No association between long-chain n-3 fatty acid intake during pregnancy and risk of type 1 diabetes in offspring in two large Scandinavian pregnancy cohorts.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether higher dietary intake of marine n-3 fatty acids during pregnancy is associated with a lower risk of type 1 diabetes in children. METHODS: The Danish National Birth Cohort (DNBC) and the Norwegian Mother, Father and Child Cohort Study (MoBa) together include 153,843 mother-child pairs with prospectively collected data on eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake during pregnancy from validated food frequency questionnaires. Type 1 diabetes diagnosis in children (n=634) was ascertained from national diabetes registries. RESULTS: There was no association between the sum of EPA and DHA intake during pregnancy and risk of type 1 diabetes in offspring (pooled HR per g/day of intake: 1.00, 95% CI 0.88, 1.14), with consistent results for both the MoBa and the DNBC. Robustness analyses gave very similar results. CONCLUSIONS/INTERPRETATION: Initiation of a trial of EPA and DHA during pregnancy to prevent type 1 diabetes in offspring should not be prioritised.

A pilot study of a virtually delivered dissonance-based eating disorder prevention program for young women with type 1 diabetes: within-subject changes over 6-month follow-up.

INTRODUCTION: In an uncontrolled study, we previously demonstrated the feasibility and preliminary efficacy of our virtual diabetes-specific version (Diabetes Body Project) of the eating disorder (ED) prevention program the Body Project. The aim of the current study was to evaluate further this program for women with type 1 diabetes (T1D) by assessing within-subject changes in outcomes from pretest over 6-month follow-up. METHODS: Young women with T1D aged 16-35 years were invited to participate in Diabetes Body Project groups. A total of 35 participants were allocated to five Diabetes Body Project groups (six meetings over 6 weeks). Primary outcome measures included ED risk factors and symptoms, and secondary outcomes included three T1D-specific constructs previously found to be associated with ED pathology: glycemic control as measured by HbA1c level, diabetes distress, and illness perceptions. RESULTS: Within-subject reductions, with medium-to-large effect sizes, were observed for the primary (ED pathology, body dissatisfaction, thin-ideal internalization, and appearance ideals and pressures) and secondary outcomes (within-condition Cohen's ds ranged from .34 to 1.70). CONCLUSION: The virtual Diabetes Body Project appears to be a promising intervention worthy of more rigorous evaluation. A randomized controlled trial with at least a 1-year follow-up is warranted to determine its efficacy compared to a control condition.

Characterisation of HNF1A variants in paediatric diabetes in Norway using functional and clinical investigations to unmask phenotype and monogenic diabetes.

AIMS/HYPOTHESIS: Correctly diagnosing MODY is important, as individuals with this diagnosis can discontinue insulin injections; however, many people are misdiagnosed. We aimed to develop a robust approach for determining the pathogenicity of variants of uncertain significance in hepatocyte nuclear factor-1 alpha (HNF1A)-MODY and to obtain an accurate estimate of the prevalence of HNF1A-MODY in paediatric cases of diabetes. METHODS: We extended our previous screening of the Norwegian Childhood Diabetes Registry by 830 additional samples and comprehensively genotyped HNF1A variants in autoantibody-negative participants using next-generation sequencing. Carriers of pathogenic variants were treated by local healthcare providers, and participants with novel likely pathogenic variants and variants of uncertain significance were enrolled in an investigator-initiated, non-randomised, open-label pilot study (ClinicalTrials.gov registration no. NCT04239586). To identify variants associated with HNF1A-MODY, we functionally characterised their pathogenicity and assessed the carriers' phenotype and treatment response to sulfonylurea. RESULTS: In total, 615 autoantibody-negative participants among 4712 cases of paediatric diabetes underwent genetic sequencing, revealing 19 with HNF1A variants. We identified nine carriers with novel variants classified as variants of uncertain significance or likely to be pathogenic, while the remaining ten participants carried five pathogenic variants previously reported. Of the nine carriers with novel variants, six responded favourably to sulfonylurea. Functional investigations revealed their variants to be dysfunctional and demonstrated a correlation with the resulting phenotype, providing evidence for reclassifying these variants as pathogenic. CONCLUSIONS/INTERPRETATION: Based on this robust classification, we estimate that the prevalence of HNF1A-MODY is 0.3% in paediatric diabetes. Clinical phenotyping is challenging and functional investigations provide a strong complementary line of evidence. We demonstrate here that combining clinical phenotyping with functional protein studies provides a powerful tool to obtain a precise diagnosis of HNF1A-MODY.

Do adolescents and emerging adults receive the diabetes care they truly need? A nationwide study of the quality of diabetes health care during the transition from paediatric to adult care.

AIMS: The aim of this study was to assess the paediatric and adult diabetes care provided to adolescents and young adults with childhood-onset type 1 diabetes during the transition. METHODS: This nationwide population-based cohort study included 776 individuals with type 1 diabetes who were last registered in the Norwegian Childhood Diabetes Registry (NCDR) between 2009 and 2012 and had received adult health care for at least 2 years. The patients' experiences were reported in a validated questionnaire. Clinical data from the annual registrations in the NCDR were coupled with data from the medical records in adult diabetes care. The longitudinal measures of glycaemic control were analysed using a growth mixture model. RESULTS: A total of 321 young people answered the questionnaire and provided written informed consent for the collection of their data from their medical records. The mean age at transfer was 18.0 years (range = 15.0-23.5 years), and the mean age at participation was 22.7 years (range = 20.9-26.7 years). Significant differences (p < 0.001) in patient experiences were found between paediatric and adult diabetes care in several areas: contact with health-care personnel, continuity of care, interval between consultations and overall satisfaction. Registry and medical records data confirmed the patient-reported experiences. The longitudinal analyses identified two groups with distinctly different trajectories of glycaemic outcome over time. Patient-provider continuity and perceived preparedness for transfer were the most influential predictors. CONCLUSIONS: This study highlights several areas to be addressed for improving health care and the transition to adult diabetes care in adolescents and young adults with type 1 diabetes, including provider continuity, individualised care and involvement of multidisciplinary teams.

Nine-fold higher risk of acute myocardial infarction in subjects with type 1 diabetes compared to controls in Norway 1973-2017.

BACKGROUND: We aimed to study the cumulative incidence and risk factors (sex, age, calendar year of diabetes onset, country of origin and educational level) of acute myocardial infarction (AMI) in subjects with type 1 diabetes and matched controls. METHODS: A nationwide cohort of subjects with type 1 diabetes diagnosed at age < 15 years in Norway during 1973-2000 was followed until the first AMI event, emigration, death or 31st of December 2017. The Norwegian Childhood Diabetes Registry was linked to five nationwide registries, and up to ten sex- and age-matched controls per case were included. RESULTS: Among 7086 subjects with type 1 diabetes, 170 (2.4%) were identified with incident AMI, compared to 193 (0.3%) of 69,356 controls. Mean age and diabetes duration at first AMI was 40.8 years and 30.6 years, respectively. The probability of AMI after 40 years of follow-up was 8.0% in subjects with type 1 diabetes and 1.1% in controls, aHR 9.05 (95% CI 7.18-11.41). In type 1 diabetes, male sex (aHR 1.45), higher age at onset of diabetes and lower education (higher compared to lower, aHR 0.38) were significantly associated with higher risk of AMI. There was no significant time trend in AMI by calendar year of diabetes onset. CONCLUSIONS: We found nine-fold excess risk of AMI in subjects with type 1 diabetes, and three-fold higher risk in subjects with low versus high education. These results highlight a strengthened focus on prevention of cardiovascular disease, and diabetes education tailored to the subjects' educational background.

A collaborative comparison of international pediatric diabetes registries.

BACKGROUND: An estimated 1.1 million children and adolescents aged under 20 years have type 1 diabetes worldwide. Principal investigators from seven well-established longitudinal pediatric diabetes registries and the SWEET initiative have come together to provide an international collaborative perspective and comparison of the registries. WORK FLOW: Information and data including registry characteristics, pediatric participant clinical characteristics, data availability and data completeness from the Australasian Diabetes Data Network (ADDN), Danish Registry of Childhood and Adolescent Diabetes (DanDiabKids), Diabetes prospective follow-up registry (DPV), Norwegian Childhood Diabetes Registry (NCDR), National Paediatric Diabetes Audit (NPDA), Swedish Childhood Diabetes Registry (Swediabkids), T1D Exchange Quality Improvement Collaborative (T1DX-QI), and the SWEET initiative was extracted up until 31 December 2020. REGISTRY OBJECTIVES AND OUTCOMES: The seven diabetes registries and the SWEET initiative collectively show data of more than 900 centers and around 100,000 pediatric patients, the majority with type 1 diabetes. All share the common objectives of monitoring treatment and longitudinal outcomes, promoting quality improvement and equality in diabetes care and enabling clinical research. All generate regular benchmark reports. Main differences were observed in the definition of the pediatric population, the inclusion of adults, documentation of CGM metrics and collection of raw data files as well as linkage to other data sources. The open benchmarking and access to regularly updated data may prove to be the most important contribution from registries. This study describes aspects of the registries to enable future collaborations and to encourage the development of new registries where they do not exist.

Feasibility of a virtually delivered eating disorder prevention program for young females with type 1 diabetes.

OBJECTIVE: This study aimed to develop a virtual diabetes-specific version of the eating disorder (ED) prevention program the Body Project, and to assess feasibility and preliminary efficacy of this program for young females with type 1 diabetes. METHOD: Young females with type 1 diabetes aged 16-35 years were invited to participate in the study. A total of 35 participants were allocated to five Diabetes Body Project groups (six meetings over 6 weeks) and completed pretest assessments; 26 participants completed all sessions and posttest assessments (<7 days after last meeting). Primary measures included ED risk factors and symptoms, and secondary outcomes included diabetes-specific constructs previously found to be associated with ED psychopathology (e.g., diabetes distress and illness perceptions). RESULTS: The ease of recruitment, timely conduct of five groups, moderate drop-out rate and appreciation of the intervention by participants indicated that the Diabetes Body Project is feasible. Meaningful reductions occurred on the primary outcomes (i.e., ED psychopathology, body dissatisfaction, and thin ideal internalization) and on internalization of appearance ideals and appearance pressures at posttest (Cohen's d ranging from .63 to .83, which are medium to large effects). Small to medium effect sizes were found for diabetes illness perceptions and distress (.41 and .48, respectively). DISCUSSION: The virtual Diabetes Body Project is a promising and much-needed intervention, worthy of more rigorous evaluation. A randomized controlled trial is warranted to determine its effectiveness compared with a control condition.

Temporal trends in diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes between 2006 and 2016: results from 13 countries in three continents.

AIMS/HYPOTHESIS: The aim of this work was to evaluate geographical variability and trends in the prevalence of diabetic ketoacidosis (DKA), between 2006 and 2016, at the diagnosis of childhood-onset type 1 diabetes in 13 countries over three continents. METHODS: An international retrospective study on DKA at diagnosis of diabetes was conducted. Data on age, sex, date of diabetes diagnosis, ethnic minority status and presence of DKA at diabetes onset were obtained from Australia, Austria, Czechia, Denmark, Germany, Italy, Luxembourg, New Zealand, Norway, Slovenia, Sweden, USA and the UK (Wales). Mean prevalence was estimated for the entire period, both overall and by country, adjusted for sex and age group. Temporal trends in annual prevalence of DKA were estimated using logistic regression analysis for each country, before and after adjustment for sex, age group and ethnic minority status. RESULTS: During the study period, new-onset type 1 diabetes was diagnosed in 59,000 children (median age [interquartile range], 9.0 years [5.5-11.7]; male sex, 52.9%). The overall adjusted DKA prevalence was 29.9%, with the lowest prevalence in Sweden and Denmark and the highest in Luxembourg and Italy. The adjusted DKA prevalence significantly increased over time in Australia, Germany and the USA while it decreased in Italy. Preschool children, adolescents and children from ethnic minority groups were at highest risk of DKA at diabetes diagnosis in most countries. A significantly higher risk was also found for females in Denmark, Germany and Slovenia. CONCLUSIONS/INTERPRETATION: DKA prevalence at type 1 diabetes diagnosis varied considerably across countries, albeit it was generally high and showed a slight increase between 2006 and 2016. Increased awareness of symptoms to prevent delay in diagnosis is warranted, especially in preschool children, adolescents and children from ethnic minority groups.

Maternal and child gluten intake and association with type 1 diabetes: The Norwegian Mother and Child Cohort Study.

BACKGROUND: The relationship between maternal gluten intake in pregnancy, offspring intake in childhood, and offspring risk of type 1 diabetes has not been examined jointly in any studies. Our aim was to study the relationship between maternal and child intake of gluten and risk of type 1 diabetes in children. METHODS AND FINDINGS: We included 86,306 children in an observational nationwide cohort study, the Norwegian Mother and Child Cohort Study (MoBa), with recruitment from 1999 to 2008 and with follow-up time to April 15, 2018. We used registration of type 1 diabetes in the Norwegian childhood diabetes registry as the outcome. We used Cox proportional hazard regression to estimate hazard ratios (HRs) for the mother's intake of gluten up to week 22 of pregnancy and offspring gluten intake when the child was 18 months old. The average time followed was 12.3 years (0.70-16.0). A total of 346 children (0.4%) children were diagnosed with type 1 diabetes, resulting in an incidence rate of 32.6/100,000 person-years. Mean gluten intake per day was 13.6 g for mothers and 8.8 g for children. There was no association between the mother's intake of gluten in pregnancy and offspring type 1 diabetes, with an adjusted HR (aHR) of 1.02 (95% confidence interval [CI] 0.73-1.43, p = 0.91) for each 10-g-per-day increment. There was an association between offspring intake of gluten and a higher risk of type 1 diabetes, with an aHR of 1.46 (95% CI 1.06-2.01, p = 0.02) for each 10-g-per-day increment. Among the limitations are the likely imprecision in estimation of gluten intake and that we only had information regarding gluten intake at 2 time points in early life. CONCLUSIONS: Our results show that, while the mother's intake of gluten in pregnancy was not associated with type 1 diabetes, a higher intake of gluten by the child at an early age may give a higher risk of type 1 diabetes.

Assessing awareness of hypoglycemia in children and adolescents with type 1 diabetes: Evaluation of established questionnaires.

OBJECTIVE: To evaluate the use of two questionnaires assessing awareness of hypoglycemia, in a pediatric type 1 diabetes (T1D) population. METHODS: Prospective observational study with children (aged 9-18 years) and parents (for children aged 2-11 years) answering the Gold and Clarke questionnaires assessing awareness of hypoglycemia. Psychometric properties of the questionnaires were evaluated, and the most appropriate cut-off score to classify participants as having normal vs impaired awareness of hypoglycemia (IAH) was determined by ability to recognize subsequent hypoglycemia and hypoglycemia severity, documented in a 4-week blood glucose diary. Questionnaires were readministered at follow-up assessment approximately 1.5 years later. RESULTS: In total, 112 participants (51% male) with median (IQR) age 13.7 (11.1-15.8) years, T1D duration 4.7 (2.2-7.8) years, and HbA1c 62 (57-73) mmol/mol (7.8%) were included. Both questionnaires demonstrated acceptable psychometric properties. Using score ≥3 to classify IAH gave a prevalence of IAH of 41% (Gold) and 22% (Clarke). When classified using the Gold questionnaire, IAH participants had higher incidences of mild asymptomatic hypoglycemia, whereas with the Clarke questionnaire, they had higher incidences of clinically significant and severe hypoglycemia. Subgroup analyses confirmed these associations only in participants aged ≥9 years. Follow-up was completed in 90% of the participants, and a change of awareness status was observed in 22% to 36%. CONCLUSIONS: The Gold and Clarke questionnaires may be used to assess awareness of hypoglycemia in pediatric T1D in those ≥9 years of age, but the more detailed Clarke questionnaire has higher specificity and is superior in predicting risk of clinically significant hypoglycemia.

The DISABKIDS generic and diabetes-specific modules are valid but not directly comparable between Denmark, Sweden, and Norway.

BACKGROUND/OBJECTIVES: Government guidance promote benchmarking comparing quality of care including both clinical values and patient reported outcome measures in young persons with type 1 diabetes. The aim was to test if the Nordic DISABKIDS health-related quality of life (HrQoL) modules were construct valid and measurement comparable within the three Nordic countries. METHODS: Data from three DISABKIDS validation studies in Sweden, Denmark, and Norway were compared using Rasch and the graphical log-linear Rasch modeling. Monte Carlo methods were used to estimate reliability coefficient and target was defined as the point with the lowest SE of the mean. Self-report data were available from 99 Danish (8-18 years), 103 Norwegian (7-19 years), and 131 Swedish (8-18 years) young people. RESULTS: For the DISABKIDS higher scores on most subscales were noted in the Norwegian population. The Swedish sample had a significantly higher score on the "Diabetes treatment" subscale and scores closer to optimal target than the other countries. For each country, construct validity and sensitivity were acceptable when accounting for differential item function (DIF) and local dependency (LD). Less LD and DIF were found if only Denmark and Norway were included. The combined model was reliable; however, some differences were noted in the scale translations relating to the stem and response alternatives, which could explain the discrepancies. CONCLUSION: The Nordic versions of the DISABKIDS questionnaires measures valid and reliable HrQoL both within and between countries when adjusted for DIF and LD. Adjusting the Likert scales to the same respond categories may improve comparability.

Geographical variation in the incidence of type 1 diabetes in the Nordic countries: A study within NordicDiabKids.

BACKGROUND: The incidence of type 1 diabetes (T1D) is high in the Nordic countries with geographic differences between as well as within countries. OBJECTIVE: To describe the geographical distribution of the incidence of T1D among children in four Nordic countries, an area where the population is considered genetically similar. METHODS: Data on children 0 to 14 years of age and diagnosed with T1D 2006 to 2011 was collected from four Nordic national pediatric quality diabetes registries. Data included year of diagnosis (2006-2011), sex, and age at diagnosis. Figures for number of children at risk during 2006 to 2011-as well as total population, proportion with foreign background and size of populated areas of geographic regions-were collected from official statistics. RESULTS: The total incidence during the study period for all four countries was 35.7/100 000 person years but differed between the countries (range 18.2-44.1; P < .001). The incidence difference between the countries was most obvious in the highest age group, 10 to 14 years of age, whereas there was no difference in the youngest age group 0 to 5 years of age. Iceland had similar incidence in the entire country, whereas the other countries had areas with different incidence. Densely populated areas, such as major cities, had the lowest incidence. CONCLUSION: The incidence of T1D differed between the Nordic countries and also between the neighboring countries and generally decreased with population density. This indicates that environmental factors may contribute to the level of incidence of T1D.

International benchmarking in type 1 diabetes: Large difference in childhood HbA1c between eight high-income countries but similar rise during adolescence-A quality registry study.

OBJECTIVES: To identify differences and similarities in HbA1c levels and patterns regarding age and gender in eight high-income countries. SUBJECTS: 66 071 children and adolescents below18 years of age with type 1 diabetes for at least 3 months and at least one HbA1c measurement during the study period. METHODS: Pediatric Diabetes Quality Registry data from Austria, Denmark, England, Germany, Norway, Sweden, the United States, and Wales were collected between 2013 and 2014. HbA1c, gender, age, and duration were used in the analysis. RESULTS: Distribution of gender and age groups was similar in the eight participating countries. The mean HbA1c varied from 60 to 73 mmol/mol (7.6%-8.8%) between the countries. The increase in HbA1c between the youngest (0-9 years) to the oldest (15-17 years) age group was close to 8 mmol/mol (0.7%) in all countries (P < .001). Females had a 1 mmol/mol (0.1%) higher mean HbA1c than boys (P < .001) in seven out of eight countries. CONCLUSIONS: In spite of large differences in the mean HbA1c between countries, a remarkable similarity in the increase of HbA1c from childhood to adolescence was found.

Development and validation of a questionnaire to assess young patients' experiences with diabetes care and transition.

AIM: To describe the development and validation of a questionnaire in a national Norwegian population-based cohort study designed to assess the experiences of young people with type 1 diabetes who had made the transition from paediatric to adult diabetes care. METHODS: The questionnaire was developed by the authors based on literature searches, focus group interviews, discussions with experts and cognitive interviews. We included 776 individuals with type 1 diabetes who were last registered in the Norwegian Childhood Diabetes Registry between 2009 and 2012 and had been receiving adult health care for at least 2 years. The data quality was analysed, factor analysis was performed, and the internal reliability, test-retest reliability and construct validity were determined. RESULTS: The response rate was 321 patients (41.4%); 57.6% were female, and the average age at recruitment was 22.9 ± 1.2 years. Seven factors were identified. Satisfactory evidence was provided for the internal consistency, reliability and construct validity of the questionnaire. All scales met the criterion of Cronbach's alpha above 0.4. The test-retest correlations ranged from 0.64 to 0.92. CONCLUSION: The thorough validation of the questionnaire proved satisfactory and indicated that it may be of value for further studies measuring patients' experiences with diabetes care and transition.

Trends and cyclical variation in the incidence of childhood type 1 diabetes in 26 European centres in the 25 year period 1989-2013: a multicentre prospective registration study.

AIMS/HYPOTHESIS: Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6 years. METHODS: Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres (representing 22 countries) that have registered newly diagnosed individuals in geographically defined regions for up to 25 years during the period 1989-2013. Poisson regression was used to estimate rates of increase and test for cyclical patterns. Joinpoint regression software was used to fit segmented log-linear relationships to incidence trends. RESULTS: Significant increases in incidence were noted in all but two small centres, with a maximum rate of increase of 6.6% per annum in a Polish centre. Several centres in high-incidence countries showed reducing rates of increase in more recent years. Despite this, a pooled analysis across all centres revealed a 3.4% (95% CI 2.8%, 3.9%) per annum increase in incidence rate, although there was some suggestion of a reduced rate of increase in the 2004-2008 period. Rates of increase were similar in boys and girls in the 0- to 4-year-old age group (3.7% and 3.7% per annum, respectively) and in the 5- to 9-year-old age group (3.4% and 3.7% per annum, respectively), but were higher in boys than girls in the 10- to 14-year-old age group (3.3% and 2.6% per annum, respectively). Significant 4 year periodicity was detected in four centres, with three centres showing that the most recent peak in fitted rates occurred in 2012. CONCLUSIONS/INTERPRETATION: Despite reductions in the rate of increase in some high-risk countries, the pooled estimate across centres continues to show a 3.4% increase per annum in incidence rate, suggesting a doubling in incidence rate within approximately 20 years in Europe. Although four centres showed support for a cyclical pattern of incidence with a 4 year periodicity, no plausible explanation for this can be given.

Maternal microchimerism in cord blood and risk of childhood-onset type 1 diabetes.

BACKGROUND: Maternal microchimerism (MMc), the transmission of small quantities of maternal cells to the fetus, is relatively common and persistent. MMc has been detected with increased frequency in the circulation and pancreas of type 1 diabetes (T1D) patients. We investigated for the first time whether MMc levels at birth predict future T1D risk. We also tested whether cord blood MMc predicted MMc in samples taken at T1D diagnosis. METHODS: Participants in the Norwegian Mother and Child Cohort study were human leukocyte antigen (HLA) class II typed to determine non-inherited, non-shared maternal alleles (NIMA). Droplet digital (dd) polymerase chain reaction (PCR) assays specific for common HLA class II NIMA (HLADQB1*03:01, *04:02, and *06:02/03) were developed and validated. MMc was estimated as maternal DNA quantity in the fetal circulation, by NIMA specific ddPCR, measured in cord blood DNA from 71 children who later developed T1D and 126 controls within the cohort. RESULTS: We found detectable quantities of MMc in 34/71 future T1D cases (48%) and 53/126 controls (42%) (adjusted odds ratio [aOR] 1.27, 95% confidence interval (CI) 0.68-2.36), and no significant difference in ranks of MMc quantities between cases and controls (Mann-Whitney P = .46). There was a possible association in the NIMA HLA-DQB1*03:01 subgroup with later T1D (aOR 3.89, 95%CI 1.05-14.4). MMc in cord blood was not significantly associated with MMc at T1D diagnosis. CONCLUSIONS: Our findings did not support the hypothesis that the degree of MMc in cord blood predict T1D risk. The potential subgroup association with T1D risk should be replicated in a larger cohort.

Lack of Association Between Maternal or Neonatal Vitamin D Status and Risk of Childhood Type 1 Diabetes: A Scandinavian Case-Cohort Study.

Studies on vitamin D status during pregnancy and risk of type 1 diabetes mellitus (T1D) lack consistency and are limited by small sample sizes or single measures of 25-hydroxyvitamin D (25(OH)D). We investigated whether average maternal 25(OH)D plasma concentrations during pregnancy are associated with risk of childhood T1D. In a case-cohort design, we identified 459 children with T1D and a random sample (n = 1,561) from the Danish National Birth Cohort (n = 97,127) and Norwegian Mother and Child Cohort Study (n = 113,053). Participants were born between 1996 and 2009. The primary exposure was the estimated average 25(OH)D concentration, based on serial samples from the first trimester until delivery and on umbilical cord plasma. We estimated hazard ratios using weighted Cox regression adjusting for multiple confounders. The adjusted hazard ratio for T1D per 10-nmol/L increase in the estimated average 25(OH)D concentration was 1.00 (95% confidence interval: 0.90, 1.10). Results were consistent in both cohorts, in multiple sensitivity analyses, and when we analyzed mid-pregnancy or cord blood separately. In conclusion, our large study demonstrated that normal variation in maternal or neonatal 25(OH)D is unlikely to have a clinically important effect on risk of childhood T1D.

Parental Smoking and Risk of Childhood-onset Type 1 Diabetes.

BACKGROUND: A few prospective studies suggest an association between maternal smoking during pregnancy and lower risk of type 1 diabetes. However, the role of unmeasured confounding and misclassification remains unclear. METHODS: We comprehensively evaluated whether maternal smoking in pregnancy predicts lower risk of childhood-onset type 1 diabetes in two Scandinavian pregnancy cohorts (185,076 children; 689 cases) and a Norwegian register-based cohort (434,627 children; 692 cases). We measured cord blood cotinine as an objective marker of nicotine exposure during late pregnancy in 154 cases and 476 controls. We also examined paternal smoking during pregnancy, in addition to environmental tobacco smoke exposure the first 6 months of life, to clarify the role of characteristics of smokers in general. RESULTS: In the pregnancy cohorts, maternal smoking beyond gestational week 12 was inversely associated with type 1 diabetes, pooled adjusted hazard ratio (aHR) 0.66 (95% CI = 0.51, 0.85). Similarly, in the Norwegian register-based cohort, children of mothers who still smoked at the end of pregnancy had lower risk of type 1 diabetes, aHR 0.65 (95% CI = 0.47, 0.89). Cord blood cotinine ≥30 nmol/L was also associated with reduced risk of type 1 diabetes, adjusted odds ratio 0.42 (95% CI = 0.17, 1.0). We observed no associations of paternal smoking during pregnancy, or environmental tobacco smoke exposure, with childhood-onset type 1 diabetes. CONCLUSION: Maternal sustained smoking during pregnancy is associated with lower risk of type 1 diabetes in children. This sheds new light on the potential intrauterine environmental origins of the disease.

A randomized comparison of three data collection models for the measurement of parent experiences with diabetes outpatient care.

BACKGROUND: The objective of this study was to compare three data collection methods for the measurement of parent experiences with hospital outpatient care for child and adolescent diabetes, based on a randomised national trial in Norway involving both pen-and-paper and electronic response options. METHODS: The sample frame was patients registered in the Norwegian Childhood Diabetes Registry. Parents of patients were randomised into the following groups (n = 2606): group A, who were posted questionnaires with only a pen-and-paper response option (n = 859); group B, who were posted questionnaires with both an electronic and a pen-and-paper response option (n = 886); and group C, who were posted questionnaires with only an electronic response option (n = 861). The three groups were compared on response rate, background variables about respondents, main study results and survey costs. Statistical analysis included logistic regression to test group differences in response probabilities and multilevel linear regression to test differences in parent experiences. RESULTS: The response rate was 61.8% for group A, 62.4% for group B and 41.6% for group C. The probability of answering was significantly higher for group A (OR = 2.3, p < 0.001) and B (OR = 2.3, p < 0.001) compared to group C. Respondent age, gender, education, living with the child and the degree of participation in consultations did not differ significantly between the three groups. Group differences in parent-reported experiences were small, varying from 1.0 (equipment and doctor contact) to 2.4 (outcome), on a scale from 0 to 100. Only one of 18 group differences was significant: the mixed group had significantly higher score than the electronic group on the organization scale (p < 0.05). The total cost of the electronic model was less than half the cost of the other models, and cost per response was 5.1 euros for the electronic model compared to 8.2 euros for group A and 7.6 euros for group B. CONCLUSIONS: The models with pen-and paper questionnaire included had more than 20% higher response rate than the model with an electronic-only response option. Background variables and parent-reported experiences were similar between the three groups, and the electronic model was the more cost-effective model.

Parent experiences of diabetes care questionnaire (PEQ-DC): reliability and validity following a national survey in Norway.

BACKGROUND: Patient experiences are acknowledged as an important aspect of health care quality but no validated instruments have been identified for the measurement of either parent or patient experiences with outpatient paediatric diabetes care. The aim of the current study was to assess the psychometric properties of a new instrument developed to measure parent experiences of paediatric diabetes care at hospital outpatient departments in Norway. METHODS: The development of the questionnaire was based on a literature review of existing questionnaires, qualitative interviews with both parents and children/adolescents, expert-group consultations, pretesting of the questionnaire and a pilot study. The national pilot study included parents of 2606 children/adolescents aged 0-17 years with Type 1 Diabetes registered in The Norwegian Childhood Diabetes Registry, a nationwide, population-based registry. Levels of missing data, ceiling effects, factor structure, internal consistency, item discriminant validity and construct validity were assessed. RESULTS: A total of 2606 patients were included in the survey, but 80 were excluded due to incorrect addresses. 1399 (55%) parents responded to the questionnaire. Low levels of missing or "not applicable" responses were found for 31 of the 35 items (< 10%), and 27 of 35 items were below the ceiling-effect criterion. Psychometric testing and theoretical considerations identified six scales: Consultation (six items), organisation (five items), equipment (three items), nurse contact (four items), doctor contact (four items) and outcome (five items). All six scales met the 0.7 criterion for Cronbach's alpha (range: 0.71-0.90). As expected, each item had a higher correlation with its hypothesised scale than with any of the other five scales. The construct validity of the Parent Experiences of Diabetes Care Questionnaire (PEQ-DC) was supported by 17 out of 18 associations with variables expected to be related to parent experiences. CONCLUSION: The psychometric testing of the PEQ-DC showed good evidence for data quality, internal consistency and construct validity. The instrument includes important aspects of diabetes care at paediatric outpatient departments from the perspective of the parent. The content validity of the PEQ-DC was secured by a rigorous development process, and the instrument was tested following a national survey in Norway, securing generalisability across Norway.