavirus vaccination, 93.4% were vaccinated. Study participants contributed 4,388,355 person-years, with median follow-up 5.66 person-years. There were 1657 CD cases, an incidence of 38.0 cases per 100,000 person-years. Compared with unvaccinated children, the adjusted HR for a CD was 1.05 (95% CI 0.86–1.28) for vaccinated children. Females had a 40% higher hazard than males. T1D was recorded for 733 participants, an incidence of 17.1 cases per 100,000 person-years. In adjusted analysis, rotavirus vaccination was not associated with risk of T1D (HR = 0.89, 95% CI 0.68–1.19). Conclusions Rotavirus vaccination has reduced diarrhoeal disease morbidity and mortality substantial since licencing in 2006. Our finding from this large cohort study did not provide evidence that rotavirus vaccination prevents CD or T1D, nor is it associated with increased risk, delivering further evidence of rotavirus vaccine safety.


2021 ◽  
Vol 9 ◽  
Author(s):  
Yen-Chu Huang ◽  
Meng-Che Wu ◽  
Yu-Hsun Wang ◽  
James Cheng-Chung Wei

Background: Asthma is one of the most burdensome childhood disorders. Growing evidence disclose intestinal dysbiosis may contribute to asthma via the gut-lung axis. Constipation can lead to alteration of the gut microbiota. The clinical impact of constipation on asthma has not been researched. Therefore, we aim to assess whether pediatric constipation influence the risk of developing asthma by a nationwide population-based cohort study.Methods: We analyzed 10,363 constipated patients and 10,363 individuals without constipation between 1999 and 2013 from Taiwan's National Health Insurance Research Database. Analysis of propensity score was utilized to match age, sex, comorbidities, and medications at a ratio of 1:1. In addition, multiple Cox regression analysis was performed to evaluate the adjusted hazard ratio of asthma. Furthermore, sensitivity tests and a stratified analysis were performed.Results: After adjustment for age, sex, comorbidities, and medications, constipated patients had a 2.36-fold greater risk of asthma compared to those without constipation [adjusted hazard ratio (aHR): 2.36, 95% C.I. 2.04–2.73, p &lt; 0.001]. Furthermore, the severity of constipation is associated with an increased risk of asthma; the adjusted hazard ratio was 2.25, 2.85, and 3.44 within &lt; 3, 3–12, and ≥12 times of laxatives prescription within 1 year, respectively (p &lt; 0.001).Conclusion: Constipation was correlated with a significantly increased risk of asthma. Pediatricians should be aware of the possibility of asthma in constipated patients. Further research is warranted to investigate the possible pathological mechanisms of this association.


Author(s):  
Shih-Yi Lin ◽  
Cheng-Li Lin ◽  
Cheng-Chieh Lin ◽  
Wu-Huei Hsu ◽  
Chung-Y. Hsu ◽  
...  

Type 1 diabetes mellitus (T1DM) has been linked to many autoimmune problems. The association between T1DM and urticaria warrants investigation. Data were extracted from the National Health Insurance Research Database (NHIRD) of Taiwan. Participants with T1DM were recruited as the case group, and that group was matched by sex and age at a ratio of 1:4 to the control group comprising those without T1DM. The study period was 1998–2011. All participants were followed up to the diagnosis of urticaria, withdrawal from the insurance program, death, or the end of the study. A multivariable Cox proportional hazard model was used to calculate the adjusted and crude hazard ratios for urticaria. A total of 5895 participants (1179 in the case group and 4716 in the control group) were followed up in the study. The total incidence rate of urticaria in patients with type 1 DM was 26.6 per 1000 person-years, and that in controls was 6.85 per 1000 person-years. Compared with the control group, the hazard ratio of urticaria in the case group was 2.84 (95% CI = 2.27–3.56). Compared with age-matched participants without T1DM, patients with type 1 DM aged <18 years had a 3.62-fold higher risk of urticaria (95% CI = 2.85–4.59). The hazard ratio in patients with an adjusted Diabetes Complications Severity Index (aDCSI) score of 1.01–2.00 per year was 2.57 (95% CI = 1.18–5.57), and that in patients with an aDCSI score of >2.00 per year was 4.47 (95% CI = 2.68–7.47). T1DM patients aged <18 years had an increased risk of urticaria, but a similar phenomenon was not observed among T1DM patients older than 18 years.


2018 ◽  
Vol 104 (4) ◽  
pp. 1148-1157 ◽  
Author(s):  
Dimitrios Chantzichristos ◽  
Anders Persson ◽  
Mervete Miftaraj ◽  
Björn Eliasson ◽  
Ann-Marie Svensson ◽  
...  

Abstract Context Patients with type 1 diabetes mellitus (T1DM) have an increased risk of Addison disease (AD) development, but prediction of those at risk is not possible. Objective To determine whether there are early clinical indicators that may denote the development of AD in adults with T1DM. Design Observational, matched-cohort study. Setting Patient data from Swedish national registries [National Diabetes Register (NDR), Inpatient Register, and Prescription Drug Register]. Participants All patients with T1DM diagnosed with concomitant AD (n = 66) among the 36,514 adult patients with T1DM in the NDR between 1998 and 2013. Each case was matched to five controls with T1DM alone (n = 330). Main Outcome Measures Clinical data and drug prescriptions were assessed prior to baseline (inclusion into the study) and prior to AD diagnosis. Analysis of covariance and estimated group proportions were used for comparisons. Results Prior to baseline, cases had a higher frequency of thyroid/antithyroid drug prescription than controls (9.1% vs 1.8%). Prior to AD diagnosis, cases had higher frequencies of diabetic retinopathy (12.1% vs 2.1%), infections requiring hospital admission (16.7% vs 2.1%), thyroid/antithyroid drug prescription (28.8% vs 7.0%), and glucagon prescription (18.2% vs 6.4%). There was no difference in glycated Hb between the groups prior to baseline or prior to AD diagnosis. Conclusions These data suggest that medical treatment of thyroid disease, a severe infection, and glucagon prescription for severe hypoglycemia should raise the suspicion of AD development in adults with T1DM. Development of diabetic retinopathy might also be associated with glucocorticoid deficiency and the development of AD among patients with T1DM.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
G M Hansen ◽  
P G Jorgensen ◽  
H U Andersen ◽  
P Rossing ◽  
M T Jensen

Abstract Background Peripheral neuropathy (PN) is a highly prevalent and feared microvascular complication in patients with type 1 diabetes (T1D). Cardiovascular disease (CVD) is the most common cause of mortality in patients with T1D. PN may act as an early indicator of CVD and can potentially contribute to the propagation of atherosclerosis and cause the disease to remain clinically silent into advanced stages. Therefore, identification of T1D patients at risk of CVD is important in assuring timely prevention and treatment. Purpose The purpose of this study was to evaluate the risk of major adverse cardiovascular events (MACE) associated with measures of PN and diastolic function (DF) in patients with T1D and no known heart disease. Furthermore, we tested the additional prognostic value of including PN and DF both alone and in combination, in the validated Steno T1D Risk Engine. Methods Patients with T1D without known heart disease were included from the Steno Diabetes Center Copenhagen. Echocardiography and quantitative testing for PN using biothesiometry to determine sensory vibration threshold were performed. The patients were divided into three categories according to sensory threshold: <20mV, 20–49 mV, and ≥50mV. DF was divided into three categories of E/e': <8, 8–12, and >12. Endpoints was first occurring MACE. Using multivariable Cox regression models adjusting for age, sex, blood pressure, BMI, HbA1c, smoking, alcohol consumption, family history of CVD, eGFR, albuminuria, and duration of diabetes, the association between PN and/or DF and the risk of MACE was analysed. Improvement in prediction of prognosis was assessed with Harrell's C-statistics and compared to Steno T1D Risk Engine. Results A total of 946 patients (51.5% males) with T1D were included. Mean age was 48.4 (SD 14.4) years and mean duration of diabetes was 25 (SD 14.3) years. In the adjusted analysis, which was mutually adjusted for measures of PN and DF, both PN and DF were associated with increased risk of MACE: Sensory threshold ≥50mV vs. <20mV: Hazard Ratio (HR) 2.18 (95% confidence interval [CI]: 1.02–4.64, p=0.044). Threshold 20–49mV vs. <20mV: HR 1.33 (95% CI: 0.77–2.30, p=0.31). Diastolic measurement E/e' >12 vs. E/e' <8: HR 2.31 (95% CI: 1.16–4.59, p=0.017), and E/e' 8–12 vs. E/e' <8: HR 1.70 (95% CI: 1.03–2.82, p=0.038). In combination, a threshold ≥50mV and E/e' >12 vs. <20mV and E7e' <8 was associated with a marked increased risk of MACE: HR 8.59 (95% CI: 2.60–28.4, p<0.001). The addition of E/e' to the Steno T1D Risk Engine improved the prediction of outcome: C-statistic 0.797, (95% CI: 0.758–0.835) vs. 0.785 (95% CI: 0.744–0.825), p<0.001. Conclusion In patients with T1D without known heart disease and with preserved ejection fraction, PN and DF are independently associated with an increased risk of MACE. However, only measures of DF improved the prediction of prognosis when added to clinical risk factors. Acknowledgement/Funding None


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