Self-report and parent-report of physical and psychosocial well-being in Dutch adolescents with type 1 diabetes in relation to glycemic control

BACKGROUND: To determine physical and psychosocial well-being of adolescents with type 1 diabetes by self-report and parent report and to explore associations with glycemic control and other clinical and socio-demographic characteristics. METHODS: Demographic, medical and psychosocial data were gathered from 4 participating outpatient pediatric diabetes clinics in the Netherlands. Ninety-one patients completed the Child Health Questionnaire-CF87 (CHQ-CF87), Centre for Epidemiological Studies scale for Depression (CES-D), and the DFCS (Diabetes-specific Family Conflict Scale). Parents completed the CHQ-PF50, CES-D and the DFCS. RESULTS: Mean age was 14.9 years (± 1.1), mean HbA(1c )8.8% (± 1.7; 6.2–15.0%). Compared to healthy controls, patients scored lower on CHQ subscales role functioning-physical and general health. Parents reported less favorable scores on the behavior subscale than adolescents. Fewer diabetes-specific family conflicts were associated with better psychosocial well-being and less depressive symptoms. Living in a one-parent family, being member of an ethnic minority and reporting lower well-being were all associated with higher HbA(1c )values. CONCLUSION: Overall, adolescents with type 1 diabetes report optimal well-being and parent report is in accordance with these findings. Poor glycemic control is common, with single-parent families and ethnic minorities particularly at risk. High HbA(1c )values are related to lower social and family functioning

Novel Leptin Receptor Mutations Identified in Two Girls with Severe Obesity Are Associated with Increased Bone Mineral Density

Background: Recessive mutations in the leptin receptor (LEPR) are a rare cause of hyperphagia and severe early-onset obesity. To date, the phenotype has only been described in 25 obese children, some of whom also had altered immune function, hypogonadotropic hypogonadism, reduced growth hormone secretion, hypothalamic hypothyroidism or reduced adult height. We provide a detailed description of the phenotype of 2 affected girls to add to this knowledge. Methods: Whole-exome sequencing and targeted sequencing were used to detect the LEPR mutations. RNA analysis was performed to assess the effect of splice-site mutations. Results: In 2 unrelated girls with severe obesity, three novel LEPR mutations were detected. Longitudinal growth data show normal childhood growth, and in the older girl, a normal adult height despite hypogonadotropic hypogonadism and the lack of an obvious pubertal growth spurt. Bone age is remarkably advanced in the younger (prepubertal) girl, and bone mineral density (BMD) is high in both girls, which might be directly or indirectly related to leptin resistance. Conclusion: The spectrum of clinical features of LEPR deficiency may be expanded with increased BMD. Future observations in LEPR-deficient subjects should help further unravel the role of leptin in human bone biology

Iron status and its association with HbA1c levels in Dutch children with diabetes mellitus type 1

Children with diabetes mellitus (DM) type 1 may be at risk for iron deficiency (ID) although this has been little studied. ID is either an absolute (depleted iron stores) or a functional (restricted iron stores due to chronic inflammation) deficiency each requiring a different therapeutic approach. Unfortunately, absolute ID is often not distinguished from functional ID. Furthermore, iron-deficient anemia may influence hemoglobin A1c (HbA1c) levels.We aimed to determine the prevalence and type of ID and investigate its association with HbA1c levels in pediatric DM type 1 patients. We performed a two-center prospective observational study in which the iron status of Dutch children with DM type 1 was determined during a regular check-up. Absolute ID and functional ID were found in 13/227 (5.7%) and 100/214 (47%) patients, respectively, while only 15/113 (13%) patients also had anemia. HbA1c levels in patients with and without a deprived iron status (absolute or functional) were not significantly different (65 ± 17 vs. 65 ± 16 mmol/mol, p = 0.815). Conclusion: Functional, but not absolute, ID was common in Dutch pediatric DM type 1 patients. HbA1c levels were not associated with ID, which can be explained by the relatively mild deprived iron status in our patients. Trial registration: NTR4642

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Background: Recessive mutations in the leptin receptor (LEPR) are a rare cause of hyperphagia and severe early-onset obesity. To date, the phenotype has only been described in 25 obese children, some of whom also had altered immune function, hypogonadotropic hypogonadism, reduced growth hormone secretion, hypothalamic hypothyroidism or reduced adult height. We provide a detailed description of the phenotype of 2 affected girls to add to this knowledge. Methods: Whole-exome sequencing and targeted sequencing were used to detect the LEPR mutations. RNA analysis was performed to assess the effect of splice-site mutations. Results: In 2 unrelated girls with severe obesity, three novel LEPR mutations were detected. Longitudinal growth data show normal childhood growth, and in the older girl, a normal adult height despite hypogonadotropic hypogonadism and the lack of an obvious pubertal growth spurt. Bone age is remarkably advanced in the younger (prepubertal) girl, and bone mineral density (BMD) is high in both girls, which might be directly or indirectly related to leptin resistance. Conclusion: The spectrum of clinical features of LEPR deficiency may be expanded with increased BMD. Future observations in LEPR-deficient subjects should help further unravel the role of leptin in human bone biology

High serum levels of growth hormone (GH) and insulin-like growth factor-I (IGF-I) during high-dose GH treatment in short children born small for gestational age.

Contains fulltext : 50261.pdf (publisher's version ) (Open Access)CONTEXT: Epidemiological studies have indicated that high serum levels of GH and IGF-I are associated with long-term risks. OBJECTIVE: The objective of the study was to evaluate the changes in serum levels of GH during overnight profiles, IGF-I, and IGF binding protein 3 (IGFBP-3) in short small for gestational age (SGA) children during GH treatment with two doses. PATIENTS: Thirty-six prepubertal short SGA children were the subjects of this study. Intervention: Subjects received 1 (group A) or 2 (group B) mg GH/m(2).d. MAIN OUTCOME MEASURES: At baseline and after 6 months of GH treatment, overnight GH profiles were performed, and serum IGF-I and IGFBP-3 levels were measured. RESULTS: After 6 months, group B had significantly higher GH levels during the profile (mean, maximum, and area under the curve above zero line) than group A (P < 0.009). In group B, maximum GH levels increased from 43.9-161 mU/liter (P < 0.0002), and in group A, from 57.2-104 mU/liter (P = 0.002). During the profile (i.e. 12 h per day), children of group B had mean GH levels of 64.4 vs. 34.8 mU/liter in group A (P = 0.001). The IGF-I and IGF-I to IGFBP-3 ratio sd scores increased significantly in both groups, but were higher in group B than A [1.5 vs. 0.2 (P = 0.002) and 1.4 vs. 0.3 (P = 0.007), respectively]. In group B, 74% of the children had IGF-I levels in the highest quintile during GH treatment compared with 19% in group A. CONCLUSION: Our study shows that high-dose GH treatment in short SGA children results in high serum GH and IGF-I levels in most children. We recommend monitoring IGF-I levels during GH therapy to ensure that these remain within the normal range

Second-tier testing for 21-hydroxylase deficiency in the Netherlands; a newborn screening pilot study.

BACKGROUND: Newborn screening (NBS) for classic congenital adrenal hyperplasia (CAH) consists of 17-hydroxyprogesterone (17-OHP) measurement with gestational age-adjusted cut-off values. A second heel puncture (HP) is performed in newborns with inconclusive results to reduce false-positives. We assessed the accuracy and turnaround time of the current CAH NBS-algorithm and compared this to alternative algorithms by performing a second-tier 21-deoxycortisol (21-DF) pilot-study. METHODS: Dried blood spots (DBS) of newborns with inconclusive and positive 17-OHP (immunoassay) first HP results were sent from regional NBS laboratories to the Amsterdam UMC Endocrine Laboratory. In 2017-2019 21-DF concentrations were analyzed by liquid chromatography-tandem mass spectrometry, in parallel with routine NBS. Diagnoses were confirmed by mutation analysis. RESULTS: 328 DBS were analyzed. 37 newborns had confirmed classic CAH, 33 were false-positive and 258 were categorized as negative in the second HP following the current algorithm. In the second-tier, all 37 confirmed CAH had elevated 21-DF concentrations, all 33 false-positives and 253/258 second HP negatives had undetectable 21-DF concentrations. The elevated 21-DF of the other five newborns may be NBS false-negatives or second-tier false-positives. Adding the second-tier to inconclusive first HPs reduced the number of false-positives to 11 and prevented all 286 second HPs. Adding the second-tier to both positive and inconclusive first HPs eliminated all false-positives at the cost of delayed referral for 31 CAH patients (1-4 days). CONCLUSION: Application of the second-tier 21-DF measurement to inconclusive first HPs improved our CAH NBS by reducing false-positives, abolishing the second HP and thereby shortening referral time

Bone mineral density and effects of growth hormone treatment in prepubertal children with Prader-Willi syndrome: a randomized controlled trial.

Item does not contain fulltextBACKGROUND: Bone mineral density (BMD) is unknown in children with Prader-Willi syndrome (PWS), but is decreased in adults with PWS. In patients with GH deficiency, BMD increases during GH treatment. OBJECTIVES: The aim of the study was to evaluate BMD in children with PWS and to study the effects of GH treatment. DESIGN: We conducted a randomized controlled GH trial. Forty-six prepubertal children were randomized into either a GH-treated group (1.0 mg/m(2) . d) or a control group for 2 yr. At start, 6, 12, and 24 months of study, total body and lumbar spine BMD were measured by dual-energy x-ray absorptiometry, and lumbar spine bone mineral apparent density (BMAD) was calculated. RESULTS: Baseline total body and lumbar spine BMD sd score (SDS) were normal [mean (sd), -0.2 SDS (1.1) and -0.4 SDS (1.2), respectively]. BMADSDS, which corrects for short stature, was also normal [mean (sd), 0.40 SDS (1.1)]. Total body BMDSDS decreased during the first 6 months of GH (P < 0.0001), but increased during the second year of treatment. After 24 months of study, total body and lumbar spine BMDSDS, and the BMADSDS did not significantly differ between GH-treated children and randomized controls (P = 0.30, P = 0.44, and P = 0.47, respectively). Results were similar when corrected for body mass index SDS. Repeated measurements analysis showed a significant positive association between IGF-I SDS and total body and lumbar spine BMDSDS, but not with BMADSDS. CONCLUSIONS: Our results show that prepubertal children with PWS have a normal BMD. GH treatment had no effect on BMD, except for a temporary decrease of total body BMDSDS in the first 6 months