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Objective: To examine the prevalence, time trends, and risk factors of diabetic retinopathy (DR) among youth with type 1 diabetes (T1D) from 11 countries (Australia, Austria, Denmark, England, Germany, Italy, Luxemburg, Netherlands, Slovenia, United States, and Wales). Subjects and Methods: Data on individuals aged 10–21 years with T1D for >1 year during the period 2000–2020 were analyzed. We used a cross‐sectional design using the most recent year of visit to investigate the time trend. For datasets with longitudinal data, we aggregated the variables per participant and observational year, using data of the most recent year to take the longest observation period into account. DR screening was performed through quality assured national screening programs. Multiple logistic regression models adjusted for the year of the eye examination, age, gender, minority status, and duration of T1D were used to evaluate clinical characteristics and the risk of DR. Results: Data from 156,090 individuals (47.1% female, median age 15.7 years, median duration of diabetes 5.2 years) were included. Overall, the unadjusted prevalence of any DR was 5.8%, varying from 0.0% (0/276) to 16.2% between countries. The probability of DR increased with longer disease duration (aORper‐1‐year‐increase = 1.04, 95% CI: 1.03–1.04, p < 0.0001), and decreased over time (aORper‐1‐year‐increase = 0.99, 95% CI: 0.98–1.00, p = 0.0093). Evaluating possible modifiable risk factors in the exploratory analysis, the probability of DR increased with higher HbA1c (aORper‐1‐mmol/mol‐increase‐in‐HbA1c = 1.03, 95% CI: 1.03–1.03, p < 0.0001) and was higher among individuals with hypertension (aOR = 1.24, 95% CI: 1.11–1.38, p < 0.0001) and smokers (aOR = 1.30, 95% CI: 1.17–1.44, p < 0.0001). Conclusions: The prevalence of DR in this large cohort of youth with T1D varied among countries, increased with diabetes duration, decreased over time, and was associated with higher HbA1c, hypertension, and smoking. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To analyze whether the coronavirus disease 2019 (COVID-19) pandemic increased the number of cases or impacted seasonality of new-onset type 1 diabetes (T1D) in large pediatric diabetes centers globally. RESEARCH DESIGN AND METHODS: We analyzed data on 17,280 cases of T1D diagnosed during 2018–2021 from 92 worldwide centers participating in the SWEET registry using hierarchic linear regression models. RESULTS: The average number of new-onset T1D cases per center adjusted for the total number of patients treated at the center per year and stratified by age-groups increased from 11.2 (95% CI 10.1–12.2) in 2018 to 21.7 (20.6–22.8) in 2021 for the youngest age-group, <6 years; from 13.1 (12.2–14.0) in 2018 to 26.7 (25.7–27.7) in 2021 for children ages 6 to <12 years; and from 12.2 (11.5–12.9) to 24.7 (24.0–25.5) for adolescents ages 12–18 years (all P < 0.001). These increases remained within the expected increase with the 95% CI of the regression line. However, in Europe and North America following the lockdown early in 2020, the typical seasonality of more cases during winter season was delayed, with a peak during the summer and autumn months. While the seasonal pattern in Europe returned to prepandemic times in 2021, this was not the case in North America. Compared with 2018–2019 (HbA1c 7.7%), higher average HbA1c levels (2020, 8.1%; 2021, 8.6%; P < 0.001) were present within the first year of T1D during the pandemic. CONCLUSIONS: The slope of the rise in pediatric new-onset T1D in SWEET centers remained unchanged during the COVID-19 pandemic, but a change in the seasonality at onset became apparent. [ABSTRACT FROM AUTHOR]

Background Not much is known about the effects of glycemic variability (GV) during the pre- and periconception period on pregnancy/perinatal complications. GV could potentially contribute to identification of high-risk pregnancies in women with type 1 diabetes. Methods An explorative retrospective cohort study was conducted between January 2014 and May 2019. Glucose data were retrieved from electronic patient charts. Pre-/periconceptional GV and GV during all three trimesters was expressed as mean glucose, standard deviation (SD), Coefficient of Variation (CV), High Blood Glucose Index (HBGI), Low Blood Glucose Index (LBGI) and Average Daily Risk Range (ADRR). Maternal and neonatal complications were summarized using a composite total complication score. Binary logistic regression analyses were conducted to assess associations between the GV measures and a total complication score>3, a maternal complication score>1 and a neonatal complication score>1. Results Of 63 eligible women, 29 women (38 pregnancies) were included. Women in the group with a total complication score>3 had a significantly higher ADRR at conception (OR 1.1, CI 1.0–1.2, p=0.048). No statistically significant correlations between complication score and any other GV metric besides the ADRR were found. Although not significant, in the group with a complication score>3, odds ratios>1 were found for SD in trimester 1 (OR 1.6, CI 0.6–4.5, p=0.357) and trimester 2 (OR 1.8, CI 0.5–6.2, p=0.376). Conclusions Presence of a positive association between GV and pregnancy and perinatal complications depends on which pregnancy period is assessed and the GV metrics that are used. [ABSTRACT FROM AUTHOR]

Aim To assess 1) the prevalence of children and adolescents with type 1 diabetes (T1D) changing from low-risk into borderline-high-risk lipid levels or from borderline-high-risk into high-risk lipid levels ('lose track of lipids') and 2) the power of a risk score including the determinants HbA1c, body mass index (BMI), gender, age, diabetes duration and ethnicity in predicting which patients lose track of lipids. Methods 651 children and adolescents with T1D were included in this longitudinal retrospective cohort study. Lipid dynamics and the impact of the risk score on losing track of lipids were evaluated. Kaplan-Meier analysis was used to estimate screening intervals. Results 31–43% percent of the patients had lost track of one or more lipids at the next lipid measurement. This happened more frequently in patients with a low-risk lipid level at start. Depending on the lipid parameter, 5% of patients with low-risk lipid levels lost track of lipids after 13–23 months. The risk score based on concomitant information on the determinants was moderately able to predict which patients would lose track of lipids on the short term. Conclusions A considerable number of children and adolescents with T1D loses track of lipids and does so within a 2-year screening interval. The predictive power of a risk score including age, BMI, gender, HbA1c, diabetes duration and ethnicity is only moderate. Future research should focus on another approach to the determinants used in this study or other determinants predictive of losing track of lipids on the short term. [ABSTRACT FROM AUTHOR]

Objective: To establish whether diabetic ketoacidosis (DKA) or HbA1c at onset is associated with year‐three HbA1c in children with type 1 diabetes (T1D). Methods: Children with T1D from the SWEET registry, diagnosed <18 years, with documented clinical presentation, HbA1c at onset and follow‐up were included. Participants were categorized according to T1D onset: (a) DKA (DKA with coma, DKA without coma, no DKA); (b) HbA1c at onset (low [<10%], medium [10 to <12%], high [≥12%]). To adjust for demographics, linear regression was applied with interaction terms for DKA and HbA1c at onset groups (adjusted means with 95% CI). Association between year‐three HbA1c and both HbA1c and presentation at onset was analyzed (Vuong test). Results: Among 1420 children (54% males; median age at onset 9.1 years [Q1;Q3: 5.8;12.2]), 6% of children experienced DKA with coma, 37% DKA without coma, and 57% no DKA. Year‐three HbA1c was lower in the low compared to high HbA1c at onset group, both in the DKA without coma (7.1% [6.8;7.4] vs 7.6% [7.5;7.8], P =.03) and in the no DKA group (7.4% [7.2;7.5] vs 7.8% [7.6;7.9], P =.01), without differences between low and medium HbA1c at onset groups. Year‐three HbA1c did not differ among HbA1c at onset groups in the DKA with coma group. HbA1c at onset as an explanatory variable was more closely associated with year‐three HbA1c compared to presentation at onset groups (P =.02). Conclusions: Year‐three HbA1c is more closely related to HbA1c than to DKA at onset; earlier hyperglycemia detection might be crucial to improving year‐three HbA1c. [ABSTRACT FROM AUTHOR]

Background: Early identification of children and adolescents with type 1 diabetes at high risk for development of complications is important, as early intervention may prevent further deterioration. Here we investigate the applicability of assessing skin advanced glycation end products (sAGEs) by skin autofluorescence (SAF) as a potential surrogate risk marker. Methods: This study included a cross-sectional analysis of SAF in 77 patients with type 1 diabetes mellitus and 118 healthy controls across age categories (11-12, 13-14, 15-16, and 17-19 years old). In patients, the impact of current and historical glycated hemoglobin (HbA1c) values, age, and duration of diabetes on SAF was studied in a retrospective cohort study and analyzed with multivariable analyses. Results: SAF was significantly and similarly higher in patients when compared with controls across all age categories (P ≤ 0.009). For patients, age, duration of diabetes, and current and historical HbA1c were associated with P SAF in univariate analysis. Multivariate analysis showed no association between HbA1c and SAF. A subgroup of patients with a HbA1c-within-target (≤7.5 %/59 mmol/mol) were observed to have high SAF. Conclusion: Children and adolescents with type 1 diabetes show higher SAF than controls. The presumed correlation of high HbA1c with high SAF does not exist in all patients. Thus, use of this non-invasive measure may provide a surrogate marker for diabetic complications, additional to HbA1c. [ABSTRACT FROM AUTHOR]

Aim This study described the incidence and prevalence of type 1 diabetes in children in the Netherlands in 2010-2011 and to compare these results with earlier studies. Methods This was a retrospective nationwide cohort study of Dutch children aged 14 years or younger. Patients were identified using health insurance reimbursement registries for hospital care and invoices for insulin. In the Netherlands, all children with diabetes are treated by hospital-based paediatricians and health care for all Dutch citizens is covered by law. Results The incidence of type 1 diabetes almost doubled between 1978-1980 and 2010-2011, from 11.1 to 21.4 per 100 000. In the youngest age group, who were under 5 years, the incidence rate doubled between 1996 and 1999 and remained stable after that. There were no relevant incidence differences between the sexes. The overall prevalence of type 1 diabetes in the Netherlands during 2009-2011 was 143.6 (95% confidence interval 141.1-146.2) per 100 000 children and was similar for boys and girls. Conclusion The incidence of type 1 diabetes in children in the Netherlands almost doubled between 1978-1980 and 2010-2011, but the incidence in children under 5 years appeared to stabilise between 1996 and 1999. There were no statistical differences between the sexes. [ABSTRACT FROM AUTHOR]

To determine whether theCLCAgene family of calcium-activated chloride channels is a modulator of the basic defect of cystic fibrosis (CF), an association study was performed with polymorphic microsatellite markers covering a 40-Mbp region spanning theCLCAgene locus on human chromosome 1p in CF patients displaying CF transmembrane conductance regulator (CFTR)-independent residual chloride conductance in gastrointestinal epithelia. Statistically significant association of the electrophysiological phenotype with the allele distribution of markers 5’ of and within theCLCAlocus was observed. Transmission disequilibrium and the significance of the association decreased within the locus fromhCLCA2towardshCLCA4. Expression of hCLCA1 and hCLCA4 in human rectal mucosa was proven by microarray analysis. TheCLCAgene region was identified to encode mediators of DIDS-sensitive anion conductance in the human gastrointestinal tract that modulate the CF basic defect. [ABSTRACT FROM AUTHOR]