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      Association of Plasma Retinol-Binding Protein 4, Adiponectin, and High Molecular Weight Adiponectin with Insulin Resistance in Non-Diabetic Hypertensive Patients

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          Abstract

          Purpose

          The aim of this study was to determine whether retinol-binding protein 4 (RBP4), adiponectin and high molecular weight (HMW) adiponectin are associated with insulin resistance (IR) and metabolic parameters in non-diabetic hypertensive patients. Also, we sought to compare the predictive values of these adipocytokines for IR in non-diabetic hypertensive patients.

          Materials and Methods

          Analyses of RBP4, adiponectin, and HMW adiponectin were performed on 308 non-diabetic hypertensives (148 males, age 58 ± 10 years, 189 non-metabolic syndrome and 119 metabolic syndrome). The homeostasis model assessment (HOMA) index for IR, lipid profiles, and anthropometric measure-ments were assessed.

          Results

          There was no significant difference in RBP4 levels according to the presence of metabolic syndrome, although adiponectin and HMW adiponectin were significantly lower in metabolic syndrome. Correlation analysis of log RBP4 with IR and metabolic indices revealed that there was no significant correlation of RBP4 with waist circumference (r = 0.056, p = 0.324), HDL cholesterol (r = 0.005, p = 0.934), ApoB/ApoAI ratio (r = 0.066, p = 0.270), and the HOMA index (r = 0.017, p = 0.756). However, adiponectin and HMW adiponectin showed significant correlations with the HOMA index (r = - 0.247, p < 0.001; r = - 0.296, p < 0.001) and metabolic parameters. With IR defined as HOMA index ≥ 2.5, HMW adiponectin did not demonstrate a superior predictive value for IR compared to adiponectin (AUC = 0.680 vs. 0.648, p = 0.083). The predictive value of RBP4 for IR was minimal (AUC = 0.534).

          Conclusion

          RBP4 was not associated with IR or metabolic indices and the predictive value for IR was minimal in hypertensives. HMW adiponectin didn't have a superior predictive value for IR compared to adiponectin. Therefore, we can suggest that RBP4 and HMW adiponectin don't have more additive information than adiponectin in non-diabetic hypertensives.

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          Most cited references24

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          Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects.

          Timothy Graham, Qin Yang, Matthias Blüher … (2006)
          Insulin resistance has a causal role in type 2 diabetes. Serum levels of retinol-binding protein 4 (RBP4), a protein secreted by adipocytes, are increased in insulin-resistant states. Experiments in mice suggest that elevated RBP4 levels cause insulin resistance. We sought to determine whether serum RBP4 levels correlate with insulin resistance and change after an intervention that improves insulin sensitivity. We also determined whether elevated serum RBP4 levels are associated with reduced expression of glucose transporter 4 (GLUT4) in adipocytes, an early pathological feature of insulin resistance. We measured serum RBP4, insulin resistance, and components of the metabolic syndrome in three groups of subjects. Measurements were repeated after exercise training in one group. GLUT4 protein was measured in isolated adipocytes. Serum RBP4 levels correlated with the magnitude of insulin resistance in subjects with obesity, impaired glucose tolerance, or type 2 diabetes and in nonobese, nondiabetic subjects with a strong family history of type 2 diabetes. Elevated serum RBP4 was associated with components of the metabolic syndrome, including increased body-mass index, waist-to-hip ratio, serum triglyceride levels, and systolic blood pressure and decreased high-density lipoprotein cholesterol levels. Exercise training was associated with a reduction in serum RBP4 levels only in subjects in whom insulin resistance improved. Adipocyte GLUT4 protein and serum RBP4 levels were inversely correlated. RBP4 is an adipocyte-secreted molecule that is elevated in the serum before the development of frank diabetes and appears to identify insulin resistance and associated cardiovascular risk factors in subjects with varied clinical presentations. These findings provide a rationale for antidiabetic therapies aimed at lowering serum RBP4 levels. Copyright 2006 Massachusetts Medical Society.
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            Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome.

            Kazuo Hara, Momoko Horikoshi, Toshimasa Yamauchi … (2006)
            The high-molecular weight (HMW) form of adiponectin, an adipocyte-derived insulin-sensitizing hormone, has been reported to be the most active form of this hormone. We investigated whether measurement of plasma HMW adiponectin levels, using our newly developed enzyme-linked immunosorbent assay system for selective measurement of human HMW adiponectin level, may be useful for the prediction of insulin resistance and metabolic syndrome. A total of 298 patients admitted for diabetes treatment or coronary angiography served as study subjects. Receiver operator characteristic (ROC) curves for the HMW ratio (HMWR; ratio of plasma level of HMW adiponectin to that of total adiponectin) and plasma total adiponectin levels were plotted to predict the presence of insulin resistance and metabolic syndrome. The area under the ROC curve (AUC) of the HMWR values to predict the presence of insulin resistance was significantly larger than that of plasma total adiponectin level in total subjects (0.713 [95% CI 0.620-0.805] vs. 0.615 [0.522-0.708], P = 0.0160). The AUC for the HMWR values to predict the presence of metabolic syndrome was significantly larger than that for plasma total adiponectin levels in men (0.806 [0.747-0.865] vs. 0.730 [0.660-0.800], P = 0.0025) and in women (0.743 [0.659-0.828] vs. 0.637 [0.532-0.742], P = 0.0458). The HMWR value has better predictive power for the prediction of insulin resistance and metabolic syndrome than plasma total adiponectin level.
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              Clustering of metabolic factors and coronary heart disease.

              H Silbershatz, W Kannel, R D'Agostino … (1999)
              The degree of clustering for common metabolic coronary disease risk factors is not well known, the antecedents of clustering are not well studied, and the impact of such clusters on coronary risk has not been assessed systematically. Prospective community sample of 2406 men and 2569 women aged 18 to 74 years at baseline. The 6 metabolically linked risk factors considered were the lowest sex-specific quintile of high-density lipoprotein cholesterol and the highest quintiles of body mass index, systolic blood pressure, triglycerides, glucose, and serum total cholesterol. At baseline the risk factor sum, represented as integer values, ranged from 0 to 6, and clusters of 3 or more risk factors occurred at twice the rate predicted by chance. After adjustment for age and obesity level, a 2.25-kg (5-lb) weight increase over 16 years was associated with an increased risk factor sum in men (+20%; P=.002) and women (+37%; P<.001), and a 2.25-kg weight loss was associated with a decreased risk factor sum in men (-48%; P<.001) and women (-40%; P<.001). Clusters of 3 or more risk factors were associated with a 2.39 (95% confidence interval, 1.56-3.36) and 5.90 (95% confidence interval, 2.54-13.73) times greater risk of coronary heart disease in men and women, respectively (both P<.001). Atherogenic risk factor clustering is common in both sexes, worsens with weight gain, and is associated with greatly increased risk of coronary disease risk in both sexes.
              Article 0 comments Cited 107 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Yonsei Med J
                Journal ID (publisher-id): YMJ
                Title: Yonsei Medical Journal
                Publisher: Yonsei University College of Medicine
                ISSN (Print): 0513-5796
                ISSN (Electronic): 1976-2437
                Publication date (Print): 01 May 2010
                Publication date (Electronic): 29 March 2010
                Volume: 51
                Issue: 3
                Pages: 375-384
                Affiliations
                [1 ]Cardiology Division, Cardiovascular Center, Yonsei University College of Medicine, Seoul, Korea.
                [2 ]Cardiovascular Genome Center, Cardiovascular Center, Yonsei University College of Medicine, Seoul, Korea.
                [3 ]Cardiovascular Research Institute, Cardiovascular Center, Yonsei University College of Medicine, Seoul, Korea.
                Author notes
                Corresponding author: Dr. Sungha Park, Division of Cardiology, Yonsei Cardiovascular Center, Yonsei University College of Medicine, 250 Seongsan-ro, Seodaemun-gu, Seoul 120-752, Korea. Tel: 82-2-2228-8455, Fax: 82-2-393-20414, shpark0530@ 123456yuhs.ac
                Article
                DOI: 10.3349/ymj.2010.51.3.375
                PMC ID: 2852793
                PubMed ID: 20376890
                SO-VID: d2514371-a851-4703-a64a-a27566e4a790
                Copyright © © Copyright: Yonsei University College of Medicine 2010
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 18 May 2009
                Date revision received : 10 August 2009
                Date accepted : 18 August 2009
                Categories
                Subject: Original Article

                ScienceOpen disciplines: Medicine
                Keywords: insulin resistance,retinol-binding proteins,hypertension,adiponectin
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: insulin resistance, retinol-binding proteins, hypertension, adiponectin

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