Psychological care in children and adolescents with type 1 diabetes in a real-world setting and associations with metabolic control.

BACKGROUND: International guidelines recommend psychosocial care for children and adolescents with type 1 diabetes. OBJECTIVE: To assess psychological care in children and adolescents with type 1 diabetes in a real-world setting and to evaluate associations with metabolic outcome. METHODS: Delivery of psychological care, HbA1c, and rates of severe hypoglycemia and diabetic ketoacidosis (DKA) in children and adolescents with type 1 diabetes from 199 diabetes care centers participating in the German diabetes survey (DPV) were analyzed. RESULTS: Overall, 12 326 out of 31 861 children with type 1 diabetes were supported by short-term or continued psychological care (CPC). Children with psychological care had higher HbA1c (8.0% vs 7.7%, P<.001) and higher rates of DKA (0.032 vs 0.021 per patient-year, P<.001) compared with children without psychological care. In age-, sex-, diabetes duration-, and migratory background-matched children, HbA1c stayed stable in children supported by CPC during follow-up (HbA1c 8.5% one year before psychological care started vs 8.4% after two years, P = 1.0), whereas HbA1c was lower but increased significantly by 0.3% in children without psychological care (HbA1c 7.5% vs 7.8% after two years, P <.001). Additional HbA1c-matching showed that the change in HbA1c during follow-up was not different between the groups, but the percentage of children with severe hypoglycemia decreased from 16.3% to 10.7% in children receiving CPC compared with children without psychological care (5.5% to 5.8%, P =.009). CONCLUSIONS: In this real-world setting, psychological care was provided to children with higher HbA1c levels. CPC was associated with stable glycemic control and less frequent severe hypoglycemia during follow-up.

Technology in Diabetes Treatment: Update and Future.

Worldwide the number of people with diabetes mellitus is increasing. There are estimations that diabetes is one of the leading causes of death. The most important goals for the treatment of diabetes are self-management of the disease and an optimal quality of diabetes control. In the therapy new technologies, like real-time continuous interstitial glucose monitoring, continuous subcutaneous insulin infusion (CSII), electronic tools for the monitoring of therapeutic approaches, automated bolus calculators for insulin and electronic tools for education and information of patients, have become widespread and play important roles. All these efforts are related to the interaction between patients, caregivers, scientists or researchers and industry. The presentation of different aspects of new technological approaches in the present article should give more information about different technologies. However, because of the rather quickly appearance of new technologies, the presentation can only be a spotlight. Further studies are mandatory to analyze the effects and long-term benefits of each technology and electronic device.

Serum Uromodulin in Children and Adolescents with Type 1 Diabetes Mellitus and Controls: Its Potential Role in Kidney Health.

INTRODUCTION: Uromodulin is a kidney-specific tubular protein, and its assessment in serum (sUMOD) reveals the potential as a novel marker for function and the integrity of renal parenchymal cells and does not directly depend on the glomerular filtration rate. Early diabetic nephropathy parallels glomerular hyperfiltration, often leading to diagnostic misinterpretation. Moreover, traditional kidney function markers are not able to diagnose structural lesions. Recent data show that sUMOD is linked to glucose intolerance in adults. Thus, we launched to assess the hypothesis that sUMOD is also associated with kidney function, biometric data, and quality of metabolic control in children/adolescents with type 1 diabetes. PATIENTS AND METHODS: Patients with type 1 diabetes (n=135) and healthy controls (n=69) were recruited to participate in the trial. Clinical, biometrical data, sUMOD, and other laboratory parameters were assessed. RESULTS: The mean concentrations of sUMOD in diabetic patients and controls were comparable (201.19±103.22 vs. 198.32±84.27 ng/mL, p=0.832). However, in contrast to healthy controls, sUMOD levels in patients with diabetes were associated with serum-creatinine (r=-0.368, p<0.0001), age (r=-0.350, p<0.0001), height (r=-0.379, p<0.0001), body weight (r=-0.394, p<0.0001), Body mass index (r=-0.292, p=0.001), daily insulin dosage (r=-0.300, p<0.0001), HbA1c (%) (r=-0.190, p=0.027), standardized HbA1c/IFCC (mmol/mol) (r=-0.189, p=0.028), and systolic (r=-0.299, p<0.0001) and diastolic (r=-0.235, p=0.006) arterial blood pressure. CONCLUSIONS: Our study shows that children/adolescents with type 1 diabetes disclose similar sUMOD concentrations as healthy controls. Serum UMOD appears to indicate higher risks for kidney tissue remodeling and possibly subsequent cardiovascular alterations. However, further studies are mandatory to settle these findings.

Electronic health technology for the assessment of physical activity and eating habits in children and adolescents with overweight and obesity IDA.

OBJECTIVE: It was the goal of the trial to study the impact of electronic healthcare technology into treatment. METHODS: One hundred and twenty-four children/adolescents (females 56%, age 13.5±2.8 years, height 1.64±0.13 m, weight 85.4±23.0 kg, body-mass index (BMI) 31.3±5.2 kg/m(2), BMI-standard deviation score (SDS) 2.50±0.5) were included. To assess physical activity and eating habits, a mobile motion sensor integrated into a mobile phone with digital camera was used. RESULTS: The children/adolescents had a significant weight reduction of 7.1±3.0 kg. BMI/BMI-SDS decreased (p<0.01). Intensity (14.1±6.4 activity units) and duration of physical activity (290.4±92.6 min/day) were assessed with sensors. Time walking: median 45.5 (range, 2.5-206.5), running 8.0 (range, 0-39.5), cycling 27.7 (range, 0-72.5), car driving 23.7 (range, 0-83.0) min/day. Comparing self-reported physical activity (walking 292.9 (range, 9.6-496.1), running 84.8 (range, 8.4-130.2) min/day) with assessment with sensors there were significant differences (p<0.01). Duration of physical activity documented by children/adolescents was higher than the assessment with motion sensors (walking 292.9 vs 45.5 min, p<0.01, running 84.8 vs 8.0 min, p<0.01). Sensor derived energy intake was higher than recommended (469.14±88.75 kcal vs 489.03±108.25 kcal, p=0.09). Performing multivariate analysis the following parameters showed associations with weight reduction (R-square=0.75): body weight (ß=-0.95, p<0.01), C-reactive protein (CRP, ß=0.15, p=0.07), physical activity, time spent in activities measured with sensors (ß=-0.18, p=0.04), stress management (ß=0.16, p=0.06), body fat mass at onset of the trial (ß=0.45, p<0.01) and body shape (ß=-0.25, p=0.01). CONCLUSION: The innovative mobile movement detection system is highly accepted by children and adolescents. The system is able to augment existing weight reduction and stabilization strategies.

LDL-apheresis: technical and clinical aspects.

The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) levels, and coronary heart disease refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are five different LDL-apheresis systems available: cascade filtration or lipid filtration, immunoadsorption, heparin-induced LDL precipitation, dextran sulfate LDL adsorption, and the LDL hemoperfusion. There is a strong correlation between hyperlipidemia and atherosclerosis. Besides the elimination of other risk factors, in severe hyperlipidemia therapeutic strategies should focus on a drastic reduction of serum lipoproteins. Despite maximum conventional therapy with a combination of different kinds of lipid-lowering drugs, sometimes the goal of therapy cannot be reached. Hence, in such patients, treatment with LDL-apheresis is indicated. Technical and clinical aspects of these five different LDL-apheresis methods are shown here. There were no significant differences with respect to or concerning all cholesterols, or triglycerides observed. With respect to elevated lipoprotein (a) levels, however, the immunoadsorption method seems to be most effective. The different published data clearly demonstrate that treatment with LDL-apheresis in patients suffering from severe hyperlipidemia refractory to maximum conservative therapy is effective and safe in long-term application.

Inpatient Rehabilitation for Children and Adolescents With Diabetes in Germany Between 2006 and 2013.

INTRODUCTION: In Germany, inpatient rehabilitation is a well-established additive option in the therapeutic concept for children and adolescents with diabetes. However, its contribution in pediatric diabetes care is not known exactly. Our objective was to analyze inpatient rehabilitation in pediatric diabetes over eight years in Germany. METHODS: We requested secondary data from the German Statutory Pension Insurance Scheme to evaluate all completed inpatient rehabilitations for children and adolescents with diabetes (ICD-code E10-14) reimbursed by this institution between 2006 and 2013. For each type of diabetes, we analyzed the distribution of admissions by year, age-group, sex, nationality, and other documented diagnoses. All analyses were conducted via remote computing with IBM SPSS Version 24. RESULTS: Between 2006 and 2013, 5,403 admissions to inpatient rehabilitation for 4,746 children and adolescents with diabetes were documented. For type 1 diabetes (T1D; 88.5% of admissions), the number of yearly admissions increased from 458 in 2006 to 688 in 2013 (p=0.013), especially for age-group>5-10. The increase for type 2 diabetes (T2D) was not significant. Admissions were more frequent for girls (53.6%, p≤0.001), age>10-15 years (42.8%, p=0.001), and German nationality (98.5%). Obesity (T1D: 11.1%; T2D: 87.9%) and mental disorders (T1D: 11.6%; T2D: 27.4%) were the most frequent documented diagnoses in addition to diabetes. CONCLUSION: This study provides a comprehensive overview of inpatient rehabilitation for children and adolescents with diabetes over many years in Germany. Until 2013, inpatient rehabilitation remained important in pediatric diabetes care, especially for children with mental disorders or obesity.

Rehabilitation in Germany 2004-2016 A Multicenter Analysis Over a Period of 13 Years in Children and Adolescents with Diabetes Mellitus.

In the treatment of children/adolescents with diabetes medical rehabilitation plays an important role. It was the aim of the survey to analyze trends in the number of patients admitted to rehabilitation, the quality of diabetes care, the incidence of acute complications, risk factors for cardiovascular co-morbidities like lipids and blood pressure and the familial status nationwide and over a period of 13 years. METHODS: Currently seven hospitals offer in-patient rehabilitation for children/adolescents with diabetes in Germany. Six hospitals participated in the survey. All children/adolescents (n=7.163) who participated in an in-patient rehabilitation 01/01/2004-31/12/2016 were included. Clinical/familial data were assessed: age, sex, family situation, type/duration of diabetes, insulin dosage, self-monitoring, acute complications, height, body weight, blood pressure and laboratory parameters. For collecting and storage of data the computer software DPV® (Diabetes-Patienten-Verlaufsdokumentation, University of Ulm, Germany) was used. Statistical analyses were performed using the programme SAS (Statistical Analysis Software 9.4, SAS Institute Inc, Cary, North Carolina, USA). RESULTS: During the study period 7.163 patients took part in 10.987 in-patient rehabilitation procedures. The yearly number of patients participating in rehabilitation remained stable. There was no change in the quality of diabetes control (HbA1c: p=0.30, fasting blood glucose: p=0.80). The incidence of severe hypoglycaemia decreased (p<0.001). The incidence of ketacidosis remained stable (p=0.18). The frequency of blood glucose self-monitoring increased (p<0.001). The same was true for patients treated with CSII (p<0.001), whereas the numbers of patients treated with CT or ICT decreased (both p<0.001). There was no change in patients' total insulin dose (p=0.01). There was a decrease of the number of patients living with both parents (p<0.001), the percentage of children/adolescents living with mother or father alone increased (p<0.001). The percentage of children/adolescents living in mixed cultural families or having a background of immigration increased (p<0.001). CONCLUSIONS: There is a change in medical rehabilitation: The number is stable, the proportion of patients using CSII increased, the number of patients living with single parents and the percentage of patients from culturally mixed families increased also.

Effects of metabolic control, patient education and initiation of insulin therapy on the quality of life of patients with type 2 diabetes mellitus.

OBJECTIVE: The objective of this study was to evaluate the impact of initiation of insulin therapy, metabolic control and structured patient education on the diabetes-related quality of life (QoL) in insulin-treated patients with type 2 diabetes mellitus. METHODS: This prospective study was conducted with 71 consecutively recruited patients with insulin-treated diabetes at the University hospital. All patients participated an inpatient diabetes treatment and teaching program (DTTP) for conventional insulin therapy (mean age 68.9 years, HbA1c 10.1+/-1.4%, diabetes duration 11.2 years (range: 0-25.5 years), body-mass-index 28.7+/-5.7 kg/m(2). Diabetes-related quality of life was assessed before and 6 months after participation in the DTTP using the standardized questionnaire of Lohr analysing the subscales: social relations, physical complaints, worries about the future, dietary restrictions, fear of hypoglycaemia, and daily struggles. RESULTS: Only patients switched on insulin therapy showed significant improvement in diabetes-related quality of life 6 months after participation in the DTTP (p=0.03), fewer physical complaints (p=0.03), fewer worries about the future (p=0.02), fewer daily struggles (p=0.01) and less fear of hypoglycaemia (p<0.001), while patients, who were already on insulin therapy showed no improvements in diabetes-related quality of life. Though, residual analysis reveals that effects on patients' QoL are mainly caused by improvements in metabolic control. CONCLUSIONS: Improvements in metabolic control have a significant effect on different diabetes-related quality of life domains in patients with diabetes mellitus. PRACTICE IMPLICATIONS: Appropriate interventions resulting in better metabolic control, such as starting on insulin therapy within a structured patient education program seem to be an effective approach to improve patients' diabetes-related quality of life.

Long-term treatment of obese children and adolescents using a telemedicine support programme.

A total of 140 obese patients (mean age 14 years) participated in a structured treatment and teaching programme (STTP) in hospital, with the aim of weight reduction. At both the start and finish of the STTP, patients underwent clinical and psychological examination. During an average hospital stay of 35 days, their mean bodyweight decreased from 82.4 kg to 76.0 kg (P < 0.001). Patients were then followed up with a telemedicine support programme. During the next 12 months, the acceptance of the telemedicine support programme declined from 93% to 46%. The body mass index was 30.5 kg/m(2) at admission and 27.7 kg/m(2) at 12-month follow-up (P < 0.05). In parallel, wellbeing and treatment satisfaction increased, and there was a positive effect on eating behaviour and exercise. Intervention was needed in up to 64% of the children and adolescents who participated in the programme, most frequently due to poor results in exercise. Telemedical follow-up care and counselling seemed to be highly effective, and allowed not only an initial weight reduction, but long-term stabilization as well.

Mortality and its Causes in a German Cohort with Diabetes Mellitus Type 1 after 20 Years of Follow-Up: The JEVIN Trial.

BACKGROUND: The JEVIN trial started as a cross-sectional study in 1989/90 in Jena. After a follow-up of more than 20 years, the mortality incidence of JEVIN participants with type 1 diabetes was surveyed. METHODS: 103 (78.6%) of the 131 JEVIN patients participating at baseline could be examined. 38 persons (36.9%) had deceased. All JEVIN survey data and routine examinations documented in the electronic patient record EMIL® of surviving and deceased participants were used for analyses. We compared the data of the surviving with the deceased participants (follow-up time: 2,166 person-years). RESULTS: The incidence rate of death was 1.75/100 person-years. Median observation time for all patients was 23.1 years (range 0.61-26.6 years). Mean age at death was 58.5 years (34.2-78.4 years), and diabetes duration 35 years (3.5-68.5 years). Most frequent causes of death were: cardiovascular diseases (48.2%, n=13) and infections (25.9%, n=7). There were no differences in age (p=0.302), diabetes duration (p=0.371), BMI (p=0.535), blood pressure (p=0.622/0.820), gender (p=0.566), and smoking status (p=0.709) between surviving and deceased persons. The mean HbA1c of the last year before death or last visit was higher in the deceased than surviving persons (7.5% vs. 7.0%; p=0.010). 57.4% of the surviving and 87.0% of the deceased participants had nephropathy (p=0.012), 79.7% vs. 89.7% retinopathy (p=0.241) and 61.4% vs. 63.3% neuropathy (p=0.860), but only nephropathy was significantly associated with increased mortality risk (HR=4.208, CI:1.226-14.440; HR=2.360, CI:0.696-8.004; HR=0.944, CI:0.436-2.043). CONCLUSIONS: In the JEVIN population with diabetes mellitus type 1 only, diabetic nephropathy was associated with higher mortality risk.

Increased carotid intima-media thickness and associations with cardiovascular risk factors in obese and overweight children and adolescents.

OBJECTIVE: Overweight and obesity in children and adolescents contribute to the development of overweight and obesity in adulthood and subsequent cardiovascular disease. It was the aim of the trial to assess vascular status and associations with cardiovascular risk factors. PATIENTS AND METHODS: Eighty-one overweight or obese children and adolescents (age 13.6 +/- 2.7 years, 62% females) hospitalised for weight reduction were consecutively recruited. In all subjects carotid intima-media thickness (IMT), body-mass index (BMI), body composition, serum lipid and blood glucose concentrations, CRP, TSH, uric acid and blood pressure values were measured. RESULTS: Mean IMT was 0.48 +/- 0.09 mm. Twenty-nine subjects (36%) had an IMT <0.45 mm, 32 (40%) an IMT > or =0.450.50 mm. Comparing children with low carotid IMT (<0.45 mm, n = 29 (36%)) with those with higher values (> or =0.45 mm, n = 52 (64%)), there were significant differences: Those with higher IMT had higher weight (73.5 +/- 17.6 vs 91.1 +/- 24.0 kg, p = 0.001), higher BMI (28.6 +/- 4.4 vs 32.7 +/- 5.5 kg/m(2), p = 0.001) and BMI-SDS (2.23 +/- 0.57 vs 2.61 +/- 0,50, p = 0.002), higher fatmass (26.3 +/- 9.5 vs 37.1 +/- 15.2 kg, p = 0.001) and a higher percentage of fat in relation to total body weight (35.2 +/- 5.5 vs 39.5 +/- 7.8 %, p = 0.010), as well as higher systolic (117.7 +/- 6.9 vs 124.6 +/- 10.6 mmHg, p = 0.004) and diastolic blood pressure values (64.4 +/- 5.5 vs 68.6 +/- 6.7 mmHg, p = 0.008), and higher serum uric acid concentrations (385.6 +/- 91.7 vs 439.9 +/- 100.5 micromol/l, p = 0.023). There was a correlation between IMT and height (r = 0.237, p = 0.033), weight (r = 0.442, p<0.001), BMI (r = 0.482, p<0.001), BMI-SDS (r = 0.449, p<0.001), fatmass (r = 0.482, p <0.001), percentage of fat (r = 0.412, p<0.001), TSH (r = 0.238, p = 0.037), uric acid (r = 0.238, p = 0.040) as well as systolic (r = 0.359, p = 0.001) and diastolic blood pressure values (r = 0.359, p = 0.001) measured spontaneously and systolic blood pressure values registered during 24 h monitoring (r = 0.344, p = 0.004). Performing multivariate analysis, an association between IMT and BMI was found (R-square = 0.263, beta = 0.525, p<0.001). CONCLUSIONS: In overweight and obese children and adolescents there is a significant association between carotid IMT and weight, BMI, BMI-SDS, blood pressure, as well as various other metabolic parameters. Based on these and other epidemiological data, demonstrating the continuing and significant increase in incidence of overweight and obesity in childhood and adolescence, comprehensive strategies for the long-term prevention and the treatment of risk factors should be emphasized with an early start in childhood.

Therapeutic Apheresis in Immunologic Renal and Neurological Diseases.

Since the mid 1970s, when membrane modules became available, plasma separation techniques have gained in importance especially in the past few years. The advantages of this method are a complete separation of the corpuscular components from the plasma and due to increased blood flow rate and higher efficacy. Systemic autoimmune diseases based on an immune pathogenesis produce autoantibodies and circulating immune complexes, which cause inflammation in the tissues of various organs. In most cases, these diseases have a poor prognosis without treatment. Therapeutic apheresis (TA) in combination with immunosuppressive therapies has led to a steady increase in survival rates over the last 40 years. The updated information on immunology and molecular biology of different immunologic diseases are discussed in relation to the rationale for apheresis therapy and its place in combination with other modern treatments. The different diseases can be treated by various apheresis methods such as therapeutic plasma exchange (TPE) with substitution solution, or with online plasma or blood purification using adsorption columns, which contain biological or non-biological agents. Here, the authors provide an overview of the most important pathogenic aspects indicating that TA can be a supportive therapy in systemic autoimmune diseases such as renal and neurological disorders. For the immunological diseases that can be treated with TA, the guidelines of the German Working Group of Clinical Nephrology and of the Apheresis Committee of the American Society for Apheresis are cited.

Trends in the management of arterial hypertension in patients with type 1 and insulin-treated type 2 diabetes mellitus over a period of 10 years (1989/1990-1994/1995). Results of the JEVIN trial.

UNLABELLED: For populations of patients with insulin-treated diabetes mellitus, information about the quality of blood pressure control, an independent risk factor for cardiovascular mortality and morbidity, is widely lacking. Hence, it was the goal of the trial to evaluate the prevalence of arterial hypertension, the quality of blood pressure control and changes in treatment modalities over a period of 10 years. PATIENTS AND METHODS: In 1989/1990, Jena's St. Vincent (JEVIN) Trial started as a prospective, population-based survey with 10-year follow-up of all patients with type 1 and insulin-treated type 2 diabetes mellitus aged 16 to 60 years and living in the city of Jena, Thuringia, Germany. RESULTS: In 1999/2000, 46 (40.4%) of 114 patients with type 1 and 104 (70.7%) of 147 patients with insulin-treated type 2 diabetes were on blood pressure-lowering drugs. Hypertension prevalence in the total population was 57.5%. It was higher in patients with insulin-treated type 2 than in type 1 diabetes (47.4% vs. 78.9%, P<.001). In 1999/2000, the number of patients with type 1, but also type 2, diabetes on blood pressure-lowering agents was higher than in 1994/1995 and 1989/1990. In the whole group, the mean blood pressure improved from 1989/1990 up to 1994/1995 and has remained constant up to the follow-up examination in 1999/2000. In 1999/2000, of those with arterial hypertension, blood pressure was higher than the 140/90-mm Hg target in 17.5% (20/114) of the patients with type 1 and in 42.2% (62/147) of the patients with insulin-treated type 2 diabetes. CONCLUSIONS: The JEVIN trial provides a useful population-based summary of the quality of blood pressure and metabolic control of patients with insulin-treated diabetes. Although the trial demonstrates an impressive improvement in the quality of blood pressure and metabolic control over the last decade, it also shows various problems: In many patients, both with type 1 and type 2 diabetes mellitus, a good blood pressure control (below 140/90 mm Hg) has not been achieved. Moreover, drug therapy, in particular concerning patients with overt nephropathy, is often inappropriate.

Identification of Predictors for Weight Reduction in Children and Adolescents with Overweight and Obesity (IDA-Insel Survey).

INTRODUCTION: Worldwide, overweight and obesity are known as posing serious health risks. Successful methods of prevention and therapy for overweight and obesity have remained elusive. It was the aim of the present trial to identify parameters and determinants to guarantee long-term weight reduction. PATIENTS AND METHODS: In total 143/159 children and adolescents (90%) with overweight and obesity completed the prospective, multicenter trial (age 13.9 ± 2.4 years, BMI 31.2 ± 5.4 kg/m², BMI-SDS 2.51 ± 0.57). During a six-week rehabilitation patients participated in a structured treatment and teaching program (STTP). Following the inpatient treatment the children and adolescents were monitored over a period of 24 months (physical examination, measurements of BMI, BMI-SDS, body composition, carotid intima-media thickness, laboratory parameters, blood pressure, and standardized questionnaires to assess socio-demographic, socio-economic parameters, eating behavior, well-being, quality of life, intelligence, intrafamilial conflicts, self-efficacy, resilience, sense of coherence, stress-management, social support, and actual body shape). RESULTS: 66% of the children and adolescents showed non-normal laboratory parameters as well as higher blood pressure and/or an increased carotid intima-media thickness. Mean thickness of carotid intima-media was 0.53 ± 0.09 mm (range, 0.40-0.80); 15% of the patients showed a normal range (<0.45 mm), 40% slightly elevated (0.45-0.50 mm) and 45% an elevated (>0.50 mm) thickness. After an inpatient treatment lasting 40.4 ± 4.1 (range, 28-49) days, children and adolescents reached a mean weight reduction of 5.52 ± 3.94 (0.4-13.3) kg (p < 0.01) accompanied by a reduction of body fat mass. Performing multivariate analyses, the most important psychological factors associated with long-term weight reduction were identified (R-square = 0.53): Well-being (ß = -0.543), resilience (ß = 0.434) and intrafamilial conflicts (ß = 0.315). CONCLUSION: The different parameters (i.e., resilience, intrafamilial conflicts, structured daily schedule) have demonstrated their utility and strategies should be developed allowing an adaption of these into the STTPs and the integration of intervention into the therapeutic setting.

Predictors and determinants for weight reduction in overweight and obese children and adolescents.

INTRODUCTION: Worldwide, overweight and obesity are known as posing serious health risks. Successful methods for weight reduction have remained elusive. This multicenter non-randomised trial aimed to identify parameters and determinants of long-term weight reduction. PATIENTS AND METHODS: A total of 143/159 overweight and obese children and adolescents (90 %) completed the prospective multicenter trial (age 13.9±2.4 years, BMI 31.2±5.4kg/m2, BMI-SDS 2.51±0.57). During a 6-week rehabilitation period the patients participated in a structured treatment and teaching program (STTP). Following in-patient treatment the children and adolescents were monitored over a period of 24 months (physical examination, measurements of BMI, BMI-SDS, body composition, carotid intima-media thickness, laboratory parameters, blood pressure, standardized questionnaires to assess socio-demographic and socio-economic parameters, eating behavior, well-being, quality of life, intelligence, intrafamilial conflicts, self-efficacy, resilience, sense of coherence, stress management, social support, actual body shape). RESULTS: 66% of the children and adolescents had abnormal laboratory parameters as well as higher blood pressure and/or an increased carotid intima-media thickness. The mean carotid intima-media thickness was 0.53±0.09mm (range 0.40 to 0.80); 15% of the patients showed normal range values (< 0.45mm), 40% a slightly elevated (≥ 0.45 to ≤ 0.50mm) and 45% an elevated (> 0.50mm) thickness. After the inpatient treatment lasting 40.4±4.1 (range 28 to 49) days, children and adolescents reached a mean weight reduction of 5.52±3.94 (0.4 to 13.3) kg (p<0.01) that was accompanied by a reduction in body fat mass. Using multivariate analyses, the most important psychological factors associated with long-term weight reduction were identified (R-square=0.53): well-being (ß=-0.543), resilience (ß=0.434), and sense of coherence (ß=0.315). CONCLUSION: The different parameters (i. e., well-being, resilience, sense of coherence) have demonstrated their utility, and strategies should be developed allowing an adaption of these into the STTPs.

Plasma copeptin in children and adolescents with type 1 diabetes mellitus in comparison to healthy controls.

UNLABELLED: In a cohort of children and adolescents with type 1 diabetes mellitus the trial tested the hypothesis that copeptin levels are associated with kidney function, biometrical data and quality of diabetes control. PATIENTS AND METHODS: A total of 141 subjects were recruited to participate in the trial: 80 patients with type 1 diabetes (13.0±3.4years, HbA1c 7.85±1.42%) and 61 healthy controls (12.4±2.8years). Clinical and socio-economic data were assessed. A sandwich immunoassay (B.R.A.H.M.S. GmbH/Thermo Fisher Scientific, Hennigsdorf/Berlin, Germany) was used for measuring plasma copeptin levels. RESULTS: The mean concentration of copeptin in the diabetic patients was 4.75±3.46pmol/l. There was a strong inverse correlation between copeptin and GFR (r=-0.86, p=0.021), as well as with total cholesterol (r=-0.23, p=0.041), LDL-cholesterol (r=-0.24, p=0.036), but not with serum creatinine, albuminuria, HbA1c, blood glucose, MAGE, CRP, systolic or diastolic blood pressure or age, diabetes duration, weight, height and BMI. Comparing patients with a diabetes duration of ⩾7years (n=45) with those with a diabetes duration <7years (n=35), patients with a longer duration of diabetes had higher copeptin levels (5.24±2.26 vs 4.13±2.86, p=0.045). Performing multivariate analyses only GFR could be identified as a parameter associated with copeptin (R-square=0.05, ß=-0.23, p=0.032). In the healthy controls mean copeptin concentration was 5.56±3.15pmol/l. The copeptin concentration and GFR were inversely correlated as well (r=-0.61, p=0.034). However, other correlation and multivariate analyses revealed no further significant results. Comparing patients with type 1 diabetes mellitus with the healthy controls, the diabetes patients revealed no significant difference with respect to copeptin (p=0.24), serum creatinine (49.8±11.9 vs 50.4±11.0µmol/l, p=0.53) or GFR (102.4±23.3 vs 104.5±19.1ml/min, p=0.47). On the other hand, patients with type 1 diabetes had lower concentrations of CRP (1.66±3.91 vs 3.21±3.04µg/ml, p=0,013), triglycerides (0.88±0.53 vs 1.13±0.60mmol/l, p=0.010), and a lower ratio of LDL-/HLD-cholesterol (1.73±0.69 vs 2.32±0.80, p<0.001), as well as lower body weight (51.3±18.0 vs 60.3±15.7kg, p=0.002) and BMI (19.7±3.8 vs 23.2±2.9kg/m(2), p<0.001). In contrast to the controls, the diabetes patients had higher blood glucose levels at the time of examination (8.2±3.8 vs 4.7±0.5mmol/l, p<0.001), higher HDL-cholesterol levels (1.59±0.34 vs 1.26±0.24mmol/l, p<0.001), as well as higher education and higher educational levels of the mothers. CONCLUSIONS: The present trial revealed a clear association between GFR and copeptin in children and adolescents with type 1 diabetes mellitus. Hence, copeptin can be considered as a marker of renal function.

Therapeutic Apheresis in Hematologic, Autoimmune and Dermatologic Diseases With Immunologic Origin.

The process of curing a patient by removing his illness by extracting blood is a very old one. Many years ago, phlebotomy was practiced to cure illness. Now, this old process, placed on a rational basis with therapeutic apheresis (TA), is being followed in clinical practice. Therapeutic plasma exchange (TPE) with hollow fiber modules has been used in different severe diseases for more than 40 years. Based on many years of experience with the extracorporeal circulation in end-stage renal disease, the authors herein give an overview of TA in immunological diseases, especially in hematologic, autoimmune and dermatologic diseases. Updated information on immunology and molecular biology of different immunological diseases is discussed in relation to the rationale for apheresis therapy and its place in combination with other modern therapies. With the introduction of novel and effective biologic agents, TA is indicated only in severe cases, such as in rapid progression despite immunosuppressive therapy and/or biologic agents. In mild forms of autoimmune disease, treatment with immunosuppressive therapies and/or biologic agents seems to be sufficient. The prognosis of autoimmune diseases with varying organ manifestations has improved in recent years, due in part to very aggressive therapy schemes. For the immunological diseases that can be treated with TA, the guidelines of the German Working Group of Clinical Nephrology and of the Apheresis Applications Committee of the American Society for Apheresis are cited. TA has been shown to effectively remove the autoantibodies from blood and lead to rapid clinical improvement.

Risk of malignancies in patients with insulin-treated diabetes mellitus: results of a population-based trial with 10-year follow-up (JEVIN).

BACKGROUND: Studies involving diabetes mellitus and malignancies show contradictory results: Many of them have found incidences of malignancies that are comparable or lower, other studies have found higher rates than those of non-diabetic subjects. Hence, the goal of the present trial was to study the possible association between diabetes mellitus and the incidence of malignancies and its outcome in a selection-free population over a longer period of time. - PATIENTS AND METHODS: All the patients (n=291) who participated in the JEVIN (Jena's St. Vincent)- trial (a prospective, 10 year follow-up, population-based intervention survey of all insulin-treated patients with type 1 and type 2 diabetes mellitus aged 16 to 60 years and living in the city of Jena [about 100,000 inhabitants], Thuringia, Germany) were assessed. The baseline examination took place in 1989/90, follow-up examinations were performed in 1994/95 and 1999/2000. - RESULTS: Up to 1999/2000, 2 patients with type 1 and 5 patients with insulin-treated type 2 diabetes mellitus developed a malignancy (incidence 0.0241). The most frequent malignancies were cancer of the colon and rectum (3 of 291 patients, incidence 0.0103). Comparing these data with the incidence of carcinoma of the colon and rectum reported by the Robert-Koch-Institute of Germany (incidence 0.0012) diabetic patients showed a 9.9-fold increased risk (p=0.042). There were no significant differences regarding incidence of total malignancies or carcinoma of the breast, the lung, renal cells or gonads. Correlation and multivariate analyses revealed no associations between the development of malignancies and patients' outcome and diabetes duration, the duration of insulin therapy, insulin dosage, the quality of diabetes control or the presence of diabetes-related long-term complications. - CONCLUSIONS: Conclusive to other data derived from selected cohorts, population-based the JEVIN-trial demonstrate an increased incidence of malignancies of the colon and rectum in insulin-treated patients with diabetes mellitus. However, for further confirmation of these interesting results more studies in larger populations over longer periods of time are necessary to explain the heterogeneous findings in patients with diabetes mellitus of an increased incidence for some cancer entities, but not for others. Knowledge of these mechanisms should have important implications for the direction of strategies to prevent the development of malignancies, or to enhance ability to make an earlier diagnosis and more effective therapies.

[Costs of therapy of insulin-treated patients with Diabetes mellitus in Germany. Results of the JEVIN trial]. / Therapiekosten bei insulinbehandelten Patienten mit Diabetes mellitus in Deutschland am Beispiel der JEVIN-Studie.

BACKGROUND AND PURPOSE: Diabetes mellitus, its treatment with oral antidiabetic drugs and insulin, self-monitoring and the development of diabetesrelated long-term complications raise multiple socioeconomic problems. Hence, diabetes is one of the major challenges to modern health care systems. To date, there are only few data analyzing diabetes-related costs. Therefore, it was the aim of this trial to assess the costs of therapy of insulin-treated patients with diabetes mellitus out of a selection-free population over a period of 5 years. PATIENTS AND METHODS: JEVIN (Jena's St. Vincent trial) is a prospective population-based trial of all patients with type 1 and insulin-treated type 2 diabetes mellitus aged 16-60 years and living in the city of Jena, Thuringia, Germany. In addition to parameters of diabetes control (relative hemoglobin A(1c) [= HbA(1c)/mean normal], long-term complications, blood pressure), the costs of therapy in respect of insulin and oral antidiabetic drugs and materials to perform self-monitoring were analyzed in 1999/2000 compared to 1994/95. In 1994/95, 244 patients, in 1999/2000, 291 patients were examined. RESULTS: During the period from 1994/95 to 1999/2000, relative HbA(1c) improved in both patients with type 1 (1.65 +/- 0.35 [n = 127] vs 1.48 +/- 0.30 [n = 114]; p < 0.0001) and insulin-treated type 2 diabetes (1.75 +/- 0.40 [n = 117] vs. 1.47 +/- 0.25 [n = 147]; p < 0.0001). The quality of blood pressure control remained constant. In 1999/2000 the costs per unit insulin for patients with type 1 diabetes were calculated at about 0.078 +/- 0.035 DM, in 1994/95 at 0.075 +/- 0.032 DM (p = 0.873). For patients with type 2 diabetes the costs were calculated at 0.070 +/- 0.032 DM in 1999/2000 and at 0.070 +/- 0.028 DM (p = 0.954) in 1994/95. In 1999/2000, to perform blood glucose self-monitoring the costs were 4.08 +/- 1.39 DM/d for patients with type 1 diabetes and 3.07 +/- 1.36 DM/d for patients with type 2 diabetes. In 1994/95 the costs for patients with type 1 diabetes amounted to 3.56 +/- 1.69 DM/d (p = 0.012), and for patients with insulin-treated type 2 diabetes mellitus to 2.77 +/- 1.66 DM/d (p = 0.138). In 1999/2000 the costs for antihypertensive drugs in 46/114 patients with type 1 diabetes were calculated at about 1.43 +/- 1.10 DM/d. In 1994/95 the costs for 32/127 patients amounted to 1.76 +/- 1.00 DM/d (p = 0.501). For 104/147 patients with insulin-treated type 2 diabetes, the costs of antihypertensive drugs were 2.02 +/- 1.48 DM/d in 1999/2000. In 1994/95 the costs amounted to 1.77 +/- 1.11 DM/d (p = 0.141) for 54/117 patients. In 1994/95 the total costs for patients with type 1 diabetes mellitus were calculated at about 7.10 +/- 2.69 DM/d. In 1999/2000 the costs amounted to 7.70 +/- 2.75 DM/d (p = 0.085). In patients with insulin-treated type 2 diabetes mellitus there was a significant increase in 1999/2000 versus 1994/95 (1994/95: 6.43 +/- 3.16, 1999/2000: 7.57 +/- 3.56 DM/d; p = 0.007). CONCLUSION: Despite a tendency toward an increase in the costs for daily life, the therapy-related costs for patients with type 1 diabetes mellitus were constant in 1999/2000 versus 1994/95. In patients with type 2 diabetes, there was an increase of about 18%. For both patients with type 1 and type 2 diabetes, the costs were substantially higher than calculated in theoretical models.

Accuracy of blood glucose meters for self-monitoring affects glucose control and hypoglycemia rate in children and adolescents with type 1 diabetes.

AIMS/HYPOTHESIS: This study investigated the accuracy of blood glucose meters for self-monitoring and its influence on glycated hemoglobin (HbA1c) levels and the frequency of hypoglycemic coma. MATERIALS AND METHODS: Self-measured and simultaneously obtained laboratory blood glucose values from 9,163 patients with type 1 diabetes <18 years of age in the German/Austrian Diabetes Prospective Documentation Initiative registry were analyzed by investigating their compliance with the International Organization for Standardization (ISO) criteria (versions 2003 and 2013) and by error grid analyses. Regression models elucidated effects on glucose control and hypoglycemia rates. RESULTS: Depending on the respective subgroup (defined by sex, age, duration of diabetes, mode of insulin therapy), 78.7-94.7% of the self-monitoring of blood glucose (SMBG) values met the old and 79.7-88.6% met the new ISO criteria. In Clarke and Parkes error grid analyses, the percentages of SMBG values in Zone A ranged between 92.8% and 94.6% (Clarke) and between 92.2% and 95.0% (Parkes). The patient group with SMBG devices measuring "far too low" (compared with the laboratory-obtained glucose levels) presented with a higher HbA1c level than those measuring "far too high," "too high," "identical/almost identical," or "too low" (based on quintiles of deviation). Performing "far too high" was associated with the highest rate of hypoglycemic coma in comparison with the other deviation quintiles. CONCLUSIONS: This study showed that current SMBG devices fulfilled neither the previous nor the new ISO criteria. Large deviations of the SMBG values from the "true" glucose levels resulted in higher HbA1c levels and markedly increased rates of hypoglycemic events.