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Sökning: WFRF:(Holl Reinhard W.)

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1.
  • Birkebaek, Niels H., et al. (författare)
  • Impact of the COVID-19 pandemic on long-term trends in the prevalence of diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes: an international multicentre study based on data from 13 national diabetes registries
  • 2022
  • Ingår i: The Lancet Diabetes and Endocrinology. - : ELSEVIER SCIENCE INC. - 2213-8587 .- 2213-8595. ; 10:11, s. 786-794
  • Tidskriftsartikel (refereegranskat)abstract
    • Background An increased prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes in children was observed in various diabetes centres worldwide during the COVID-19 pandemic. We aimed to evaluate trends in the prevalence of diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes before and during the COVID-19 pandemic, and to identify potential predictors of changes in diabetic ketoacidosis prevalence during the pandemic.Methods For this international multicentre study, we used data from 13 national diabetes registries (Australia, Austria, Czechia, Denmark, Germany, Italy, Luxembourg, New Zealand, Norway, Slovenia, Sweden, USA [Colorado], and Wales). The study population comprised 104 290 children and adolescents aged 6 months to younger than 18 years, who were diagnosed with type 1 diabetes between Jan 1, 2006, and Dec 31, 2021. The observed diabetic ketoacidosis prevalence in 2020 and 2021 was compared to predictions based on trends over the pre-pandemic years 2006-19. Associations between changes in diabetic ketoacidosis prevalence and the severity of the COVID-19 pandemic and containment measures were examined with excess all-cause mortality in the whole population and the Stringency Index from the Oxford COVID-19 Government Response Tracker.Findings 87 228 children and adolescents were diagnosed with type 1 diabetes between 2006 and 2019, 8209 were diagnosed in 2020, and 8853 were diagnosed in 2021. From 2006 to 2019, diabetic ketoacidosis at diagnosis of type 1 diabetes was present in 23 775 (27middot3%) of 87 228 individuals and the mean annual increase in the prevalence of diabetic ketoacidosis in the total cohort from 2006 to 2019 was 1middot6% (95% CI 1middot3 to 1middot9). The adjusted observed prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes was 39middot4% (95% CI 34middot0 to 45middot6) in 2020 and 38middot9% (33middot6 to 45middot0) in 2021, significantly higher than the predicted prevalence of 32middot5% (27middot8 to 37middot9) for 2020 and 33middot0% (28middot3 to 38middot5) for 2021 (p<0middot0001 for both years). The prevalence of diabetic ketoacidosis was associated with the pandemic containment measures, with an estimated risk ratio of 1middot037 (95% CI 1middot024 to 1middot051; p<0middot0001) per ten-unit increase in the Stringency Index for 2020 and 1middot028 (1middot009 to 1middot047; p=0middot0033) for 2021, but was not significantly associated with excess all-cause mortality.Interpretation During the COVID-19 pandemic, there was a marked exacerbation of the pre-existing increase in diabetic ketoacidosis prevalence at diagnosis of type 1 diabetes in children. This finding highlights the need for early and timely diagnosis of type 1 diabetes in children and adolescents.Funding German Federal Ministry for Education and Research, German Robert Koch Institute, German Diabetes Association, German Diabetes Foundation, Slovenian Research Agency, Welsh Government, Central Denmark Region, and Swedish Association of Local Authorities and Regions.Copyright (c) 2022 Elsevier Ltd. All rights reserved.
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2.
  • Dawed, Adem Y., et al. (författare)
  • Variation in the plasma membrane monoamine transporter (PMAT) (encoded by SLC29A4) and organic cation transporter 1 (OCT1) (encoded by SLC22A1) and gastrointestinal intolerance to metformin in type 2 diabetes : An IMI direct study
  • 2019
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 42:6, s. 1027-1033
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE Gastrointestinal adverse effects occur in 20–30% of patients with metformin-treated type 2 diabetes, leading to premature discontinuation in 5–10% of the cases. Gastrointestinal intolerance may reflect localized high concentrations of metformin in the gut. We hypothesized that reduced transport of metformin via the plasma membrane monoamine transporter (PMAT) and organic cation transporter 1 (OCT1) could increase the risk of severe gastrointestinal adverse effects. RESEARCH DESIGN AND METHODS The study included 286 severe metformin-intolerant and 1,128 metformin-tolerant individuals from the IMI DIRECT (Innovative Medicines Initiative: DIabetes REsearCh on patient straTification) consortium. We assessed the association of patient characteristics, concomitant medication, and the burden of mutations in the SLC29A4 and SLC22A1 genes on odds of intolerance. RESULTS Women (P < 0.001) and older people (P < 0.001) were more likely to develop metformin intolerance. Concomitant use of transporter-inhibiting drugs increased the odds of intolerance (odds ratio [OR] 1.72, P < 0.001). In an adjusted logistic regression model, the G allele at rs3889348 (SLC29A4) was associated with gastrointestinal intolerance (OR 1.34, P = 0.005). rs3889348 is the top cis-expression quantitative trait locus for SLC29A4 in gut tissue where carriers of the G allele had reduced expression. Homozygous carriers of the G allele treated with transporter-inhibiting drugs had more than three times higher odds of intolerance compared with carriers of no G allele and not treated with inhibiting drugs (OR 3.23, P < 0.001). Use of a genetic risk score derived from rs3889348 and SLC22A1 variants found that the odds of intolerance were more than twice as high in individuals who carry three or more risk alleles compared with those carrying none (OR 2.15, P = 0.01). CONCLUSIONS These results suggest that intestinal metformin transporters and concomitant medications play an important role in the gastrointestinal adverse effects of metformin.
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4.
  • Charalampopoulos, Dimitrios, et al. (författare)
  • Exploring Variation in Glycemic Control Across and Within Eight High-Income Countries: A Cross-sectional Analysis of 64,666 Children and Adolescents With Type 1 Diabetes
  • 2018
  • Ingår i: Diabetes Care. - : AMER DIABETES ASSOC. - 0149-5992 .- 1935-5548. ; 41:6, s. 1180-1187
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE International studies on childhood type 1 diabetes (T1D) have focused on whole-country mean HbA(1c) levels, thereby concealing potential variations within countries. We aimed to explore the variations in HbA(1c) across and within eight high-income countries to best inform international benchmarking and policy recommendations. RESEARCH DESIGN AND METHODS Data were collected between 2013 and 2014 from 64,666 children with T1D who were amp;lt; 18 years of age across 528 centers in Germany, Austria, England, Wales, U.S., Sweden, Denmark, and Norway. We used fixed-and random-effects models adjusted for age, sex, diabetes duration, and minority status to describe differences between center means and to calculate the proportion of total variation in HbA(1c) levels that is attributable to between-center differences (intraclass correlation [ICC]). We also explored the association between within-center variation and childrens glycemic control. RESULTS Sweden had the lowest mean HbA(1c) (59mmol/mol [7.6%]) and together with Norway and Denmark showed the lowest between-center variations (ICC amp;lt;= 4%). Germany and Austria had the next lowest mean HbA(1c) (61-62 mmol/mol [7.7-7.8%]) but showed the largest center variations (ICC similar to 15%). Centers in England, Wales, and the U.S. showed low-to-moderate variation around high mean values. In pooled analysis, differences between counties remained significant after adjustment for children characteristics and center effects (P value amp;lt; 0.001). Across all countries, children attending centers with more variable glycemic results had higher HbA(1c) levels (5.6mmol/mol [0.5%] per 5mmol/mol [0.5%] increase in center SD of HbA(1c) values of all children attending a specific center). CONCLUSIONS A tsimilar average levels of HbA(1c), countries display different levels of center variation. The distribution of glycemic achievement within countries should be considered in developing informed policies that drive quality improvement.
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5.
  • Hanberger, Lena, 1957-, et al. (författare)
  • Type 1 diabetes during adolescence : International comparison between Germany, Austria, and Sweden.
  • 2018
  • Ingår i: Pediatric Diabetes. - : John Wiley & Sons. - 1399-543X .- 1399-5448. ; 19:3, s. 506-511
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: By using pediatric diabetes quality registries in Austria, Germany, and Sweden treatment of type 1 diabetes and the outcome of care during the vulnerable adolescence period were compared.METHODS: Data in DPV, broadly used in Austria and Germany, and Swediabkids used in Sweden, from clinical visits in the year 2013 on 14 383 patients aged 11 to 16 years regarding hemoglobin A1c (HbA1c), insulin regimen, body mass index (BMI)-SD score (SDS), blood pressure, hypoglycemia, ketoacidosis, and smoking habits were analyzed.RESULTS: Patients in Sweden had fewer clinical visits per year (P < .05), lower insulin dose per kg (P < .001), and lower proportion of fast acting insulin compared with Germany and Austria (P < .001). The proportion of pump users was higher in Sweden (P < .001). Patients in Sweden had lower mean HbA1c levels (Austria: 64 mmol/mol, Germany: 63 mmol/mol, and Sweden: 61 mmol/mol [8.0%, 7.9%, and 7.7%, respectively]; P < .001). The frequency of severe hypoglycemia was higher in Sweden while it was lower for ketoacidosis (3.3% and 1.1%, respectively) than in Austria (1.1% and 5.3%) and Germany (2.0% and 4.4%) (P < .001). Girls in all 3 countries had higher HbA1c and BMI-SDS than boys.CONCLUSIONS: Sharing data between diabetes registries and nations enables us to better understand differences in diabetes outcome between countries. In this particular comparison, pediatric patients with diabetes in Sweden were more often treated with insulin pump, had lower HbA1c levels and a higher rate of severe hypoglycemia. Patients in Austria and Germany used rapid acting insulin analogs more often and had a lower rate of ketoacidosis.
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6.
  • Mortensen, Henrik B., et al. (författare)
  • New definition for the partial remission period in children and adolescents with type 1 diabetes
  • 2009
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 32:8, s. 1384-1390
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE To find a simple definition of partial remission in type 1 diabetes that reflects both residual beta-cell function and efficacy of insulin treatment. RESEARCH DESIGN AND METHODS A total of 275 patients aged <16 years were followed from onset of type 1 diabetes. After 1, 6, and 12 months, stimulated C-peptide during a challenge was used as a measure of residual beta-cell function. RESULTS By multiple regression analysis, a negative association between stimulated C-peptide and A1C (regression coefficient -0.21, P < 0.001) and insulin dose (-0.94, P < 0.001) was shown. These results suggested the definition of an insulin dose-adjusted A1C (IDAA1C) as A1C (percent) + [4 x insulin dose (units per kilogram per 24 h)]. A calculated IDAA1C < or =9 corresponding to a predicted stimulated C-peptide >300 pmol/l was used to define partial remission. The IDAA1C < or =9 had a significantly higher agreement (P < 0.001) with residual beta-cell function than use of a definition of A1C < or =7.5%. Between 6 and 12 months after diagnosis, for IDAA1C < or =9 only 1 patient entered partial remission and 61 patients ended partial remission, for A1C < or =7.5% 15 patients entered partial remission and 53 ended, for a definition of insulin dose < or =0.5 units . kg(-1) . 24 h(-1) 5 patients entered partial remission and 66 ended, and for stimulated C-peptide (>300 pmol/l) 9 patients entered partial remission and 49 ended. IDAA1C at 6 months has good predictive power for stimulated C-peptide concentrations after both 6 and 12 months. CONCLUSIONS A new definition of partial remission is proposed, including both glycemic control and insulin dose. It reflects residual beta-cell function and has better stability compared with the conventional definitions.
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7.
  • Prinz, Nicole, et al. (författare)
  • Who benefits most from outpatient lifestyle intervention? An IMI-SOPHIA study on pediatric individuals living with overweight and obesity
  • 2023
  • Ingår i: Obesity. - 1930-7381. ; 31:9, s. 2375-2385
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The first-line approach for childhood obesity is lifestyle intervention (LI); however, success varies. This study aimed first to identify distinct subgroups of response in children living with overweight and obesity and second to elucidate predictors for subclusters. Methods: Based on the obesity patient follow-up registry the APV (Adipositas-Patienten-Verlaufsdokumentation) initiative, a total of 12,453 children and adolescents (median age: 11.5 [IQR: 9.7–13.2] years; BMI z score [BMIz]: 2.06 [IQR: 1.79–2.34]; 52.6% girls) living with overweight/obesity and participating in outpatient LI were studied. Longitudinal k-means clustering was used to identify individual BMIz response curve for up to 2 years after treatment initiation. Multinomial logistic regression was used to elucidate predictors for cluster membership. Results: A total of 36.3% of children and adolescents experienced “no BMIz loss.” The largest subcluster (44.8%) achieved “moderate BMIz loss,” with an average delta-BMIz of −0.23 (IQR: −0.33 to −0.14) at study end. A total of 18.9% had a “pronounced BMIz loss” up to −0.61 (IQR: −0.76 to −0.49). Younger age and lower BMIz at LI initiation, larger initial BMIz loss, and less social deprivation were linked with higher likelihood for moderate or pronounced BMIz loss compared with the no BMIz loss cluster (all p < 0.05). Conclusions: These results support the importance of patient-tailored intervention and earlier treatment escalation in high-risk individuals who have little chance of success.
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