Transition to adult diabetes care in Germany-High risk for acute complications and declining metabolic control during the transition phase.

OBJECTIVE: There is evidence that transition from pediatric to adult health care is frequently associated with deterioration of health in youths with type 1 diabetes (T1D). The aim of this study was to compare metabolic control, acute complications and microvascular complications in adolescents and young adults before and after transfer to an adult treatment center with respect to the time between first visit in the adult center and last visit in pediatric treatment. METHODS: All data were collected during routine care and retrieved from the German/Austrian DPV database. We analyzed data as of March 2017. RESULTS: We found 1283 young adults with available data of the last pediatric treatment year and the first year after transition to adult care. HbA1c increased significantly from 8.95% (74 mmol/mol) before to 9.20% (77 mmol/mol) in the first year after transition. Frequency of DKA with hospitalization (0.10-0.191 per annum, P < .0001) and severe hypoglycemia (0.23-0.46 per annum, P = .013) doubled during transition. Microvascular complications increased dramatically depending on the time between first visit in adult treatment and last visit in pediatric care. We could not find a significant correlation of this rise of microvascular complications to the duration of transition (short or long). CONCLUSION: This phase of life bears a high risk for detrimental outcome in young adults with T1D. Structured transition programs with case management are therefore needed to improve the transition process and outcomes.

[Evaluation and Utilization - Quality Management in a Paediatric University Outpatient Department]. / Evaluation und Inanspruchnahme - Qualitätssicherung in der pädiatrischen Ambulanz einer Universitätsklinik.

BACKGROUND: Based on an increasing number of outpatient treatments, an extensive demand planning is necessary to ensure the quality of medical care. University outpatient clinics are special parts of this sector and therefore it is necessary that a research demonstrates the nearly uninvestigated position of a paediatric outpatient clinic. PATIENTS: The research at the university hospital for children and adolescents in Leipzig started in 2009 to survey 2283 of in total 9391 patients and the physicians. METHODS: Sociodemographic data as well as economic and medical facts were determined by using questionnaires. In each case a questionnaire was answered by the children or their accompanying persons and a separate one was completed by the respective doctor. RESULTS: The results created a foundation, on the basis of patient volume per day and per daytime. Less than 20% of the children admitted to consult the clinic for their first time. The majority of patients visit them because of a letter of referral. Most of the patients (58%) were younger than 6 years old. Approximately 35% of patients did not come from the city region of Leipzig. CONCLUSION: The investigation evidenced the necessity of a day and night operating institution for children in the region of Leipzig as well as the high specialisation of the outpatient clinic. In need of further investigation is the cooperation between several physicians to find out if this lots of medical examination are necessary or if there took place overlapping.

Overweight and Obesity Based on Four Reference Systems in 18,382 Paediatric Patients with Type 1 Diabetes from Germany and Austria.

AIM: To evaluate the prevalence of overweight and obesity in paediatric type 1 diabetes (T1D) subjects, based on four commonly used reference populations. METHODS: Using WHO, IOTF, AGA (German pediatric obesity), and KiGGS (German Health Interview and Examination Survey for Children and Adolescents) reference populations, prevalence of overweight (≥90th percentile) and obesity (≥97th percentile) and time trend between 2000 (n = 9,461) and 2013 (n = 18,382) were determined in 2-18-year-old T1D patients documented in the German/Austrian DPV database. RESULTS: In 2000, the overweight prevalence was the highest according to IOTF (22.3%), followed by WHO (20.8%), AGA (15.5%), and KiGGS (9.4%). The respective rates in 2013 were IOTF (24.8%), WHO (22.9%), AGA (18.2%), and KiGGS (11.7%). Obesity prevalence in 2000 was the highest according to WHO (7.9%), followed by AGA (4.5%), IOTF (3.1%), and KiGGS (1.8%). In 2013, the respective rates were WHO (9.6%), AGA (6.2%), IOTF (4.5%), and KiGGS (2.6%). Overall, the prevalence of overweight and obesity increased from 2000 to 2006 (p < 0.001) but showed stabilization thereafter in girls and overweight in boys. CONCLUSION: Overweight and obesity prevalence in T1D subjects differs significantly if it is assessed by four separate reference populations. More detailed assessment of each child is required to determine obesity-related risks.

Diabetes mellitus in children and adolescents with genetic syndromes.

BACKGROUND: Several genetic syndromes are associated with diabetes mellitus (DM). This study aimed to analyse data from the DPV database with regard to frequency, treatment strategies and long-term complications in paediatric DM patients with genetic syndromes, including Turner syndrome (TS), Prader-Willi syndrome (PWS), Friedreich ataxia (FA), Alström syndrome (AS), Klinefelter syndrome (KS), Bardet-Biedl syndrome (BBS), Berardinelli-Seip syndrome (BSS) and Down syndrome (DS). METHODS: Longitudinal data for 43 521 patients with DM onset at age < 20 years were collected from 309 treatment centres in Germany and Austria using the DPV software. Data included anthropometric parameters, type of diabetes, mean age, age at diabetes onset, daily insulin dose, HbA 1c , micro- and macroalbuminuria, retinopathy and dyslipidaemia. Descriptive statistics and standard statistical tests were used for data analysis. RESULTS: In total, 205 DM patients had one of the following syndromes: DS (141 patients), TS (24), PWS (23), FA (5), AS (5), KS (4), BBS (2) and BSS (1). Diabetes-specific antibodies were positive in the majority of patients with DS, TS and FA. CONCLUSION: Despite the well-known association between DM and certain syndromic disorders, the number of affected patients in the German and Austrian paediatric diabetic population is very low. Nevertheless, physicians should be aware of syndromic forms of diabetes. Joint multicentre analyses are needed to draw relevant conclusions.

Vaspin is related to gender, puberty and deteriorating insulin sensitivity in children.

BACKGROUND: Visceral adipose tissue-derived serine protease inhibitor (vaspin) has been suggested as a novel adipocytokine related to obesity and insulin sensitivity in adults. DESIGN: We quantified vaspin serum concentrations in 65 lean and 67 obese children and aimed to evaluate the relationship of vaspin with physical development, obesity, and metabolic and cardiovascular phenotypes in children. We further assessed the acute vaspin response to glucose provocation in 20 obese adolescents and evaluated tissue expression patterns of vaspin in humans. RESULTS: Vaspin levels were significantly higher in girls than in boys. In girls, vaspin increased with age and pubertal stage, whereas there was no change with development in boys. Obese girls had lower vaspin serum levels than those of lean controls, but there was no significant correlation with body mass index (BMI). Independent of sex, age and BMI, lower vaspin was associated with better insulin sensitivity, with higher systolic blood pressure and impaired endothelial function. In response to glucose provocation during an oral glucose tolerance test, vaspin serum levels declined by approximately 25% in adolescents with hyperinsulinemia, whereas there was no significant decline in normoinsulinemic patients. In support of our clinical data, we not only confirmed vaspin mRNA expression in adipose tissue but also found consistent expression of vaspin in the liver and indications for expression in the pancreas and the skin. CONCLUSION: We showed that gender differences in circulating vaspin levels develop during pubertal progression in girls. Although vaspin's association with obesity remains controversial, vaspin was increased with worsening insulin resistance already in children and was acutely down-regulated following glucose provocation in insulin-resistant adolescents independent of obesity. Besides adipose tissue, vaspin expression in the liver and the pancreas may potentially contribute to circulating vaspin levels and their regulation.

Entities and frequency of neonatal diabetes: data from the diabetes documentation and quality management system (DPV).

AIMS: The aim of this study was to elucidate the entities and the frequency of neonatal diabetes mellitus (NDM) in a large representative database for paediatric diabetes patients in Germany and Austria. METHODS: Based on the continuous diabetes data acquisition system for prospective surveillance (DPV), which includes 51,587 patients with onset of diabetes before the age of 18 years from 299 centres in Germany and Austria, we searched for patients with onset of diabetes mellitus in the first 6 months of life. RESULTS: Ninety patients were identified, comprising 0.17% of all paediatric cases in the DPV registry. This represented an incidence of approximately one case in 89,000 live births in Germany. A monogenic basis for NDM was established in 30 subjects (seven UPD6, 10 KCNJ11, seven ABCC8, two FOXP3, two PDX1, one INS, one EIF2AK3). Pancreatic hypoplasia or agenesis was reported in 10 patients and seven subjects were classified as having Type 1 diabetes by their centres. Transient neonatal diabetes (TNDM) accounted for approximately 10% of all cases with NDM. No aetiology was defined in 41 subjects, which may reflect incomplete genetic testing or novel genetic aetiologies. CONCLUSION: Based on a large database, we identified a higher rate of NDM in Germany than has been reported previously. Full molecular genetic testing should be performed in all patients diagnosed before 6 months of age.

[Building bridges during transition of patients with type 1 diabetes. Adult medical and pediatric point of views]. / Brücken bauen bei der Transition von Patienten mit Typ-1-Diabetes. Internistische und pädiatrische Perspektiven.

The transition of patients with type 1 diabetes from pediatric to adult care services is challenging not only for patients but also for pediatricians and the further care providing physician. Around the time of transition, metabolic control is often unstable. Furthermore, psychiatric comorbidities or social background should be considered. Follow-up by a specialist, i.e. adults' endocrinologist/diabetologist, should be guaranteed. Typical differences between pediatric and adult health care services may hamper a successful transition. The handing-over of health care should be planned early and the timing should be adapted to the medical and psychosocial condition of the patient. An interdisciplinary transfer clinic seems the optimal setting for a successful transition. Close cooperation between pediatricians and adults' diabetologists is a prerequisite.

Changes in the use of analogue insulins in 37 206 children and adolescents with type 1 diabetes in 275 German and Austrian centers during the last twelve years.

AIMS: To describe changes in insulin treatment in children and adolescents in Germany/Austria regarding short acting (SA)- and long acting (LA) insulin analogues in different age groups over the last twelve years. METHODS: Use of different insulins and treatment regimens were analysed in 37 206 children and adolescents with the age of 0-20 years from 276 German and Austrian centers that were registered in the DPV-database (Dec. 2007). The group was subdivided into 4 age groups (A: 0-4 years; B:5-9 years;C:10-14 years,D:15-19 years). We further analysed the use of analogues from onset of diabetes. RESULTS: A significantly increasing percentage of pediatric patients in all age groups with Type 1 Diabetes use analogue insulins. In 2007, 48.5% used SA, 45.8% LA. 87.2% of pumps were running with short acting analogue. Age specific analysis: A: 2000: 9.1%SA, 0.7%LA vs. 2007: 50.0%SA, 10.0%LA; B: 2000:5.6%SA, 1.4%LA vs. 2007: 36.8%SA, 27.5%LA C: 2000:14.3%SA, 3.4%LA vs. 2007: 45.3%SA, 49.1%LA D: 2000:26.3%SA, 3.2%LA vs. 2007: 59.1%SA, 61.9%LA. This increase in usage of analogues was also found at onset of diabetes. Corrected for age, center and diabetes duration HbA1c was significantly lower in the group with regular insulin (8.18+/-0.047%) than with SA (8.32+/-0.048%) (p<0.0001) and BMI-SDS was only marginal lower in the group with regular insulin (0.45+/-0.01 kg/m (2)) than with SA (0.47+/-0.15) (p>0.007). Similar differences in HbA1c (8.09+/-0.05% vs. 8.40+/-0.05%) and BMI-SDS where seen when NPH was compared with LA respectively. After change to SA the reduction of severe hypoglycemia with (6.1/100 pat.years) and without coma (6.2/100 pat.years) was significant and after change to LA for severe hypoglycemia without coma respectively. CONCLUSIONS: Long-term data for the use of new drugs are sparse. In our analysis patients are followed not under study conditions. Still the higher BMI and HbA1c with either SA or LA usage have to be discussed carefully in the context of increasing use of both, long acting and short acting analogues and possible problems with reimbursement.

Comparison of continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI) in paediatric Type 1 diabetes: a multicentre matched-pair cohort analysis over 3 years.

AIMS: To conduct a multicentre, matched-pair cohort analysis comparing glycaemic control and adverse events of continuous subcutaneous insulin infusion (CSII) with multiple daily injections (MDI) in paediatric patients. METHODS: Using standardized computer-based prospective documentation, HbA(1c), insulin dose, body mass index-standard deviation score (BMI-SDS), rate of hypoglycaemia, rate of diabetic ketoacidosis (DKA) and intensity of care were analysed in 434 matched pairs during a follow-up period of 3 years after initiation of MDI or CSII. RESULTS: HbA(1c) was significantly lower in the CSII group during the first year of new regimen (CSII 7.5 +/- 0.05 vs. MDI 7.7 +/- 0.06; P < 0.05), but rose to the same level as in the MDI group during year 3. Insulin requirement remained significantly lower in the CSII group. The BMI-SDS increased in both study groups, with no significant difference. The rate of severe hypoglycaemia decreased significantly after the change of regimen (CSII 17.87 +/- 2.85 vs. MDI 25.14 +/- 3.79; P < 0.05) and during year 3 of the regimen, particularly when compared with baseline (-21% vs. -16%). The rate of DKA was lower at baseline in the CSII group and remained significantly lower over all 3 years. Intensity of care was the same in both subsets. CONCLUSIONS: Employing a large cohort, this matched-pair analysis has demonstrated over a 3-year study period that CSII is a safe form of intensive insulin therapy with similar glycaemic effects, but with significantly reduced rates of hypoglycaemia and DKA and a lower insulin requirement when compared with MDI.

Indications for insulin pump therapy in different age groups: an analysis of 1,567 children and adolescents.

AIMS: The German working group for pump therapy in paediatric patients has defined seven indications for continuous subcutaneous insulin infusion (CSII): dawn phenomenon, reduction of severe hypoglycaemia, improvement of hyperglycaemia, more flexibility, motivation, failure of injection therapy and pregnancy. In this study we analysed age-specific differences for starting CSII in four age groups (group A: 0-4 years; group B: 5-9 years; group C: 10-14 years; group D: 15-19 years). We also investigated whether glycaemic goals could be reached. METHODS: A total of 1567 children and adolescents (mean age 12.4 years, mean diabetes duration 5.2 years) with documented indications for CSII from the DPV-database (December 2005) were included. RESULTS: Dawn phenomenon (27.4%), reduction of hypoglycaemia (20%) and improvement of hyperglycaemia (18.1%) were the commonest indications for starting CSII. Indications differed by age group (P < 0.0001). In infants and toddlers (group A, n = 138) reduction of hypoglycaemia (42.5%) was the commonest indication. For adolescents (group C, n = 789/group D, n = 408) dawn phenomenon (32.1/21.7%) and flexibility (21.7/25.8%) were the main indications. The rate of severe hypoglycaemia with coma in patients commencing CSII in order to reduce hypoglycaemia fell (12.1/100 patient years before CSII vs. 5.8 after 1 year, 4.49 at study end). Glycated haemoglobin (HbA(1c)) in patients with the treatment goal 'improvement of hyperglycaemia' was lowered significantly in the first year of CSII (HbA(1c) start: 8.8%; after 1 year: 8.5%, P < 0.01) and was stable thereafter (8.8% after 36 months). CONCLUSIONS: CSII in children and adolescents is safe and can reduce the rate of severe hypoglycaemia without deterioration in glycaemic control. In patients with poor glucose control, a significant reduction in HbA(1c) can be achieved in the first year.

Evaluation of patients' opinion and metabolic control after transfer of young adults with type 1 diabetes from a pediatric diabetes clinic to adult care.

BACKGROUND: Transferring adolescents with diabetes from pediatric to adult care remains a challenge and the outcome is often unknown. The aims of this study were to determine the patients' perception of transfer arrangements and to analyze health care use and metabolic control. METHODS: A telephone questionnaire was conducted for patients who had been transferred from the pediatric clinic to adult care between 1995 and 2003. Of 161 identified patients, 101 (58 females, 43 males, mean age 22.1 +/- 2.4 years) were interviewed. Pediatric case notes and, if available (n = 44), current notes were analyzed to validate answers from the interview. RESULTS: After transfer, 52.5% of patients changed their health care provider at least once. The mean frequency of changes was 1.47. There was a significant decrease in clinic attendance rate after transition (8.5 +/- 2.3/years vs. 6.7 +/- 3.2/years). Patients criticized the lack of arrangements, poor information about transfer and the specific age for transition (18 years) set by legislation. The transfer was considered a negative experience by 58 patients. The patients assumed their metabolic control (HbA1c) was better than it really was (7.5 +/- 1.3% vs. 8.3 +/- 1.6%, p < 0.05). Actual HbA1c from case notes pre- and post-transfer did not change significantly (8.5 +/- 1.5% vs. 8.4 +/- 1.7%, n = 44, p = 0.441). CONCLUSION: The establishment of transition clinics and closer cooperation between specialists in pediatric and adult medicine is mandatory. Such changes are demanded by patients and would ensure better uptake of health care services after transfer.

[Epidemiology, treatment and prevention of type 2 diabetes in children and adolescents]. / Epidemiologie, Behandlungsstrategie und Prävention von Typ 2-Diabetes bei Kindern und Jugendlichen.

Changes in food consumption and exercise are fueling a worldwide increase in obesity in children and adolescents. As a consequence of this dramatic development an increasing rate of type 2 diabetes can be observed in children and adolescents in many countries. Development of strategies for therapy of type 2 diabetes and implementation of prevention of obesity and type 2 diabetes in this age group should be primary health care goals.

[Treatment of adolescents with type 2 diabetes]. / Behandlung von Jugendlichen mit Typ-2-Diabetes.

BACKGROUND: A worldwide increased incidence of adolescents with type 2 diabetes mellitus is evident. Only few substances are available for treatment of adolescents with type 2 diabetes. We report on our experience of treatment in the diabetes centre in Leipzig, Germany. PATIENTS AND METHODS: At the moment we care for three patients with type 2 diabetes (two girls and one boy) age 16 - 17 years. We retrospectively analyzed the patients records for symptoms at onset, BMI, HbA1c and treatment for a maximum of 4 years. RESULTS: None of the adolescents had typical symptoms at onset. All had first or second degree relatives with type 2 diabetes. Diagnosis was made using oral glucose tolerance test. BMI at onset was 26 kg/m (2) (90.-97 percent) to 35.2 kg/m (2) (>99.5 percent). Fasting and stimulated insulin and c-peptide levels were elevated in all cases. An elevated HbA1c level was found in one patient. Two patients had further metabolic symptoms like hypertriglyceridemia or hyperurikemia. We started with metformin after dietary instructions in all cases. One girl is on insulin at the moment and the boy stopped metformin after weight reduction of 24.5 kg. CONCLUSIONS: In Germany type 2 diabetes is diagnosed more frequently at an early age. Adolescents with type 2 diabetes should be treated in a centre for pediatric diabetology. Treatment should consist of an individualized care for all aspects of type 2 diabetes.

Higher frequency of paronychia (nail bed infections) in pediatric and adolescent patients with type 1 diabetes mellitus than in non-diabetic peers.

OBJECTIVE: Paronychia occurs frequently in adolescents, but there are no data about its prevalence in adolescents with type 1 diabetes mellitus (DM1). We investigated the presence and characteristics of nail-bed infections in a group of adolescent patients with DM1 aged 10-20 years. METHODS: Ninety-three children and adolescents with DM1 and 100 healthy age-matched controls were studied using a structured questionnaire. Frequency, duration and treatment of paronychia and, in the DM1 group, duration of DM, mean HbA1c, frequency of hypoglycemia, footwear and foot care were evaluated. All patients with DM1 underwent a complete neurological examination including vibration perception, thermal perception, and light touch perception. RESULTS: Adolescents with DM1, particularly girls, had a higher frequency of paronychia than controls (34.4% vs 23%; p < 0.01). Diabetic patients with paronychia were older than those without and had a longer duration of DM1, while there was no difference in long-term HbA1c between the groups. Vibration perception was impaired in all regions measured, compared to healthy adolescents. Subclinical neuropathy and microalbuminuria was found to be more frequent in patients with paronychia than in those without. CONCLUSION: We conclude that foot examination is important and mandatory in adolescents with DM1.

Reduced expression of Th1-associated chemokine receptors on peripheral blood lymphocytes at diagnosis of type 1 diabetes.

We investigated the expression of Th1- and Th2-associated chemokine receptors on peripheral blood lymphocytes at diagnosis and in the first phase of type 1 diabetes. Peripheral blood mononuclear cells (PBMCs) of 25 patients with newly diagnosed type 1 diabetes, 10 patients with longstanding type 1 diabetes, and 35 healthy control subjects were examined for expression of the chemokine receptors CXCR4 (naive T-cells), CCR5 and CXCR3 (Th1 associated), and CCR3 and CCR4 (Th2 associated) on CD3+ lymphocytes. Furthermore, we analyzed chemokine serum levels (monocyte chemoattractant protein [MCP]-1, macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, and RANTES [regulated on activation, normal T-cell expressed and secreted]) and phytohemagglutinin (PHA)-stimulated cytokine secretion of Th1- (gamma-interferon [IFN-gamma] and tumor necrosis factor-alpha [TNF-alpha]) and Th2 (interleukin [IL]-4 and -10)-associated cytokines by PBMC. The patients with newly diagnosed type 1 diabetes were followed for these parameters at 6-12 months after diagnosis. The PBMCs of patients with newly diagnosed but not with longstanding type 1 diabetes showed reduced expression of the Th1-associated chemokine receptors CCR5 (P < 0.001 vs. control subjects) and CXCR3 (P < 0.002 vs. control subjects). This reduction correlated with reduced IFN-gamma and TNF-alpha production of PBMCs after PHA stimulation and reversed 6-12 months after diagnosis to normal levels. CCR4 cells were reduced in both newly diagnosed and longstanding type 1 diabetic patients, which correlated to reduced PHA-stimulated IL-4 production. MIP-1alpha and MIP-1beta levels were considerably elevated in a subgroup of patients with newly diagnosed diabetes. We assume that Th1-associated peripheral T-cells are reduced in a narrow time window at the time of diagnosis of diabetes, possibly due to extravasation in the inflamed pancreas. Thus, chemokine receptor expression of peripheral blood lymphocytes may be a useful surrogate marker for the immune activity of type 1 diabetes (e.g., in intervention trials).