Jesús García-Buela

Hyperleptinemia in uremic patients undergoing conservative management, peritoneal dialysis, and hemodialysis: A comparative analysis

We performed a cross-sectional study in a wide sample of patients with chronic renal failure undergoing conservative therapy (CTh) (n = 79), peritoneal dialysis (PD) (n = 75), and hemodialysis (HD) (n = 51), with the aim of analyzing the impact of the different modes of therapy on serum leptin levels. We used a multivariate approach, taking into consideration the potential effects of other epidemiological, dialysis-related, nutritional, and hormonal factors on serum leptin. Leptin levels were higher in patients treated with PD (median, 36 ng/mL) than in those undergoing CTh (10.8 ng/mL) or HD (5.4 ng/mL) (P < 0.0005). This difference persisted after controlling for gender, body mass index, and fasting insulin levels, suggesting that imbalances in these factors may only partially explain the differences found between the three modes of therapy. Leptin levels showed a significant negative correlation with peritoneal protein losses in PD patients but were poorly associated with factors such as proteinuria, daily peritoneal glucose absorption (PD), renal function, or adequacy of dialysis. Leptin and insulin-like growth factor-I (IGF-I) were significantly correlated in PD patients, but the study design did not allow for establishing a meaning for this correlation. In conclusion, serum leptin levels are increased in PD patients when compared with CTh or HD patients. Differences in gender distribution, fat mass, and insulin levels may partially explain these findings, but other undefined factors also may have a role in producing these results.

Marked GH secretion after ghrelin alone or combined with GH-releasing hormone (GHRH) in obese patients.

objectives  Ghrelin is a 28‐amino‐acid peptide, predominantly produced by the stomach. It displays a strong GH‐releasing activity mediated by the hypothalamus–pituitary GH secretagogue (GHS)‐receptor (GHS‐R). There are different studies that suggest the importance of ghrelin in feeding and weight homeostasis. In obesity there is a markedly decreased GH secretion. For both children and adults, the greater the body mass index (BMI), the lower the GH response to provocative stimuli, including the response to GHRH. However, the response to the natural GH secretaogogue ghrelin is unclear at the present time. The aim of the present study was to evaluate the GH response to ghrelin alone or combined with GHRH in a group of obese patients, in order to further understand the deranged GH secretory mechanisms in obesity and to clarify the mechanism of action of ghrelin.

Hyperleptinemia is not correlated with markers of protein malnutrition in chronic renal failure: A cross-sectional study in predialysis, peritoneal dialysis and hemodialysis patients

Background: Serum leptin levels are increased in chronic renal failure (CRF) and may potentially contribute to protein malnutrition in this disorder. Method: Following a cross-sectional design, we performed a nutritional survey in a wide sample of uremic patients treated conservatively (n = 87), with peritoneal dialysis (n = 71) and with hemodialysis (n = 53). Then, we analyzed the correlation between serum leptin levels and markers of protein malnutrition. We used a multivariate approach, taking into consideration the confounding effect of other factors on the correlation between hyperleptinemia and protein malnutrition. Main Results: Both univariate and multivariate analysis disclosed a poor correlation between hyperleptinemia and markers of protein malnutrition. In fact, there were trends to a positive correlation between leptinemia and body protein stores, as estimated from the scrutinized markers. Persistence of the basic correlation between general intake, fat mass and leptin in CRF could partially explain these findings, but neither a negative correlation between leptin levels nor protein nutritional state could be disclosed after controlling for this factor. Conclusions: Our results do not support a first-line role for hyperleptinemia in the genesis of protein malnutrition of uremia.

The decreased growth hormone response to growth hormone releasing hormone in obesity is associated to cardiometabolic risk factors.

The aim of the present study was to evaluate the relationship between GHRH-induced GH secretion in obese premenopausal women and cardiovascular risk markers or insulin resistance. Premenopausal obese women, aged 35–52 years, were studied. GH secretion, IGF-I, serum cardiovascular risk markers, insulin, leptin, mid-waist and hip circumference, total body fat, and truncal fat were measured. Subjects were classified as meeting the criteria for GH deficiency (GHD) when peak GH after stimulation with GHRH was ≤3 μg/L. Mean total and LDL cholesterol, fasting insulin, and HOMA-IR were all higher, in subjects who would have been classified as GH-deficient compared with GH-sufficient. Peak GH secretion after stimulation was inversely associated with fasting insulin (R = −0.650, P = .012), HOMA-IR (R = −0.846, P = .001), total cholesterol (R = −0.532, P = .034), and LDL cholesterol (R = −0.692, P = .006) and positively associated with HDL cholesterol (R = 0.561, P = .037). These data strongly suggest a role for insulin resistance in the decreased GH secretion of obesity and that the blunted GH secretion of central obesity could be the pituitary expression of the metabolic syndrome.

Short-term regulation of peptide YY secretion by a mixed meal or peritoneal glucose-based dialysate in patients with chronic renal failure

BACKGROUND Malnutrition is very prevalent among patients with chronic renal failure. The role of derangements in the gut-brain axis for regulation of appetite in the genesis of anorexia of these patients has not been adequately investigated. Design. Following a randomized, crossover design, we analysed plasma levels of peptide YY (PYY)(1-36) and PYY(3-36) both fasting and after a standardized oral mixed meal or intraperitoneal glucose infusion in 10 stable uraemic patients undergoing peritoneal dialysis and 8 healthy controls, matched for age, gender and body mass index. Main results. Median baseline plasma levels of PYY(1-36) in the different provocation tests oscillated between 406 and 460 pg/mL in patients, as compared with 73 and 100 pg/mL in controls (P < 0.001). Corresponding values for PYY(3-36) oscillated between 235 and 267 pg/mL in patients, versus 56 and 70 pg/mL in controls (P < 0.001). The association of high levels of PYY(3-36) and normal levels of acylated ghrelin (when compared with healthy controls) configurated a markedly pro-anorexigenic pattern in patients. Neither oral intake nor intraperitoneal glucose resulted in significant changes in plasma levels of PYY(1-36) or PYY(3-36) in subjects with renal failure, in contrast with the expected postprandial rise observed in healthy controls (41% for PYY(1-36), P = 0.04 and 32% for PYY(3-36), P = 0.02, median values). CONCLUSIONS Baseline plasma levels of PYY(1-36) or PYY(3-36) are markedly elevated in patients with renal failure undergoing peritoneal dialysis. Provocation studies disclose a marked disregulation in the postprandial secretion of these anorexigenic peptides, when compared with healthy controls. These findings may contribute to clarify the complex pathogenesis of anorexia of chronic renal failure.

Altered fasting and postprandial plasma ghrelin levels in patients with liver failure are normalized after liver transplantation

CONTEXT Anorexia is a problem of paramount importance in patients with advanced liver failure. Ghrelin has important actions on feeding and weight homeostasis. Experimental data exist, which suggest that ghrelin could protect hepatic tissue. Both fasting and post-oral glucose tolerance test (OGTT) ghrelin concentrations are controversial in liver cirrhosis and are unknown after liver transplantation. OBJECTIVE Our aim was to study fasting ghrelin concentrations and their response to an OGTT in liver failure patients before and after liver transplantation. DESIGN AND METHODS We included 21 patients with severe liver failure studied before (pretransplantation, PreT) and 6 months after liver transplantation (posttransplantation, PostT), and 10 age- and body mass index-matched healthy or overweight subjects as the control group (Cont). After an overnight fast, 75 g of oral glucose were administered; glucose, insulin, and ghrelin were obtained at baseline and at times 30, 60, 90, and 120 min. RESULTS Fasting ghrelin (median and range, pg/ml) levels were lower in PreT: 539 (309-1262) than in Cont: 643 (523-2163), P=0.045. Fasting ghrelin levels increased after liver transplantation, 539 (309-1262) vs 910 (426-3305), for PreT and PostT respectively, P=0.001. The area under the curve (AUC) of ghrelin (pg/ml min) was lower in PreT: 63,900 (37,260-148,410) than in Cont: 76,560 (56,160-206,385), P=0.027. The AUC of ghrelin increased in PostT, 63,900 (37,260-148,410) vs 107,595 (59,535-357,465), for PreT and PostT respectively, P=0.001. Fasting levels and the AUC of ghrelin were similar in PosT and Cont. CONCLUSIONS Decreased fasting and post-OGTT ghrelin levels in liver failure patients were normalized after liver transplantation.

Effect of low-GDP bicarbonate–lactate-buffered peritoneal dialysis solutions on plasma levels of adipokines and gut appetite-regulatory peptides. A randomized crossover study

BACKGROUND Malnutrition is common in patients treated with peritoneal dialysis (PD). Previous studies have disclosed disturbances in the hormonal axes regulating appetite in these patients. The effect of newer biocompatible PD solutions on these disorders is undetermined. METHODS Using a crossover randomized design, 21 patients stable on PD underwent 5 weeks of therapy with each of classic glucose degradation product (GDP)-rich lactate-buffered PD solutions (L) and newer low-GDP bicarbonate-lactate-buffered PD solutions (BL). At the end of each phase, we scrutinized patients for adequacy markers, peritoneal transport (peritoneal equilibration test with 3.86% glucose-based solutions), general biochemical markers and, more specifically, cytokines, adipokines (leptin and adiponectin) and selected gastrointestinal peptides which regulate appetite in the short term [ghrelin, peptide YY, cholecystokinin, glucagon-like peptide 1 (GLP1)]. For plasma GLP1 levels, we analysed a group of healthy, sex-, age- and body mass index-matched controls. RESULTS Use of BL solutions was associated with higher plasma levels of acylated (but not total) ghrelin (median 243 BL versus 141 pg/mL L, P = 0.05), adiponectin (median 20.2 BL versus 17.6 mcg/mL L, P = 0.008) and growth hormone (median 1.8 BL versus 1.0 ng/mL L, P = 0.013), without significant differences for the other cytokines, leptin or gut peptides scrutinized. We did not observe significant differences between L and BL solutions concerning estimations of adequacy, peritoneal transport or general biochemical markers. CONCLUSIONS Use of GDP-free, neutral-pH, bicarbonate-lactate-buffered PD solutions is associated with higher plasma levels of acylated ghrelin and adiponectin than classic solutions. These findings may contribute to explaining improved appetite scores and overall survival rates reported with the use of so-called biocompatible PD solutions.

Effect of oral glucose administration on rebound growth hormone release in normal and obese women: the role of adiposity, insulin sensitivity and ghrelin.

Context Metabolic substrates and nutritional status play a major role in growth hormone (GH) secretion. Uncovering the mechanisms involved in GH secretion following oral glucose (OG) administration in normal and obese patients is a pending issue. Objective The aim of this study was to investigate GH after OG in relation with adiposity, insulin secretion and action, and ghrelin secretion in obese and healthy women, to further elucidate the mechanism of GH secretion after OG and the altered GH secretion in obesity. Participants and Methods We included 64 healthy and obese women. After an overnight fast, 75 g of OG were administered; GH, glucose, insulin and ghrelin were obtained during 300 minutes. Insulin secretion and action indices and the area under the curve (AUC) were calculated for GH, glucose, insulin and ghrelin. Univariate and multivariate linear regression analyses were employed. Results The AUC of GH (μg/L•min) was lower in obese (249.8±41.8) than in healthy women (490.4±74.6), P=0.001. The AUC of total ghrelin (pg/mL•min) was lower in obese (240995.5±11094.2) than in healthy women (340797.5±37757.5), P=0.042. There were significant correlations between GH secretion and the different adiposity, insulin secretion and action, and ghrelin secretion indices. After multivariate analysis only ghrelin AUC remained a significant predictor for fasting and peak GH.