Implications of the Matrix Metalloproteinases, Their Tissue Inhibitors and Some Other Inflammatory Mediators Expression Levels in Children Obesity-Related Phenotypes.

OBJECTIVES: Matrix metalloproteinases (MMPs) are calcium-dependent zinc-containing endo-peptidases engaged in many biological processes including adipogenesis, angiogenesis, and tissue remodeling. Fat tissue infiltration by peripheral leukocytes plays an important role in transition of fat tissue residual, non-inflammatory status into the pro-inflammatory one, resulting in fat tissue inflammation and expansion as well as production of many mediators like adipokines and cytokines. The aim of this study was to investigate the expression of MMPs, their endogenous tissue inhibitors (TIMPs), and selected inflammatory mediators in leukocytes and plasma of children with simple obesity to find their associations with obesity-related phenotypes. MATERIAL AND METHODS: Twenty-six overweight/obese children and twenty-three healthy volunteers participated in the study. The leukocyte mRNA expression levels of MMP-2, -9, -12 -14, TIMP-1, -2, and IL-6 were analyzed by the real time quantitative PCR. Plasma MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios as well as the concentrations of MMP-9, TIMP-1, IL-1 beta, IL-6, TNF- alpha, leptin and resistin were tested by ELISA assays. Gelatin zymography was used to assess the activity of the leukocyte MMPs proteins. RESULTS: The obese children showed the following: a) increased expression of leukocyte TIMP-1 and slight elevation (close to statistical significance) of leukocyte MMP-9 (p = 0.054), the decline in MMP-2, b) elevation of plasma MMP-9, leptin, and MMP9/TIMP1 ratio, c) reduced expression of plasma TNF-alpha and MMP-2/TIMP-2 ratio. Several negative correlations were found: TIMP2 vs. ALT (r = -0.536), AST (r = -0.645) and TTG (r = -0.438), IL-6 vs. GGTP (r = -0.815), and MMP12 vs. TTG (r = -0.488), leptin vs. ALT (r = -0.569), MMP-9 vs. total cholesterol (r = -0.556). The only positive correlation was that of plasma leptin level vs. GGTP (r = 0.964). CONCLUSIONS: At the beginning of obesity development (children), possibly compensatory reactions prevail, reflected here by an increase in the expression of leukocyte MMPs inhibitor TIMP-1, decrease in the level of leukocyte MMP-2 and plasma MMP-2, MMP2/TIMP-2 ratio, low plasma TNF-alpha and negative correlations between the expression of TIMP-2 and liver (AST, ALT) or fat (TTG) inflammatory markers.

The effects of 3-year growth hormone treatment and body composition in Polish patients with Silver-Russell syndrome.

INTRODUCTION: Silver-Russell syndrome (SRS) is characterized by clinical and genetic heterogeneity. SRS is the only disease entity associated with (epi)genetic abnormalities of 2 different chromosomes: 7 and 11. In SRS, the 2 most frequent molecular abnormalities are hypomethylation (loss of methylation) of region H19/IGF2:IG-DMR on chromosome 11p15.5 (11p15 LOM) and maternal uniparental disomy of chromosome 7 (upd(7)mat). Therapy with recombinant human growth hormone (rhGH) is implemented to increase body height in children with SRS. The effect of the administered rhGH on height, weight, body mass index (BMI), body composition, and height velocity in patients with SRS during 3 years of rhGH therapy was analysed. MATERIAL AND METHODS: 31 SRS patients (23 with 11p15 LOM, 8 with upd(7)mat) and 16 patients small for gestational age (SGA) as a control group were diagnosed and followed up in The Children's Memorial Health Institute. Patients were eligible for the 2 Polish rhGH treatment programmes [for patients with SGA or with growth hormone deficiency (GHD)]. Anthropometric parameters were collected in all patients. Body composition using bioelectrical impedance was measured in 13 SRS and 14 SGA patients. RESULTS: Height, weight, and weight for height (SDS) at baseline of rhGH therapy were lower in SRS patients than in the SGA control group: -3.3 ± 1.2 vs. -2.6 ± 06 (p = 0.012), -2.5 vs. -1.9 (p = 0.037), -1.7 vs. -1.1 (p = 0.038), respectively. Height SDS was increased from -3.3 ± 1.2 to -1.8 ± 1.0 and from -2.6 ± 0.6 to -1.3 ± 0.7 in the SRS and SGA groups, respectively. Patients with 11p15 LOM and upd(7) mat achieved similar height, 127.0 ± 15.7 vs. 128.9 ± 21.6 cm, and -2.0 ± 1.3 vs. -1.7 ± 1.0 SDS, respectively. Fat mass percentage decreased in SRS patients from 4.2% to 3.0% (p < 0.05) and in SGA patients from 7.6% to 6.6% (p < 0.05). CONCLUSIONS: Growth hormone therapy has a positive influence on the growth of SRS patients. Regardless of molecular abnormality type (11p15 LOM vs. upd(7)mat), height velocity was similar in SRS patients during 3 years of rhGH therapy.

Guidelines for Preventing and Treating Vitamin D Deficiency: A 2023 Update in Poland.

Introduction: All epidemiological studies suggest that vitamin D deficiency is prevalent among the Polish general population. Since vitamin D deficiency was shown to be among the risk factors for many diseases and for all-cause mortality, concern about this problem led us to update the previous Polish recommendations. Methods: After reviewing the epidemiological evidence, case-control studies and randomized control trials (RCTs), a Polish multidisciplinary group formulated questions on the recommendations for prophylaxis and treatment of vitamin D deficiency both for the general population and for the risk groups of patients. The scientific evidence of pleiotropic effects of vitamin D as well as the results of panelists' voting were reviewed and discussed. Thirty-four authors representing different areas of expertise prepared position statements. The consensus group, representing eight Polish/international medical societies and eight national specialist consultants, prepared the final Polish recommendations. Results: Based on networking discussions, the ranges of total serum 25-hydroxyvitamin D concentration indicating vitamin D deficiency [<20 ng/mL (<50 nmol/L)], suboptimal status [20-30 ng/mL (50-75 nmol/L)], and optimal concentration [30-50 ng/mL (75-125 nmol/L)] were confirmed. Practical guidelines for cholecalciferol (vitamin D3) as the first choice for prophylaxis and treatment of vitamin D deficiency were developed. Calcifediol dosing as the second choice for preventing and treating vitamin D deficiency was introduced. Conclusions: Improving the vitamin D status of the general population and treatment of risk groups of patients must be again announced as healthcare policy to reduce a risk of spectrum of diseases. This paper offers consensus statements on prophylaxis and treatment strategies for vitamin D deficiency in Poland.

Pituitary stalk thickening in patients under 18 years of age - the most common causes and diagnostic procedures.

INTRODUCTION: Pituitary stalk thickening (PST) is a rare abnormality in children, and it may be challenging due to its diverse clinical picture. AIM OF THE STUDY: The aim of the study is to summarize the data on the causes and diagnostic procedures of PST. MATERIAL AND METHODS: Papers were searched in the PubMed database identifying published randomized clinical trials, reviews, systematic reviews, meta-analyses, and case reports. RESULTS: The most common causes of a thickened pituitary stalk in children are germ cell tumours (GCTs), Langerhans cell histiocytosis (LCH), and lymphocytic infundibulo-neurohypophysitis (LINH). Neurosarcoidosis, pituitary tuberculosis, granulomatosis, or specific inflammations were only reported in the paediatric population as case studies. PST mainly affects teenagers and is often detected with brain magnetic resonance imaging (MRI) in patients with central diabetes insipidus (CDI). It is not possible to differentiate the causes of PST with the use of the MRI image alone. Although various biochemical and oncological markers and other imaging tests are used, the diagnosis of PST remains a significant diagnostic challenge for clinicians. The final diagnosis is made based on histopathological examination. The indications for a biopsy are not uniform. Most experts, including the authors of the 2021 British consensus, recommend biopsy in the case of PST with a stalk lesion diameter ≥ 6.5-7 mm. CONCLUSIONS: The differential diagnosis of PST is a challenge. The diagnostic and treatment strategy should be individually adapted. Patients should be diagnosed in large clinical centres with experience in this field.

Could I-FABP Be an Early Marker of Celiac Disease in Children with Type 1 Diabetes? Retrospective Study from the Tertiary Reference Centre.

Patients with type 1 diabetes (T1D) are at higher risk of celiac disease (CD). Recently, intestinal fatty acid binding protein (I-FABP) has been shown to be a serological biomarker of impaired intestinal barrier in CD. Thus, the aim of this study was to verify whether I-FABP could be an early marker of CD in pediatric T1D patients. I-FABP was measured in sera of patients with T1D (n = 156), active CD (n = 38), T1D with active CD (T1D-CD, n= 51), and age-matched healthy children (n = 55). Additionally, I-FABP was determined in T1D patients with negative CD serology at least one year before CD diagnosis (T1D-CD-1, n = 22), in CD patients on a gluten-free diet (CD-GFD, n = 36), and T1D-CD patients on GFD (T1D-CD-GFD, n = 39). Sera were tested using immunoenzymatic assay. Significantly increased levels of I-FABP were found in the T1D, active CD, and T1D-CD groups (1153 ± 665, 1104 ± 916, and 1208 ± 878, respectively) in comparison to healthy with controls (485 ± 416, p < 0.05). GFD induced a significant decrease in I-FABP levels in CD and T1D-CD groups (510 ± 492 and 548 ± 439, respectively). Interestingly, in T1D-CD-1 and T1D, I-FABP levels were comparable (833 ± 369 vs. 1153 ± 665), and significantly increased in relation to healthy controls and T1D-CD values on GFD. The results indicate that the epithelial barrier is disrupted in T1D patients independently of CD development; therefore, I-FABP cannot serve as an early marker of CD in T1D patients. Although GFD can improve epithelial recovery, the question remains as to whether GFD could exert beneficial effects on the intestinal barrier in early stages of T1D.

Influence of emotional intelligence on glycemic control in adolescents with diabetes type 1.

INTRODUCTION: Psychological factors can have a significant impact on diabetes control. We aimed to evaluate the correlation between emotional intelligence and glycemic control in type one diabetes (T1D) adolescents. MATERIAL AND METHODS: This prospective study enrolled 97 consecutive children admitted to our department and aged 15 to 17 with T1D. The Emotional Intelligence Questionnaire INTE was used to measure emotional intelligence. The results were correlated with a glycemic control status, measured by current and mean (since the diagnosis of T1D, minimum four tests per year) and hemoglobin A1c (HbA1c). An additional questionnaire collected the demographic and social data. RESULTS: Our study found a significant, negative correlation between HbA1c level and the ability to utilize emotions to support thinking and actions (Factor I of the INTE questionnaire). There was no significant correlation between emotional intelligence General Score or Factor II (the ability to recognize emotions) and glycemic control. CONCLUSIONS: A higher ability to utilize emotions to support thinking and actions positively correlates with metabolic control in the adolescent population with T1D. The appropriate emotional intelligence training and better psychological care may improve the metabolic outcomes of children with T1D. This merits further study.

Endocrine disorders in a patient with a suspicion of a mitochondrial disease, MELAS syndrome - a case report and literature review.

MELAS syndrome (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) is a genetically determined disease caused by mutations in mitochondrial DNA. We present a girl who was suspected of MELAS syndrome during the diagnostic evaluation of short stature. The patient suffered from symptoms potentially indicating mitochondrial disease, such as muscular weakness, cranial nerve VI palsy, headaches, retinitis pigmentosa, sensory-neural hearing loss, and elevated lactic acid. T2-weighted brain MRI showed hyperintense lesions in the white matter. Muscular biopsy revealed ragged red fibres. Genetic evaluation did not detect the most common mutations in the MT-TL1 gene and MT-ND5 gene. Endocrine tests led to the confirmation of growth hormone deficiency, and so replacement treatment was started. After 1 year of recombinant growth hormone therapy the patient was diagnosed with diabetes. At the age of 14 years the LH-RH test showed prepubertal values. Endocrine disorders may be one of the first manifestations of MELAS syndrome. In differential diagnosis of short stature, less common causes, such as mitochondrial diseases, should be taken into consideration.

The quality of life in adult patients treated for Cushing's disease in childhood.

INTRODUCTION: Numerous studies assessed the quality of life (QoL) of adult patients after Cushing's disease (CD) treatment. Available professional literature reveals that hypercortisolemia caused by CD may negatively impact the mood and social life. However, data on QoL of adult patients after CD treatment in childhood are scarce. Aim of the study: To study the QoL of adult patients treated for CD in childhood. MATERIAL AND METHODS: Eighteen out of 29 adult patients diagnosed in childhood with CD and/or treated at one center participated in a survey and completed WHO Quality of Life-BREF questionnaire. The influence of selected prognostic factors for the QoL has been analyzed. Patients data were compared with a control group with the same age and sex. RESULTS: Participants (10 women and 8 men) were at the mean age of 28.93 years (19.75-40.33). No significant difference in the QoL was noted between analyzed patients and controls. Patients with hypopituitarism had lower results in domain 4 in comparison with patients without hypopituitarism (p = 0.31) and lower results in domain 2 in comparison with the control group (p = 0.045). Patients with a higher age at disease onset had lower results of the QoL in domain 1 (p = 0.031). CONCLUSIONS: During long-term follow-up the QoL of patients after CD treatment in childhood is not significantly different wit QoL of healthy controls. Further studies are needed to expand the knowledge of factors that may contribute to the QoL in CD patients who were treated in childhood.

Above 40% of Polish children and young adults with type 1 diabetes achieve international HbA1c target - results of a nationwide cross-sectional evaluation of glycemic control: The PolPeDiab HbA1c study.

BACKGROUND: Youth with type 1 diabetes (T1D) (16-18 y.o.) present worst disease control of all age groups and need structured interventions. Those should be based on unbiased, national-scale outcomes, which have not yet been successfully assessed in Poland. OBJECTIVE: To evaluate the glycemic control in young patients with T1D in Poland. METHOD: All pediatric diabetes care centers and the nine largest centers for adults with T1D were invited to this cross-sectional study, conducted in March 2018. Eligibility was defined as age ≤ 30 years and diabetes duration ≥1 year. Blinded samples of capillary blood and clinical questionnaires were sent to coordinating center, where HbA1c was measured by high-pressure liquid chromatography. RESULTS: Nine adult and 25/28 pediatric centers participated, providing data for 1255 patients (50.8% males), mean age 12.3 years (95%CI:12.1-12.6) for children and 23.2 years (22.9-23.6) for adults; mean diabetes duration 7.1 years (6.8-7.3). This covered ~8% of pediatric population and 2% of 18-30-years-olds with T1D. Mean HbA1c was comparable between children and adults (57 mmol/mol [7.4%], 95%CI:56-57 mmol/mol [7.3-7.4%] vs. 57 mmol/mol [7.4%], 95%CI:56-60 mmol/mol [7.3-7.6%], p = 0.1870). Overall, 45.2% of patients achieved ISPAD target (<53 mmol/mol [<7.0%]). During the month preceding the study, 0.9% of patients experienced severe hypoglycemia and 0.4% suffered ketoacidosis. HbA1c was related to the method of insulin therapy, continuous glucose monitoring use and body weight (p < 0.0001). CONCLUSIONS: In Polish children and young adults with T1D glycemic control expressed as HbA1c is promising in the light of ISPAD guidelines. Our results confirm the known associations between better glycemic control and the use of new technologies and maintaining optimal body weight.

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Macimorelin in Children with Suspected Growth Hormone Deficiency: An Open-Label, Group Comparison, Dose-Escalation Trial.

BACKGROUND/AIMS: Diagnosis of growth hormone deficiency (GHD) in children requires the use of provocative growth hormone (GH) stimulation tests, which can have limited reliability and are potentially contraindicated in some patients. This is the first paediatric study to test the safety, tolerability, and pharmacokinetics (PK)/pharmacodynamics (PD) of macimorelin, an oral GH secretagogue, approved for diagnosis of adult GHD. METHODS: In this open-label, group comparison, single-dose escalation trial (EudraCT 2018-001988-23), sequential cohorts of patients (C1-C3) received ascending single doses of macimorelin: 0.25 (C1), 0.5 (C2), and 1.0 (C3) mg/kg. Primary endpoints were safety and tolerability, and secondary endpoints were PK/PD. RESULTS: Twenty-four patients aged between 2 and <18 with suspected GHD participated in the study. No macimorelin-related adverse events were reported, and macimorelin was well tolerated. Plasma macimorelin concentrations increased with dose: mean areas under the curve were 6.69 (C1), 18.02 (C2), and 30.92 (C3) h × ng/mL; mean maximum concentrations were 3.46 (C1), 8.13 (C2), and 12.87 (C3) ng/mL. GH concentration increased following macimorelin administration: mean times of maximum measured concentration were 52.5 (C1), 37.5 (C2), and 37.5 (C3) min. CONCLUSION: All 3 doses of macimorelin had excellent safety and tolerability with PK/PD profiles in expected ranges. These results support the use of 1.0 mg/mL macimorelin in a Phase 3 test validation trial in children.

Giant plurihormonal pituitary adenoma in a child - case study.

OBJECTIVES: To describe the case of a 12-year-old girl with a rare plurihormonal pituitary macroadenoma secreting prolactin (PRL), growth hormone (GH), thyroid-stimulating hormone (TSH), and alpha subunit (α-SU). CASE PRESENTATION: The patient experienced recurrent headaches and progressing loss of vision in one eye. During the examination, abnormalities such as tall stature, coarse facial features, enlarged feet and hands, tachycardia, hand tremor, hyperhidrosis, galactorrhea, and goiter were observed. Head magnetic resonance imaging (MRI) revealed a solid tumor in the anterior and middle cranial fossa, measuring 80 × 50 × 55 mm. A stereotactic biopsy revealed plurihormonal Pit-1 positive pituitary adenoma secreting PRL, GH, and TSH. A pituitary hyperfunction with PRL, GH, TSH, and α-SU excess was diagnosed. The patient was successfully treated pharmacologically with dopamine agonists and somatostatin analogue, and a decrease of tumor volume (30%) was achieved. CONCLUSIONS: When neurosurgery is not possible, long-term pharmacological treatment of plurihormonal pituitary macroadenoma can be a safe and relatively effective alternative.

Effects of Recombinant Human Growth Hormone Treatment, Depending on the Therapy Start in Different Nutritional Phases in Paediatric Patients with Prader-Willi Syndrome: A Polish Multicentre Study.

Recombinant human growth hormone (rhGH) treatment is an established management in patients with Prader-Willi syndrome (PWS), with growth promotion and improvement in body composition and possibly the metabolic state. We compared anthropometric characteristics, insulin-like growth factor 1 (IGF1) levels, metabolic parameters and the bone age/chronological age index (BA/CA) in 147 children with PWS, divided according to age of rhGH start into four groups, corresponding to nutritional phases in PWS. We analysed four time points: baseline, rhGH1 (1.21 ± 0.81 years), rhGH2 (3.77 ± 2.17 years) and rhGH3 (6.50 ± 2.92 years). There were no major differences regarding height SDS between the groups, with a higher growth velocity (GV) (p = 0.00) and lower body mass index (BMI) SDS (p < 0.05) between the first and older groups during almost the whole follow-up. IGF1 SDS values were lower in group 1 vs. other groups at rhGH1 and vs. groups 2 and 3 at rhGH2 (p < 0.05). Glucose metabolism parameters were favourable in groups 1 and 2, and the lipid profile was comparable in all groups. BA/CA was similar between the older groups. rhGH therapy was most effective in the youngest patients, before the nutritional phase of increased appetite. We did not observe worsening of metabolic parameters or BA/CA advancement in older patients during a comparable time of rhGH therapy.

Diabetic Retinopathy in Children with Type 1 Diabetes-Occurrence and Screening Using Optical Coherence Tomography.

PURPOSE: To describe the occurrence of diabetic retinopathy, the principles for pediatric care of patients with diabetes, and the utility of optical coherence tomography. Pediatric patients with type 1 diabetes should be screened for diabetic retinopathy upon the lapse of 5 years following the diagnosis. The patients in the time of puberty, who should be screened promptly after the diabetes diagnosis, and patients with type 2 diabetes are the exceptions. Special attention must be paid not only to retinopathy, but also to other possible concomitant conditions, such as cataract, refractive errors, or neuropathy. New techniques, such as optical coherence tomography angiography (OCTA), may contribute greatly to the early detection of retinopathy, facilitating the decision to modify the treatment. The application of modern insulin pumps with continuous glucose monitoring systems has greatly diminished the incidence rate of early symptoms of diabetic retinopathy in the pediatric population.

Long-term follow up of carbohydrate metabolism and adverse events after termination of Omnitrope® treatment in children born small for gestational age.

BACKGROUND: Recombinant human growth hormone (rhGH) therapy can affect carbohydrate metabolism and lead to impaired glucose tolerance during treatment. In addition, short children born small for gestational age (SGA) are predisposed to metabolic abnormalities. This study assessed the long-term safety of rhGH (Omnitrope®) use in short children born SGA. METHODS: This was a follow-up observational study of patients from a phase IV study. The baseline visit was the final visit of the phase IV study. Further visits were planned after 6 months (F1), 1 year (F2), 5 years (F3), and 10 years (F4). The primary objective was to evaluate the long-term effect of rhGH treatment on the development of diabetes mellitus; secondary objectives included incidence/severity of adverse events (AEs). RESULTS: In total, 130 subjects were enrolled in the follow-up study; 99 completed F1, 88 completed F2, and 13 completed F3 (no subject reached F4). The full analysis set for evaluation comprised 118 patients (64 female). Mean (standard deviation) duration of follow up was 39.6 (24.4) months. No subject was newly diagnosed with diabetes. The results for carbohydrate metabolism parameters were consistent with this finding. A total of 144 AEs were reported in 54 subjects; these were mostly of mild-to-moderate intensity (96.5%) and not suspected to be related to previous rhGH treatment (94.4%). Serious AEs (n = 18) were reported in eight patients; three (in one patient) were suspected as possibly related to previous rhGH treatment (anemia, menorrhagia, oligomenorrhoea). One fatal event occurred (sepsis), which was judged as not related to previous rhGH treatment. CONCLUSIONS: None of the participating subjects, who had all been previously treated with Omnitrope® in a phase IV study, developed diabetes during this follow-up study. In addition, no other unexpected or concerning safety signals were observed.

The Effects of Sampling Lateralization on Bilateral Inferior Petrosal Sinus Sampling for Pediatric Cushing's Disease-A Single Endocrinology Centre Experience and Review of the Literature.

Background: This study aims to analyze the diagnostic accuracy of bilateral inferior petrosal sinus sampling (BIPSS), the gold standard test for the differential diagnosis of ACTH-dependent Cushing's syndrome (CS) in a group of pediatric patients with Cushing's disease (CD). Methods: This is a retrospective analysis which include 12 patients with hypercortisolemia and inconclusive pituitary MRI, who underwent bilateral inferior petrosal sinus sampling (BIPSS) and transsphenoidal surgery (TSS) from 2004 to 2020 in the Children's Memorial Health Institute (CMHI) Warsaw, Poland. Pituitary origin of ACTH secretion was considered if baseline central to peripheral (C/P) ACTH level ratio was ≥ 2 or C/P ratio was ≥ 3 after human corticotropin-releasing hormone (hCRH) stimulation. The diagnosis was histologically confirmed in almost all cases after TSS. Results: The diagnostic accuracy of BIPSS reached 75% at baseline and 83.3% after CRH stimulation. The compatibility of localization of a microadenoma by BIPSS with the surgical location was 66.7%. Conclusions: Owing to its high diagnostic effectiveness, BIPSS remains the best test to differentiate CD from EAS. The indications for the procedure should be carefully considered, because EAS in the pediatric population, unlike in adults, is extremely rare. Moreover BIPSS has only limited value for indicating tumor localization.

Growth hormone improves short stature in children with Shwachman-Diamond syndrome.

INTRODUCTION: Shwachman-Diamond syndrome (SDS) is a rare, autosomal recessive multisystemic disorder characterized by pancreatic insufficiency and bone marrow failure. Short stature is a recognized feature of SDS syndrome; however, systemic data concerning recombinant human growth hormone (rGH) treatment are limited. Aim of the study: To assess the effect of rGH treatment in patients with SDS. MATERIAL AND METHODS: Retrospective data were collected from patients with SDS and growth hormone deficiency (GHD) treated with rGH in the Children's Memorial Health Institute in Warsaw. The annual growth velocity (GV) and height standard deviation score (SD) were compared for up to 2 years of rGH treatment. RESULTS: Six SDS patients (M : F = 1 : 5) treated with rGH were identified. The median age of starting rGH therapy was 7.5 years, with a mean baseline height SD of -4.06 (range: -6.3 to -2.3 SD). The height SD significantly improved to -3.3 (p = 0.002) and then -3.03 (p = 0.002), following 1 and 2 years of treatment, respectively. The average GV for the patients prior to starting treatment was 4.9 cm/year (range: 3.1-6.5 cm/year), which significantly improved to 7.6 cm/year (range: 5.7-9.6 cm/year) after 1 year of rGH treatment (p = 0.020) and to 6.7 cm/year at the end of 2 years. CONCLUSIONS: Our study has shown that rGH treatment significantly improves the height SDS and GV of patients with SDS and GHD without any side effects. Further research is required to analyse the long-term effect of rGH therapy in patients with SDS.

Correlation of Genotype and Perinatal Period, Time of Diagnosis and Anthropometric Data before Commencement of Recombinant Human Growth Hormone Treatment in Polish Patients with Prader-Willi Syndrome.

Genotype-phenotype correlation in patients with Prader-Willi syndrome (PWS) has still not been fully described. We retrospectively analysed data of 147 patients and compared groups according to genetic diagnosis: paternal deletion of chromosome 15q11-q13 (DEL 15, n = 81), maternal uniparental disomy (UPD 15, n = 10), excluded DEL 15 (UPD 15 or imprinting centre defect, UPD/ID, n = 30). Group DEL 15 had an earlier genetic diagnosis and recombinant human growth hormone (rhGH) start (p = 0.00), with a higher insulin-like growth factor 1 (IGF1) level compared to group UPD/ID (p = 0.04). Among perinatal characteristics, there was only a tendency towards lower birth weight SDS in group UPD 15 (p = 0.06). We also compared data at rhGH start in relation to genetic diagnosis age-group 1: age ≤9 months, group 2: >9 months ≤ 2 years, group 3: > 2 years. Group 1 had the earliest rhGH start (p = 0.00), with lower body mass index (BMI) SDS (p = 0.00) and a tendency towards a higher IGF1 level compared to group 3 (p = 0.05). Genetic background in children with PWS is related to time of diagnosis and rhGH start, with a difference in IGF1 level before the therapy, but it seems to have little impact on perinatal data. Early genetic diagnosis leads to early rhGH treatment with favourable lower BMI SDS.

Influence of puberty on retinal microcirculation in children with type 1 diabetes without retinopathy using optical coherence tomography angiography.

BACKGROUND: This study aimed to assess the influence of pubertal status on the results of optical coherence tomography angiography (OCTA) in children with type 1 diabetes (T1D). METHODS: We enrolled 167 consecutive children with T1D. Retinal superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel density data underwent analysis. We divided the study population into three subgroups depending on the pubertal status. RESULTS: Analysis of the prepubertal and pubertal subgroups revealed statistically significant differences in foveal thickness (FT) (p < 0.05) and foveal SCP (p < 0.02). Analyzing subgroups of the prepubertal and postpubertal children, we observed statistically significant differences in FT (p < 0.03), whole SCP (p < 0.02), and foveal SCP (p < 0.02). Comparison of the pubertal and postpubertal subjects revealed differences in parafoveal DCP (p < 0.003). In the groups matched depending on diabetes duration, we observed differences between prepubertal, pubertal, and postpubertal children in FT, PFT, and parafoveal SCP and DCP. CONCLUSION: Our data suggest that in a cohort of pubertal children with a short duration of diabetes, alterations in retinal vessel density occur early and progress during puberty.

Lack of effect of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed type 1 diabetes: a randomised controlled trial.

INTRODUCTION: The gut microbiota may be relevant in the development of type 1 diabetes (T1D). We examined the effects of Lactobacillus rhamnosus GG and Bifidobacterium lactis Bb12 on beta-cell function in children with newly diagnosed T1D. RESEARCH DESIGN AND METHODS: Children aged 8-17 years with newly (within 60 days) diagnosed T1D were enrolled in a double-blind, randomised controlled trial in which they received L. rhamnosus GG and B. lactis Bb12 at a dose of 109 colony-forming units or placebo, orally, once daily, for 6 months. The follow-up was for 12 months. The primary outcome measure was the area under the curve (AUC) of the C-peptide level during 2-hour responses to a mixed meal. RESULTS: Ninety-six children were randomised (probiotics, n=48; placebo n=48; median age 12.3 years). Eighty-eight (92%) completed the 6-month intervention, and 87 (91%) completed the follow-up at 12 months. There was no significant difference between the study groups for the AUC of the C-peptide level. For the secondary outcomes at 6 months, there were no differences between the study groups. At 12 months, with one exception, there also were no significant differences between the groups. Compared with the placebo group, there was a significantly increased number of subjects with thyroid autoimmunity in the probiotic group. However, at baseline, there was also a higher frequency of thyroid autoimmunity in the probiotic group. There were no cases of severe hypoglycemia or ketoacidosis in any of the groups. No adverse events related to the study products were reported. CONCLUSIONS: L. rhamnosus GG and B. lactis Bb12, as administered in this study, had no significant effect in maintaining the residual pancreatic beta-cell function in children with newly diagnosed T1D. It remains unclear which probiotics, if any, alone or in combination, are potentially the most useful for management of T1D. TRIAL REGISTRATION NUMBER: NCT03032354.

Comparison of Frequency and Severity of Sleep-Related Breathing Disorders in Children with Simple Obesity and Paediatric Patients with Prader-Willi Syndrome.

Sleep-related breathing disorders (SRBDs) can be present in children with simple obesity and with Prader-Willi syndrome (PWS) and influence an individual diagnostic and treatment approach. We compared frequency and severity of SRBDs in children with simple obesity and with PWS, both without and on recombinant human growth hormone (rhGH) treatment, and correlation of SRBDs with insulin resistance tests. A screening polysomnography-polygraphy (PSG), the oral glucose tolerance test (OGTT) and homeostasis model assessment of insulin resistance (HOMA-IR) were analysed in three groups of patients-with simple obesity (group 1, n = 30, mean age 14.2 years), patients with PWS without the rhGH therapy (group 2, n = 8, mean age 13.0 years) and during the rhGH treatment (group 3, n = 17, mean age 8.9 years). The oxygen desaturation index (ODI) was significantly higher in groups 2 and 3, compared to group 1 (p = 0.00), and hypopnea index (HI) was higher in group 1 (p = 0.03). Apnea-hypopnea index (AHI) and apnea index (AI) results positively correlated with the insulin resistance parameters in groups 1 and 3. The PSG values worsened along with the increasing insulin resistance in children with simple obesity and patients with PWS treated with rhGH that may lead to a change in the patients' care.