Christian Denzer

The outcome of childhood obesity management depends highly upon patient compliance

Over the last 20 years, obesity in childhood and adolescence has become a major public health concern due to dramatically increasing prevalence rates. We evaluated the outcome of 294 children (135 girls, 159 boys) aged 6–16 years (median 10.9 years) enrolled in a single centre outpatient obesity intervention programme consisting of periodical visits to the outpatient unit with regular medical and dietetic counselling aiming at a modification of dietary and activity patterns of patients and parents. The average number of visits to the outpatient unit was 3.6 (SD 2.7) with a mean visit interval of 62.1 days. A mean drop-out rate of 27.5% between each scheduled appointment occurred. In a stepwise regression model, neither reduction of the standard deviation score of patients’ body mass index (BMI-SDS) nor dietary counselling contributed to the total number of visits. The only significant contributor was the patients’ initial BMI-SDS explaining 4.6% of the variance of attended visits adjusted for age and sex. Segregation of the patients into an “obesity” (initial BMI-SDS ≥90th percentile, at least three visits attended, n =59) and an “excessive obesity” (initial BMI-SDS ≥99th percentile, at least four visits attended, n =75) subgroup showed a mean reduction of BMI-SDS in the “obesity” group at visit three of 0.14 (SD 0.21, P <0.0001), and in the “excessive obese” group at visit four of 0.17 (SD 0.22, P <0.001). In a stepwise regression model, the mean interval between visits and regular dietary counselling explained 11.7% of the variance of BMI-SDS reduction at visit three in both subgroups. Conclusion: there is an urgent need for efficient strategies to improve adherence of outpatients to obesity treatment since, in terms of reduction in body mass index standard deviation score, a beneficial outcome can be achieved for compliant obese children and adolescents.

Parental diabetes, pubertal stage, and extreme obesity are the main risk factors for prediabetes in children and adolescents: a simple risk score to identify children at risk for prediabetes.

Objectives:  The current worldwide increase of prediabetes defined as impaired fasting glucose or impaired glucose tolerance and type 2 diabetes mellitus (T2DM) coincides the increase of obesity. However, it is unclear that which children have an increased risk and should be screened for prediabetes.

Subclinical hypothyroidism and dyslipidemia in children and adolescents with type 1 diabetes mellitus

OBJECTIVE Recent epidemiological evidence suggests that subclinical hypothyroidism (SCH), defined as elevated TSH concentrations with normal circulating levels of triiodothyronine (T3) and thyroxine (T4), is associated with dyslipidemia and cardiovascular disease in adult populations. As currently no data are available on the prevalence of SCH and its potential association with lipoprotein profile in children and adolescents with type 1 diabetes (T1DM), we investigated the prevalence of SCH and associated lipid levels in young diabetic patients. DESIGN AND METHODS Cross-sectional analysis of 22,747 children, adolescents, and young adults (age <25 years) with T1DM with normal T3 and T4 and either normal TSH (≥0.5 to <4.0 mIU/l, euthyroid group) or elevated TSH (≥4.0 to <25.0 mIU/l, SCH group) and simultaneous measurement of serum lipid and lipoprotein status. RESULTS The prevalence rate of SCH in the study population was 7.2%. Adjusted for age, gender, diabetes duration, current insulin dose, HbA1c, and BMI z-score, patients with SCH had significantly higher levels of total cholesterol (178.7 vs 175.3 mg/dl, P<0.001) and LDL-cholesterol (97.0 vs 93.7 mg/dl, P<0.001) compared with euthyroid patients. CONCLUSIONS SCH is a common finding in children, adolescents, and young adults with T1DM. SCH is associated with increased levels of total cholesterol, and LDL-cholesterol adjusted for potential confounders. SCH-associated increases in lipid and lipoprotein levels may therefore add to an increased long-term cardiovascular risk in young patients with T1DM.

Severe Early-Onset Obesity Due to Bioinactive Leptin Caused by a p.N103K Mutation in the Leptin Gene.

Context: Congenital leptin deficiency is a very rare cause of severe early-onset obesity. We recently characterized a mutation in the leptin gene (p.D100Y), which was associated with detectable leptin levels and bioinactivity of the hormone. Case Description: We now describe two siblings, a 9-year-old girl and a 6-year-old boy with severe early-onset obesity and hyperphagia, both homozygous for a c.309C>A substitution in the leptin gene leading to a p.N103K amino acid exchange in the protein and detectable circulating levels of leptin. In vitro experiments in a heterologous cell system demonstrated that the mutated protein was biologically inactive. Treatment with sc recombinant human leptin led to rapid improvement of eating behavior and weight loss. Conclusions: Sequencing of the leptin gene may need to be considered in hyperphagic, severely obese children with detectable levels of circulating leptin.

Depression, metabolic control, and antidepressant medication in young patients with type 1 diabetes.

Recent literature suggests an association between type 1 diabetes (T1D) and depression. So far, most studies explored this link in adult populations, with few data being available on diabetes and depression from minors and young adults. This study aimed to look for associations between symptoms of depression/antidepressant treatment and metabolic outcomes of T1D.

Prevalence and phenotypic characterization of MC4R variants in a large pediatric cohort

Objective:We aimed to determine the prevalence of melanocortin-4 receptor (MC4R) variants in a large German cohort of children with obesity in a pediatric outpatient clinic and to ascertain whether there is a specific phenotype associated with loss-of-function variants as previously reported.Study Design:Eight hundred and ninety-nine patients from our pediatric obesity clinic were screened for MC4R variants by DNA sequencing after PCR amplification. Retrospective statistical analysis of anthropometric and metabolic characteristics was performed, comparing patients with and without MC4R variants across the entire cohort (n=586) as well as in case–control analysis using patients with common sequence MC4R individually matched for age, sex and body mass index standard deviation score (SDS) (n=11 case–control pairs).Results:We identified heterozygous variants within the coding region of the MC4R gene in n=22 (2.45%) patients. Fourteen (1.56%) had a variant that impaired receptor function. One new frameshift (p.F152Sfs), an yet unpublished nonsense mutation (p.Q156X) and one nonsynonymous variation (p.V65E) described in the Mouse Genome Database were detected. Across the whole cohort, at all ages, mean height SDS in subjects with impaired receptor function was higher than in patients with common sequence MC4R. In matched individuals, this trend persisted (8 of the 11 pairs) within the case–control setting. No differences were found regarding metabolic characteristics.Conclusions:The observed prevalence of mutations causing impaired receptor function in this large cohort is comparable to other pediatric cohorts. MC4R deficiency tends to lead to a taller stature, confirming previous clinical reports. The association of MC4R mutations with a distinct phenotype concerning metabolic characteristics remains questionable.

A case of phace syndrome and acquired hypopituitarism

BackgroundPHACE is a neurocutaneous syndrome associated with: Posterior fossa brain malformations, large “segmental” facial hemangiomas, arterial cerebrovascular-, cardiovascular-, and eye anomalies.Case vignetteWe are reporting a girl with PHACE syndrome. The patient had a congenital right-sided facial hemangioma with plaque-morphology. At age 11 years and 2 months she presented with short stature, markedly decreased growth velocity and signs and symptoms suggestive of hypothyroidism. Magnetic Resonance Imaging (MRI) of the brain revealed complex structural and cerebrovascular arterial anomalies, including an empty sella. Testing of pituitary function revealed multiple pituitary dysfunctions, including absolute growth hormone deficiency, hypogonadotropic hypogonadism, central hypothyroidism, and secondary adrenal insufficiency.ConclusionsThis case suggests the necessity to screen all patients with PHACE syndrome and intracranial malformations for pituitary dysfunction at regular intervals.

Thyroid dysfunction and hepatic steatosis in overweight children and adolescents

Overt or subclinical hypothyroidism is a common finding in adult populations affected by non‐alcoholic fatty liver disease (NAFLD). Currently, there are only sparse data available on the association of thyroid dysfunction and NAFLD in obese children and adolescents.

Sleep and glycemic control in adolescents with type 1 diabetes

Increasing evidence link sleep curtailment and circadian misalignment with adverse metabolic outcome. Adolescents might be most affected, given their late sleep timing and early school and work start times.

Mild Hypothermia in a Child with Low-Dose Risperidone

Risperidone is a widely used, second-generation antipsychotic approved for treating schizophrenia as well as for treating aggression in children and adolescents with mental retardation. The substance has a well-established risk profile including alterations of body temperature. Apart from hyperthermia with and without full-blown malignant neuroleptic syndrome, low body temperatures (hypothermia) have also been reported anecdotally, usually appearing in the context of comedication. Here, we report a case of hypothermia associated with a low-dose risperidone monotherapy in a child.