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Circulating zinc-α2-glycoprotein levels are low in newly diagnosed patients with metabolic syndrome and correlate with adiponectin.

ABSTRACT: Zinc-α2-glycoprotein (ZAG) is a novel adipokine that reduces insulin resistance, protecting against type 2 diabetes. However, past studies have been contradictory. This cross-sectional study aims to investigate the association of circulating ZAG with metabolic syndrome (MetS) in middle-aged and older Chinese adults.Four hundred eighty nine individuals (234 healthy controls and 255 MetS patients) were examined. All individuals were screened for MetS according to the diagnostic guidelines of the United States National Cholesterol Education Program (NCEP) Expert Panel Adult Treatment Panel (ATP) III criteria. Circulating ZAG and ADI levels were measured by ELISA. Blood fat, glucose and insulin were measured with a commercial kit. Circulating ZAG levels were compared with various parameters in study subjects.Plasma ZAG levels were lower in MetS patients compared to those of the healthy controls (35.0 ± 11.7 vs. 46.1 ± 18.6 mg/L, P < 0.01). ZAG showed a positive correlation with age, HDL-C, HOMA-β and ADI, but a negative correlation with Fat%, BMI, WHR, blood pressure, triglycerides, FFA, FBG, 2 h-BG, fasting insulin, 2 h-Ins, HbA1c and HOMA-IR (P < 0.01). When the population was divided according to tertiles of ADI, subjects in the highest tertile had the highest ZAG levels. The analysis of ROC curves revealed that the best cutoff value for plasma ZAG to predict MetS was 45.2 mg/L (sensitivity 92%, specificity 59%, and AUC 0.80).We found that circulating ZAG levels were decreased in patients with MetS. In fact, circulating ZAG decreased progressively with an increasing number of MetS components and associated with ADI levels, suggesting that ZAG is related to IR and MetS and may be a sensitizer.ChiCTR-OCC-11001422. Registered 23 June 2011.

SUBMITTER: Lei L

PROVIDER: S-EPMC5556976 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Project description:ObjectivesTo explore zinc-α2-glycoprotein (ZAG), leptin, high-molecular-weight adiponectin (HMW-ADPN), and tumor necrosis factor-alpha (TNF-α) levels in serum and subcutaneous and visceral white adipose tissue (sWAT and vWAT) among normal weight (NW) and overweight/obese (OW/OB) patients with colorectal cancer (CRC).MethodsA total of 76 Chinese CRC patients (42 NW + CRC, 34 OW/OB + CRC) and 40 healthy controls were recruited. Serum levels of the adipokines of interest were measured by an enzyme-linked immunosorbent assay method, and their mRNA levels in sWAT and vWAT were determined by reverse transcription quantitative PCR methods.ResultsSerum ZAG levels in the NW + CRC group were significantly increased by 11.7% compared with the healthy controls. Serum leptin levels in the OW/OB + CRC group were found to be increased by 57.7%, while HMW-ADPN levels were decreased by 23.5% when compared with the NW + CRC group of CRC patients. Additionally, ZAG mRNA levels in sWAT were significantly reduced by 78.8% in OB + CRC in comparison with NW + CRC patients. ZAG mRNA levels were negatively associated with body mass index (BMI) in sWAT but positively correlated with BMI in vWAT. TNF-α mRNA levels in vWAT of OB + CRC patients were significantly increased by 2.8-fold when compared with NW + CRC patients. In particular, CRC was independently associated with serum ZAG levels. The risk of CRC in participants with high tertile serum ZAG levels was 5.84-fold higher than in those with low tertile ZAG levels after adjusting for age, gender, and other confounders [odds ratio (OR) = 6.84, 95% confidence interval (CI) 1.70-27.54, P = 0.03]. The CRC risk in participants with high tertile leptin levels was only 10.7% of those with low tertile leptin levels (OR = 0.11, 95% CI 0.01-0.89, P = 0.04). The area under the receiver operating characteristic (ROC) curve of ZAG was 0.66 (95% CI 0.54-0.77, P < 0.05). At the cutoff value of 1.42 µg/mL serum ZAG, the sensitivity and specificity for differentiating patients with CRC from controls were 62.2 and 69.2%, respectively.ConclusionSerum ZAG levels were significantly increased in CRC patients. Subjects with higher circulating ZAG and lower leptin levels were more likely to have CRC than those with lower ZAG and higher leptin levels. Serum ZAG might be a potential diagnostic biomarker for CRC in the Chinese population.

Project description:Introduction: Zinc-?2-glycoprotein (ZAG) is a novel adipokine, which is involved in metabolic syndrome (MetS). This study aimed to investigate the relationship between serum ZAG and MetS in Chinese adults, who diagnosed according to the 2005 International Diabetes Federation (IDF) criteria. Methods: A group of 151 MetS patients, 84 patients with central obesity and 70 healthy controls were enrolled. General clinical information, serum samples were obtained from all subjects and serum ZAG levels were determined via the commercial ELISA kits. Results: Serum ZAG levels were the highest in the control group, then gradually decreased with the severity of the metabolic abnormalities increased (8.78 ± 1.66 ?g/mL for control vs. 8.37 ± 1.52 ?g/mL for central obesity vs. 7.98 ± 0.94 ?g/mL for MetS, P < 0.05). It was also decreased progressively with an increasing number of the MetS components (P for trend = 0.002). Additionally, serum ZAG/fat mass ratio was calculated and the similar changes were observed in the three groups (0.85 ± 0.53 ?g/mL/kg for control vs. 0.39 ± 0.10 ?g/mL/kg for central obesity vs. 0.36 ± 0.08 ?g/mL/kg for MetS, P < 0.05). In the multiple regression analysis, group was a strong independent factor contributing to serum ZAG levels (P < 0.001). Furthermore, compared with subjects with the highest tertile of ZAG, subjects in the lowest tertile of ZAG had 1.946-fold higher risk of MetS (95% CI 1.419-6.117, P = 0.004). This phenomenon still existed after controlling for age, gender (Model 1), ALP, AST, Cr, UA, Urea based on Model 1 (Model 2), grip strength, smoking, drinking, birth place, current address, education level, manual labor, and exercise frequency based on Model 2 (Model 3). Receiver operation characteristic (ROC) curve analysis revealed that serum ZAG might serve as a candidate biomarker for MetS (sensitivity 57.6%, specificity 70.0% and area under the curve 0.655), and serum ZAG/fat mass ratio showed improved diagnosis value accuracy, with ROC curve area of 0.951 (95% CI, 0.920-0.983, P < 0.001), and 90.7% sensitivity and 88.6% specificity. Conclusions: Serum ZAG levels were lowered in patients with MetS and central obesity. The decreased serum ZAG levels were associated with the increased risks of MetS. Serum ZAG, especially serum ZAG/fat mass ratio might be the candidate diagnostic biomarkers for MetS.

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Circulating zinc-α2-glycoprotein levels are low in newly diagnosed patients with metabolic syndrome and correlate with adiponectin.

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