|Adiponectin changes in HCV-Genotype 4: relation to liver histology and response to treatment.|
M Derbala, N Rizk, S Al-Kaabi, A Amer, F Shebl, A Al Marri, I Aigha, D Alyaesi, H Mohamed, H Aman, N Basem
Journal of viral hepatitis
Recently, attention has been focussed on adiponectin and its changes in different types of chronic liver disease. Its relation to hepatic fibrosis and insulin resistance in post-hepatitis liver disease is not clear. The aim of this study was to clarify the adiponectin changes in genotype 4 hepatitis C virus (HCV)-infected patient in relation to liver histology and insulin resistance, and its usefulness as a predictor of hepatic fibrosis and response to treatment. Total adiponectin and its high molecular weight (HMW) form as well as insulin levels were studied in 92 chronic HCV, genotype 4 and 66 healthy control volunteers. Neither total adiponectin (r = 0.101, P = 0.220) nor HMW adiponectin (r = 0.081, P = 0.328) correlated with viral load. Total and not HMW adiponectin was significantly correlated with hepatic fibrosis and inflammation (r = 0.267, P = 0.002, r = 0.278, P 0.001, respectively).In addition, total adiponectin (r = 0.224, P = 0.002) and HMW adiponectin (r = 0.266, P 0.0006) significantly correlated with insulin resistance. As fibrosis did not correlate with insulin resistance (r = 0.081, P = 0.204), the correlation between total adiponectin and fibrosis was not mediated by insulin resistance. Multivariable regression analysis, (including pretreatment cases and controls) revealed that total adiponectin was significantly associated with gender, being lower among male subjects (X(2) = 13.04, P = 0.0001). The multivariable regression model supported the lack of association between insulin resistance and total adiponectin levels (X(2) = 1.88, P = 0.171), while non cirrhotics had significantly lower total adiponectin levels than cirrhotics (X(2) = 10.90, P = 0.004) and lower level of inflammation significantly lower total adiponectin levels than more severe inflammation (X(2) = 8.95, P = 0.003). Total or HMW adiponectin did not yield receiver operating characteristic (ROC) curves with area under the curve (AUC) >75%, thus the cutoff points have poor sensitivity/specificity as predictors of fibrosis. However, as a predictor of end-of-treatment response, the ROC curve of adiponectin index gave yield an AUC = 81.4%. We can conclude that total adiponectin level, in HCV genotype 4 patients, increases with progression of hepatic fibrosis regardless of insulin resistance. Its high molecular form does not have such correlation. The adiponectin changes are not related to viral load, insulin resistance or other demographic data suggesting that this change is histologically related. In spite of this, no adiponectin cutoff level had reasonable sensitivity/specificity for predicting hepatic fibrosis stage, while this may be used as a predictor for antiviral response possibly reflecting improvement in hepatic inflammation post treatment.
|Adiponectin levels and its association with hyperglycaemia in adult Filipino participants in the 2003--04 National Nutrition and Health Survey.|
Paz-Pacheco E, Lim-Abrahan MA, Sy RA, Jasul GV, Sison CM, Laurel AF
Diab Vasc Dis Res
Our objective was to determine the association of serum adiponectin levels with the presence of IFG or DM in Filipinos. This case control study used sera of adult participants in the Philippines' NNHeS: 2003-04. Subjects were divided into: normoglycaemic control, impaired fasting glucose, and type 2 diabetes mellitus. Seventy-seven prediabetic and 83 diabetic subjects were included in the prediabetic and diabetic groups, respectively. There was no significant difference in adiponectin values between control and prediabetic subjects. Diabetic subjects had significantly lower mean serum adiponectin levels (10.7 versus 14.2 microg/ml, p=0.0198) compared with age- and BMI-matched control subjects. Diabetic subjects were found most frequently (43.53%) in the lowest tertile (1.6-7.2 microg/ml) and least frequently (20%) in the highest tertile (14-84 microg/ml) of adiponectin values. We conclude that Filipinos with diabetes mellitus had significantly lower adiponectin levels compared with normoglycaemic subjects.
|Effect of antipsychotics on peptides involved in energy balance in drug-naive psychotic patients after 1 year of treatment.|
Rocio Perez-Iglesias,Jose Luis Vazquez-Barquero,Jose Antonio Amado,Ana Berja,Maria Teresa Garcia-Unzueta,Jose María Pelayo-Terán,Eugenio Carrasco-Marín,Ignacio Mata,Benedicto Crespo-Facorro
Journal of clinical psychopharmacology
Weight gain has become one of the most common and concerning side effects of antipsychotic treatment. The mechanisms whereby antipsychotics induce weight gain are not known. It has been suggested that peptides related to food intake and energy balance could play a role in weight gain secondary to antipsychotic therapy. To better understand the pathophysiology of antipsychotic-induced weight gain, we studied the effects of 3 antipsychotic drugs (haloperidol, olanzapine, and risperidone) on peptides involved in energy balance (insulin, ghrelin, leptin, adiponectin, visfatin, and resistin) in a population of drug-naive patients with first episode of psychosis.A significant increase in weight (10.16 kg [SD, 8.30 kg]; P < 0.001), body mass index (3.56 kg/m [SD, 2.89 kg/m]; P < 0.001), and fasting insulin (3.93 muU/mL [SD, 3.93 muU/mL]; P = 0.028), leptin (6.76 ng/mL [SD, 7.21 ng/mL]; P < 0.001), and ghrelin (15.47 fmol/mL [SD, 47.90 fmol/mL]; P = 0.009) plasma levels were observed. The increments in insulin and leptin concentrations were highly correlated with the increment in weight and body mass index and seem to be a consequence of the higher fat stores. The unexpected increase in ghrelin levels might be related with the causal mechanism of weight gain induced by antipsychotics. Finally, the 3 antipsychotics had similar effects in all parameters evaluated.
|Analytical validation and biological evaluation of a high molecular-weight adiponectin ELISA.|
Madhur K Sinha, Traci Songer, Qiang Xiao, John H Sloan, Jin Wang, Shaoquen Ji, William E Alborn, Randy A Davis, Michael M Swarbrick, Kimber L Stanhope, Bruce M Wolfe, Peter J Havel, Todd Schraw, Robert J Konrad, Philipp E Scherer, Jehangir S Mistry
BACKGROUND: Of the 3 circulating multimeric forms of adiponectin, the high-molecular-weight (HMW) form, as measured by size-exclusion and/or immunoblotting techniques, is a better index of insulin sensitivity for monitoring health and disease than is total adiponectin. We aimed to develop a simple ELISA to measure HMW adiponectin. METHODS: We pretreated serum or plasma samples with digestion solution containing proteinase K (Millipore, ESDS). HMW (Millipore, EZHMWA-64K) and total adiponectin (Millipore, EZHADP-61K) concentrations were measured in treated and untreated samples, respectively, from 108 individuals and from 20 morbidly obese patients before and at 1, 3, 6, and 12 months after gastric-bypass surgery. RESULTS: The ELISA has a dynamic range of 3-200 microg/L and a detection limit of 0.8 microg/L. Intraassay and interassay CVs were 4% and 10%, respectively. Sample-dilution curves paralleled the calibration curves. Fast protein liquid chromatography profiles of the proteinase K-treated samples revealed predominantly HMW adiponectin. Values for HMW adiponectin produced with this method are comparable with those obtained with Western blot analysis (y = 0.77x - 0.15; r = 0.96; n = 56). Body mass index (BMI)- and sex-related changes were more pronounced for HMW adiponectin and percentage of HMW adiponectin than for total adiponectin. HMW and total adiponectin increased after bypass surgery, but changes in HMW adiponectin were more pronounced and preceded changes in total adiponectin. CONCLUSION: This simple, rapid ELISA for HMW adiponectin recognizes the HMW isoform, produces results closely correlated with those obtained with Western blotting, and appears to better distinguish BMI-, sex-, and weight loss-associated differences than assays for total adiponectin.