No increased incidence of venous thrombosis or pulmonary embolism after SARS-CoV-2 vaccination in Germany.

OBJECTIVES: Vaccination is one of the most effective measures to combat the COVID-19 pandemic. The main reason for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination hesitancy is the potential side-effects. This study aimed to investigate the incidence of venous thrombosis and pulmonary embolism in patients who received SARS-CoV-2 vaccination. STUDY DESIGN: This was a retrospective cohort study. METHODS: Individuals aged ≥18 years who received an initial vaccination for COVID-19 in one of 1134 general practices in Germany between April and June 2021 were included in the study. Vaccinated patients were matched to unvaccinated individuals by age, sex, index month (April to June 2020 [unvaccinated cohort] or April to June 2021 [vaccinated cohort]) and diagnoses that may be associated with an increased incidence of thrombosis documented within 12 months before the index date. The incidences of thrombosis and non-fatal pulmonary embolism as a function of COVID-19 vaccination were analysed. RESULTS: The present study included 326,833 individuals who were vaccinated against COVID-19 and 326,833 matched unvaccinated individuals. During the follow-up period, 406 vaccinated patients and 342 individuals in the control group received a diagnosis of thrombosis or non-fatal pulmonary embolism. This resulted in an incidence rate of 11.9 vs 11.3 cases per 1000 patient-years for vaccinated vs unvaccinated individuals, respectively, and a non-significant overall incidence rate ratio (IRR: 1.06; 95% confidence interval [CI]: 0.93-1.22). The highest IRR was observed in the 41-60 years age group (IRR: 1.30; 95% CI: 0.98-1.73), and the lowest IRR was seen in the 18-40 years age group (IRR: 0.6; 95% CI: 0.0-1.05); however, none of the individual age group incidence rates was significant. CONCLUSIONS: The results indicate that the occurrence of thrombosis or pulmonary embolism after COVID-19 vaccination is a coincidental finding rather than a consequence of vaccination.

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.

The Transatlantic HbA1c gap: differences in glycaemic control across the lifespan between people included in the US T1D Exchange Registry and those included in the German/Austrian DPV registry.

AIM: To compare HbA1c levels across the lifespan in people with type 1 diabetes in the USA with those in Germany/Austria, and to examine potential differences in HbA1c levels between sexes, insulin delivery methods and minority status. METHODS: Data were extracted from the US T1D Exchange Registry (n=18 381 participants from 73 sites) and from the German/Austrian Prospective Diabetes Follow-up Registry, the DPV (n=32 643 participants from 362 sites). Mean HbA1c was calculated for each year of age for individuals aged ≤25 years, and at 2-year age intervals for individuals aged >25 years. Curves for mean HbA1c by age were estimated using locally weighted scatterplot smoothing. HbA1c differences between registries, sexes, insulin delivery methods, and minority status were assessed by age group using multiple linear regression. RESULTS: In both registries, mean HbA1c increased by ~11 mmol/mol (1.0%) between the ages of 9 and 18 years, although at quite different absolute levels: from 66 mmol/mol (8.2%) to 77 mmol/mol (9.2%) in the T1D Exchange Registry, and from 56 mmol/mol (7.3%) to 66 mmol/mol (8.2%) in the DPV. Sex differences were observed in the DPV only. In the T1D Exchange Registry, injection users had higher mean HbA1c than pump users across the lifespan, whereas in the DPV higher HbA1c levels in injection users were observed in the age groups 6 to <12 years, 12 to <18 years, and 30 to <50 years (P < 0.001). Minority status was significantly associated with higher HbA1c in most age groups in both registries. CONCLUSIONS: Significant differences in HbA1c were noted between the USA and Germany/Austria, with disparities more pronounced in early childhood through to young adulthood. Further studies should identify causes for these disparities.

Diabetes distress in young adults with early-onset Type 1 diabetes and its prospective relationship with HbA1c and health status.

AIM: This study aimed to determine cross-sectional relationships between diabetes distress and health-related variables, and prospective associations between diabetes distress and future glycaemic control (HbA1c ) and health status among young adults with early-onset Type 1 diabetes. METHODS: Data were collected from a nationwide cohort study of adults whose Type 1 diabetes onset occurred from 0 to 4 years of age during 1993-2002. Questionnaire surveys were conducted in 2012-2013 and 2015-2016 (N = 584). Diabetes distress was assessed via the Problem Areas in Diabetes (PAID) scale (0-100 points), depressive symptoms via the Patient Health Questionnaire-9 (PHQ-9) and health status via the 12-Item Short Form Health Survey (SF-12) questionnaire. Multivariable linear regression analyses were applied to cross-sectional and longitudinal data. RESULTS: In the cross-sectional analyses, higher PAID scale total scores (representing higher distress levels) were observed in women than in men and in participants with more severe depressive symptoms. PAID scores were lower in individuals with better physical and mental health. A 1 mmol/mol increase in HbA1c was associated with a 0.28-point increase [95% confidence interval (95% CI) 0.20, 0.36] in diabetes distress. In longitudinal analyses adjusting for age, sex, socio-economic index and HbA1c at baseline, a 10-point higher PAID score at baseline was associated with a 1.82 mmol/mol higher HbA1c level (95% CI 0.43, 3.20) and a 2.48-point lower SF-12 mental health score (95% CI -3.55, -1.42) three years later. CONCLUSIONS: The cross-sectional and longitudinal analyses results suggest that diabetes distress impairs health-related outcomes in young adults with early-onset diabetes.

Inequalities in glycaemic control, hypoglycaemia and diabetic ketoacidosis according to socio-economic status and area-level deprivation in Type 1 diabetes mellitus: a systematic review.

AIM: The aim of this systematic review was to examine the associations of individual-level as well as area-level socio-economic status and area-level deprivation with glycaemic control, hypoglycaemia and diabetic ketoacidosis in people with Type 1 diabetes mellitus. METHODS: Ovid MEDLINE was searched to identify relevant cohort, case-control or cross-sectional studies published between January 2000 and June 2015. Search results were screened by title, abstract and keywords to identify eligible publications. Decisions on inclusion or exclusion of full texts were made independently by two reviewers. The Newcastle-Ottawa Scale was used to estimate the methodological quality of included studies. Quality assessment and extracted data of included studies were synthesized narratively and reported according to the PRISMA statement. RESULTS: Literature search in Ovid MEDLINE identified 1345 eligible studies. Twenty studies matched our inclusion and exclusion criteria. Two articles were additionally identified through hand search. According to the Newcastle-Ottawa Scale, most of the studies were of average quality. Results on associations of socio-economic status and area-level deprivation with glycaemic control and hypoglycaemia were contradictory between studies. By contrast, lower socio-economic status and higher area-level deprivation were associated with a higher risk for diabetic ketoacidosis in all except one study. CONCLUSIONS: Lower socio-economic status and higher area-level deprivation are associated with a higher risk of experiencing diabetic ketoacidosis in people with Type 1 diabetes mellitus. Access to care for socially deprived people needs to be expanded to overcome impairing effects on the course of the condition and to reduce healthcare disparities.

No change in type 2 diabetes prevalence in children and adolescents over 10 years: Update of a population-based survey in South Germany.

Objective of this study was to analyze prevalence changes in type 2 diabetes (T2D) among children and adolescents over the last 10 years. We performed a cross-sectional survey in Baden-Württemberg (BW), Germany, by using a written questionnaire and comparing these results with T2D prevalence data from the same area retrieved in 2004/2005. In 2016, 50 patients with T2D under 20 years of age were registered in BW, Germany, which corresponds to a prevalence rate of 2.42 per 100 000 (95% confidence interval [CI]: 1.75-3.09). The prevalence rate found in the same geographic area 10 years prior was 2.30 per 100 000 (95% CI: 1.70-2.90). Overall, 70% of T2D patients of this age group were treated by adult diabetologists. Concisely the prevalence of T2D in children and adolescents is still low in South Germany, remaining practically unchanged over the past decade.

Risk of recurrent severe hypoglycemia remains associated with a past history of severe hypoglycemia up to 4 years: Results from a large prospective contemporary pediatric cohort of the DPV initiative.

OBJECTIVES: In a contemporary cohort of youth with type 1 diabetes, we examined the interval between episodes of severe hypoglycemia (SH) as a risk factor for recurrent SH or hypoglycemic coma (HC). METHODS: This was a large longitudinal observational study. Using the DPV Diabetes Prospective follow-up data, we analyzed frequency and timing of recurrent SH (defined as requiring assistance from another person) and HC (loss of consciousness or seizures) in 14 177 youths with type 1 diabetes aged <20 years and at least 5 years of follow-up. RESULTS: Among 14 177 patients with type 1 diabetes, 72% (90%) had no, 14% (6.8%) had 1 and 14% (3.2%) >1 SH (HC). SH or HC in the last year of observation was highest with SH in the previous year (odds ratio [OR] 4.7 [CI 4.0-5.5]/4.6 [CI 3.6-6.0]), but remained elevated even 4 years after an episode (OR 2.0 [CI 1.6-2.7]/2.2 [CI 1.5-3.1]). The proportion of patients who experienced SH or HC during the last year of observation was highest with SH/HC recorded during the previous year (23% for SH and 13% for HC) and lowest in those with no event (4.6% for SH and 2% for HC) in the initial 4 years of observation. CONCLUSIONS: Even 4 years after an episode of SH/HC, risk for SH/HC remains higher compared to children who never experienced SH/HC. Clinicians should continue to regularly track hypoglycemia history at every visit, adjust diabetes education and therapy in order to avoid recurrences.

Seasonal variation in month of diagnosis in children with type 1 diabetes registered in 23 European centers during 1989-2008: little short-term influence of sunshine hours or average temperature.

BACKGROUND: The month of diagnosis in childhood type 1 diabetes shows seasonal variation. OBJECTIVE: We describe the pattern and investigate if year-to-year irregularities are associated with meteorological factors using data from 50 000 children diagnosed under the age of 15 yr in 23 population-based European registries during 1989-2008. METHODS: Tests for seasonal variation in monthly counts aggregated over the 20 yr period were performed. Time series regression was used to investigate if sunshine hour and average temperature data were predictive of the 240 monthly diagnosis counts after taking account of seasonality and long term trends. RESULTS: Significant sinusoidal pattern was evident in all but two small centers with peaks in November to February and relative amplitudes ranging from ± 11 to ± 38% (median ± 17%). However, most centers showed significant departures from a sinusoidal pattern. Pooling results over centers, there was significant seasonal variation in each age-group at diagnosis, with least seasonal variation in those under 5 yr. Boys showed greater seasonal variation than girls, particularly those aged 10-14 yr. There were no differences in seasonal pattern between four 5-yr sub-periods. Departures from the sinusoidal trend in monthly diagnoses in the period were significantly associated with deviations from the norm in average temperature (0.8% reduction in diagnoses per 1 °C excess) but not with sunshine hours. CONCLUSIONS: Seasonality was consistently apparent throughout the period in all age-groups and both sexes, but girls and the under 5 s showed less marked variation. Neither sunshine hour nor average temperature data contributed in any substantial way to explaining departures from the sinusoidal pattern.

Multiple sclerosis in children and adolescents: incidence and clinical picture - new insights from the nationwide German surveillance (2009-2011).

BACKGROUND AND PURPOSE: Pediatric multiple sclerosis (MS) clinical and incidence data have been reported for several countries but valid age dependent incidence data are not yet available. The true incidence of pediatric MS in Germany was estimated and the clinical characteristics at diagnosis according to the 2005 McDonald criteria are described. METHODS: Between 2009 and 2011 active prospective nationwide surveillance for MS in children and adolescents ≤15 years included all pediatric hospitals, MS centers and private practices specialized in MS. Data were adjusted for under-reporting by capture-recapture from an independent second source. RESULTS: The estimated incidence of pediatric MS was 0.64 per 100,000 person-years with clear increase from age group ≤10 (0.09/100,000) to 2.64 per 100,000 in age group 14-15 years. All had relapsing-remitting disease with polysymptomatic onset in half of the cases. Spinal MRI with positive findings in two-thirds of patients contributed to diagnosis. CONCLUSION: Using an active prospective surveillance system and the McDonald criteria for first MS diagnosis the age-related incidence of pediatric MS in Germany was uncovered and is more common than in previous estimates. Thorough application of McDonald criteria and inclusion of spinal MRI data allowed for early diagnosis in almost 90% of cases.

Corrigendum: Incidence, prevalence and care of type 1 diabetes in children and adolescents in Germany: Time trends and regional socioeconomic situation.

[This corrects the article on p. 57-78 in vol. 8.].

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.

Age-period-cohort modelling of type 1 diabetes incidence rates among children included in the EURODIAB 25-year follow-up study.

AIMS: Specific patterns in incidence may reveal environmental explanations for type 1 diabetes incidence. We aimed to study type 1 diabetes incidence in European childhood populations to assess whether an increase could be attributed to either period or cohort effects. METHODS: Nineteen EURODIAB centres provided single year incidence data for ages 0-14 in the 25-year period 1989-2013. Case counts and person years were classified by age, period and cohort (APC) in 1-year classes. APC Poisson regression models of rates were fitted using restricted cubic splines for age, period and cohort per centre and sex. Joint models were fitted for all centres and sexes, to find a parsimonious model. RESULTS: A total of 57,487 cases were included. In ten and seven of the 19 centres the APC models showed evidence of nonlinear cohort effects or period effects, respectively, in one or both sexes and indications of sex-specific age effects. Models showed a positive linear increase ranging from approximately 0.6 to 6.6%/year. Centres with low incidence rates showed the highest overall increase. A final joint model showed incidence peak at age 11.6 and 12.6 for girls and boys, respectively, and the rate-ratio was according to sex below 1 in ages 5-12. CONCLUSION: There was reasonable evidence for similar age-specific type 1 diabetes incidence rates across the EURODIAB population and peaks at a younger age for girls than boys. Cohort effects showed nonlinearity but varied between centres and the model did not contribute convincingly to identification of environmental causes of the increase.

Trends in childhood type 1 diabetes incidence in Europe during 1989-2008: evidence of non-uniformity over time in rates of increase.

AIMS/HYPOTHESIS: The aim of the study was to describe 20-year incidence trends for childhood type 1 diabetes in 23 EURODIAB centres and compare rates of increase in the first (1989-1998) and second (1999-2008) halves of the period. METHODS: All registers operate in geographically defined regions and are based on a clinical diagnosis. Completeness of registration is assessed by capture-recapture methodology. Twenty-three centres in 19 countries registered 49,969 new cases of type 1 diabetes in individuals diagnosed before their 15th birthday during the period studied. RESULTS: Ascertainment exceeded 90% in most registers. During the 20-year period, all but one register showed statistically significant changes in incidence, with rates universally increasing. When estimated separately for the first and second halves of the period, the median rates of increase were similar: 3.4% per annum and 3.3% per annum, respectively. However, rates of increase differed significantly between the first half and the second half for nine of the 21 registers with adequate coverage of both periods; five registers showed significantly higher rates of increase in the first half, and four significantly higher rates in the second half. CONCLUSIONS/INTERPRETATION: The incidence rate of childhood type 1 diabetes continues to rise across Europe by an average of approximately 3-4% per annum, but the increase is not necessarily uniform, showing periods of less rapid and more rapid increase in incidence in some registers. This pattern of change suggests that important risk exposures differ over time in different European countries. Further time trend analysis and comparison of the patterns in defined regions is warranted.

Costs of paediatric diabetes care in Germany: current situation and comparison with the year 2000.

AIMS: To estimate direct costs of paediatric Type 1 diabetes care and associated factors in Germany for the year 2007 and to compare results with the costs for the year 2000. METHODS: Our study includes clinical data and charges for any diabetes-related health care service of 14,185 continually treated subjects with paediatric diabetes aged < 20 years [52.5% male, mean age (SD) 12.1 (4.2) years], derived from a nationwide prospective patient documentation system (DPV). Health-care utilization was valued in monetary terms by using inpatient and outpatient medical fees and retail prices (perspective of the statutory health insurance). Associations between average total diabetes-related costs or various single cost categories per patient and age, sex, migration background, diabetes duration, and metabolic control were analysed by multiple regression procedures and by a two-part model for hospitalization costs. Total direct costs in the whole paediatric diabetes population in Germany were estimated. Mean costs per patient as well as total costs in the German paediatric diabetes population in 2007 were compared to 2000 costs (inflated to the year 2007). RESULTS: Mean direct diabetes-associated costs per subject were €3524 (inter-quartile range: 1831-4743). Main cost categories were hospitalization (32%), glucose self-monitoring (29%), insulin pump therapy (18%), and insulin (15%). Based on the present estimation, the total costs of paediatric diabetes care in Germany exceeded €110 million in 2007. Compared with estimates of the year 2000, average costs per patient had increased by 20% and total costs for German paediatric diabetes care by 47%. CONCLUSIONS: Direct costs for paediatric Type 1 diabetes care increased between 2000 and 2007, probably partly because of new therapeutic strategies and an increase in diabetes prevalence.

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.

[Frequency and influencing factors of ketoacidosis at diabetes onset in children and adolescents--a long-term study between 1995 and 2009]. / Häufigkeit und Einflussfaktoren der Ketoazidose bei Diabetesmanifestation im Kindes- und Jugendalter--eine Langzeitstudie von 1995 bis 2009.

BACKGROUND: Diabetic ketoacidosis (DKA) is a frequent acute complication at onset of type 1 diabetes. It is assumed that increased public awareness about diabetes symptoms may reduce DKA rate at diabetes onset. To investigate the time-dependent trend in DKA prevalence we analysed the frequency and determinants of DKA at disease onset over 15 years in pediatric patients. PATIENTS AND METHODS: The prevalence of DKA at disease onset was analysed in individuals aged ≤18 years treated for the first time from 1995-2009 within 7 days after diagnosis in pediatric centers. Simple and multiple logistic regression analysis was performed to investigate influencing factors on DKA prevalence. Change of the probability of ketoacidosis over years were modelled in the logistic regression as linear trend. RESULTS: 16 562 individuals from 170 institutions were studied with a mean age of 9.2 ± 4.2 years. DKA (pH <7.3) was present in 20.8% of patients without a significant trend between 1995 and 2009 (p=0.222). DKA prevalence was higher in children ≤5 years (26.3%) and in the age group 10-15 years (21.7%) than in individuals aged 5-10 years (16.4%) and 15-18 years (16.9%, p<0.001). Girls had DKA more often than boys (21.2% vs. 19.3%, p=0.002). DKA frequency was increased in individuals with migration background (26.5% vs. 19.2%, p<0.001). CONCLUSIONS: DKA prevalence at diabetes onset was constant at about 21% during the last 15 years. Very young children, pubertal adolescents, girls and individuals with migration background are at higher risk for DKA at diagnosis. To prevent DKA earlier diagnosis of type 1 diabetes is warranted especially in these patient groups.

Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data.

AIMS/HYPOTHESIS: We investigated whether children who are heavier at birth have an increased risk of type 1 diabetes. METHODS: Relevant studies published before February 2009 were identified from literature searches using MEDLINE, Web of Science and EMBASE. Authors of all studies containing relevant data were contacted and asked to provide individual patient data or conduct pre-specified analyses. Risk estimates of type 1 diabetes by category of birthweight were calculated for each study, before and after adjustment for potential confounders.Meta-analysis techniques were then used to derive combined ORs and investigate heterogeneity between studies. RESULTS: Data were available for 29 predominantly European studies (five cohort, 24 case-control studies), including 12,807 cases of type 1 diabetes. Overall, studies consistently demonstrated that children with birthweight from 3.5 to 4 kg had an increased risk of diabetes of 6% (OR 1.06 [95% CI 1.01-1.11]; p=0.02) and children with birthweight over 4 kg had an increased risk of 10% (OR 1.10 [95% CI 1.04-1.19]; p=0.003), compared with children weighing 3.0 to 3.5 kg at birth. This corresponded to a linear increase in diabetes risk of 3% per 500 g increase in birthweight (OR 1.03 [95% CI 1.00-1.06]; p=0.03). Adjustments for potential confounders such as gestational age, maternal age, birth order, Caesarean section, breastfeeding and maternal diabetes had little effect on these findings. CONCLUSIONS/INTERPRETATION: Children who are heavier at birth have a significant and consistent, but relatively small increase in risk of type 1 diabetes.