Family and household structure are associated with acute type 1 diabetes complications: results of cross-sectional analyses.

AIM: To examine the association of family/household structure with short-term diabetes complications in adolescents and emerging adults with early-onset type 1 diabetes in more detail. METHODS: Data on 1690 11-21-year-olds with type 1 diabetes were used to estimate associations of family/household structure with self-reported severe hypoglycaemia, hospitalizations for severe hypoglycaemia or diabetic ketoacidosis, applying multiple negative binomial regression. RESULTS: Compared with living with both biological parents living with a single mother was associated with an increased rate of hospitalizations for ketoacidosis (incidence rate ratio 1.71, 95% CI 1.00-2.82). Incidence rate ratio of hospitalizations for ketoacidosis was similar (1.67, 95% CI 0.91-3.07) if the mother lived with a partner, however, hypoglycaemia-related hospitalizations increased (3.66, 95% CI 1.54-8.71). Participants living with a single father had 4.43 (95% CI 1.30-15.05) /10.42 (95% CI 1.55-70.22) times higher rates of severe hypoglycaemia and related hospitalizations, while living with a father and his partner was associated with an increased incidence rate ratio of hospitalizations for ketoacidosis (3.48, 95% CI 0.96-12.63) compared with living with both biological parents. CONCLUSIONS: Findings of our exploratory analyses point to different self-reported diabetes outcomes depending on the family/household structure. If confirmed in future studies, they may help to identify young people with diabetes at risk of short-term diabetes complications.

Evaluation of lipoprotein-associated phospholipase A2 as a marker for renal microvasculopathy in adolescents with Type 1 diabetes.

AIM: To assess the relevance of lipoprotein-associated phospholipase A2 activity as a diagnostic and prognostic marker for renal microvascular diseases. METHODS: We analysed lipoprotein-associated phospholipase A2 activity and lysophosphatidylcholine levels (as a surrogate marker of oxidative stress) in 165 adolescents (aged 17.0 ± 2.3 years) with a history of Type 1 diabetes greater than 10 years. Clinical data were obtained from the German/Austrian nationwide Diabetes-Patients Follow-up (DPV) registry at blood collection and on average 2.4 ± 1.3 years later at follow-up. Relationships between lipoprotein-associated phospholipase A2 activity and clinical, demographic and laboratory variables, lysophosphatidylcholine levels and presence of albuminuria were evaluated by multivariable linear and logistic regression. RESULTS: Lipoprotein-associated phospholipase A2 activity was higher in male than female adolescents (P = 0.002). Albuminuria was present in 14% (22/158) of participants at baseline, and 5% (4/86) of participants without albuminuria at baseline developed albuminuria until follow-up. Lipoprotein-associated phospholipase A2 activity was associated neither with present nor with incident albuminuria. Lysophosphatidylcholine did not correlate with lipoprotein-associated phospholipase A2 activity. Cross-sectional bivariate correlation as well as multivariable linear regression analysis revealed a negative correlation of lipoprotein-associated phospholipase A2 activity with HbA1c and HDL-cholesterol. CONCLUSIONS: Lipoprotein-associated phospholipase activity was not associated with surrogate markers for oxidative stress and early diabetic nephropathy. The association of decreased lipoprotein-associated phospholipase A2 activity with poor glucose control might limit its function as a predictor of micro- and macrovascular diseases in Type 1 diabetes.

Associations of area deprivation and urban/rural traits with the incidence of type 1 diabetes: analysis at the municipality level in North Rhine-Westphalia, Germany.

AIM: To analyse the associations of area deprivation and urban/rural traits with the incidence of type 1 diabetes in the German federal state of North Rhine-Westphalia. METHODS: Data of incident type 1 diabetes cases in children and adolescents aged <20 years between 2007 and 2014 were extracted from a population-based diabetes register. Population data, indicators of area deprivation and urban/rural traits at the municipality level (396 entities) were obtained from official statistics. Area deprivation was assessed in five groups based on quintiles of an index of multiple deprivation and its seven deprivation domains. Poisson regression accounting for spatial dependence was applied to investigate associations of area deprivation and urban/rural traits with type 1 diabetes incidence. RESULTS: Between 2007 and 2014, 6143 incident cases were reported (99% completeness); the crude incidence was 22.3 cases per 100 000 person-years. The incidence decreased with increasing employment and environmental deprivation (relative risk of the most vs. the least deprived municipalities: 0.905 [95% CI: 0.813, 1.007] and 0.839 [0.752, 0.937], respectively) but was not associated with the composite deprivation index. The incidence was higher in more peripheral, rural, smaller and less densely populated municipalities, and the strongest association was estimated for the location trait (relative risk of peripheral/very peripheral compared with very central location: 1.231 [1.044, 1.452]). CONCLUSIONS: The results suggest that the type 1 diabetes risk is higher in more remote, more rural, less densely populated and less deprived areas. Urban/rural traits were stronger predictors of type 1 diabetes risk than area deprivation indicators.

Incidence and presentation of new-onset type 1 diabetes in children and adolescents from Germany during the COVID-19 pandemic 2020 and 2021: Current data from the DPV Registry.

AIMS: To determine whether the incidence of type 1 diabetes mellitus (T1D), autoantibody-negative diabetes, and diabetic ketoacidosis (DKA) at diabetes onset in 2020 and 2021 changed when compared to long-standing trends. METHODS: Our study is based on diabetes manifestation data of the 0.5-<18-year-old children/adolescents from the German multicenter Diabetes Prospective Follow-up Registry. Based on long-term pre-pandemic trends from 2011 to 2019, we estimated adjusted incidence rate ratios (IRR) for T1D and DKA, and prevalence rate ratios (PRR) regarding autoantibody status with 95 % confidence intervals (CI) for the years 2020 and 2021 (observed versus predicted rates), using multivariable negative binomial or beta-binomial regression, respectively. RESULTS: We analyzed data of 30,840 children and adolescents with new-onset T1D. The observed incidences were significantly higher than the predicted incidences (IRR2020 1.13 [1.08-1.19]; IRR2021 1.20 [1.15-1.26]). The prevalence of autoantibody-negative diabetes did not change (PRR2020 0.91 [0.75-1.10]; PRR2021 1.03 [0.86-1.24]). The incidence of DKA during the pandemic was higher than predicted (IRR2020 1.34 [1.23-1.46]; IRR2021 1.37 [1.26-1.49]). CONCLUSIONS: An increase in the incidences of T1D and DKA, but not of autoantibody-negative diabetes was observed during both pandemic years. Further monitoring and efforts for DKA prevention at onset are necessary.

Prevalence trends of type 1 and type 2 diabetes in children and adolescents in North Rhine-Westphalia, the most populous federal state in Germany, 2002-2020.

AIMS: To estimate the prevalence and temporal trends of type 1 and type 2 diabetes mellitus in children and adolescents (type 1 diabetes: 0-19 years, type 2 diabetes: 10-19 years) in North Rhine-Westphalia (NRW), Germany, from 2002 to 2020. METHODS: The NRW Diabetes Registry records new cases based on three data sources (median completeness of ascertainment 99% for type 1 diabetes, 94% for type 2 diabetes). We determined age- and/or sex-standardized prevalence estimates (95% confidence intervals) per 100,000 individuals. Differences in age and sex, as well as time trends, were examined by Poisson regression. Furthermore, joinpoint regression was used to evaluate changes in prevalence trends over time. RESULTS: At the end of 2020, the estimated type 1 diabetes prevalence was 247.1 (240.3; 253.9) with an annual increase of 2.9% (2.7%; 3.1%). The type 2 diabetes prevalence was 12.7 (10.6; 14.9) and increased by 6.4% (5.6%; 7.3%) per year. The prevalence trends were not uniform over the total period and flattened considerably in recent years. CONCLUSIONS: The prevalence of type 1 and type 2 diabetes has increased significantly but at a lower rate in recent years. Continued surveillance of the prevalence is essential for the planning of health care resources and prevention measures.

The effects of direct feedback and practice on metaphor performance in children with learning disabilities.

Children with learning disabilities may have a problem in interpreting metaphor and need specific guidance and practice. This study found that direct feedback and practice could significantly increase metaphor performance of these children. Further descriptive analyses indicated that grade and reading levels of the subjects correlated with their metaphor performance.

Frequency and cost of diabetic ketoacidosis in Germany--study in 12,001 paediatric patients.

AIMS: Recently, medical expenditures were found to be 2-fold increased in paediatric patients with diabetic ketoacidotic events (DKA) in the U.S., in particular due to hospitalization. Aim of our study was to analyse DKAs and associated costs in Germany, where structured diabetes care including education is available for all patients. METHODS: For all 12,001 diabetic patients 0-19 years of age (52.6% male, mean age (SD) 12.6 (3.9) years) documented in a German-wide database, all DKAs were assessed, as well as costs for diabetes-related treatment. Associations between costs and DKA were estimated using log-linear models. RESULTS: 457 (3.8%) patients had at least 1 DKA during 2007. Total annual costs for patients without, with 1, or ≥ 2 DKAs were € 3,330 (95%-CI 3,292-3,368), € 6,935 (CI 6,627-7,244), and € 10,728 (CI 9,813-11,644), respectively, with largest differences for hospitalization costs (€ 693, € 4,145, € 8,092). Age-sex-diabetes duration-adjusted cost ratios for patients with 1, or ≥ 2 DKAs compared to patients without DKA were 2.2 (CI 2.1-2.3) and 3.6 (CI 3.1-4.1), respectively. CONCLUSIONS: In Germany, paediatric diabetic patients with DKA had up to 3.6-fold higher diabetes-related costs compared to those without DKA. This cost excess was higher compared to a U.S. study, however, the proportion of patients with DKA was much lower (3.8% versus 14.9%). The lower frequency of DKA in Germany may be due to a higher access to and utilization of diabetes education. Interventions should reduce DKA and resulting hospital admission in pediatric patients in order to reduce costs and improve quality of life.

Regulation of prostaglandin endoperoxide H synthase-2 induction by dioxin in rat hepatocytes: possible c-Src-mediated pathway.

The tumor promoter 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to increase the expression of prostaglandin endoperoxide H synthase (PGHS)-2. This study focused on the regulatory mechanism of TCDD-mediated transcriptional activation of PGHS-2. Treatment of rat hepatocytes with TCDD led to a dose-dependent induction of PGHS-2 mRNA levels associated with an increased synthesis of prostaglandin E(2), whereas expression of PGHS-1 was not affected. In vitro experiments with c-Src inhibitors, such as herbimycin A and geldanamycin, and in vivo studies with c-Src-deficient mice indicated that up-regulation of PGHS-2 but not the cytochrome P450 gene CYP1A1 by TCDD is mediated via a c-Src-dependent pathway. Transient transfection studies with different reporter constructs of the murine PGHS-2 promoter mutated in the xenobiotic-responsive element (XRE) or CCAAT/enhancer binding protein (C/EBP) element revealed that a C/EBP-binding site is an important regulatory cis-acting factor for trans-activation of the PGHS-2 gene by TCDD. Consistent with transfection studies, gel mobility shift assays showed that TCDD led to an enhanced DNA-binding activity of C/EBP beta transcription factor. The experimental data presented in this article reveal a XRE-independent and c-Src-mediated activation of the PGHS-2 gene by TCDD through the C/EBP response element located in its promoter region.