Quality of Life of Short-Statured Children Born Small for Gestational Age or Idiopathic Growth Hormone Deficiency Within 1 Year of Growth Hormone Treatment.

Aside from clinical endpoints like height gain, health-related quality of life has also become an important outcome indicator in the medical field. However, the data on short stature and health-related quality of life is inconsistent. Therefore, we examined changes in health-related quality of life in German children with idiopathic growth hormone deficiency or children born small for gestational age before and after 12 months of human growth hormone treatment. Children with idiopathic short stature without treatment served as a comparison group. At baseline, health-related quality of life data of 154 patients with idiopathic growth hormone deficiency (n = 65), born small for gestational age (n = 58), and idiopathic short stature (n = 31) and one parent each was collected. Of these, 130 completed health-related quality of life assessments after 1-year of human growth hormone treatment. Outcome measures included the Quality of Life in Short Stature Youth questionnaire, as well as clinical and sociodemographic data. Our results showed that the physical, social, and emotional health-related quality of life of children treated with human growth hormone significantly increased, while untreated patients with idiopathic short stature reported a decrease in these domains. Along with this, a statistically significant increase in height in the treated group can be observed, while the slight increase in the untreated group was not significant. In conclusion, the results showed that human growth hormone treatment may have a positive effect not only on height but also in improving patient-reported health-related quality of life of children with idiopathic growth hormone deficiency and children born small for gestational age.

Area Deprivation and Regional Disparities in Treatment and Outcome Quality of 29,284 Pediatric Patients With Type 1 Diabetes in Germany: A Cross-sectional Multicenter DPV Analysis.

OBJECTIVE: This study analyzed whether area deprivation is associated with disparities in health care of pediatric type 1 diabetes in Germany. RESEARCH DESIGN AND METHODS: We selected patients <20 years of age with type 1 diabetes and German residence documented in the "diabetes patient follow-up" (Diabetes-Patienten-Verlaufsdokumentation [DPV]) registry for 2015/2016. Area deprivation was assessed by quintiles of the German Index of Multiple Deprivation (GIMD 2010) at the district level and was assigned to patients. To investigate associations between GIMD 2010 and indicators of diabetes care, we used multivariable regression models (linear, logistic, and Poisson) adjusting for sex, age, migration background, diabetes duration, and German federal state. RESULTS: We analyzed data from 29,284 patients. From the least to the most deprived quintile, use of continuous glucose monitoring systems (CGMS) decreased from 6.3 to 3.4% and use of long-acting insulin analogs from 80.8 to 64.3%, whereas use of rapid-acting insulin analogs increased from 74.7 to 79.0%; average HbA1c increased from 7.84 to 8.07% (62 to 65 mmol/mol), and the prevalence of overweight from 11.8 to 15.5%, but the rate of severe hypoglycemia decreased from 12.1 to 6.9 events/100 patient-years. Associations with other parameters showed a more complex pattern (use of continuous subcutaneous insulin infusion [CSII]) or were not significant. CONCLUSIONS: Area deprivation was associated not only with key outcomes in pediatric type 1 diabetes but also with treatment modalities. Our results show, in particular, that the access to CGMS and CSII could be improved in the most deprived regions in Germany.

Recruiting young pre-symptomatic children for a clinical trial in type 1 diabetes: Insights from the Fr1da insulin intervention study.

BACKGROUND: Although detection of children at high risk of developing type 1 diabetes and diagnosis of early stages is possible, up to now there exists no approved therapy to delay or prevent type 1 diabetes. Thus it is vital to develop evidence-based interventions. For this a sufficient number of trial participants is crucial but difficult to obtain especially in asymptomatic children. AIM: Identifying family characteristics that lead to or impede trial participation and analyze reasons stated by families for non-participation. METHODS: Participants for the Fr1da Insulin Intervention study are recruited from the Fr1da study, a population based screening for early stage type 1 diabetes in Bavaria. Families with eligible children were invited to enroll. We analyzed sex and age of the child, distance of the family to the study center in Munich and the existence of a first degree family member with type 1 as possible influential factors for study participation. We also analyzed reasons stated by families who declined study participation in a phone interview. RESULTS: Of 146 eligible children 77 (53%) were enrolled into the trial. None of the tested family characteristics differed significantly between the enrolling and the families not participating, but in general enrolling families lived closer to the study site than families not participating. This is also reflected in the reasons given by non-participating families. The most frequent reason stated were time restrictions. The second most frequent reason was the venous blood draw. CONCLUSION: The factors for non-participation identified in this project need be taken into account for the design of future trials in young children to ensure proper recruitment and thus to generate valid results for medical treatment of children. More research on the reason of participation and non-participation in clinical trials is needed.

Self-reported regular alcohol consumption in adolescents and emerging adults with type 1 diabetes: A neglected risk factor for diabetic ketoacidosis? Multicenter analysis of 29 630 patients from the DPV registry.

BACKGROUND: The risk of hypoglycemia increases after alcohol consumption in patients with type 1 diabetes. This study aimed to investigate the association between metabolic control and self-reported alcohol consumption in young patients with type 1 diabetes. MATERIALS AND METHODS: N = 29 630 patients with type 1 diabetes aged 12 to <30 years (median age 17.0 [14.9, 18.3] years, duration of diabetes 6.8 [3.3, 10.9] years, 53% male) from the German/Austrian DPV registry were analyzed. Patients were categorized into abstainers, low-risk drinkers, and at-risk drinkers. BMI, HbA1c, and rates of severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) were compared between alcohol consumption groups using multivariable hierarchical regression models. The association between alcohol use and smoking status was assessed using χ 2 test. RESULTS: Overall, 10.8% of the patients reported regular alcohol consumption. Proportion of alcohol use as well as the amount of alcohol consumed increased with age and were higher in males than in females (all P < .05). Patients with Turkish migration background reported less alcohol consumption. HbA1c, SH rate, and DKA rate (adjusted for age, gender, duration of diabetes, therapy) were significantly lower in abstainers than in patients drinking alcohol (all P < .05). Smoking status was significantly associated with alcohol consumption (P < .001). CONCLUSION: Self-reported alcohol consumption is likely to be underreported when collected in face-to-face settings such as doctors' visits. Nevertheless, our data revealed a significant association between higher alcohol consumption and worse glycemic control, in particular higher DKA rates. Information about alcohol-induced complications is of great importance in diabetes education in young people with type 1 diabetes.

Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11ß-hydroxylase deficiency.

Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1, a gene encoding 11ß-hydroxylase, represents a rare autosomal recessive Mendelian disorder of aberrant sex steroid production. Unlike CAH caused by 21-hydroxylase deficiency, the disease is far more common in the Middle East and North Africa, where consanguinity is common often resulting in identical mutations. Clinically, affected female newborns are profoundly virilized (Prader score of 4/5), and both genders display significantly advanced bone ages and are oftentimes hypertensive. We find that 11-deoxycortisol, not frequently measured, is the most robust biochemical marker for diagnosing 11ß-hydroxylase deficiency. Finally, computational modeling of 25 missense mutations of CYP11B1 revealed that specific modifications in the heme-binding (R374W and R448C) or substrate-binding (W116C) site of 11ß-hydroxylase, or alterations in its stability (L299P and G267S), may predict severe disease. Thus, we report clinical, genetic, hormonal, and structural effects of CYP11B1 gene mutations in the largest international cohort of 108 patients with steroid 11ß-hydroxylase deficiency CAH.

Biologically inactive leptin and early-onset extreme obesity.

Mutations in the gene encoding leptin (LEP) typically lead to an absence of circulating leptin and to extreme obesity. We describe a 2-year-old boy with early-onset extreme obesity due to a novel homozygous transversion (c.298G→T) in LEP, leading to a change from aspartic acid to tyrosine at amino acid position 100 (p.D100Y) and high immunoreactive levels of leptin. Overexpression studies confirmed that the mutant protein is secreted but neither binds to nor activates the leptin receptor. The mutant protein failed to reduce food intake and body weight in leptin-deficient ob/ob mice. Treatment of the patient with recombinant human leptin (metreleptin) rapidly normalized eating behavior and resulted in weight loss.