Plasma ghrelin in obesity before and after weight loss after laparoscopical adjustable gastric banding

Weight reduction after gastric bypass surgery has been attributed to a decrease of the orexigenic peptide ghrelin, which may be regulated by insulin and leptin. This study examined effects of long-term weight loss after laparoscopical adjustable gastric banding on plasma ghrelin and leptin concentrations and their relationship with insulin action. Severely obese patients (15 women, three men, 36 +/- 12 yr) underwent clinical examinations every 3 months and modified oral glucose tolerance tests to assess parameters of insulin sensitivity and secretion every 6 months. After surgery, body mass index fell from 45.3 +/- 5.3 to 37.2 +/- 5.3 and 33.6 +/- 5.5 kg/m(2) at 6 and 12 months, respectively (P < 0.0001). This was associated with lower (P < 0.0001) plasma glucose, insulin, insulin resistance, waist circumference, and blood pressure. Plasma leptin decreased from 27.6 +/- 9.5 to 17.7 +/- 9.8 (P = 0.0005) and 12.7 +/- 5.1 ng/ml (P < 0.0001). Plasma ghrelin was comparable before and at 6 months (234 +/- 53; 232 +/- 53 pmol/liter) but increased at 12 months (261 +/- 72 pmol/liter; P = 0.05 vs. 6 months). At 6 and 12 months, ghrelin levels correlated negatively with fasting plasma insulin levels and hepatic insulin extraction but not with body mass or insulin action.In conclusion, prolonged weight loss results in a rise of fasting ghrelin concentrations that correlates with fasting insulin concentrations but not improvement of insulin sensitivity.     

Plasma leptin is associated with insulin resistance independent of age, body mass index, fat mass, lipids, and pubertal development in nondiabetic adolescents

OBJECTIVE: The rising epidemic worldwide in overweight and obese children requires urgent attention. Leptin has been found to be associated with body weight control and possibly affects insulin sensitivity. Since insulin resistance is associated with obesity in adults and possibly in adolescents, we set out to investigate the association of plasma leptin level with various anthropometric indices, body fat mass (FM), lipids, and insulin resistance (IR) index in nondiabetic adolescents. DESIGN: A cross-sectional study from three high schools in Taipei City in Taiwan. SUBJECTS: A total of 402 nondiabetic subjects (162 boys and 240 girls; age range, 10-19 y; mean age, 15.8+/-1.9 y, and mean body mass index (BMI), 24.8+/-4.6 kg/m(2)) were recruited. MEASUREMENTS: The fasting plasma leptin, plasma glucose, insulin, lipids, and anthropometric indices including height, weight, waist (WC) and hip circumferences, and waist-to-hip ratio (WHR) were examined. Total body FM and percentage body fat (FM%) were obtained from dual-energy X-ray absorptiometry. The homeostasis model was applied to estimate the degree of IR. RESULTS: The plasma leptin levels were significantly higher in girls (17.45+/-10.13 ng/ml) than boys (8.81+/-6.71 ng/ml, P<0.001). The plasma leptin levels were positively correlated to BMI, WC, WHR, FM, FM%, and triglycerides (TG). The IR index was positively correlated to BMI, WC, WHR, FM, FM%, TG, and leptin. Using the multivariate linear regression models, we found that plasma leptin remains significantly associated with IR index even after adjusting for age, gender, BMI, FM, WC, Tanner stage, and TG. CONCLUSION: Plasma leptin was associated with IR index independent of age, gender, BMI, FM, WC, Tanner stage, and TG. Plasma leptin levels in adolescents could be a predictor for the development of the metabolic syndrome disorders and cardiovascular diseases.     

The associations between plasma adiponectin, ghrelin levels and cardiovascular risk factors

OBJECTIVE: Ghrelin is a recently discovered peptide, which is produced primarily in the stomach. This orexigenic peptide participates not only in the induction of mealtime hunger but also in long-term body weight regulation and energy homeostasis. Adiponectin is a protein secreted by adipocytes, and has been proposed to mediate obesity-related insulin resistance. Moreover, concentrations of adiponectin are reduced in individuals with obesity, insulin resistance and cardiovascular disease. However, human data are sparse about the direct relationship between adiponectin, ghrelin and cardiovascular risk factors including insulin resistance. DESIGN: Three hundred and thirty-eight elderly Korean women (mean age+/-s.d., 72.3+/-5.5 years) were included in the present study. METHODS: Plasma ghrelin and adiponectin levels were measured by RIA. Anthropometric measurements were taken and a 75 g oral glucose tolerance test performed. Fasting insulin and lipid profile were measured and insulin resistance was determined using the homeostasis model assessment insulin resistance index (HOMA-R) and the quantitative insulin sensitivity check index. RESULTS: Plasma adiponectin levels were negatively correlated with central obesity indices such as waist circumference (r=-0.27, P<0.001) and waist-to-hip ratio (WHR) (r=-0.32, P<0.001), and with insulin resistance indices such as fasting insulin (r=-0.17, P=0.004) and HOMA-R (r=-0.13, P=0.035). Plasma ghrelin levels were negatively correlated with WHR (r=-0.12, P=0.03), but plasma adiponectin and ghrelin levels were not correlated (r=0.03, P=0.66). Multiple regression analysis showed that adiponectin was associated with WHR, fasting insulin and fasting glucose levels. When ghrelin was used as a dependent variable, only WHR remained in the final fitted model. CONCLUSION: Fasting plasma adiponectin and ghrelin levels were found to be associated with central obesity or insulin resistance. However, plasma adiponectin and ghrelin concentrations were not associated with each other in elderly Korean women.     

Cross-sectional and prospective relationships of fasting plasma ghrelin concentrations with anthropometric measures in pima Indian children

Ghrelin, a recently discovered GH secretagogue with orexigenic effects, is proposed to be a regulator of energy balance. To test whether fasting plasma ghrelin concentrations predict future gain in body weight or adiposity, we measured weight, height, body mass index (BMI), percentage of body fat (by dual energy x-ray absorptiometry), and fasting plasma concentrations of ghrelin, insulin, and glucose in 10-yr-old Pima Indians (n = 40; 13 males and 27 females) and subsequent weight, height, and BMI 1.7 +/- 0.6 yr later. At baseline, the fasting plasma ghrelin concentration was negatively associated with height (r = -0.52; P = 0.0006), weight, (r = -0.37; P = 0.02), percentage of body fat (r = -0.33, P = 0.04), and fasting plasma insulin concentration (r = -0.41; P = 0.01). In multiple regression models adjusting for gender and fasting plasma insulin, the fasting plasma ghrelin concentration was an independent determinant of height (beta = -13.9; P = 0.02), but not weight or BMI. Prospectively, the baseline fasting plasma ghrelin concentration was not an independent determinant of the relative rate of increase in weight, height, or adiposity. In conclusion, the fasting plasma ghrelin concentration was lower in taller and fatter Pima Indian children, but did not independently predict baseline weight, adiposity, or future growth rates. These data do not support a direct relationship between the fasting plasma ghrelin concentration and subsequent relative changes in height or weight in growing children.     

Ghrelin does not regulate the GH response to insulin-induced hypoglycaemia in children but could be involved in the regulation of cortisol secretion

OBJECTIVE: Ghrelin activates the growth hormone secretagogue receptor GHS-R. It strongly stimulates GH secretion and has a role in energy homeostasis. The relationship between plasma ghrelin and cortisol levels during insulin-induced hypoglycaemia in prepubertal and pubertal children has not yet been investigated. The aim of the present study was to establish whether insulin-induced hypoglycaemia stimulates ghrelin secretion and whether changes in ghrelin concentrations are related to changes in GH and cortisol in children. DESIGN AND PATIENTS: We studied a group of 20 children and adolescents (five girls, 15 boys, mean age 10.8 +/- 3.7 years) undergoing insulin tolerance tests (ITTs) for clinical investigation of GH deficiency. MEASUREMENTS: Stimulation tests were performed to investigate the relationship between ghrelin, GH, cortisol and glucose levels according to age and pubertal stage by determining the ghrelin profiles during insulin-induced hypoglycaemia (at 0, 60 and 120 min). RESULTS: Ghrelin was significantly and inversely related to body weight, height, body mass index (BMI) and age of children (P < 0.05). Significant changes in ghrelin levels (P = 0.00013) were found after the insulin bolus, with a decline at 60 min and an increase to baseline values at 120 min. Changes in cortisol levels were negatively correlated with changes in ghrelin at 60 min (r = -0.59, P = 0.004) and at 120 min (r = -0.605, P = 0.003). CONCLUSIONS: This study shows that ghrelin might not regulate the GH response to insulin-induced hypoglycaemia in prepubertal and pubertal children. A role for ghrelin in the regulation of cortisol secretion can be hypothesized concerning the negative correlation between changes in ghrelin and cortisol. Furthermore, the results imply that ghrelin secretion is age dependent and is a function of growth.     

Plasma adiponectin concentrations in children: relationships with obesity and insulinemia

Adiponectin, a novel adipokine with anti-inflammatory and insulin-sensitizing properties, has been found to have independent negative associations with obesity and hyperinsulinemia/insulin resistance in adults. We measured fasting plasma adiponectin and insulin concentrations and body composition (dual-energy x-ray absorptiometry or doubly labeled water) in 30 5-yr-old (11 boys and 19 girls) and 53 10-yr-old (17 boys and 36 girls) Pima Indian children. A subgroup of 20 children (5 boys and 15 girls) had all measurements at both 5 and 10 yr of age. Cross-sectionally, plasma adiponectin concentrations were negatively correlated with percentage body fat and fasting plasma insulin concentrations at both 5 yr (r = -0.35, P = 0.06, r = -0.42, P = 0.02) and 10 yr (r = -0.46, P = 0.001, r = -0.38, P = 0.005) of age. At age 10 yr, percentage body fat (P = 0.03) but not fasting plasma insulin (P = 0.59) was independently associated with fasting plasma adiponectin concentrations. Longitudinally, plasma adiponectin concentrations decreased with increasing adiposity. In summary, these results confirm our previously reported findings in adults of an inverse relationship between plasma adiponectin concentrations and adiposity in children. Longitudinal analyses indicated that hypoadiponectinemia is a consequence of the development of obesity in childhood. We did not find evidence that adiponectin is an early mediator of obesity-induced insulin resistance, a preliminary observation that needs to be confirmed in studies using a more direct measurement of insulin action than the one used in this investigation.     

Circulating acylated and total ghrelin and galanin in children with insulin-treated type 1 diabetes: relationship to insulin therapy, metabolic control and pubertal development

OBJECTIVE: To study the circulating levels of two gut-derived peptides in children with type 1 (insulin-dependent) diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Plasma levels of ghrelin, both total ghrelin (TG) and the acylated form (AG), and galanin and their relationships with insulin dosage, metabolic control, IGFBP-1, body mass and pubertal development were evaluated in 91 children, aged 11.1 +/- 2.7 years, affected by IDDM and treated with insulin. Ninety-one healthy children were selected as controls. RESULTS: Body mass index (BMI)-adjusted levels of both forms of ghrelin were reduced in IDDM compared with healthy subjects, with greater values in prepubertal than pubertal IDDM subjects. A negative association was found between AG and fasting insulin serum levels and insulin resistance [measured by using the homeostasis model assessment of insulin resistance (HOMA IR)] among the healthy children. IDDM children showed a negative association of their plasma ghrelin (both acylated and total) with daily insulin dosage, and the three adiposity indices (BMI, skinfold thickness and percentage fat mass). IGFBP-1 levels were higher among the IDDM children without any association with ghrelin serum values. BMI-adjusted plasma levels of galanin were higher among IDDM compared to healthy subjects, irrespective of sex or pubertal development. Greater values for galanin were found among pubertal than prepubertal subjects in both groups without any significant differences between the genders. A positive association was found between galanin and BMI in both groups and between galanin and haemoglobin A1c (HbA1c) among the IDDM children. No relationship existed between either galanin and fasting serum insulin among the healthy subjects or galanin and both insulin dosage or duration of treatment among the IDDM subjects. CONCLUSIONS: The associations found between both ghrelin and galanin with adiposity indices could be considered as an indirect signal of involvement of the two peptides in the development of the nutritional status of the IDDM adolescents. The reduction in both forms of ghrelin could be involved in the development of the body mass increase of IDDM subjects with opposite effects, either influencing insulin sensitivity or exerting a compensatory restraint of feeding.     

Determinants of homocysteine during weight reduction in obese children and adolescents

Plasma homocysteine levels have been shown to be associated with indexes of obesity and insulin resistance in obese children and adolescents. We, therefore, investigated the contribution of changes in body composition, markers of insulin resistance, folate, and vitamin B(12) to changes in homocysteine during a weight reduction program in obese children and adolescents. Thirty-seven obese white girls (mean SD; age, 12 +/- 1.8 years, body mass index [BMI], 26.9 +/- 5.25) and 19 obese white boys (age, 11.9 +/- 1.7 years; BMI, 26.2 +/- 5.2) were investigated for body composition, fasting total plasma homocysteine (tHcy), insulin, C-peptide, folate, and vitamin B(12) before and after a 3-week weight reduction program including physical activities. During weight reduction BMI, fat mass (FM), percentage fat mass, insulin, and C-peptide decreased significantly, whereas homocysteine and vitamin B(12) showed a significant increase. Folate and lean body mass (LBM) remained unchanged. tHcy concentration before weight reduction was a function of age, folate, and C-peptide, whereas tHcy concentration after weight reduction was a function of folate and baseline LBM. Changes in tHcy during weight reduction correlated significantly with baseline LBM and were related inversely to changes in LBM during weight reduction. Children who increased LBM showed lower increases in tHcy compared with children who lost LBM. In multiple linear regression analysis, only baseline LBM contributed independently and significantly to changes in tHcy. Our study suggests that LBM has a significant impact on tHcy metabolism during weight reduction.     

Significance of leptin and high-molecular weight adiponectin in the general population of Japanese male adolescents

Adipokines play crucial roles in obesity-related insulin resistance in adults, but little is known in the general adolescent population. This study was designed to investigate the relationships between adipokines and metabolic parameters, the insulin resistance index, and proinflammatory cytokines in the general population of Japanese male adolescents. We studied 662 Japanese male high school students aged 16 to 17 years and 282 healthy Japanese male adults aged 30 to 61 years who received annual health checkups. High-molecular weight (HMW) adiponectin levels were significantly lower in adolescents (4.18 +/- 2.24 microg/mL) than in adults (4.84 +/- 3.20 microg/mL), despite body mass index (BMI) being significantly lower in adolescents. The HMW adiponectin levels correlated negatively with BMI and the homeostasis model assessment of insulin resistance index (HOMA-IR) in adults. In adolescents, HMW adiponectin correlated negatively with BMI and waist circumference, but not with HOMA-IR or other metabolic parameters except high-density lipoprotein cholesterol. Leptin levels correlated positively with HOMA-IR, triglycerides, tumor necrosis factor alpha, interleukin 6, and monocyte chemoattractant protein 1 and negatively with high-density lipoprotein cholesterol even after adjustment for BMI. These findings suggest that serum leptin is a more useful biomarker of fat accumulation-related insulin resistance, inflammation, and metabolic abnormalities than HMW adiponectin in the general population of male adolescents. The inverse correlation between adiponectin and insulin resistance may manifest in the later phase of obesity development.     

Morning preprandial plasma ghrelin and catecholamine concentrations in patients with phenylketonuria and normal controls: evidence for catecholamine-mediated ghrelin regulation

Patients with phenylketonuria (PKU) have a diet-controlled deficiency in the conversion of phenylalanine (Phe) to tyrosine (Tyr), leading to decreased production of noradrenaline, adrenaline, and dopamine. Poor diet control results in high plasma Phe and low plasma Tyr and catecholamine concentrations. Ghrelin, a recently described gastrointestinal hormone that is elevated in the fasting state and low in the fed state, is considered a major appetite-stimulating hormone, possibly involved in the generation of obesity and insulin resistance. We evaluated morning preprandial plasma ghrelin levels in 14 diet-controlled and 15 poorly controlled PKU patients and 20 age- and body mass index (BMI)-matched healthy children (controls) and correlated its concentrations with those of Phe and catecholamines as well as with their BMI and 24-h nutrient intake. Plasma ghrelin levels were measured by RIA, plasma catecholamine concentrations were determined by HPLC with electrochemical detection, and Phe and Tyr levels were measured in an amino acid analyzer. The ghrelin concentration (744 +/- 25 ng/liter) in diet-controlled patients did not differ from that in controls (802 +/- 26 ng/liter; P > 0.05). On the contrary, the ghrelin concentration was significantly reduced in poorly controlled patients (353 +/- 23 ng/liter; P < 0.0001). Ghrelin correlated negatively with Phe in all three groups, whereas it correlated positively with catecholamine levels and energy intake and negatively with BMI only in diet-controlled patients and controls. We conclude that ghrelin secretion may receive positive direct or indirect input from catecholamines. The absence of a correlation between ghrelin and catecholamines, energy intake, or BMI in PKU patients on an inadequate diet may be due to dysregulation of their neuroendocrine system and might be affected by high Phe levels in the stomach and/or central nervous system.     

Association between the insulin resistance of puberty and the insulin-like growth factor-I/growth hormone axis

To test the hypothesis that the relative insulin resistance of puberty is associated with changes in IGF-I levels, we compared IGF-I, IGF binding protein-3 (IGFBP-3), and IGFBP-1 levels to insulin resistance [M(lbm), milligrams glucose used per kilogram of lean body mass (LBM) per minute] measured during euglycemic, hyperinsulinemic clamp studies in 342 children and adolescents. IGF-I levels rose and fell during the Tanner stages of puberty in a pattern that closely followed the rise and fall of insulin resistance. IGF-I levels were significantly related to M(lbm) in boys (P = 0.0006) and girls (P = 0.02). IGF-I was significantly related to fasting insulin levels only in girls (P = 0.006; boys, P = 0.26), and this relation was significantly influenced in girls by body fat (P = 0.007), with the strongest association between IGF-I and fasting insulin seen in thin girls. IGFBP-1 correlated negatively with insulin resistance in both boys (P = 0.0004) and girls (P = 0.04), whereas IGFBP-3 correlated positively with insulin resistance in boys (P = 0.0004) but not girls (P = 0.85). These data suggest that the GH/IGF-I axis is an important contributor to the insulin resistance of puberty.     

Association between adipocyte fatty acid-binding protein levels and childhood obesity in Korean children

Adipocyte fatty acid-binding protein (A-FABP) is a newly recognized adipokine that plays a role in the development of obesity and insulin resistance in adults. We investigated the association between A-FABP levels and obesity and insulin resistance in school-aged children. One hundred sixty-one 9-year-old Korean children (80 boys and 81 girls) voluntarily participated in this study at school-based health examinations. Weight, height, waist circumference, and blood pressure were measured. Fasting plasma glucose, triglycerides, high-density lipoprotein cholesterol, insulin, and A-FABP levels were measured; and insulin resistance was estimated by the homeostasis model assessment. Subjects with higher body mass index (BMI) percentiles had correspondingly higher concentrations of A-FABP in both boys and girls. Subjects within the highest quartile of A-FABP levels had correspondingly poor metabolic risk profiles (BMI, waist circumference, triglycerides, high-density lipoprotein cholesterol, fasting insulin, and homeostasis model assessment of insulin resistance) compared with those in the lowest A-FABP quartile (P < .01). Serum A-FABP concentrations were significantly correlated with BMI (r = 0.58, P < .01) and waist circumference (r = 0.51, P < .01). However, the significant correlation between serum A-FABP and insulin resistance faded after adjustment for BMI. Adipocyte fatty acid-binding protein was closely associated with obesity or abdominal obesity in children; however, the independent relationship between A-FABP and insulin resistance in children is still unclear and remains to be determined.     

Plasma ghrelin, body fat, insulin resistance, and smoking in clinically healthy men: the atherosclerosis and insulin resistance study

The purpose of the study was to examine whether insulin sensitivity was associated with fasting plasma ghrelin concentrations in a population-based sample of 58-year-old clinically healthy Caucasian men. The methods used were dual-energy x-ray absorptiometry (DXA) for measurement of body composition and a conventional euglycemic hyperinsulinemic clamp, measuring glucose infusion rate (GIR) that was adjusted for fat-free mass. Plasma ghrelin was measured by radioimmunoassay. The results showed that ghrelin was not associated with GIR adjusted for fat-free mass or with GIR adjusted for body mass, and body fat, or waist circumference. Plasma ghrelin correlated negatively to body fat (-0.46, P<.001) and waist circumference (-0.45, P<.001). Ghrelin was also inversely related to systolic and diastolic blood pressure (r=-.29 and r=-0.34, respectively, P<.01) and positively to high-density lipoprotein (HDL) cholesterol (0.33, P<.01), and low-density lipoprotein (LDL) particle size (0.34, P<.001), but these associations did not remain after adjustment for body fat. Plasma ghrelin was associated with current smoking independent of waist circumference. Among current smokers, circulating plasma concentrations were higher in those who had smoked during the hour preceding the blood sample than those who had smoked 2 to 12 hours ago (P=.043). The conclusion is that whole body insulin sensitivity was not associated with plasma ghrelin concentrations. Body fatness was the strongest determinant of circulating ghrelin. It was found that acute smoking may affect ghrelin levels.     

Ghrelin and adiponectin in patients with Cushing's disease before and after successful transsphenoidal surgery

BACKGROUND: Ghrelin, an endogenous ligand of the GH secretagogue receptor that exerts orexigenic activity, is negatively correlated with body mass index (BMI) and insulin resistance. Conversely, low levels of adiponectin (ApN), a circulating adipocytokine with antidiabetic, antiatherogenic and anti-inflammatory properties, have been found in several insulin-resistant conditions. Although Cushing's syndrome causes several metabolic and hormonal changes leading to insulin resistance and central obesity, few data concerning the impact of glucocorticoid excess on ghrelin and ApN levels are so far available. DESIGN: We evaluated ghrelin and ApN levels in 14 women (age +/- SE 39.5 +/- 3.9 years, BMI +/- SE 25.8 +/- 1.4 kg/m2) with Cushing's disease (CD) at baseline and after successful transsphenoidal surgery (TSS) and in 14 age- and BMI-matched healthy women. RESULTS: Despite similar levels of fasting glucose, insulin, homeostatic model assessment-estimated insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) values, patients with CD had ghrelin levels lower than controls (117.8 +/- 21.5 vs. 269.6 +/- 51.4 pmol/l, P < 0.01), and ghrelin levels did not correlate with ACTH, cortisol, androgen and GH levels. Patients and controls showed similar ApN levels (11.1 +/- 1.6 vs. 11.5 +/- 2.0 mg/l), which correlated negatively with insulin, HOMA-IR and BMI and positively with QUICKI and high density lipoprotein (HDL)-cholesterol only in controls. At 10.2 +/- 0.7 months after successful TSS, patients showed a significant increase in ghrelin levels compared to pretreatment values (342.5 +/- 25.6 vs. 117.8 +/- 21.5 pmol/l, P < 0.005) along with significant modifications in BMI, insulin, HOMA-IR and HDL-cholesterol and no change in ApN levels. In two patients tested on days 2-4 after TSS, no modification in ghrelin and ApN levels was observed, despite a dramatic reduction in cortisol levels. CONCLUSION: Cortisol excess did not directly affect ghrelin and ApN levels in patients with CD. The observation that ghrelin levels were low during the active phase of CD and increased after recovery suggests that glucocorticoids may influence ghrelin levels indirectly by modulating adiposity and metabolic signals over the long term.     

Saturated fat intake and insulin resistance in men with coronary artery disease. The Stanford Coronary Risk Intervention Project Investigators and Staff

BACKGROUND. To determine whether there is an association between diet and plasma insulin concentration that is independent of obesity, we studied the relation of dietary composition and caloric intake to obesity and plasma insulin concentrations in 215 nondiabetic men aged 32-74 years with angiographically proven coronary artery disease. METHODS AND RESULTS. After adjusting for age, the intake of saturated fatty acids and cholesterol were positively correlated (p less than 0.05) with body mass index (r = 0.18, r = 0.16), waist-to-hip circumference ratio (r = 0.21, r = 0.22), and fasting insulin (r = 0.26, r = 0.23). Carbohydrate intake was negatively correlated with body mass index (r = -0.21), waist-to-hip ratio (r = -0.21), and fasting insulin (r = -0.16). Intake of monounsaturated fatty acids did not correlate significantly with body mass index or waist-to-hip circumference ratio but did correlate positively with fasting insulin (r = 0.24). Intake of dietary calories was negatively correlated with body mass index (r = -0.15). In multivariate analysis, intake of saturated fatty acids was significantly related to elevated fasting insulin concentration independently of body mass index. CONCLUSIONS. These cross-sectional findings in nondiabetic men with coronary artery disease suggest that increased consumption of saturated fatty acids is associated independently with higher fasting insulin concentrations.     

Determinants of haemostatic risk factors for coronary heart disease in obese children and adolescents

OBJECTIVE: To investigate the contribution of serum lipids, parameters of glucose metabolism, body composition and cardiovascular fitness to the variance of several haemostatic risk factors for coronary heart disease (CHD) in obese children and adolescents. SUBJECTS AND MEASUREMENTS: Forty-two healthy, obese children and adolescents (20 male, 22 female, age 12.6 +/- 3.2y; body mass index (BMI), 30.4 +/- 5.3 kg/m2), were screened for haemostatic and metabolic risk factors for CHD. Thirty-five of the participants (18 male, age 13.5 +/- 2.9y; BMI, 29.9 +/-4.5kg/m2; 17 female, age 12.8+/-2.1 y, BMI, 31.1 +/- 5.3 kg/m2) were assessed for cardiovascular fitness by means of incremental cycle ergometer exercise. RESULTS: After adjustment for age, fat mass correlated significantly with plasminogen activator inhibitor-1 antigen (PAI-1-Ag) in boys and girls and factor VIIc only in girls. Children with lower power output (< or = 2.77W/kg) showed significantly higher values for factor VIIc, fibrinogen and tissue-type plasminogen activator antigen (tPA-Ag). Neither body composition nor cardiovascular fitness contributed independently to the variance of the determined haemostatic risk factors, except PAI-1-Ag, which has been shown to be determined by fat mass. In multiple linear regression analysis, triglycerides and PAI-1-Ag explained significant independent proportions of the variance of tPA-Ag. Factor VIIc was explained by C-peptide, insulin and fibrinogen. Von Willebrand factor antigen (vWF-Ag) was significantly related to glucose and insulin. CONCLUSION: The results suggest that in obese children and adolescents the haemostatic risk factors factor VIIc, vWF-Ag and tPA-Ag are mainly determinated by plasma insulin and triglyceride concentrations, but are primarily independent of body composition and cardiovascular fitness.     

Oral glucose load inhibits circulating ghrelin levels to the same extent in normal and obese children

OBJECTIVE: The presence of both the GH secretagogue (GHS) receptor and ghrelin in the pancreas indicates an involvement of this hormone in glucose metabolism. Ghrelin secretion is increased by fasting and energy restriction, decreased by food intake, glucose load, insulin and somatostatin in normal adults; however, food intake is not able to inhibit circulating ghrelin levels in children, suggesting that the profile of ghrelin secretion in children is different from that in adults. Moreover, how ghrelin secretion is regulated in childhood as a function of fat mass is still unclear. DESIGN AND SUBJECTS: We studied the effect of oral glucose load (75 g solution orally) on circulating total ghrelin levels in 14 obese children (group A, four boys and 10 girls, aged 9.3 +/- 2.3 years) and 10 lean children (group B, five boys and five girls, aged 9.7 +/- 3.8 years). MEASUREMENTS: In all the sessions, blood samples were collected every 30 min from 0 up to +120 min. GH, insulin and glucose levels were assayed at each time point. RESULTS: Glucose peaks following an oral glucose tolerance test (OGTT) in groups A and B were similar; however, both basal and OGTT-stimulated insulin levels in group A were higher than in group B (P < 0.05). Basal total ghrelin levels in group A (281.3 +/- 29.5 pg/ml) were lower (P < 0.0005) than in group B (563.4 +/- 81.5 pg/ml). In both groups A and B, the OGTT inhibited total ghrelin levels (P < 0.005). In terms of absolute values, total ghrelin levels in group A were lower (P < 0.0005) than those in group B at each time point after glucose load. The percentage nadir in total ghrelin levels recorded in group A (-25% at 90 min) was similar to that recorded in group B (-31% at 120 min). Total ghrelin levels were negatively associated with BMI (r = 0.5, P < 0.005) but not with glucose or insulin levels. CONCLUSION: Ghrelin secretion is reduced in obese children. It is, however, equally sensitive in both obese and lean children to the inhibitory effect of oral glucose load.     

Anthropometric predictors of serum fasting insulin in 9- and 15-year-old children and adolescents

BACKGROUND AND AIM: As the prevalence of overweight and obesity increases, the risk of insulin resistance rises. The aim was to study the association between anthropometric measurements and fasting insulin concentration in a population-based sample of 9- and 15-year-old children and adolescents. METHODS AND RESULTS: Subjects were randomly selected 9- and 15-year-old pupils (n=262) in a cross-sectional, population-based study. Weight and height, waist, hip and mid-arm-circumference and subcutaneous skinfolds were measured using standard procedures. Fasting insulin was measured. In general the mean anthropometric measurements increased across insulin quartiles. Higher fasting insulin concentration was seen in overweight children and adolescents than in those of normal weight (8.3+/-4.4 vs. 4.9+/-3.6 mmol/L and 11.0+/-4.4 vs. 9.0+/-4.2 mmol/L in 9- and 15 year-olds, respectively). The odds ratio for having insulin in the highest quartile (age and gender-specific) was, when compared with the lowest quartile, 7.2 (95% CI 3.0-17.2) for body mass index and 6.9 (2.8-16.7) for waist circumference. Other measurements of body fatness were less predictive. About 14-20% of children defined as being of normal weight had high fasting insulin values, i.e., were in the highest quartile of fasting insulin. CONCLUSIONS: Body fatness is positively related to fasting insulin concentration in 9- and 15-year-old children. A large number of normal-weight individuals with high fasting insulin concentration was observed, and these children could be at increased risk of weight gain, compared with normal-weight individuals with normal fasting insulin concentration.     

Association between insulin-like growth factor binding protein-2 levels and cardiovascular risk factors in Korean children

Emerging evidence has indicated that insulin-like growth factor binding protein-2 (IGFBP-2) may be involved in the development of obesity and insulin resistance like IGFBP-1. The aim of this study was to measure serum IGFBP-2 levels in overweight and obese children and to compare these levels with those of controls. We also analyzed the associations between IGFBP-2 and insulin sensitivity indices and cardiovascular risk factors. 134 Korean children including 55 overweight and 59 obese subjects were enrolled. We measured anthropometric values and determined fasting serum levels of IGFBP-2, glucose, insulin, lipid profiles, and insulin sensitivity indices including the homeostatic model assessment of insulin resistance (HOMA-IR) and the Quantitative Insulin Sensitivity Check Index (QUICKI). The subjects were subgrouped based on body mass index (BMI) and pubertal stage, and association analyses between IGFBP-2 levels and measured factors were performed in each group. Serum IGFBP-2 levels in overweight or obese children were significantly lower than those of controls regardless of pubertal development. Serum IGFBP-2 levels were negatively correlated with weight, BMI, waist circumference, fasting insulin levels, and HOMA-IR but were positively correlated with QUICKI. The associations were stronger in pubertal children than those in prepubertal children. However, no association was observed between serum IGFBP-2 levels and auxological or metabolic parameters in children with normal BMIs. These results suggested that IGFBP-2 might be a promising marker for early recognition of insulin resistance, particularly in overweight or obese children, regardless of pubertal stage.     

Effect of sex hormone administration on circulating ghrelin levels in peripubertal children

BACKGROUND: Ghrelin levels gradually decrease throughout childhood and with advancing pubertal stage. The change during puberty is more pronounced in boys than girls. OBJECTIVE: The objective of the study was to investigate whether the pubertal drop in ghrelin secretion is modified by the increase in sex hormones. PATIENTS AND METHODS: Ghrelin levels were measured in 34 short peripubertal children (17 boys and 17 girls) aged 8-12.5 yr before and after sex hormone priming for GH stimulation testing. RESULTS: In boys, priming with testosterone increased testosterone to pubertal levels (23.7 +/- 7.1 nmol/liter), which in turn induced a marked decrease in ghrelin (from 1615.8 +/- 418.6 to 1390.0 +/- 352.0 pg/ml) and leptin (from 8.0 +/- 4.5 to 5.8 +/- 3.2 ng/ml) and an increase in IGF-I (from 162.7 +/- 52.8 to 291.1 +/- 101.6 ng/ml) (P < 0.001 for all parameters). In girls, priming with estrogen led to a supraphysiological increase in estradiol levels (1313.8 +/- 438.0 pmol/liter), which had no effect on ghrelin, leptin, or IGF-I. There was no correlation between ghrelin levels and levels of sex hormones, leptin, or body mass index in either boys or girls. CONCLUSIONS: A pharmacological increase in sex hormones is associated with a marked decline in circulating levels of ghrelin in boys but not girls. Additional longitudinal studies through puberty are needed to elucidate the physiological interaction between sex hormones and ghrelin.