Serial plasma concentrations of adiponectin, leptin, and resistin during therapy in children with acute lymphoblastic leukemia.

PURPOSE: To investigate adipocytokine secretion, at diagnosis and during chemotherapy in children with the acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Serial measurements (6/patient) of the anti-inflammatory cytokine adiponectin and the proinflammatory adipocytokines leptin and resistin were performed at diagnosis and in nearly the entire period of therapy (up to 21 months), in 9 patients with ALL aged 2 to 7 years (median 4.3 y). Body mass index and leukemic burden were estimated at the same time points and correlated with adipocytokine levels. Nine healthy children matched for age, sex, and body mass index were used as controls. RESULTS: At diagnosis, mean adiponectin levels were low (P<0.001) and mean leptin and resistin levels were high, compared with controls (P<0.001). During maintenance phase, adiponectin increased significantly (P=0.024), whereas leptin and resistin decreased (P=0.018 and P=0.020, respectively), compared with baseline values. However, adiponectin, despite its progressive increase, remained at lower levels toward the end of the maintenance phase, compared with controls, (P<0.001). Delta (final-baseline) mean adiponectin was negatively correlated with leukemic burden (P=0.019), whereas delta mean leptin and resistin were positively correlated with it (P=0.011 and P=0.031, respectively). CONCLUSIONS: Low-plasma adiponectin and high leptin and resistin level are present at the ALL diagnosis. Adipocytokines alterations are progressively restored during therapy.

Serial plasma concentrations of PYY and ghrelin during chemotherapy in children with acute lymphoblastic leukemia.

PURPOSE: To investigate peptide YY (PYY) and ghrelin secretion, at diagnosis and during chemotherapy in children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Measurements were performed at diagnosis, after the induction-consolidation phase and at standard time points before each cycle in 9 patients with ALL aged 2 to 7 years (median 4.3 y). Body mass index (BMI) and leukemic burden were estimated at the same time points and correlated with PYY and ghrelin levels. Nine healthy children matched for age and sex were used as controls. RESULTS: At diagnosis, mean PYY levels were high (P<0.0001) and mean active ghrelin were low, compared with controls (P<0.001). Compared with baseline values, PYY increased significantly after the induction-consolidation phase (P=0.033), and returned progressively to pretreatment levels after the sixth cycle, whereas ghrelin fluctuated and stabilized at significantly higher levels (P=0.024) after the eighth cycle of chemotherapy. However, ghrelin was still low, compared with controls (P<0.001), after the eighth cycle. Delta (final-baseline) mean PYY was negatively correlated with delta mean BMI SD score (-0.612, P=0.010) and positively with leukemic burden (0.529, P=0.015), whereas delta mean ghrelin was positively correlated with delta mean BMI SD score (0.626, P=0.009) and negatively with leukemic burden (-0.567, P=0.012). CONCLUSIONS: PYY and ghrelin play a major role in pathogenesis of anorexia-cachexia syndrome in pediatric ALL patients.

The adiponectin-to-leptin ratio in women with polycystic ovary syndrome: relation to insulin resistance and proinflammatory markers.

Central adiposity plays an important role in the insulin resistance of the polycystic ovary syndrome (PCOS) through the dysregulated production of various adipokines. Polycystic ovary syndrome has also been described as a low-grade inflammation state characterized by elevated levels of C-reactive protein (CRP). Furthermore, CRP is a strong independent predictor of the metabolic syndrome and cardiovascular disease. Recently, the adiponectin-to-leptin (A/L) ratio has been proposed as a potential atherogenic index in obese type 2 diabetic patients. The aim of this study was to evaluate the potential role of the A/L ratio in the metabolic and proinflammatory phenotype of PCOS. We studied 74 Greek women with PCOS (38 normal-weight and 36 overweight-obese women). The A/L ratio was negatively correlated with BMI (r = -0.79 P < .001), homeostasis model assessment (r = -0.642, P < .001), triglycerides (r = -0.67, P < .001), and total cholesterol (r = -0.38, P < .01), and positively correlated with high-density lipoprotein cholesterol (r = 0.38, P < .01) and sex hormone-binding globulin (r = 0.39, P = .001). After controlling for BMI, the A/L ratio was independently associated with insulin resistance indexes and triglycerides. Furthermore, the A/L ratio was negatively correlated with CRP (r = -0.746, P < .0001). Multiple regression analysis revealed that BMI and the A/L ratio were the only independent significant determinants of CRP (beta = .436, P = .003 and beta = -.398, P = .007, respectively). Studying normal-weight and overweight-obese women separately, we found an independent association between the A/L ratio and CRP in both groups (beta = -.460, P = .009 in normal-weight women and beta = -.570, P = .001 in overweight-obese women). In conclusion, the A/L ratio may serve as a biomarker of both insulin resistance and low-grade inflammation, providing the link between these cardiovascular risk factors in women with PCOS.

Increased plasma adiponectin concentrations in poorly controlled patients with phenylketonuria normalize with a strict diet: evidence for catecholamine-mediated adiponectin regulation and a complex effect of phenylketonuria diet on atherogenesis risk factors.

Adiponectin (Adpn), an adipose tissue-derived hormone, prevents endothelial inflammation and early atherogenesis. Classic phenylketonuria (PKU), an inborn error of phenylalanine (Phe) metabolism, results in a reduction of catecholamine biosynthesis and requires treatment with lifelong low-Phe diet to prevent mental dysfunction and allow proper intellectual development. In this study, we evaluated the effect of the quality of PKU diet on plasma Adpn concentrations and related biochemical indices of endothelial dysfunction and atherogenesis. Patients with PKU were divided into groups A (n = 18), who were on a strict diet, and B (n = 18), who were on a loose diet, after evaluation of their 30-day dietetic diaries and measurement of Phe blood concentrations. Twenty healthy children of similar ages and body mass indexes served as controls (group C). Group A patients had normal circulating catecholamines and Adpn and decreased tumor necrosis factor alpha concentrations and low-density lipoprotein cholesterol/apolipoprotein B ratio compared with groups B and C. Despite these favorable parameters, however, homocysteine concentration was twice as high in group A compared with groups B and C. Interestingly, group B patients under loose dietary control had significantly elevated Adpn concentrations compared with groups A and C and increased tumor necrosis factor alpha and an unfavorable lipid profile, but normal levels of homocysteine. These data support the hypothesis that catecholamines inhibit Adpn secretion and that the elevated Adpn of the poorly controlled patients might moderate their risk for endothelial dysfunction and atherogenesis. Homocysteine production appears to be unfavorably affected by a strict PKU diet, diverging from the rest of the atherogenesis risk factors, which were improved in the well-controlled patients.

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.

Effect of adiponectin gene polymorphisms on circulating adiponectin and insulin resistance indexes in women with polycystic ovary syndrome.

BACKGROUND: We examined the possible association of adiponectin gene polymorphisms with polycystic ovary syndrome (PCOS) and their influence on serum adiponectin and insulin resistance indexes in Greek women with PCOS. METHODS: We genotyped samples from 100 women with PCOS characterized with respect to body mass index (BMI), glucose and insulin concentrations during an oral glucose tolerance test (OGTT), lipid profile, and serum adiponectin concentrations and from 140 healthy controls for the 45T>G and 276G>T polymorphisms in the adiponectin gene. RESULTS: The distributions of genotypes and alleles of both polymorphisms were no different in women with PCOS and controls, indicating that the individual polymorphisms are not associated with increased risk for PCOS. However, the two polymorphisms were found to be associated with insulin resistance indexes among women with PCOS and to influence adiponectin production. In particular, carriers of the TG genotype at position +45 had greater hyperinsulinemia, as estimated by the area under the curve for insulin (AUC(insulin)) during the OGTT, than those with the TT genotype (P <0.05), and this was independent of age and BMI. In addition, women with PCOS with the GG or GT genotypes at position +276 had a higher BMI (P = 0.01) and greater AUC(insulin) (P = 0.01) than carriers of the TT genotype. The latter genotype was found less frequently among overweight/obese women with PCOS than in normal-weight individuals (P = 0.002). In addition, the presence of the GG or GT genotype was associated with lower serum adiponectin than the TT genotype, independent of age, BMI, and insulin concentrations (P = 0.03). Serum adiponectin was negatively correlated with serum triglycerides and insulin resistance indexes and positively with HDL-cholesterol. CONCLUSIONS: Adiponectin gene polymorphisms at positions +45 and +276 are not associated with PCOS. However, these genomic variants may influence production of adiponectin and the metabolic variables related to insulin resistance/metabolic syndrome in patients with PCOS.

Circulating peptide YY concentrations are higher in preterm than full-term infants and correlate negatively with body weight and positively with serum ghrelin concentrations.

BACKGROUND: Peptide YY (PYY) and ghrelin are gastrointestinal tract-derived hormones that play roles in the regulation of food intake and energy balance. Negative energy balance often occurs in hospitalized preterm infants. METHODS: To measure serum concentrations of PYY in preterm and full-term infants and to investigate their correlations with anthropometric characteristics, food intake, and serum ghrelin concentrations, we measured serum PYY and ghrelin concentrations by RIA in 62 healthy preterm infants [mean (SD) gestational age, 32.0 (2.1) weeks; postnatal age, 40.9 (14.8) days] and 15 healthy full-term infants of comparable postnatal age. All of the infants were formula-fed every 3 h. RESULTS: PYY concentrations were significantly higher in preterm [1126.2 (215.4) ng/L] than in full-term infants [825.3 (234.4) ng/L; P < 0.001]. In the entire study population, serum PYY concentrations correlated negatively with gestational age and anthropometric measurements (birth weight, body weight, body length, body mass index, and head circumference) and positively with serum ghrelin concentrations, whereas there was no significant correlation between PYY concentration and caloric intake or weight gain. Multiple regression analysis, after correction for prematurity, revealed that serum PYY concentrations correlated independently with serum ghrelin concentrations and infant body weight or body mass index. CONCLUSIONS: Circulating concentrations of PYY may increase in preterm infants to compensate for the negative body-weight balance. The physiologic mechanisms behind the correlation between PYY and ghrelin remain to be elucidated.