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.

Impact of regular physical activity on blood glucose control and cardiovascular risk factors in adolescents with type 2 diabetes mellitus--a multicenter study of 578 patients from 225 centres.

INTRODUCTION: Regular physical activity (RPA) is a major therapeutic recommendation in children and adolescents with type 2 diabetes mellitus (T2DM). We evaluated the association between frequency of RPA and metabolic control, cardiovascular risk factors, and treatment regimes. METHODS: The Pediatric Quality Initiative (DPV), including data from 225 centers in Germany and Austria, provided anonymous data of 578 patients (10-20 yr; mean 15.7 ± 2.1 yr; 61.9% girls) with T2DM. Patients were grouped by the frequency of their self-reported RPA per week: RPA 0, none; RPA 1, 1-2×/wk; RPA 2, >2×/wk. RESULTS: The frequency of RPA ranged from 0 to 9×/wk (mean 1.1×/wk ±1.5). 55.7% of the patients reported no RPA (58.1% of the girls). Hemoglobin A1c (HbA1c) differed significantly among RPA groups (p < 0.002), being approximately 0.8 percentage points lower in RPA 2 compared to RPA 0. Body mass index (BMI-SDS) was higher in the groups with less frequent RPA (p < 0.00001). Multiple regression analysis revealed a negative association between RPA and HbA1c (p < 0.0001) and between RPA and BMI-SDS (p < 0.01). The association between RPA and high density lipoprotein (HDL)-cholesterol was positive (p < 0.05), while there was no association to total cholesterol, low density lipoprotein (LDL)-cholesterol or triglycerides. Approximately 80% of the patients received pharmacological treatment (oral antidiabetic drugs and/or insulin) without differences between RPA groups. CONCLUSION: More than half of the adolescents with T2DM did not perform RPA. Increasing physical activity was associated with a lower HbA1c, a lower BMI-SDS, a higher HDL-cholesterol, but not with a difference in treatment regime. These results suggest that regular exercise is a justified therapeutic recommendation for children and adolescents with T2DM.

Type 1 Diabetes Mellitus in the First Years of Life - Onset, Initial Treatment, and Early Disease Course.

OBJECTIVE: This study investigated the onset and the choice of treatment in children with very early onset of type 1 diabetes mellitus (T1D). METHODS: The study included 5,763 patients from the German Diabetes Patient Follow-up registry with onset of T1D in the first 4 years of life from January 2010 - June 2022. The analysis included diabetes-specific parameters, anthropometric data, and mode of treatment at onset, within the first and second year of T1D. Three groups were compared according to age at onset (G1: 223 patients 6-<12 months, G2: 1519 patients 12-<24 months, G3: 4001 patients 24-48 months). RESULTS: In 12.3% of all cases in childhood and adolescence, the incidence of diabetes in the first 4 years of life was rare. At the onset, clinical status was worse and diabetic ketoacidosis (DKA) rates were higher in G1 and G2 (52.3% and 46.5%, respectively) compared to G3 (27.3% (p<0.001)). G1 and G2 were significantly more likely to be treated with insulin pump therapy (CSII) 2 years after onset (98.1% and 94.1%, respectively)) compared to G3 (85.8%, p<0.001). Median HbA1c after 2 years did not differ between groups (G1: 7.27% (56.0 mmol/mol), G2: 7.34% (56.7 mmol/mol) and G3: 7.27% (56.0 mmol/mol)) or when comparing CSII vs MDI. The rate of severe hypoglycemia (SH) and DKA during the first 2 years of treatment did not differ among the three groups, ranging from 1.83-2.63/100 patient-years (PY) for DKA and 9.37-24.2/100 PY for SH. Children with T1D under 4 years of age are more likely to be diagnosed with celiac disease but less likely to have thyroiditis than older children with T1DM. CONCLUSIONS: Young children with T1D had high rates of DKA at onset and were predominantly treated with insulin pump therapy during the first 2 years. The median HbA1c for all three groups was<7.5% (58 mmol/mol) without increased risk of SH or DKA. The use of continuous glucose monitoring (CGM) was not associated with lower HbA1c in children under 48 months.

[Morning hyperglycemia in children and adolescents with type 1 diabetes and different modes of therapy: an evaluation of the DPV data pool]. / Morgenhyperglykämie bei Kindern und Jugendlichen mit Typ-1-Diabetes bei unterschiedlichen Therapieformen: Eine Auswertung des DPV-Datenpools.

Early morning hyperglycemia is frequent among children and adolescents with type 1 diabetes. Reasons are a dawn phenomenon, a Somogyi phenomenon or a lack of insulin in the morning hours. Only few studies are published regarding incidence and relation to different modes of basal insulin treatment in this population.We analyzed all cases recorded in the DPV register from 1995 to 2010. 5 839 patients from 128 centers with at least 3 blood glucose measurements during the last night of a hospital stay were included.24.2% of patients showed a morning hyperglycemia above 200 mg/dl. 8.6% showed a dawn phenomenon, 7.0 % a lack of insulin and 2.0% a Somogyi phenomenon. A dawn phenomenon was significantly less frequent in patients treated with an insulin pump (1.1%) compared to long acting insulin analogs Glargin and Levemir (5.4%) or NPH insulin (8.2%). Lack of insulin was again less frequent during insulin pump treatment compared to other treatments (1.9% vs. 4.9% vs. 5.3%). Median rise of blood glucose levels was 33.4 mg/dl between midnight and 6 a.m. Mode of basal insulin treatment is an important factor: while treatment with an insulin pump led to a blood glucose fall of 28.5 mg/dl between 3 and 6 a.m., treatment with insulin analog or NPH insulin resulted in a rise of 28.5 or 35.9 mg/dl, respectively.This study shows that insulin pump treatment reduces the frequency of morning hyperglycemia caused by the dawn phenomenon or a lack of insulin.

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.

[Individualization of diabetes treatment by automated insulin delivery]. / Individualisierung der Diabetestherapie durch Automatisierung der Insulingabe.

Insulin pumps and glucose sensors have been shown to be effective in improving diabetes treatment and reducing acute complications according to data from registries. Therefore, in pediatric diabetology the use of at least one technical device is standard. Both devices can also be combined to form automated insulin delivery (AID) systems.Many AID systems have been tested in clinical trials and have proven to be safe and effective. The supply situation in Germany currently only allows one system to be prescribed for people insured by the statutory health insurances. Currently, children younger than 7 years of age cannot be treated with this system. The reasons for this are legal hurdles and lack of certification by the manufacturers. The CE certification can also lead to problems with insulin prescriptions. Open-source systems are non-regulated variants to circumvent existing regulatory conditions. There are risks here for both users and prescribers.For permanent use a thorough knowledge of the features of each AID system is necessary for both the user and the practitioner. Complete automation does not yet work. For the evaluation of the AID treatment, the metric data of the glucose sensors, the time in range and the glucose management index are the recognized and suitable parameters, because they allow a consultation based on real data from the daily life of people with diabetes.As all glucose sensors are read out via cloud-based software or the data are obtained directly and automatically from a telephone-linked receiver device, this provides the ideal technical basis for telemedical care, which still needs to be configured.

Sensor-augmented pump therapy from the diagnosis of childhood type 1 diabetes: results of the Paediatric Onset Study (ONSET) after 12 months of treatment.

AIMS/HYPOTHESIS: The value of managing children with type 1 diabetes using a combination of insulin pump and continuous glucose monitoring starting from diagnosis for improving subsequent glycaemic control and preserving residual beta cell function was determined. METHODS: A total of 160 children (aged 1-16 years, mean ± SD: 8.7 ± 4.4 years; 47.5% girls) were randomised to receive insulin pump treatment with continuous glucose monitoring or conventional self-monitoring blood glucose measurements. The primary outcome was the level of HbA(1c) after 12 months. Other analyses included fasting C-peptide, glycaemic variability, sensor usage, adverse events, children's health-related quality of life and parent's wellbeing. RESULTS: HbA(1c) was not significantly different between the two groups, but patients with regular sensor use had lower values (mean 7.1%, 95% CI 6.8-7.4%) compared with the combined group with no or low sensor usage (mean 7.6%, 95% CI 7.3-7.9%; p=0.032). At 12 months, glycaemic variability was lower in the sensor group (mean amplitude of glycaemic excursions 80.2 ± 26.2 vs 92.0 ± 33.7; p=0.037). Higher C-peptide concentrations were seen in sensor-treated 12- to 16-year-old patients (0.25 ± 0.12 nmol/l) compared with those treated with insulin pump alone (0.19 ± 0.07 nmol/l; p=0.033). Severe hypoglycaemia was reported only in the group without sensors (four episodes). CONCLUSION/INTERPRETATION: Sensor-augmented pump therapy starting from the diagnosis of type 1 diabetes can be associated with less decline in fasting C-peptide particularly in older children, although regular sensor use is a prerequisite for improved glycaemic control. TRIAL REGISTRATION: ISRCTN.org ISRCTN05450731 FUNDING: Medtronic International Trading Sàrl, Tolochenaz, Switzerland.

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.

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.

Metabolic decompensation in children with type 1 diabetes mellitus associated with increased serum levels of the soluble leptin receptor.

OBJECTIVE: Type 1 diabetes mellitus (T1DM) leads to increased serum levels of the soluble leptin receptor (sOB-R) by an as yet unknown cellular mechanism. The aim of our study was to investigate potential metabolic factors that may be associated with the induction of the sOB-R release from its membrane receptor. MATERIALS AND METHODS: Twenty-five children (aged between 1.5 and 17.0 years) were studied at the onset of T1DM. Blood samples were collected before (n = 25), during the first 18 h (mean +/- S.D. 11.1 +/- 4.3 h, n = 16) and 92 h (47.5 +/- 22.5 h; n = 14) after beginning insulin therapy. Serum sOB-R and leptin levels were determined by in-house immunoassays. RESULTS: The sOBR-level and the molar sOB-R/leptin ratio were significantly higher before than after starting insulin treatment (P < 0.05). In contrast, leptin levels were significantly lower (P < 0.05) before insulin therapy. The correlation between sOB-R and blood glucose (r = 0.49; P < 0.05), as well as sOB-R with parameters of ketoacidosis, such as pH (r = -0.72), base excess (r = -0.70), and bicarbonate (r = -0.69) (P < 0.0001) at diagnosis of T1DM remained significant during the first 18 h of insulin treatment. Multiple regression analysis revealed that base excess predicted 41.0% (P < 0.001), age 16.4% (P < 0.05), and height SDS 13.9% (P < 0.01) of the sOB-R variance. CONCLUSIONS: Metabolic decompensation in children with new onset T1DM is associated with dramatic changes of the leptin axis; serum levels of sOB-R are elevated and of leptin are reduced. The molar excess of sOB-R over leptin (median 11.3) in this condition may contribute to leptin insensitivity. Upregulation of the soluble leptin receptor appears to be a basic mechanism to compensate for intracellular substrate deficiency and energy-deprivation state.

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).

Clinical characteristics of type 2 diabetes mellitus in overweight European caucasian adolescents.

AIM: To present the clinical features of Type 2 diabetes mellitus (T2DM) in overweight European Caucasian children and adolescents. METHODS: We report the clinical characteristics of 16 non-syndromal overweight European Caucasian adolescents with T2DM (10 boys, 6 girls, SDS-BMI in median +2.8, range +1.6 to +3.4) treated in 5 specialised centres for obesity and diabetes. RESULTS: None of the adolescents manifested with ketoacidosis. 13 were asymptomatic (3 adolescents with polyuria), 12 showed features of metabolic syndrome (dyslipidaemia or hypertension), 8 demonstrated acanthosis nigricans and 12 had relatives with T2DM. 11 adolescents were extremely obese and all patients were pubertal. Mean age at diagnosis was 14.2 years (range 11.0 - 16.9). Median insulin was 19 microU/ml, insulin resistance index (HOMA) 8.5, C-peptide 2.3 ng/ml, HbA1c 6.9 %, fasting blood glucose 176 mg/dl and blood glucose at 2 hours with the oGTT 229 mg/dl at manifestation. Fasting blood glucose and HBA1c were in the normal range in 4 and 6 adolescents respectively, while oGTT always fitted the diagnosis of T2DM. CONCLUSION: Since T2DM occurred in Caucasian overweight adolescents and is frequently asymptomatic, it is essential that clinicians perform diagnostic procedures to identify T2DM in high-risk groups of overweight Caucasian adolescents (extreme obesity, features of metabolic syndrome, relatives with T2DM).

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.

Clinical aspects of obesity in childhood and adolescence.

The level of fatness of a child at which morbidity acutely and/or later in life increases is determined on an acturial basis. Direct measurements of body fat content, e.g. hydrodensitometry, bioimpedance, or DEXA, are useful tools in scientific studies. However, body mass index (BMI) is easy to calculate and is generally accepted now to be used to define obesity in children and adolescents clinically. An increased risk of death from cardiovascular disease in adults has been found in subjects whose BMI had been greater than the 75th percentile as adolescents. Childhood obesity seems to substantially increase the risk of subsequent morbidity whether or not obesity persists into adulthood. The genetic basis of childhood obesity has been elucidated to some extent through the discovery of leptin, the ob gene product, and the increasing knowledge on the role of neuropeptides such as POMC, neuropeptide Y (NPY) and the melanocyte concentrating hormone receptors (for example, MC4R). Environmental/exogenous factors largely contribute to the development of a high degree of body fatness early in life. Twin studies suggest that approximately 50% of the tendency toward obesity is inherited. There are numerous disorders including a number of endocrine disorders (Cushing's syndrome, hypothyroidism, etc.) and genetic syndromes (Prader-Labhard-Willi syndrome, Bardet Biedl syndrome, etc.) that can present with obesity. A simple diagnostic algorithm allows for the differentiation between primary or secondary obesity. Among the most common sequelae of primary childhood obesity are hypertension, dyslipidemia, back pain and psychosocial problems. Therapeutic strategies include psychological and family therapy, lifestyle/behaviour modification and nutrition education. The role of regular exercise and exercise programmes is emphasized. Surgical procedures and drugs used in adult obesity are still not generally recommended in children and adolescents with obesity. As obesity is the most common chronic disorder in industrialized societies, its impact on individual lives as well as on health economics has to be recognized more widely. This review is aimed towards defining the clinical problem of childhood obesity on the basis of current knowledge and towards outlining future research areas in the field of energy homoesostasis and food intake in relation to child health. Finally, one should aim to increase public awareness of the ever increasing health burden and economic dimension of the childhood obesity epidemic that is present around the globe.

Increased serum soluble leptin receptor levels in children and adolescents with type 1 diabetes mellitus.

OBJECTIVE: We investigated whether or not serum levels of the soluble leptin receptor (sOB-R) and leptin are related to anthropometric and metabolic changes during pubertal development of children and adolescents with type 1 diabetes mellitus. DESIGN AND METHODS: Blood levels of sOB-R, leptin and HbA1C, as well as body-mass index (BMI), diabetes duration and daily insulin doses, were determined in 212 (97 girls; 115 boys) children with type 1 diabetes mellitus and compared with the sOB-R serum levels in 526 healthy children and adolescents. RESULTS: OB-R serum levels and parallel values of the molar ratio between sOB-R and leptin were significantly higher in children with diabetes than in normal children (P<0.05) in almost all investigated Tanner stages. Furthermore, in the entire group of patients, we demonstrated statistically significant correlations (P<0.02) between sOB-R and the duration of diabetes (r=0.30), HbA1c levels (r=0.32) and the insulin dose (r=0.18). Multiple-regression analysis revealed that HbA1c (12.4%), height (7.9%) and duration of diabetes (8.7%) contributed to 29% variance of sOB-R in diabetic children. CONCLUSIONS: Our data suggest that poor glycemic control in diabetes may lead to increased serum levels of sOB-R. This regulation of sOB-R appears to be independent of leptin, but may have an impact on leptin action. The consequently developing molar excess of sOB-R related to leptin could reduce leptin sensitivity and may, therefore, influence leptin-related anthropometric and metabolic abnormalities.