Relationship between Serum Sirtuin 1 and Growth Hormone/Insulin-like Growth Factor 1 Concentrations in Children with Growth Hormone Deficiency and Idiopathic Short Stature.

Sirtuin 1 (SIRT1) inhibits growth hormone (GH) intracellular signaling for the insulin-like growth factor 1 (IGF-1) synthesis via the janus kinase (JAK)/signal transducer and activator of transcription proteins (STATs) pathway. The aim of this study was to compare SIRT1 concentrations in children with GH deficiency (GHD) and so-called idiopathic short stature (ISS, non-GH deficient), in order to determine the possible impact of changes in serum SIRT1 concentrations on the GH-IGF-1 axis. The study group included 100 short-stature children: 38 with GHD and 62 with ISS (maxGH in two stimulation tests <10 and ≥10 ng/mL, respectively). The control group consisted of 47 healthy, normal-height children. For each child, the concentrations of SIRT1, IGF-1 and insulin-like growth factor-binding protein 3 (IGFBP-3) were determined and the IGF-1/IGFBP-3 molar ratio was calculated. The level of SIRT1 was significantly higher in both groups of short children than in the controls (p < 0.0001), but there were no differences between GHD and ISS (mean ± SD: 0.89 ± 0.45 for ISS; 1.24 ± 0, 86 for GHD; and 0.29 ± 0.21 for controls). A significant negative correlation was found between SIRT1 and height standard deviation score (SDS), IGF-1 and IGF-1/IGFBP-3, but not between SIRT1 and maxGH. Elevated SIRT1 levels may serve as one of the mechanisms through which the secretion of IGF-1 is reduced in children with short stature; however, further research is required to confirm this issue.

Transient Isolated, Idiopathic Growth Hormone Deficiency-A Self-Limiting Pediatric Disease with Male Predominance or a Diagnosis Based on Uncertain Criteria? Lesson from 20 Years' Real-World Experience with Retesting at One Center.

In the majority of children with growth hormone (GH) deficiency (GHD), normal GH secretion may occur before the attainment of final height. The aim of the study was to assess the incidence of persistent and transient GHD and the effectiveness of recombined human GH (rhGH) therapy in children with isolated, idiopathic GHD with respect to the moment of therapy withdrawal and according to different diagnostic criteria of GHD. The analysis included 260 patients (173 boys, 87 girls) with isolated, idiopathic GHD who had completed rhGH therapy and who had been reassessed for GH and IGF-1 secretion. The incidence of transient GHD with respect to different pre- and post-treatment criteria was compared together with the assessment of GH therapy effectiveness. The incidence of transient GHD, even with respect to pediatric criteria, was very high. Normal GH secretion occurred before the attainment of near-final height. Application of more restricted criteria decreased the number of children diagnosed with GHD but not the incidence of transient GHD among them. Poor response to GH therapy was observed mainly in the patients with normal IGF-1 before treatment, suggesting that their diagnosis of GHD may have been a false positive. Further efforts should be made to avoid the overdiagnosis GHD and the overtreatment of patients.

Comparison of the Clinical Utility of Two Insulin Resistance Indices: IRI-HOMA and IRI-Belfiore in Diagnosing Insulin Resistance and Metabolic Complications in Children Based on the Results Obtained for the Polish Population.

Background: Recognizing insulin resistance (IR) in children remains challenging due to uncertain IRI-HOMA cut-offs and unclear recommendations for evaluating IR based on OGTT. In our study, we compare the effectiveness of IRI-HOMA and IRI-Belfiore (OGTT-based) in detecting IR and its metabolic complications in children. Methods: The analysis included 553 children who were hospitalized at the Department of Endocrinology and Metabolic Diseases of the Polish Mother's Memorial Hospital Research Institute (PMMH-RI) in Lodz, Poland, between 2002 and 2018 due to various reasons-of these, 67.5% were girls. All underwent OGTT for glucose and insulin assessment. IR diagnosis relied on IRI-HOMA and IRI-Belfiore. IR based on IRI-HOMA was evaluated using three criteria: (A) >2.5; (B) >2.67 in boys and >2.22 in girls before puberty and >5.22 and >3.82 during puberty, respectively; (C) >95th percentile according to charts for IRI-HOMA in children. Results: Prepubertal children exhibited significantly lower IRI-HOMA and IRI-Belfiore than their pubertal counterparts (p < 0.00005). IRI-HOMA and IRI-Belfiore values positively correlated with age and BMI SDS value (p < 0.000001 for all calculations). As many as 26% to 46.9% of children with normal IRI-HOMA showed elevated IRI-Belfiore, with notably higher levels of triglycerides, a lower HDL cholesterol fraction, and a lower HDL/total cholesterol ratio in this subgroup. Conclusions: A notable proportion of children exhibited elevated IRI-Belfiore levels despite having normal IRI-HOMA values. This suggests the possibility of peripheral IR preceding hepatic IR in children-omitting an OGTT may therefore lead to overlooking cases of IR. Children diagnosed with IR via OGTT displayed significantly poorer lipid profiles compared to those without IR (characterized by normal values in both IRI-HOMA and IRI-Belfiore). This underscores the ability of OGTT-derived IR indices to identify individuals at risk of developing complications associated with obesity and IR before the onset of metabolic syndrome (MS) symptoms. If IR is already detected in children based on fasting glucose and insulin levels (IRI-HOMA), further evaluation may not be warranted, as OGTT results often simply confirm the diagnosis.

Sirtuin 1 serum concentration in healthy children - dependence on sex, age, stage of puberty, body weight and diet.

Introduction: Sirtuin 1 (SIRT1) is known to be involved in sensing cellular energy levels and regulating energy metabolism. This study aimed to evaluate fasting serum SIRT1 levels in healthy children, and to analyse the influence of age, sex, puberty, body weight, height, and diet on its concentration. Methods: 47 healthy children aged 4-14 with weight and height within normal range and no chronic disease were included into the study. Fasting serum SIRT1 concentrations were estimated by Enzyme Linked Immunosorbent Assay (ELISA). Results: Results showed that serum SIRT1 concentrations in healthy children did not differ with respect to sex, age, height, weight and puberty. Whereas, it appeared that a higher frequency of fruits, vegetables and dairy products consumption was associated with an increase in serum SIRT1 levels. Discussion: Studying SIRT1 in the context of children's health may have implications for a broader understanding of growth processes, pubertal development, metabolic disorders and nutrition.