Éva Lányi

Plasma levels of acylated ghrelin during an oral glucose tolerance test in obese children

Objective: Ghrelin is an acylated peptide with octanoyl modification, which is essential for its GH-releasing ability. Coexpression of GH secretagogue receptor (GHS-R) and ghrelin in the pancreas suggests that this peptide is involved in glucose metabolism. The other form of the molecule, the non-acylated ghrelin, has been reported to be devoid of any pituitaric endocrine activities. Previous reports demonstrated that plasma total ghrelin levels decrease after oral glucose administration in obese children, but no data are available about the plasma levels of acylated ghrelin. Therefore, in the present study the plasma levels of acylated ghrelin were measured in obese and control children during oral glucose tolerance test (OGTT). Materials and methods: Acylated ghrelin response to OGTT was evaluated in 11 obese and 9 age-matched control children. All subjects received 0.75 g/kg (maximum 75 g) glucose solution orally after an overnight fast. Acylated ghrelin, insulin, glucose, and GH were determined at 0, 30, 60 and 120 min, and leptin at 0 min of the OGTT. Results: Plasma basal levels of acylated ghrelin were significantly lower in the obese children than in the controls (66.3±6.7 vs 97.2±14.4 pg/ml, p<0.05). The plasma acylated ghrelin concentration decreased significantly at 30 and 60 min in the control group (53.3±9.9 and 57.4±7.0 pg/ml, p<0.05), but not in the obese group (64.7±9.6 and 49.3±4.6 pg/ml) as compared to the basal value. In the obese group the acylated ghrelin level was significantly higher at 120 min, than at 0 min (91.6±9.8 vs 66.3±6.7 pg/ml, p<0.05). Conclusions: There was no rapid fall in plasma levels of acylated ghrelin in obese children after OGTT at 30 min, but there was an increase at 120 min, suggesting that the dynamic of the response to OGTT is slower and there is an upregulation of active ghrelin in the second half of OGTT in obese children.

Ghrelin and acyl ghrelin in preterm infants and maternal blood: relationship with endocrine and anthropometric measures

OBJECTIVE The objective of the present study was to examine the association of acylated and total ghrelin levels at birth in preterm infants with anthropometric features and with related hormones in infants and their mothers. DESIGN Prospective, descriptive study. METHODS In total 23 pregnant women and their 26 preterm infants were involved in the study (3 twin pregnancies; gestational age, 25-35 weeks). Maternal and umbilical vein blood samples were taken after the delivery. Serum acylated and total ghrelin, leptin, cortisol, insulin, GH, and glucose were determined. RESULTS The mean level of acylated ghrelin concentration was higher in the maternal than in the cord blood (P<0.01) and there was a significant correlation between the fetal and maternal acylated ghrelin levels (P<0.01). The total ghrelin concentration was higher in neonates than in mothers (P<0.01), but there was no correlation between them. The multivariate regression analysis for fetal acylated and maternal total ghrelin as dependent variables shows that the fetal acylated ghrelin has two independent predictors, the maternal acylated ghrelin (P<0.01) and the fetal cortisol (P<0.05), whereas the maternal total ghrelin has only one independent predictor, the maternal glucose (P<0.05). CONCLUSIONS These data provide the first evidence that umbilical cord acylated ghrelin concentrations are lower than in maternal blood and support the hypothesis that the acylation process in the fetus is partly affected by cortisol and the placenta may play a role in this process.

Urinary cytokine response to asymptomatic bacteriuria in type 1 diabetic children and young adults

Abstract:  It has been reported that urinary interleukin‐6 (IL‐6) and IL‐8 levels are decreased in adult diabetic women with asymptomatic bacteriuria (ASB) when compared with non‐diabetic women with ASB. Such impaired cytokine excretion might play a role in the higher prevalence of ASB among diabetic subjects. The aim of this study was to examine the urinary IL profile in children and young adults with type 1 diabetes mellitus (T1DM) with and without ASB. Midstream clean voiding urine samples were collected and cultured from 133 patients with T1DM (age: 15.6 ± 5.7 yr) and 178 controls (14.1 ± 4.7 yr) for two consecutive days. ASB was diagnosed in the case of ≥105 bacteria/mL. The urinary IL‐6 and IL‐8 concentrations were determined, and the presence of leukocyturia was also recorded. The prevalence of ASB was 16.5% in diabetic subjects and 2.8% in controls (p = 0.001). There was no difference between the diabetic and the control groups in the prevalence of ‘IL‐6‐uria’ (21.9 vs. 18.0%; p = 0.41), but IL‐8 was more frequently detectable in the diabetic group (47.4 vs. 27.5%; p = 0.001). In individuals with ASB, the IL‐8 level was similar in the diabetic (median: 70.0 pg/mg creatinine) and control group (42.3 pg/mg creatinine; p = 0.8). Indeed, the IL‐8 levels were higher in diabetic subjects with ASB as compared with those without it (70.0 vs. <3.1 pg/mg creatinine; p = 0.001), and there was a significant association between the urinary IL‐8 concentration and the bacterial count (p = 0.001). Diabetic patients with leukocyturia had higher IL‐8 concentration than those without it (20.9 vs. <3.1 pg/mg creatinine; p = 0.003). Weak significant correlation was found between urinary IL‐8 and hemoglobin A1c (HbA1c) (r = 0.4; p = 0.002). The sensitivity and specificity of leukocyturia were 50 and 89.9% in the whole population and those of IL‐8 were 74.1 and 67.5%, respectively. In diabetic patients, 36.4% of the bacteriuria were gram‐negative and 63.6% gram‐positive. Our results suggest that diabetic children with ASB mount an IL‐8 response to pathogens, which is comparable to non‐diabetic children with bacteriuria. Thus, early in the natural history of diabetes, there are no significant changes in the IL response of children with ASB, as previously reported in adults.

Uncoupling protein-2 gene polymorphisms are associated with obesity in Hungarian children

To determine the frequency of common polymorphisms of genes associated with energy metabolism among normal weight and overweight/obese children to look for effects on childhood obesity.

Selective association of endogenous ouabain with subclinical organ damage in treated hypertensive patients

According to previous studies endogenous ouabain (EO) closely correlates with high blood pressure, congestive heart failure and kidney disease in humans. Our aims were to analyse associations between plasma, urinary EO level and various markers of cardiovascular damage in treated hypertensive patients. Forty-one adult patients with hypertension and/or diabetes mellitus (DM) and/or chronic kidney disease (CKD) were studied. We assessed plasma and urinary EO, pro-brain natriuretic peptide and catecholamines, profile of ambulatory blood pressure monitor and cardiovascular status by echocardiography and echo-tracking. The highest level of plasma EO (19.7±9.5 pmol l–1) was measured in hypertensive patients with DM and CKD. The nighttime mean arterial blood pressure independently correlated with the level of plasma EO (P=0.004), while independent predictor of the β-stiffness of carotid artery was the urinary EO (P=0.011). Elevated level of EO was associated with nighttime blood pressure and subclinical organ damage in treated hypertensive patients, suggesting possible role of EO in the pathogenesis of impaired diurnal blood pressure rhythm and arterial stiffness.

Ghrelin, metabolic and hormonal parameters during OGTT in patients with obesity and anorexia nervosa

Anorexia and obesity are the opposite states of body weight and body fat, but it is not known that regulating mechanisms of body weight are the same or not? Anorexia nervosa (AN) is associated with high levels, obesity with low levels of ghrelin. The most effective suppressor of ghrelin is the glucose load, but the regulating role of glucose or insulin in – ghrelin suppression is questionable. This study examined the associations of ghrelin levels with leptin, glucose, insulin and growth hormone (GH) during oral glucose tolerance test (OGTT) in anorectic, overweight and normal females. Participants included overweight-OW ( n = 11), anorexia nervosa-AN ( n = 14) and normal weight-NW ( n = 10) females. The fall in serum ghrelin at 30 min during OGTT was significantly lower in the OW group than in other groups ( p = 0.026). In AN subjects, significant correlation has been found between ghrelin and GH during the OGTT ( p = 0.0001). In OW and NW subjects, the multiple regression analysis showed that the glucose was the only independent predictor of ghrelin during the OGTT (OW, p = 0.003; NW, p = 0,004). Ghrelin secretion during OGTT may be controlled by different mechanisms in individuals with anorexia nervosa than in overweight individuals.

Effects of energy expenditure gene polymorphisms on obesity-related traits in obese children

OBJECTIVE To assess the frequencies of common polymorphisms of genes associated with energy expenditure among Hungarian obese children and investigate their influences on obesity-related traits and metabolic complications of common childhood obesity. RESEARCH METHODS AND PROCEDURES In a total of 528 obese children (age 13.2±2.6 years) an oral glucose tolerance test and determination of fasting serum lipid levels were carried out, blood pressure and resting energy expenditure were measured and the children were genotyped for the following gene polymorphisms: Trp64Arg of β3-adrenoreceptor (ADRB3), -3826 A/G of uncoupling protein (UCP)-1, exon 8 45 bp del/ins and -866 G/A of UCP-2, -55 C/T of UCP-3, and Pro12Ala of peroxisome-proliferator activated receptor gamma-2. RESULTS Carriers of the ADRB3 Arg64 allele had a significantly higher relative body weight and relative body mass index compared with non-carriers. The UCP-2 exon 8 del/ins polymorphism was associated with higher degree of obesity, insulin resistance, dyslipideamia and lower adjusted metabolic rate. Children with UCP-3 -55 T/T genotype had a significantly lower adjusted metabolic rate than the C allele carriers. CONCLUSION We found evidence for associations between common polymorphisms of the ADRB3, the UCP-2 and UCP-3 genes and basic metabolic rate as well as level and metabolic consequences of common obesity among Hungarian school-aged children.

Effects of Mono- and Dual Blockade of the Renin-Angiotensin System on Markers of Cardiovascular Status in Hypertensive Patients with Mild and Moderate Renal Failure

Background/Aims: Dual renin-angiotensin system (RAS) blockade has no more efficiency to decrease cardiovascular mortality than mono-blockade. Our goal was to explore differences between other cardiovascular markers in patients with RAS blockade. Methods: We analyzed two groups of patients treated with a long-term ACE inhibitor (MONO-group, n = 20) and an ACE inhibitor and angiotensin II receptor blocker (DUAL-group, n = 15). Ambulatory blood pressure monitoring, echocardiography, arterial stiffness and levels of catecholamine, endogenous ouabain (EO), pro-brain natriuretic peptide and more types of urinary albumin measurements were performed. Results: In the DUAL-group, we found significantly better cardiac parameters, but the levels of EO and urinary albumins were similar in both groups. The level of EO correlates with nighttime mean arterial blood pressure (R = 0.556, p = 0.032) and arterial β-stiffness (R = 0.512, p = 0.042). Urinary immuno-unreactive albumin showed a relationship with diastolic dysfunction of the heart (R = –0.508, p = 0.045) diurnal index of diastolic blood pressure (R = –0.569, p = 0.021) in the MONO-group. Conclusion: Cardiac parameters were more prosperous in the DUAL-group, but the levels of EO did not differ between groups. The level of EO correlated with blood pressure and arterial stiffness markers in the MONO-group only. The urinary immuno-unreactive albumin may be a new marker of cardiovascular conditions.

255 Active Ghreline Levels in Childhood Obesity

Introduction: No data are available about the plasma levels of active ghrelin (AGH) in obesity. The present study investigates the AGH levels in obese and control children during oral glucose tolerance test.Patients and methods: Eleven obese (age [mean ± SEM]: 14.3 ± 0.9 yr, body mass index (BMI): 30.2 ± 1.6 kg/m2) and nine age-matched control (age: 15.8 ± 0.5 yr, BMI: 21.2 ± 0.7 kg/m2) children were investigated. AGH, insulin, glucose, growth hormone (GH) were determined by commercially available RIA kits before and 30, 60 and 120 min after glucose load (75g). Plasma leptin concentrations were measured at 0 min by RIA kit. Comparative analyses between and within groups were calculated by Mann-Whitney U test and ANOVA followed by Dunett post hoc test. Data are expressed as mean ± SEM.Results: Fasting plasma insulin (32.4 ± 5.6 vs. 16.2 ± 3.0 microU/ml) and leptin (15.2 ± 1.3 vs. 7.2 ± 1.7 microg/l) levels were significantly higher, while AGH (66.3 ± 6.7 vs 97.2 ± 14.4 pg/ml) and GH (0.5 ± 0.2 vs. 3.1 ± 0.8 microg/l) concentrations were significantly lower in obese children, than in controls. The AGH levels decreased significantly at 30 and 60 min in the control group (30 min: 53.3 ± 9.9; 60 min: 57.4± 7.0 pg/ml), but not in the obese group (30 min: 64.7 ± 9.6 pg/ml; 60 min: 49.3 ± 4.6 pg/ml). After 60 min AGH increased in both groups, especially in obese children. Thus, in the obese group the AGH levels at 120 min (91.6 ± 9.8 pg/ml) were significantly higher than the baseline levels (66.3 ± 6.7 pg/ml), while they were lower in controls.Conclusion: The results suggest that the AGH response to glucose is blunted in the first hour and upregulated in the second hour in the obese children.Introduction: No data are available about the plasma levels of active ghrelin (AGH) in obesity. The present study investigates the AGH levels in obese and control children during oral glucose tolerance test.Patients and methods: Eleven obese (age [mean ± SEM]: 14.3 ± 0.9 yr, body mass index (BMI): 30.2 ± 1.6 kg/m2) and nine age-matched control (age: 15.8 ± 0.5 yr, BMI: 21.2 ± 0.7 kg/m2) children were investigated. AGH, insulin, glucose, growth hormone (GH) were determined by commercially available RIA kits before and 30, 60 and 120 min after glucose load (75g). Plasma leptin concentrations were measured at 0 min by RIA kit. Comparative analyses between and within groups were calculated by Mann-Whitney U test and ANOVA followed by Dunett post hoc test. Data are expressed as mean ± SEM.Results: Fasting plasma insulin (32.4 ± 5.6 vs. 16.2 ± 3.0 microU/ml) and leptin (15.2 ± 1.3 vs. 7.2 ± 1.7 microg/l) levels were significantly higher, while AGH (66.3 ± 6.7 vs 97.2 ± 14.4 pg/ml) and GH (0.5 ± 0.2 vs. 3.1 ± 0.8 microg/l) concentrations were significantly lower in obese children, than in controls. The AGH levels decreased significantly at 30 and 60 min in the control group (30 min: 53.3 ± 9.9; 60 min: 57.4± 7.0 pg/ml), but not in the obese group (30 min: 64.7 ± 9.6 pg/ml; 60 min: 49.3 ± 4.6 pg/ml). After 60 min AGH increased in both groups, especially in obese children. Thus, in the obese group the AGH levels at 120 min (91.6 ± 9.8 pg/ml) were significantly higher than the baseline levels (66.3 ± 6.7 pg/ml), while they were lower in controls.Conclusion: The results suggest that the AGH response to glucose is blunted in the first hour and upregulated in the second hour in the obese children.