Ghrelin In Children Research Articles

Risk factors associated with low bone mineral density in children with idiopathic scoliosis: a scoping review

BackgroundChildren with idiopathic scoliosis (IS) have a high risk of osteoporosis and IS with low bone mineral density (BMD) are susceptible to curve progression. This review aims to explore the risk factors of low BMD in children with IS.MethodsStudies were retrieved from 5 databases that were published up to January 2022. Search terms are keywords in titles or abstracts, including subject headings related to “Scoliosis”, “Bone Mineral Density”, and “Risk Factors”. Observational studies on risk factors of low BMD in children with IS were enrolled in this review. The number of studies, sample size, outcome measures, research type, endocrine, and lifestyle-related factors, gene/signal pathway, and other contents were extracted for qualitative analysis.ResultsA total of 56 studies were included in this scoping review. Thirty studies involved genetic factors that may affect BMD, including the Vitamin-D receptor gene, RANK/RANKL signal pathway, the function of mesenchymal stem cells, Runx2, Interleukin-6 (IL-6), and miR-145/β-catenin pathway. Eight studies mentioned the influence of endocrine factors on BMD, and the results showed that serum levels of IL-6, leptin and its metabolites, and ghrelin in children with IS were different from the age-matched controls. In addition, there were 18 articles on lifestyle-related factors related to low BMD in children with IS, consisting of physical activity, calcium intake, Vitamin D level, and body composition.ConclusionsGenetic, endocrine, and lifestyle-related factors might relate to low BMD and even osteoporosis in IS. To prevent osteoporosis, the effectiveness of regular screening for low BMD risk factors in children with IS needs to be investigated. Additionally, clear risk factors suggest strategies for bone intervention. Future studies should consider the effectiveness of calcium and vitamin D supplements and physical activity in BMD improvement.

O-05: Ghrelin in Children with Intestinal Failure Receiving Long-term Parenteral Nutrition

O-05: Ghrelin in Children with Intestinal Failure Receiving Long-term Parenteral Nutrition

Changes in ghrelin and nesfatin-1 in children with growth hormone deficiency treated by recombinant human growth hormone

This study aims to investigate the effects of recombinant human growth hormone (rhGH) on serum nesfatin-1 and ghrelin in children with growth hormone deficiency (GHD), in order to provide a reliable basis for the effectiveness and safety of applying rhGH in treating GHD children in the clinic. A total of 30 GHD pediatric patients were selected as the observation group. According to the peak of GH, these patients were divided into two subgroups: complete absence of growth hormone (CGHD) group and partial absence of growth hormone (PGHD) group. At the same time, 20 healthy children of normal height with matching age and gender were randomly selected as a normal control group. Serum ghrelin and nesfatin-1 levels were detected in children in the control group and observation group before rhGH treatment, and at 3 and 6 months after treatment. After 3 and 6 months of treatment, the height and growth rate of children in the PGHD and CGHD groups significantly increased ( P < 0.05), but their body weights did not significantly change ( P > 0.05), compared with those before treatment. Before treatment, ghrelin was higher in the PGHD group than in the control group, while ghrelin was lower in the CGHD group than in the control group. In addition, nesfatin-1 was higher in these two subgroups, compared with that in the control group. At pretreatment, and after 3 and 6 months of treatment, ghrelin and nesfatin-1 both decreased in the PGHD group, while ghrelin increased and nesfatin-1 decreased in the CGHD group. It was confirmed that ghrelin and nesfatin-1 were closely correlated with GHD. Furthermore, rhGH has a significant effect on children with GHD, and can significantly accelerate the annual growth rate.

Leptin and ghrelin in chronic kidney disease: their associations with protein-energy wasting.

This study aimed to evaluate plasma concentrations of leptin and total ghrelin in children with chronic kidney disease (CKD) and assess their roles in protein-energy wasting (PEW). This study consisted of three different CKD populations [CKD group (20 patients with non-dialysis CKD), dialysis group (39 patients on dialysis), and kidney transplant (KTx) group (35 KTx recipients)] and control group (18 healthy children). Plasma leptin and total ghrelin levels were measured. Multi-frequency bioimpedance analysis was used for the assessment of fat and lean mass. PEW was defined using criteria including body mass, muscle mass, growth, serum albumin level, and protein intake. While plasma leptin levels did not differ among the study groups, total ghrelin levels were significantly higher in the dialysis group (P< 0.001). Seven dialysis patients (18%) and one CKD patient (5%) but none of the KTx recipients met the criteria of PEW. Dialysis patients with PEW had lower plasma leptin levels compared to their counterparts (P= 0.018); however, total ghrelin levels did not differ between the two groups (P= 0.10). Low leptin level in dialysis patients was independently associated with lower fat mass index (P< 0.001) and lower height-specific SD scores of BMI (P= 0.019). PEW is prevalent in dialysis patients. Low levels of leptin seem to be associated with PEW. Our result suggests that low leptin levels may be a consequence rather than a cause of PEW. Longitudinal studies are required to investigate this complex relationship between leptin and PEW in pediatric dialysis patients.

Elevated ratio of acylated to unacylated ghrelin in children and young adults with Prader–Willi syndrome

Prader–Willi syndrome (PWS) is characterized by a switch from failure to thrive to excessive weight gain and hyperphagia in early childhood. Hyperghrelinemia may be involved in the underlying mechanisms of the switch. The purpose of this study is to evaluate acylated ghrelin (AG) and unacylated ghrelin (UAG) levels in PWS and investigate their associations with hyperphagia. This is a cross-sectional clinical study conducted in three PWS expert centers in the Netherlands and France. Levels of AG and UAG and the AG/UAG ratio were determined in 138 patients with PWS (0.2–29.4 years) and compared with 50 age-matched obese subjects (4.3–16.9 years) and 39 healthy controls (0.8–28.6 years). AEBSF was used to inhibit deacylation of AG. As a group, PWS patients had higher AG but similar UAG levels as healthy controls (AG 129.1 vs 82.4 pg/ml, p = 0.016; UAG 135.3 vs 157.3 pg/ml, resp.), resulting in a significantly higher AG/UAG ratio (1.00 vs 0.61, p = 0.001, resp.). Obese subjects had significantly lower AG and UAG levels than PWS and controls (40.3 and 35.3 pg/ml, resp.), but also a high AG/UAG ratio (1.16). The reason for the higher AG/UAG ratio in PWS and obese was, however, completely different, as PWS had a high AG and obese a very low UAG. PWS patients without weight gain or hyperphagia had a similar AG/UAG ratio as age-matched controls, in contrast to those with weight gain and/or hyperphagia who had an elevated AG/UAG ratio. The switch to excessive weight gain in PWS seems to coincide with an increase in the AG/UAG ratio, even prior to the start of hyperphagia.Electronic supplementary materialThe online version of this article (doi:10.1007/s12020-015-0614-x) contains supplementary material, which is available to authorized users.

Plasma Levels of Acylated Ghrelin in Children with Pulmonary Hypertension Associated with Congenital Heart Disease.

This study aims to estimate plasma levels of acylated ghrelin in children with pulmonary hypertension (PH) associated with congenital heart disease (CHD) and to correlate the levels of acylated ghrelin with endothelin-1 (ET-1), nitric oxide (NO), and clinical hemodynamic parameters. We investigated the plasma concentration of acylated ghrelin, ET-1, NO, and the hemodynamic parameters in 20 children with CHD, 20 children with PH-CHD, and 20 normal children. Plasma-acylated ghrelin and NO levels were significantly higher in CHD group than in control subjects (P < 0.001). Moreover, plasma-acylated ghrelin, ET-1, and NO levels were significantly elevated in PH-CHD group compared with the CHD group (P < 0.05). In PH-CHD children, plasma-acylated ghrelin levels correlated positively with pulmonary artery systolic pressure (PASP; r = 0.740, P < 0.001), pulmonary artery diastolic pressure (PADP; r = 0.613, P = 0.004), right ventricular systolic pressure (RVSP; r = 0.642, P = 0.002), mean pulmonary arterial hypertension (mPAP; r = 0.685, P = 0.001), right ventricle diameter (RVD; r = 0.473, P = 0.035), pulmonary artery trunk diameter (PAD; r = 0.613, P = 0.004), NO (r = 0.463, P = 0.04), and ET-1 (r = 0.524, P = 0.018). Plasma-acylated ghrelin levels were elevated both in CHD and in PH-CHD. Increased acylated ghrelin levels correlated positively with ET-1, NO, PASP, PADP, RVSP, mPAP, RVD, and PAD. Acylated ghrelin may be a new biomarker of PH-CHD.

The Levels of Ghrelin in Children with Cyanotic and Acyanotic Congenital Heart Disease

The cause of growth retardation in congenital heart disease is multifactorial. The relationship between congenital heart disease (CHD), malnutrition, and growth retardation is well documented. Ghrelin has effects on nutrient intake and growth. Ghrelin exerts potent GH-releasing activity and stimulates food intake. Circulating ghrelin levels are increased in anorexia and cachexia, reduced in obesity and restored by weight recovery. The relation between ghrelin and congenital heart disease is evident in adults but it is not studied well in pediatric age. The aim of the present study is to evaluate the serum ghrelin in congenital heart disease. We measured serum ghrelin, using ELISA technique in 60 patients with congenital heart disease (20 with acyanotic congenital heart disease with no heart failure (HF), 15 with cyanotic congenital heart disease with no HF) and 25 patients with congenital heart disease (cyanotic or acyanotic) with HF, in addition to 30 age and sex matched children as a control group. All children were subjected to measurement of height, weight, body mass index (BMI). In comparison to controls, serum ghrelin levels were significantly higher in patients with congenital heart disease (acyanotic patients and cyanotic with or without HF than in the control group (p=0.01). Also ghrelin level was significantly increased in children with cyanotic congenital heart disease than in those with acyanotic congenital heart disease. Patient with congenital heart disease with evidence of HF had significant higher levels of serum ghrelin than those with congenital heart disease without HF. Weight, height and BMI were significantly lower in cyanotic and acyanotic patients compared to the control group (p=0.001), also these measures were significantly reduced in patients with congenital heart disease with HF than in those without heart failure. There was a significant negative correlation between serum ghrelin and BMI in patients with heart failure, cyanotic patients and acyanotic patients; (r = -0.608, -0.831 and -0.458) and (p = 0.007, 0.02 and 0.017) respectively. In onclusion, serum ghrelin levels is elevated in children with acyanotic and cyanotic congenital heart disease with or without HF. Increased ghrelin levels represents malnutrition and growth retardation in these patients. This may suggest that ghrelin may have an important role as a compensatory mechanism in the regulation of the metabolic balance in these patients.

Assessment of serum acylated ghrelin in children and adolescents with chronic liver diseases: relation to nutritional status.

Because ghrelin is one of the key hormones in regulating feeding behavior and caloric status, it was suggested that ghrelin behavior might be closely associated with malnutrition state of patients with chronic liver disease (CLD). Thus, we aimed to assess serum ghrelin levels in children with CLD and its relation to anthropometric parameters and severity of CLD. Forty CLD patients were studied in comparison to 40 controls. All subjects were subjected to history, anthropometric, and laboratory assessment of liver functions and serum acylated ghrelin. Ghrelin was higher in patients than controls being higher with progress of Child's grade and with deterioration of liver functions. Hyperghrelinemia was detected in 62.5% of cases. Ghrelin correlated negatively with body mass index standard deviation score (BMISDS (r = −0.95, P < 0.001)), triceps skin fold thickness (TSFT (r = −0.88, P < 0.001)), and subscapular skin fold thickness (SSFT (r = 0.83, P < 0.001)) percentiles. In conclusion, hyperghrelinemia may represent a compensatory mechanism trying to overcome malnutrition state complicating CLD and can be used as a parameter for early detection and assessment of the severity of malnutrition in children with CLD.

Relation between ghrelin level and treatment response in functional constipation

Ghrelin stimulates gastrointestinal motility. Although there are some experimental and clinical studies supporting the role of ghrelin for gastrointestinal motility disorders, limited research for constipation has been published. The purpose of this study was to evaluate the possible role of ghrelin in the pathophysiology of functional constipation in childhood. Forty-three newly diagnosed constipated children aged 1-6 years and 25 healthy age-matched controls were included. Serum ghrelin levels were analyzed initially in both groups. Treatment protocol consisted of dietary modification, lactulose, and administration of pediatric enema. Ghrelin levels of children with functional constipation were reanalyzed after two monthsof treatment. Initial serum ghrelin levels of constipated patients were found to be lower than those of healthy children (p<0.001). Ghrelin levels increased during therapy. The differences between initial and second month serum ghrelin levels of constipated patients were found to be statistically significant (p<0.05). Our data supports the potential role of ghrelin in children with functional constipation. Observation of an increase in serum ghrelin levels with nonspecific treatment supports the hypothesis that low serum ghrelin levels might be a result rather than the cause of constipation.

Do Children with Adenotonsillar Hypertrophy have Lower IGF-1 and Ghrelin Levels than the Normal Children?

This study was designed to determine serum insulin-like growth factor-1 (IGF-1) and plasma ghrelin levels in male children with adenoid and tonsillar hypertrophy and compare them with healthy controls. This study included 29 male prepubertal children between the ages of 6.5 and 10 years (mean age 8.8 +/- 2.5 years) with obstructive adenoid and tonsillar hypertrophy and 20 normal male controls between the ages of 5.7 and 10.8 years (mean age 8.2 +/- 2.9 years). Plasma ghrelin and serum IGF-1 levels were measured at 8.30, in the morning. Children with adenoid and tonsillar hypertrophy had significantly depressed serum IGF-1 levels (203 +/- 150 ng ml(-1)) and plasma ghrelin levels (175 +/- 66 pg ml(-1)) compared with healthy controls (354 +/- 242 ng ml(-1) and 243 +/- 93 pg ml(-1), respectively, P < 0.05). Depressed levels of ghrelin in children with adenoid and tonsillar hypertrophy lead to decreased appetite and insufficient energy intake. Lower serum levels of IGF-1 in children with adenoid and tonsillar hypertrophy may be secondary to deficient growth hormone stimulation by ghrelin.

GH response to ghrelin in subjects with congenital GH deficiency: evidence that ghrelin action requires hypothalamic–pituitary connections

Evaluation of GH response to ghrelin in patients with GH deficiency (GHD) may help to elucidate the site and mechanism of action of ghrelin. We aimed to investigate the GH-releasing effect of ghrelin in children and young adults with childhood-onset GHD. All subjects underwent ghrelin testing and neuro-imaging examination. Magnetic resonance imaging evidenced the presence of a vascular pituitary stalk (VPS) or its complete absence (PSA). Seventeen prepubertal children and nine adult patients with childhood-onset GHD were selected for the study. The children were enrolled at a median age of 5.8 years. The adult subjects were included at a median age of 23.3 years. The diagnosis of GHD in the adult patients had been established at a median age of 8.5 years. Ghrelin was administered at a dose of 1 microg/kg body weight, i.v. at time zero, and blood for GH determination was obtained at 0, 15, 30, 45, 60, 75, 90, 105 and 120 min. Median GH response after ghrelin was similar between children and adults. Median peak GH response to ghrelin (7.45 microg/l, IQR: 3.9-11.3 microg/l) was significantly higher in patients with VPS (10.9 microg/l, IQR: 2.4-15.1 mcirog/l) than in those with PSA (IQR: 2.3-6.7 microg/l; P=0.001). It was significantly higher in subjects with isolated GHD (12.5 microg/l, IQR: 10.8-15.5 microg/l) than in those with multiple pituitary hormone deficiencies (5.15 microg/l, IQR: 2.4-9.0 microg/l; P=0.003). No correlation was found between the GH peak after ghrelin and body mass index. The GH response to ghrelin in patients with congenital hypopituitarism depends on the degree of the anatomical abnormalities and lends further support to the assumption that the main action of the peptide is exerted at the hypothalamic level and requires the integrity of hypothalamic-pituitary connections.

Osteoprotegerin and RANKL Serum Levels and Their Relationship with Serum Ghrelin in Children with Chronic Renal Failure and on Dialysis

Background: Osteoprotegerin (OPG) and receptor activator of the nuclear factor ĸB ligand (RANKL) constitute a complex system of mediators involved in the regulation of bone resorption process. Ghrelin, a growth hormone secretagogue, has been shown to modulate proliferation and differentiation of osteoblasts. The present study was carried out to evaluate the serum concentrations of OPG and sRANKL in children with chronic renal impairment (CRI) and on dialysis, and to establish a possible relationship between their serum levels and that of ghrelin. Methods: 33 patients including 10 patients with CRI, 12 peritoneal dialysis (PD) and 11 hemodialysis (HD) patients and 22 healthy controls were enrolled into the study. OPG, sRANKL and ghrelin levels were studied with radioimmunoassay. Results: Serum OPG levels in CRI, PD and HD groups were significantly higher than the healthy controls (p = 0.002, p < 0.001, p < 0.001, respectively) whereas sRANKL levels were significantly lower than the healthy controls (p = 0.03, p = 0.01, p = 0.001, respectively). Ghrelin levels were significantly higher in CRI, PD and HD groups compared to healthy controls (p = 0.001, p < 0.001, p < 0.001, respectively). We observed a negative correlation between the sRANKL and OPG levels (r = –0.27, p = 0.04) as well as between sRANKL and ghrelin levels (r = –0.31, p = 0.02). OPG levels showed a positive correlation with ghrelin levels (r = 0.63, p < 0.001). Conclusion: We found a lower RANKL bioactivity index in children with CRI and on dialysis. The mechanism and the role of elevated OPG and low sRANKL in uremia are unclear, but they might partly represent a compensatory mechanism to the negative balance of bone remodeling in renal bone disease in children. Additionally, we demonstrated for the first time that ghrelin and the RANKL/OPG system have a close relationship in CRF. Therefore, ghrelin may be of importance in mediating the effects of the RANKL/OPG system in renal bone disease.