Martina Persson

OBJECTIVE: Autoantibodies have long been recognized as biomarkers of islet autoimmunity in type 1 diabetes, but their role in the pathogenesis is not fully understood. The aim of this study was to analyze clinical and hereditary characteristics of children presenting with and without autoantibodies at type 1 diabetes diagnosis. RESEARCH DESIGN AND METHODS: Data were collected from children (<18 years) at the time of diabetes diagnosis as part of Sweden's national Better Diabetes Diagnosis study. Participants were categorized based on the presence or absence of autoantibodies. Variables compared were age at diagnosis, sex, HbA1c, diabetic ketoacidosis (DKA), parental heredity of type 1 and type 2 diabetes, level of C-peptide, BMI SD score (SDS), and HLA genotype. We used t tests, χ2 tests, and logistic regression for comparisons. RESULTS: Of the 2,753, children, 169 (6.1%) were autoantibody-negative at type 1 diabetes diagnosis. Of those, 66% were boys compared with 56% of children with autoantibodies (P = 0.009). Also, children without autoantibodies had higher HbA1c at diagnosis (11.3 vs. 10.8% [100 vs. 94 mmol/mol], P = 0.003), were less likely to present with DKA (9 vs. 15%, P = 0.039), and more likely to have parental history of type 2 diabetes (8 vs. 2%, P < 0.001) compared with children with autoantibodies. We did not observe differences for age at diagnosis, C-peptide levels, BMI-SDS, or HLA genotype between the children with and without autoantibodies. CONCLUSIONS: We identified differences in clinical characteristics when comparing children with and without autoantibodies at type 1 diabetes diagnosis, highlighting potential heterogeneity in the disease's pathogenesis across subgroups.

Objective: To estimate the effect on healthcare resource use after introducing the World Health Organization diagnostic criteria (WHO‐2013) for gestational diabetes mellitus (GDM) compared to former criteria in Sweden (SWE‐GDM).Design: A cost‐analysis alongside the Changing Diagnostic Criteria for Gestational Diabetes (CDC4G) randomised controlled trial.Setting: Sweden, with risk‐factor based screening for GDM.Population: 47 080 pregnant women and their infants.Methods: A register‐based cost‐analysis from a healthcare perspective alongside a stepped‐wedge cluster RCT of switching from SWE‐GDM to WHO‐2013 criteria in 2018. Analyses were made on the population level and repeated in the subgroup affected by the intervention, that is, those with plasma glucose values between SWE‐GDM and WHO‐2013 criteria. Sensitivity analysis by bootstrapping was performed.Main Outcome Measures: Estimated costs for obstetric surveillance (including GDM‐management), delivery and neonatal healthcare until 28 days postpartum.Results: On a population level, the WHO‐2013 criteria were associated with increased costs of obstetric surveillance (adjusted mean [bootstrap confidence interval]) €94.0 [24.5–169.1], delivery care €20.4 [−33.5 to 75.4] and neonatal care €331.0 [75.1–589.0] per pregnancy, and in the affected subgroup €606.9 [377.7–872.4], €348.5 [126.0–542.0] and €129.3 [−559.0 to 980.9] respectively.Conclusions: Implementation of the WHO‐2013 criteria in Sweden was associated with increased costs for obstetric surveillance and delivery on a population level, driven by the affected subgroup. The increased costs for neonatal care were associated with large uncertainty. A detailed understanding of the changes in resource use can guide decisions to mitigate cost increases.

Studies on pain in preterm infants have usually been confined to observations of painful procedures, and information from extremely preterm infants is limited. Using registry data from a Swedish nationwide cohort, this study explored the epidemiology of pain in very preterm infants, its causes, assessments, and treatment strategies. We included liveborn infants <32 weeks' gestational age (GA) discharged between January 2020 and June 2024. Proportions of infants exposed to potentially painful procedures, experiencing pain, assessed with pain scales, and receiving pharmacological treatment were calculated by each postnatal day. Among 3686 infants (mean birthweight 1176 g, GA 28.2 weeks), 11.6% had a painful condition and 84.1% were exposed to at least 1 potentially painful procedure. In total, 74.6% experienced pain, corresponding to 28,137/185,008 (15.2%) days of neonatal care. For every 2-week increase in GA, significantly lower proportions of infants experienced pain. In infants <28 weeks of GA, proportions with reported pain were approximately half the rate of painful procedures, while in infants born at 28 to 31 weeks, reported pain closely matched exposure to painful procedures. Pain scales were used in 75.0% of the infants. Pharmacological pain treatment was administered to 81.7% of infants, primarily topically or orally. Among infants with pain, proportions treated intravenously were larger at higher GAs. Despite effective analgesia/anesthesia, many very preterm infants experience pain. Visualizing pain epidemiology, procedures, conditions, and treatment by postnatal and gestational age may guide clinical management and generate research hypotheses to reduce short- and long-term adverse effects.

OBJECTIVE: To compare the prevalence of parental diabetes between children with and without type 1 diabetes (T1D), and to compare clinical characteristics at diagnosis of T1D in children with, versus without, a family history of diabetes. RESEARCH DESIGN AND METHODS: Parental diabetes among children with T1D was compared with a general population cohort. Clinical characteristics were compared by family history of diabetes in parents and grandparents of 3,603 children with T1D using relative risk (RR) and ANOVA. RESULTS: Children with T1D more often had parents with type 2 diabetes (T2D) (RR 1.88; P < 0.001) than did children without diabetes. Children with T1D and a family history of T2D were more likely to be overweight or obese (P = 0.002). CONCLUSIONS: A family history of T2D and being overweight may contribute to increased risk of T1D.

Background: The World Health Organisation (WHO) 2013 diagnostic criteria for gestational diabetes mellitus (GDM) has been criticised due to the limited evidence of benefits on pregnancy outcomes in different populations when switching from previously higher glycemic thresholds to the lower WHO-2013 diagnostic criteria. The aim of this study was to determine whether the switch from previous Swedish (SWE-GDM) to the WHO-2013 GDM criteria in Sweden following risk factor-based screening improves pregnancy outcomes. Methods and findings: A stepped wedge cluster randomised trial was performed between January 1 and December 31, 2018 in 11 clusters (17 delivery units) across Sweden, including all pregnancies under care and excluding preexisting diabetes, gastric bypass surgery, or multifetal pregnancies from the analysis. After implementation of uniform clinical and laboratory guidelines, a number of clusters were randomised to intervention (switch to WHO-2013 GDM criteria) each month from February to November 2018. The primary outcome was large for gestational age (LGA, defined as birth weight >90th percentile). Other secondary and prespecified outcomes included maternal and neonatal birth complications. Primary analysis was by modified intention to treat (mITT), excluding 3 clusters that were randomised before study start but were unable to implement the intervention. Prespecified subgroup analysis was undertaken among those discordant for the definition of GDM. Multilevel mixed regression models were used to compare outcome LGA between WHO-2013 and SWE-GDM groups adjusted for clusters, time periods, and potential confounders. Multiple imputation was used for missing potential confounding variables. In the mITT analysis, 47 080 pregnancies were included with 6 882 (14.6%) oral glucose tolerance tests (OGTTs) performed. The GDM prevalence increased from 595/22 797 (2.6%) to 1 591/24 283 (6.6%) after the intervention. In the mITT population, the switch was associated with no change in primary outcome LGA (2 790/24 209 (11.5%) versus 2 584/22 707 (11.4%)) producing an adjusted risk ratio (aRR) of 0.97 (95% confidence interval 0.91 to 1.02, p = 0.26). In the subgroup, the prevalence of LGA was 273/956 (28.8%) before and 278/1 239 (22.5%) after the switch, aRR 0.87 (95% CI 0.75 to 1.01, p = 0.076). No serious events were reported. Potential limitations of this trial are mainly due to the trial design, including failure to adhere to guidelines within and between the clusters and influences of unidentified temporal variations. Conclusions: In this study, implementing the WHO-2013 criteria in Sweden with risk factor-based screening did not significantly reduce LGA prevalence defined as birth weight >90th percentile, in the total population, or in the subgroup discordant for the definition of GDM. Future studies are needed to evaluate the effects of treating different glucose thresholds during pregnancy in different populations, with different screening strategies and clinical management guidelines, to optimise women’s and children’s health in the short and long term. Trial registration: The trial is registered with ISRCTN (41918550).

Aims/hypothesis: Children and adults born preterm have an increased risk of type 1 diabetes. However, there is limited information on risk patterns across the full range of gestational ages, especially after extremely preterm birth (23–27 weeks of gestation). We investigated the risk of type 1 diabetes in childhood and young adulthood across the full range of length of gestation at birth. Methods: Data were obtained from national registers in Finland, Norway and Sweden. In each country, information on study participants and gestational age was collected from the Medical Birth Registers, information on type 1 diabetes diagnoses was collected from the National Patient Registers, and information on education, emigration and death was collected from the respective national register sources. Individual-level data were linked using unique personal identity codes. The study population included all individuals born alive between 1987 and 2016 to mothers whose country of birth was the respective Nordic country. Individuals were followed until diagnosis of type 1 diabetes, death, emigration or end of follow-up (31 December 2016 in Finland, 31 December 2017 in Norway and Sweden). Gestational age was categorised as extremely preterm (23–27 completed weeks), very preterm (28–31 weeks), moderately preterm (32–33 weeks), late preterm (34–36 weeks), early term (37–38 weeks), full term (39–41 weeks; reference) and post term (42–45 weeks). HRs and 95% CIs from country-specific covariate-adjusted Cox regression models were combined in a meta-analysis using a common-effect inverse-variance model. Results: Among 5,501,276 individuals, 0.2% were born extremely preterm, 0.5% very preterm, 0.7% moderately preterm, 4.2% late preterm, 17.7% early term, 69.9% full term, and 6.7% post term. A type 1 diabetes diagnosis was recorded in 12,326 (0.8%), 6364 (0.5%) and 16,856 (0.7%) individuals at a median age of 8.2, 13.0 and 10.5 years in Finland, Norway and Sweden, respectively. Individuals born late preterm or early term had an increased risk of type 1 diabetes compared with their full-term-born peers (pooled, multiple confounder-adjusted HR 1.12, 95% CI 1.07, 1.18; and 1.15, 95% CI 1.11, 1.18, respectively). However, those born extremely preterm or very preterm had a decreased risk of type 1 diabetes (adjusted HR 0.63, 95% CI 0.45, 0.88; and 0.78, 95% CI 0.67, 0.92, respectively). These associations were similar across all three countries. Conclusions/interpretation: Individuals born late preterm and early term have an increased risk of type 1 diabetes while individuals born extremely preterm or very preterm have a decreased risk of type 1 diabetes compared with those born full term. Graphical

OBJECTIVE: To examine the prevalence and predictive factors for celiac disease (CD) after a diagnosis of type 1 diabetes (T1D) in children and adolescents, to improve the current screening guidelines. RESEARCH DESIGN AND METHODS: The association between sex, age at T1D diagnosis, HLA, and diabetes autoantibodies, and a diagnosis of CD was examined in 5,295 children with T1D from the Better Diabetes Diagnosis study in Sweden. RESULTS: The prevalence of biopsy-proven CD was 9.8%, of which 58.2% already had a CD diagnosis before or at T1D onset. Almost all, 95.9%, were diagnosed with CD within 5 years after the T1D diagnosis. Younger age at the T1D diagnosis and being homozygote for DQ2 increased the risk of CD after T1D, but neither sex nor diabetes-related autoantibodies were associated with the risk. CONCLUSIONS: Age at and time after diabetes diagnosis should be considered in screening guidelines for CD in children with T1D.