Danish Diabetes Birth Registry 2: a study protocol of a national prospective cohort study to monitor outcomes of pregnancies of women with pre-existing diabetes.

INTRODUCTION: Despite technological developments and intensified care, pregnancies in women with pre-existing diabetes are still considered high-risk pregnancies. The rate of adverse outcomes in pregnancies affected by diabetes in Denmark is currently unknown, and there is a limited understanding of mechanisms contributing to this elevated risk. To address these gaps, the Danish Diabetes Birth Registry 2 (DDBR2) was established. The aims of this registry are to evaluate maternal and fetal-neonatal outcomes based on 5 years cohort data, and to identify pathophysiology and risk factors associated with short-term and long-term outcomes of pregnancies in women with pre-existing diabetes. METHODS AND ANALYSIS: The DDBR2 registry is a nationwide 5-year prospective cohort with an inclusion period from February 2023 to February 2028 of pregnancies in women with all types of pre-existing diabetes and includes registry, clinical and questionnaire data and biological samples of mother-partner-child trios. Eligible families (parents age ≥18 years and sufficient proficiency in Danish or English) can participate by either (1) basic level data obtained from medical records (mother and child) and questionnaires (partner) or (2) basic level data and additional data which includes questionnaires (mother and partner) and blood samples (all). The primary maternal outcome is Hemoglobin A1c (HbA1c) levels at the end of pregnancy and the primary offspring endpoint is the birth weight SD score. The DDBR2 registry will be complemented by genetic, epigenetic and metabolomic data as well as a biobank for future research, and the cohort will be followed through data from national databases to illuminate possible mechanisms that link maternal diabetes and other parental factors to a possible increased risk of adverse long-term child outcomes. ETHICS AND DISSEMINATION: Approval from the Ethical Committee is obtained (S-20220039). Findings will be sought published in international scientific journals and shared among the participating hospitals and policymakers. TRIAL REGISTRATION NUMBER: NCT05678543.

Associations between disordered eating behaviors and HbA1c in young people with type 1 diabetes: a systematic review and meta-analysis.

BACKGROUND: In type 1 diabetes, disordered eating behaviors (DEBs) can adversely impact HbA1c. Diabetes-adapted DEB questionnaires assess intentional insulin omission, whereas generic questionnaires do not. Given the number of studies describing DEB-HbA1c associations published over the past decade, an updated systematic review is warranted. OBJECTIVE: The study aimed to examine the associations between disordered eating behaviors (DEBs) assessed by generic and diabetes-adapted questionnaires (and subscales) and HbA1c among young people (<29 years) with type 1 diabetes. METHODS: A systematic search was conducted in PubMed, Embase, PsycInfo, and CINAHL databases. Observational studies examining associations between DEB as assessed by questionnaires and HbA1c were included. Publication information, DEB and HbA1c characteristics, and DEB-HbA1c associations were extracted. Hedges' g was calculated for mean HbA1c differences between groups with and without DEB. RESULTS: The systematic search yielded 733 reports, of which 39 reports representing 35 unique studies met the inclusion criteria. Nineteen studies assessing DEB by diabetes-adapted questionnaires (n=5,795) and seven using generic questionnaires (n=2,162) provided data for meta-analysis. For diabetes-adapted questionnaires, DEB was associated with higher HbA1c (g=0.62 CI=0.52; 0.73) with a similar effect size when restricted to validated questionnaires (g=0.61; CI=0.50; 0.73). DEB was not associated with HbA1c for generic questionnaires (g=0.19; CI=-0.17; 0.55), but significantly associated with higher HbA1c for validated generic questionnaires (g=0.32; 95% CI=0.16-0.48). Participant and HbA1c collection characteristics were often inadequately described. CONCLUSION: Diabetes-adapted DEB questionnaires should be used in youth with type 1 diabetes because they capture intentional insulin omission and are more strongly associated with HbA1c than generic DEB questionnaires.

Psychiatric Morbidity in Women With Previous Gestational Diabetes Mellitus: A Nationwide Register-Based Cohort Study.

OBJECTIVE: To investigate associations between previous gestational diabetes mellitus (GDM) and incident psychiatric morbidity, and to explore the role of subsequent diabetes development in psychiatric morbidity risk. RESEARCH DESIGN AND METHODS: A nationwide register-based cohort study including all women delivering in Denmark from 1997 to 2018 was conducted. GDM exposure was based on diagnosis code, whereas psychiatric morbidity outcome was based on diagnosis code and psychopharmacological medication use. Multiple Cox regression and mediation analyses were performed. RESULTS: In a study population of 660,017 women, previous GDM was associated with increased risk of depression based on diagnosis code and/or medication use (adjusted hazard ratio [aHR] 1.22 [95% CI 1.18-1.27]), any psychiatric diagnosis (aHR 1.20 [95% CI 1.13-1.27]), and any psychopharmacological medication use (aHR 1.21 [95% CI 1.17-1.25]). Moreover, risk of depressive and anxiety disorders, as well as antidepressant and antipsychotic medication use, was increased, with aHRs ranging from 1.14 (95% CI 1.05-1.25) to 1.32 (95% CI 1.22-1.42). No associations were found regarding substance use disorders, psychotic disorders, bipolar disorders, postpartum psychiatric disease, or anxiolytic medication use. Psychiatric morbidity risk was higher in women with versus without subsequent diabetes development. However, GDM history affected risk estimates only in women without subsequent diabetes. Subsequent diabetes mediated 35-42% of the associations between GDM and psychiatric morbidity. CONCLUSIONS: GDM was associated with increased psychiatric morbidity risk. Subsequent diabetes development played a significant role in future psychiatric morbidity risk after GDM, although it only partly explained the association.

A Systematic Review of Instruments Measuring the Division of Care Responsibilities between Children with Type 1 Diabetes and their Parents.

BACKGROUND: The division of care responsibilities between parents and children with type 1 diabetes, and an optimal transfer of responsibilities from parent to child over time are assumed to be key for optimal diabetes outcomes during childhood and adolescence. However, an overview of instruments assessing this division as well as their psychometric qualities is currently lacking. OBJECTIVE: The study aims to 1) identify all existing instruments, 2) evaluate their psychometric properties, and 3) provide an overview of scoring methods. METHODS: Pubmed and PsycINFO were searched using a priori-defined search string. Peerreviewed studies in English using an instrument assessing the division of diabetes care responsibilities between children (6-18 years) and parents were included. In total, 84 of 725 articles qualified, covering 62 unique samples. RESULTS: Thirteen questionnaires were identified. The Diabetes Family Responsibility Questionnaire (DFRQ) was most frequently used across studies. Instructions, content and number of tasks, response options, and scoring methods varied across questionnaires. Recent studies often adapted questionnaires, contributing to the heterogeneity across measures. Overall, reporting and quality of psychometric properties was suboptimal. CONCLUSION: The division of diabetes care responsibilities can be operationalized with various instruments, each having its strengths and weaknesses but all with limited psychometric support. To measure the division of diabetes care responsibilities more adequately, an updated version of the popular DFRQ or a new scale needs to be developed and evaluated.

Long-Term Metabolic Outcomes after Gestational Diabetes Mellitus (GDM): Results from the Odense GDM Follow-Up Study (OGFUS).

Aims: To compare metabolic profiles and the long-term risk of metabolic dysfunction between women with previous gestational diabetes mellitus (pGDM) and women without pGDM (non-GDM) matched on age, prepregnancy body mass index (BMI), and parity. Methods: In total, 128 women with pGDM (median follow-up: 7.8 years) and 70 non-GDM controls (median follow-up: 10.0 years) completed a 2 h oral glucose tolerance test (OGTT) with assessment of glucose, C-peptide, insulin, and other metabolic measures. Additionally, anthropometrics, fat mass, and blood pressure were assessed and indices of insulin sensitivity and beta cell function were calculated. Results: The prevalence of type 2 diabetes mellitus (T2DM) was significantly higher in the pGDM group compared to the non-GDM group (26% vs. 0%). For women with pGDM, the prevalence of prediabetes (38%) and the metabolic syndrome (MetS) (59%) were approximately 3-fold higher than in non-GDM women (p's < 0.001). Both insulin sensitivity and beta cell function were significantly reduced in pGDM women compared to non-GDM women. Conclusion: Despite similar BMI, women with pGDM had a substantially higher risk of developing T2DM, prediabetes, and the MetS compared to controls. Both beta cell dysfunction and reduced insulin sensitivity seem to contribute to this increased risk.

Hypoglycaemia and diabetes-specific quality of life in adolescents with type 1 diabetes.

AIMS: To examine whether frequency, perceived severity and fear of hypoglycaemia are independently associated with diabetes-specific quality of life in adolescents with type 1 diabetes. METHODS: Cross-sectional self-reported data on demographics, frequency and perceived severity of both self-treated and severe hypoglycaemia, fear of hypoglycaemia (Hypoglycaemia Fear Survey-Child version) and diabetes-specific quality of life (Pediatric Quality of Life Diabetes Module; PedsQL-DM) were obtained from the project 'Whose diabetes is it anyway?'. Hierarchical regression analyses were performed for the total scale and recommended summary scores of the PedsQL-DM as dependent variables; independent variables were entered in the following steps: (1) age, gender and HbA1c , (2) frequency of hypoglycaemia, (3) perceived severity of hypoglycaemia and (4) fear of hypoglycaemia. RESULTS: Adolescents (12-18 years; n = 96) completed questionnaires. In the first three steps, female gender (p < 0.05), higher HbA1c (p < 0.05), higher frequency of severe hypoglycaemia (p < 0.05) and higher perceived severity of severe (p < 0.05) and self-treated hypoglycaemia (p < 0.001) were significantly associated with lower diabetes-specific quality of life (ß ranging from 0.20 to 0.35). However, in the final model only fear of hypoglycaemia was significantly associated with QoL (p < 0.001). Adolescents with greater fear reported lower diabetes-specific quality of life, with 52% explained variance. This pattern was observed across subdomains of diabetes-specific quality of life. CONCLUSIONS: Fear of hypoglycaemia was the only factor independently associated with diabetes-specific quality of life, whereas frequency and perceived severity of hypoglycaemia were not. These findings highlight the importance of awareness and assessment of fear of hypoglycaemia in clinical practice.

The division and transfer of care responsibilities in paediatric type 1 diabetes: A qualitative study on parental perspectives.

AIM: To determine which factors other than child age play a role in the division and transfer of diabetes care responsibilities between parents and children with type 1 diabetes. DESIGN: Qualitative focus group study. METHODS: Across four sites in the Netherlands, 18 parents (13 mothers) of children (9-14 years) with type 1 diabetes participated in four focus groups in 2015-2016, as part of the research project 'Whose diabetes is it anyway?'. Qualitative content analysis and the constant comparison method were used to analyse the data. RESULTS: According to parents, the transfer process included both direct and indirect tasks, had different levels (remembering, deciding, performing), was at times a difficult and stressful process, and showed large variation between families. A large number of child, parent and context factors were identified that affected the division and transfer of diabetes care responsibilities according to parents. Both positive and negative consequences of the transfer process were described for parental and child health, behaviour and well-being. Parental final evaluations of the division and transfer of diabetes care responsibilities appeared to be dependent on parenting values. CONCLUSION: How families divide and transfer diabetes care tasks appeared to be affected by a complex interplay of child, parent and context characteristics, which had an impact on several parent and child domains. IMPACT: Parents struggle with the right timing of transfer, which calls for more support from diabetes nurses. The identified factors can be used as input for integrating a more family-based approach into current age-based guidelines, to improve regular care.