Axel Dost

Improved Metabolic Control in Children and Adolescents With Type 1 Diabetes A trend analysis using prospective multicenter data from Germany and Austria

OBJECTIVE To investigate the temporal trend of metabolic control and potential predictors in German and Austrian children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS This study is based on a large, multicenter database for prospective longitudinal documentation of diabetes care in Germany and Austria. Data from 30,708 patients documented in 305 diabetes centers between 1995 and 2009 were analyzed. Generalized linear mixed regression models were used to adjust trend analysis for relevant confounders. RESULTS Unadjusted mean HbA1c decreased from 8.7 ± 1.8% in 1995 to 8.1 ± 1.5% in 2009. In multiple regression analysis, treatment year, age, sex, diabetes duration, migration background, BMI-SDS, and daily insulin dose were significant predictors of metabolic control (P < 0.001). After multiple adjustment, mean HbA1c decreased significantly by 0.038% per year (95% CI 0.032–0.043%), average odds ratio (OR) per year for HbA1c >7.5% (>9.0%) was 0.969 (95% CI 0.961–0.977) (0.948, 95% CI 0.941–0.956). Intensified insulin regimen was associated with lower frequency of poor metabolic control (HbA1c >9%; P = 0.005) but not with average HbA1c (P = 0.797). Rate of severe hypoglycemia and hypoglycemic coma decreased significantly (relative risk [RR] per year 0.948, 95% CI 0.918–0.979; RR 0.917, 95% CI 0.885–0.950) over the study period. Diabetic ketoacidosis rate showed no significant variation over time. CONCLUSIONS This study showed a significant improvement in metabolic control in children and adolescents with type 1 diabetes during the past decade and a simultaneous decrease in hypoglycemic events. The improvement was not completely explained by changes in the mode of insulin treatment. Other factors such as improved patient education may have accounted for the observed trend.

Arterial hypertension determined by ambulatory blood pressure profiles: contribution to microalbuminuria risk in a multicenter investigation in 2,105 children and adolescents with type 1 diabetes.

OBJECTIVE—Arterial hypertension is a key player in the development of diabetes complications. We used a nationwide database to study risk factors for abnormal 24-h blood pressure regulation and microalbuminuria in children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS—Ambulatory blood pressure monitoring was performed in 2,105 children and adolescents from 195 pediatric diabetes centers in Germany and Austria. Individual least median squares (LMS)-SD scores were calculated for diurnal and nocturnal systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressure according to normalized values of a reference population of 949 healthy German children. The nocturnal blood pressure reduction (dipping) was calculated for SBP as well as DBP. RESULTS—In diabetic children, nocturnal blood pressure in particular was significantly elevated (SBP +0.51, DBP +0.58, MAP +0.80 LMS-SD) and dipping of SBP DBP, and MAP was significantly reduced (P < 0.0001). Age, diabetes duration, sex BMI, A1C, and insulin dose were related to altered blood pressure profiles; dipping, however, was only affected by age, female sex, and A1C. The presence of microalbuminuria was associated with nocturnal DBP (P < 0.0001) and diastolic dipping (P < 0.01). CONCLUSIONS—Our observations revealed a clear link between the quality of metabolic control and altered blood pressure regulation even in pediatric patients with short diabetes duration. Nocturnal blood pressure in particular seems to mainly contribute to diabetes complications such as microalbuminuria.

Growth in Children and Adolescents with Type 1 Diabetes

OBJECTIVE To investigate the effect of type 1 diabetes on growth and adult height. STUDY DESIGN Data from 22 651 children (10 494 females) with type 1 diabetes documented at onset of the disease from specialized centers in Germany and Austria were analyzed. Patients of non-German and non-Austrian origin and patients with celiac disease were excluded from the analysis. Near-adult height data were available in 1685 patients. RESULTS At the time of diagnosis of type 1 diabetes, the mean age of the 22 651 children was 8.8 ± 4.2 years, with a mean height SDS of 0.22 ± 1.0. The 1685 patients with diabetes onset before age 11 years reached a mean adult height of -0.16 ± 1.0 SDS. Mean adult height was was 167.1 ± 6.2 cm (-0.16 ± 0.97 SDS) in females (n = 846) and 179.6 ± 7.1 cm (-0.17 ± 1.0 SDS) in males (n = 839). Mean duration of diabetes was 9.1 ± 2.6 years, and mean Hemoglobin A1c concentration was 7.9% ± 1.2% (63 ± 10 mmol/mol). In a multivariate regression model, adult height was positively correlated with height at onset of diabetes (P < .0001) and negatively with mean Hemoglobin A1c (P < .0001) and duration of diabetes (P = .0015). CONCLUSION Height at the time of diagnosis of type 1 diabetes is above average. Even with intensive insulin therapy, growth and adult height remain indicators of metabolic diabetes control in the 21st century.

Children and adolescents with type 1 diabetes in Germany are more overweight than healthy controls: results comparing DPV database and CrescNet database

Abstract Aims: To describe the development of weight in children and adolescents with type 1 diabetes in Germany. Methods: We analyzed the body mass index (BMI) of the most recent treatment year of each patient with diabetes in the Pediatric Quality Initiative (DPV) database. BMI SD score (SDS) was calculated based on pooled historical German normative data (AGA) and based on healthy children from the CrescNet database. Thus, 25,762 children and adolescents with diabetes were compared with more than 75,000 healthy controls. Results: BMI-SDS was 0.49±0.88 and 0.26±0.79 when children and adolescents, respectively, with diabetes were compared with AGA reference or with CrescNet controls from the same year. In both analyses, female patients (0.57±0.89 and 0.30±0.79) had significantly higher BMI-SDS than male patients (0.41±0.86 and 0.22±0.78; p<0.0001). Analysis of different age groups showed highest BMI-SDS in patients below 6 years (0.61 and 0.56, respectively). After adjustment for metabolic control, center, and insulin treatment, BMI-SDS was significantly influenced by diabetes duration, age, and female gender. Conclusions: BMI of children and adolescents with type 1 diabetes is higher compared with healthy children measured in the same year. Especially, very young children and adolescent girls are at risk for overweight independent of annual trends.

Tracking of Metabolic Control from Childhood to Young Adulthood in Type 1 Diabetes

OBJECTIVE This prospective longitudinal survey was designed to follow patients with diabetes from disease onset in childhood over an extended period of time including puberty until young adulthood with respect to metabolic control. STUDY DESIGN An electronic diabetes patient documentation system used in diabetes centers in Austria and Germany was utilized for standardized data collection. Complete documentation of metabolic control for prepuberty (≤ 13 years), puberty (14-19 years), and adulthood (≥ 20 years) was available in 1146 patients. RESULTS Median age at diabetes manifestation was 7.2 (IQR 4.7-9.4) years; 49% were male. In the prepubertal stage, median glycated hemoglobin A1c (HbA1c) was 7.5 (IQR 6.8-8.3), during puberty 8.0 (IQR 7.3-8.9), and after puberty 7.8 (IQR 7.1-9.0). A significant intra-individual correlation was found for prepuberty to puberty HbA1c levels (R = 0.55, P < .001), puberty to adulthood (R = 0.59, P < .001), as well as prepuberty to adulthood (R = 0.30, P < .001). When patients were divided into tertiles of prepubertal HbA1c, HbA1c increased in all 3 groups over time, however, significant group differences tracked into adulthood (P < .001 at all stages). A regression model identified pre-pubertal HbA1c as a significant and relevant predictor of metabolic control in young adulthood adjusted for confounders (P < .001). CONCLUSIONS This survey provides evidence for long-term tracking of metabolic control from childhood until adulthood, suggesting an early focus on metabolic control.

Practical aspects of managing preschool children with type 1 diabetes

Day‐to‐day variations in diet and physical exercise, large variations in the glucose response to small changes in insulin doses, and high insulin sensitivity are characteristic of preschool children with diabetes. Hence, difficulties in achieving adequate metabolic control and stable glycaemia in preschool children are common. In addition, hypoglycaemic episodes tend to be frequent and severe in this age group. Problems identifying and treating hypoglycaemia present an additional challenge for the diabetes team and for the family caring for the young child with diabetes. Specific glucose targets are provided for this age group: premeal levels of 6‐12 mmol 1−1 (110‐220 mg dl−1) with bedtime levels above 8 mmol 1−1 (140 mg dl−1). It is important to note that children who suffer severe hypoglycaemic events at a young age show evidence of subtle cognitive deficits when tested during adolescence. The question of whether or not the years before pubertal onset contribute less towards the development of diabetes‐related microvascular complications than do the years starting with the onset of puberty remains controversial. Twice‐daily or multiple insulin injections, dietary adjustments and considerations, home blood‐glucose monitoring, family education, support groups and 24‐h hotline information facilities can help to achieve good metabolic control without severe hypoglycaemia in the preschool child. In general, good metabolic control without severe hypoglycaemia can be achieved using frequent counselling and a caring team approach.

Tracking and Prediction of Arterial Blood Pressure From Childhood to Young Adulthood in 868 Patients With Type 1 Diabetes A multicenter longitudinal survey in Germany and Austria

OBJECTIVE—Arterial blood pressure was followed in 868 patients with type 1 diabetes aged 6.0–19.9 years in 95 centers in Germany and Austria. RESEARCH DESIGN AND METHODS—European blood pressure reference data for 28,043 children and adolescents were used with respect to age and sex. Data were stratified into three groups: prepubertal, pubertal, and postpubertal. RESULTS—Up to 4% of the participants in the younger age-groups and 13.9% of the postpubertal patients exhibited blood pressure values >97th centile. Blood pressure levels correlated with A1C level and BMI Z score. Tracking of blood pressure revealed that children with elevated blood pressure had higher blood pressure in adolescence and young adulthood. CONCLUSIONS—Patients with higher blood pressure in childhood showed elevated blood pressure later in life. We need to focus on the diagnosis of hypertension in children with type 1 diabetes and to study the efficacy of early intervention.

Factors contributing to partial remission in type 1 diabetes: analysis based on the insulin dose‐adjusted HbA1c in 3657 children and adolescents from Germany and Austria

Insulin dose‐adjusted hemoglobin A1c (HbA1C, IDAA1c) correlates well with stimulated C‐peptide levels, but has not yet been evaluated in a large cohort of patients with Type 1 diabetes (T1D).

Higher Relative Risk for Multiple Sclerosis in a Pediatric and Adolescent Diabetic Population: Analysis From DPV Database

OBJECTIVE Type 1 diabetes and multiple sclerosis (MS) are typical autoimmune diseases in children and young adults. We assessed the co-occurrence of type 1 diabetes and MS by estimating the relative risk (RR) for MS in a pediatric and adolescent diabetic population and looked for possible influencing factors. RESEARCH DESIGN AND METHODS Within the Diabetes Patienten Verlaufsdokumentation (DPV)-Wiss Project, from January 1995 to October 2012, data from 56,653 patients with type 1 diabetes were collected in 248 centers in Germany and Austria. Published data on German and Mid-European MS prevalence were taken for comparison. Multivariable regression analysis was used to identify confounders for co-occurrence of type 1 diabetes and MS. RESULTS The RR for MS in patients with type 1 diabetes was estimated at 3.35–4.79 (95% CI 1.56–7.21 and 2.01–11.39, respectively). Immigration status in all patients (P < 0.05) and the presence of thyroid antibodies in male patients only (P = 0.05) were identified as influencing factors on MS incidence within the DPV database. The month-of-birth pattern revealed that risk was higher during the spring and summer months in the population with type 1 diabetes and MS in comparison with the population with type 1 diabetes. CONCLUSIONS The present cohort study demonstrates a higher risk of co-occurrence of MS in a pediatric and adolescent diabetic population. Immigration status and thyroid antibodies in male patients were independent risk indicators for the incidental rate of MS. Diabetic patients born during spring and summer had a higher risk for the development of MS. We suggest that environmental factors modulate the individual’s risk for the co-occurrence of both diseases.

Pulse pressure in children and adolescents with type 1 diabetes mellitus in Germany and Austria

Impaired blood pressure regulation contributes to the development of diabetic complications. The influence of systolic (SBP) vs. diastolic blood pressure (DBP) is still controversial. Peripheral pulse pressure (PP), the difference between SBP and DBP, is an indicator for arterial stiffness. Only little data are available for PP in children. Therefore, we studied PP regulation in type 1 diabetic children and adolescents.