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.