RESUMEN
BACKGROUND: Ghrelin is a recently discovered protein hormone mainly synthesized in the gastric endocrine cells. This hormone not only is a potent growth hormone secretagogue but also is involved in the regulation of food ingestion and energy metabolism. Derangements in ghrelin secretion in patients with chronic renal failure (CRF) have not been fully evaluated. OBJECTIVE: Our aim has been to quantify serum concentrations of total ghrelin in a group of patients with CRF on chronic therapy with both haemodialysis (HD) and peritoneal dialysis (PD) in comparison with a group of patients on conservative management (predialysis). PATIENTS AND MEASUREMENTS: We studied 68 CRF patients treated by HD (n = 30, 16 men, age 61.2 +/- 1.8 years) and PD groups (n = 38, 21 men, age 54.4 +/- 1.7 years). A group of 19 uraemic patients on conservative management served as the control. Serum concentrations of ghrelin, leptin, insulin, IGF I and GH were measured in all subjects. RESULTS: Patients undergoing HD showed similar concentrations of ghrelin in comparison with the control group (9491 +/- 787 vs 9280 +/- 918 pg/ml, NS). However, PD patients exhibited baseline ghrelin concentrations significantly lower than those found in patients on conservative management (3230 +/- 216 pg/ml, P < 0.0001). Men and women showed similar serum ghrelin levels in both HD (9845.9 +/- 1071 vs 9085 +/- 1194 pg/ml) and PD patients (3214 +/- 297 vs 3250 +/- 324 pg/ml). Hypertension and diabetes mellitus did not influence ghrelin levels. Serum GH levels were positively correlated with serum ghrelin concentrations in both HD (r = 0.46, P < 0.05) and PD (r = 0.53, P < 0.001) patients; however, no relationships between ghrelin, leptin, insulin and IGF I were found. CONCLUSIONS: These results suggest that PD is accompanied by a striking decrement in baseline ghrelin concentrations in comparison with values found both in HD and control patients. Further studies are necessary to determine mechanisms involved in ghrelin regulation in uraemic patients.
Asunto(s)
Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapia , Hormonas Peptídicas/sangre , Diálisis Renal , Adulto , Estudios de Casos y Controles , Complicaciones de la Diabetes/sangre , Eritropoyetina/uso terapéutico , Femenino , Ghrelina , Hormona del Crecimiento/sangre , Humanos , Hipertensión/sangre , Hipertensión/complicaciones , Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Fallo Renal Crónico/complicaciones , Leptina/sangre , Lípidos/sangre , Masculino , Persona de Mediana Edad , Diálisis Peritoneal , Proteínas Recombinantes , Análisis de RegresiónRESUMEN
BACKGROUND AND OBJECTIVE: High levels of some adipocytokines have been reported in patients with chronic renal failure, but little information is available on adipocytokine concentrations in uraemic patients under different modalities of therapy. Our aims were (1) to quantify the serum concentrations of leptin, adiponectin and resistin in uraemic patients on peritoneal dialysis (PD) and haemodialysis (HD), in comparison with patients on conservative management, and (2) to study the relationships between adipocytokine levels and previous atherosclerotic vascular disease. PATIENTS AND MEASUREMENTS: We studied 82 dialysis patients treated by PD (n = 44, 23 males and 21 females, mean age 54.4 +/- 1.8 years) or HD (n = 38, 22 males and 16 females, age 60.8 +/- 1.6 years). A group of 19 uraemic patients on conservative management served as the control. Serum concentrations of leptin, adiponectin and resistin were measured in all subjects. Information on vascular disease (cerebral vascular, peripheral vascular and heart disease) was obtained from a detailed medical history. RESULTS: PD patients showed significantly higher serum leptin concentrations [median (interquartile range), 28.7 (13.0-71.9) microg/l] than those found in patients on HD [9.7 (4.7-31.9) microg/l, P < 0.01] or in conservative management [5.9 (4.3-38.6) microg/l, P < 0.05]. Adiponectin concentrations were similar in the three groups of patients (mean +/- SEM, 48.0 +/- 4.5 mg/l in PD, 57.7 +/- 4.4 mg/l in HD, and 44.4 +/- 7.0 mg/l in controls, NS). Patients treated by both PD and HD exhibited resistin concentrations significantly higher than those found in controls (26.3 +/- 0.99 and 27.5 +/- 1.4 microg/l, respectively, vs. 17.3 +/- 1.0 microg/l, P < 0.001). Leptin concentrations were positively correlated with body mass index (BMI) (r = 0.287, P < 0.01) and adiponectin levels were negatively related to BMI (r = -0.416, P < 0.001) and the homeostatic model assessment (HOMA-R) index (r =-0.216, P < 0.05). Leptin, adiponectin and resistin levels in patients with previous vascular events were similar to those found in patients without these complications. Logistic regression analysis did not demonstrate any relationship between serum adipocytokine concentrations and the presence of vascular disease of any type. A significant relationship between resistin and heart disease [odds ratio (OR) 1.80 (1.03-3.15), P = 0.039] was found when analysing subgroups of patients. CONCLUSIONS: These data suggest that leptin levels are higher in PD patients, and resistin levels are higher in PD and HD patients in relation to patients on conservative management, whereas adiponectin concentrations are similar in the three groups. These results do not support the presence of a clinically relevant relationship between adipocytokines and previous episodes of vascular disease in the whole population or in patients classified in subgroups, with the only exception of a relationship between resistin levels and heart disease.
Asunto(s)
Enfermedades Cardiovasculares/sangre , Hormonas Ectópicas/sangre , Péptidos y Proteínas de Señalización Intercelular/sangre , Fallo Renal Crónico/sangre , Leptina/sangre , Adiponectina , Biomarcadores/sangre , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/terapia , Distribución de Chi-Cuadrado , Femenino , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Diálisis Peritoneal , Análisis de Regresión , Diálisis Renal , ResistinaRESUMEN
OBJECTIVE: Adipose tissue is a hormonally active system that produces and releases different bioactive substances. Leptin, adiponectin and resistin are some of the recently discovered adipocytokines that participate in the regulation of intermediate metabolism. The aim of this study was to evaluate the circulating levels of leptin, adiponectin and resistin in patients with thyroid dysfunction before and after normalization of thyroid function with appropriate therapy. PATIENTS AND MEASUREMENTS: We studied 20 patients with hyperthyroidism (16 women and 4 men; mean age 47.2 +/- 3.9 years) and 20 patients with hypothyroidism (17 women and 3 men; 51.5 +/- 4.1 years). A group of 20 euthyroid subjects served as control group. Patients were evaluated at the time of diagnosis and again after normalization of thyroid function with appropriate therapy. Serum concentrations of free T4 (FT4), total T3, TSH, insulin, leptin, adiponectin and resistin were measured in all subjects. RESULTS: Hyperthyroid patients showed significantly decreased leptin levels in comparison with controls (11.0 +/- 1.1 vs. 30.4 +/- 5.0 microg/l, P < 0.001). No significant differences in adiponectin levels between hyperthyroid and control groups were found (27.8 +/- 4.0 vs. 46.0 +/- 12.0 mg/l, NS). Patients with hyperthyroidism exhibited reduced resistin levels in comparison with euthyroid subjects (6.4 +/- 0.8 vs. 8.4 +/- 0.7 microg/l, P < 0.05). Normalization of circulating thyroid hormone was accompanied by a nonsignificant increase in leptin levels (12.9 +/- 1.7 microg/l, P < 0.01 vs. control) and no significant modification both in adiponectin (32.0 +/- 7.1 mg/l, NS) and resistin (5.4 +/- 0.7 microg/l, NS) levels. Adjustment of adipocytokine concentrations for body mass index (BMI) showed that treatment of hyperthyroidism induced a significant reduction in adjusted resistin concentrations (0.21 +/- 0.03 vs. 0.28 +/- 0.03 microg/l/BMI units, P < 0.05), with no changes in adjusted leptin and adiponectin. Hypothyroid patients showed significantly lower leptin levels compared with the controls (16.0 +/- 3.5 vs. 30.4 +/- 5.0 microg/l, P < 0.05). Adiponectin levels in patients with hypothyroidism (71.8 +/- 16.0 mg/l) were similar to those in the control group and were not modified with therapy. Resistin levels were significantly reduced among hypothyroid patients (5.8 +/- 1.0 microg/l, P < 0.05), and were not increased after levothyroxine therapy. A significant rise in BMI-corrected leptin levels was observed after replacement therapy, with no changes in adiponectin- and resistin-corrected values. CONCLUSIONS: The results suggest that (1) low serum leptin levels are present in both hyperthyroid and hypothyroid patients but are only increased after therapy in the latter; (2) resistin might be implicated in the insulin resistance state that accompanies thyrotoxicosis; and (3) inadequate secretion of adiponectin seems to have no role in metabolic changes associated with thyroid dysfunction.
Asunto(s)
Tejido Adiposo/metabolismo , Citocinas/sangre , Hipertiroidismo/sangre , Hipotiroidismo/sangre , Péptidos y Proteínas de Señalización Intercelular , Adiponectina , Adulto , Estudios de Casos y Controles , Femenino , Hormonas Ectópicas/sangre , Humanos , Hipertiroidismo/tratamiento farmacológico , Hipotiroidismo/tratamiento farmacológico , Leptina/sangre , Masculino , Persona de Mediana Edad , Proteínas/análisis , Análisis de Regresión , Resistina , Resultado del TratamientoRESUMEN
Generalized lipodystrophy is a rare disorder of adipose tissue, whose etiology remains unknown. Pathophysiology of this disorder is characterized by generalized loss of body fat associated with an infrequent form of diabetes mellitus (lipoatrophic diabetes). Main features of this form of diabetes mellitus are the severe insulin resistance and the absence of ketoacidosis. Lipodystrophy can be congenital or acquired. In the acquired form, metabolic disturbances usually begin in the first years of life and the response to conventional treatment is very poor. Some alterations in serum adipocytokines have been described in this disease. We report the case of a 74-year-old woman with acquired generalized lipodystrophy who presented with low-normal serum concentrations of leptin, low adiponectin and resistin levels, and high serum levels of TNF alpha. Patient was initially treated with fenofibrate, metformin and high doses of subcutaneous insulin achieving an adequate metabolic control. During this period, serum adipocytokines were periodically measured. We comment on the different etiopathogenic mechanisms and the therapeutic modalities of this rare syndrome.