Novel adiponectin-resistin (AR) and insulin resistance (IRAR) indexes are useful integrated diagnostic biomarkers for insulin resistance, type 2 diabetes and metabolic syndrome: a case control study

Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Cardiovascular Diabetology (Impact Factor: 4.02). 01/2011; 10(1):8. DOI: 10.1186/1475-2840-10-8
Source: PubMed


Adiponectin and resistin are adipokines which modulate insulin action, energy, glucose and lipid homeostasis. Meta-analyses showed that hypoadiponectinemia and hyperresistinemia are strongly associated with increased risk of insulin resistance, type 2 diabetes (T2DM), metabolic syndrome (MS) and cardiovascular disease. The aim of this study was to propose a novel adiponectin-resistin (AR) index by taking into account both adiponectin and resistin levels to provide a better indicator of the metabolic homeostasis and metabolic disorders. In addition, a novel insulin resistance (IRAR) index was proposed by integration of the AR index into an existing insulin resistance index to provide an improved diagnostic biomarker of insulin sensitivity.
In this case control study, anthropometric clinical and metabolic parameters including fasting serum total adiponectin and resistin levels were determined in 809 Malaysian men (208 controls, 174 MS without T2DM, 171 T2DM without MS, 256 T2DM with MS) whose ages ranged between 40-70 years old. Significant differences in continuous variables among subject groups were confirmed by ANCOVA or MANCOVA test using 1,000 stratified bootstrap samples with bias corrected and accelerated (BCa) 95% CI. Spearman's rho rank correlation test was used to test the correlation between two variables.
The AR index was formulated as 1+log10(R0)-log10(A0). The AR index was more strongly associated with increased risk of T2DM and MS than hypoadiponectinemia and hyperresistinemia alone. The AR index was more strongly correlated with the insulin resistance indexes and key metabolic endpoints of T2DM and MS than adiponectin and resistin levels alone. The AR index was also correlated with a higher number of MS components than adiponectin and resistin levels alone. The IRAR index was formulated as log10(I0G0)+log10(I0G0)log10(R0/A0). The normal reference range of the IRAR index for insulin sensitive individuals was between 3.265 and 3.538. The minimum cut-off values of the IRAR index for insulin resistance assessment were between 3.538 and 3.955.
The novel AR and IRAR indexes are cost-effective, precise, reproducible and reliable integrated diagnostic biomarkers of insulin sensitivity for screening subjects with increased risk of future development of T2DM and MS.

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    • "Los niveles de adiponectina y resistina y su asociación con marcadores metabólicos y de inflamación pueden ser utilizados para definir el estatus inmunometabólico en individuos con RI, calculando el índice adiponectina-resistina (AR index ) propuesto por Lau y cols., 2011 17 y la relación proporcional en la producción sérica de resistina y adiponectina (R/A). Por otra parte, en el desarrollo de RI se ha implicado un componente genético importante a través de la expresión de genes de susceptibilidad 1,16 . "
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    ABSTRACT: Introduction: Insulin resistance (IR) is a disease with genetic susceptibility characterized by the increase in storage and irregular body fat distribution, and impaired production of adipokines. Objective: The objective was to investigate the relationship between 3'UTR+62G>A RETN gene polymorphism, with adiponectin-resistin index (ARindex), adiposity, and inmuno-metabolic markers. Methods: In this cross-sectional study, 260 individuals characterized as Mexican-Mestizo and classified in lean and overweight, and IR and without-IR, were included. Anthropometrics, body composition, body fat distribution and inflammation and metabolic markers were measured by routine methods, RETN 3'UTR+62G>A alleles were identified by PCR-RFLP and soluble insulin, total adiponectin and resistin were measured by ELISA methods. Results: The +62G allele frequencies for lean and overweight individuals were different P=0.0343 (95.4% and 98.4%, respectively). The lean GA genotype carriers showed significant low measures of ARindex, adiposity, and inmuno-metabolic markers, than the GG genotype carriers. We found differences between individuals with IR and without-IR: in ARindex (P=0.002), adiponectin (P=0.002) and resistin levels (P=0.033): 1.102 ± 0.03, 5.167 ± 0.36ug/mL and 8.827 ± 0.42ng/mL versus 1.336 ± 0.07, 3.577 ± 0.34ug/mL and 10.480 ± 0.65ng/mL. Showed correlations with inflammation markers, distribution and body fat storage (r=0.262 to 0.414), PA polymorphism is associated with overweight. The presence of the +62A allele was associated with increase of total adiponectin, ARindex, resistin levels, metabolic markers and body fat storage. ARindex can be an early indicator of insulin resistance.
    Nutricion hospitalaria: organo oficial de la Sociedad Espanola de Nutricion Parenteral y Enteral 11/2013; 28(6):1867-76. DOI:10.3305/nh.2013.28.6.6912 · 1.04 Impact Factor
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    • "It is expressed in human macrophages and has documented regulatory effects on metabolism, adipogenesis and inflammatory reactions [31-33]. Peripheral levels of resistin are upregulated in subjects with insulin resistance and in obesity [34,35], and resistin signaling involves both toll-like receptor (TLR)4 [36] and the IGF-1 receptor [37]. "
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    ABSTRACT: Severe fatigue is a major health problem in fibromyalgia (FM). Obesity is common in FM, but the influence of adipokines and growth factors is not clear. The aim was to examine effects of exercise on fatigue, in lean, overweight and obese FM patients. In a longitudinal study, 48 FM patients (median 52 years) exercised for 15 weeks. Nine patients were lean (body mass index, BMI 18.5 to 24.9), 26 overweight (BMI 25 to 29.9) and 13 obese. Fatigue was rated on a 0 to 100 mm scale (fibromyalgia impact questionnaire [FIQ] fatigue) and multidimensional fatigue inventory (MFI-20) general fatigue (MFIGF). Higher levels in FIQ fatigue and MFIGF indicate greater degree of fatigue. Free and total IGF-1, neuropeptides, adipokines were determined in serum and cerebrospinal fluid (CSF). Baseline FIQ fatigue correlated negatively with serum leptin (r = -0.345; P = 0.016) and nerve growth factor (NGF; r = -0.412; P = 0.037). In lean patients, baseline MFIGF associated negatively with serum resistin (r = -0.694; P = 0.038). FIQ Fatigue associated negatively with CSF resistin (r = -0.365; P = 0.073). Similarly, FIQ fatigue (r = -0.444; P = 0.026) and MFIGF correlated negatively with CSF adiponectin (r = -0.508; P = 0.01). In lean patients, FIQ fatigue (P = 0.046) decreased after 15 weeks. After 30 weeks, MFIGF decreased significantly in lean (MFIGF: P = 0.017), overweight (MFIGF: P = 0.001), and obese patients (MFIGF: P = 0.016). After 15 weeks, total IGF-1 increased in lean (P = 0.043) patients. ∆Total IGF-1 differed significantly between lean and obese patients (P = 0.010). ∆Total IGF-1 related negatively with ∆MFIGF after 15 weeks (r = -0.329; P = 0.050). After 30 weeks, ∆FIQ fatigue negatively correlated with ∆NGF (r = -0.463; P = 0.034) and positively with ∆neuropeptide Y (NPY) (r = 0.469; P = 0.032). Resistin increased after 30 weeks (P = 0.034). ∆MFIGF correlated negatively with ∆resistin (r = -0.346; P = 0.031), being strongest in obese patients (r = -0.815; P = 0.007). In obese patients, ∆FIQ fatigue after 30 weeks correlated negatively with ∆free IGF-1 (r = -0.711; P = 0.032). Exercise reduced fatigue in all FM patients, this effect was achieved earlier in lean patients. Baseline levels of resistin in both serum and CSF associated negatively with fatigue. Resistin was increased after the exercise period which correlated with decreased fatigue. Changes in IGF-1 indicate similar long-term effects in obese patients. This study shows reduced fatigue after moderate exercise in FM and indicates the involvement of IGF-1 and resistin in these beneficial effects. Trial registration NCT00643006
    Arthritis research & therapy 02/2013; 15(1):R34. DOI:10.1186/ar4187 · 3.75 Impact Factor
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    • "It is well-known that natriuretic peptides are secreted almost exclusively by cardiac tissue and their levels are increased in patients with HF [31]. It has been hypothesized that the ADN increase could be a compensatory effect in order to restore metabolic homeostasis, due to its anti-inflammatory and insulin-sensitizing effects [32,33]. Abnormalities in glucose regulation, such as impaired glucose tolerance and insulin resistance, have been shown to correlate with HF severity [34]. "
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    ABSTRACT: Background The role of systemic and myocardial adiponectin (ADN) in dilated cardiomyopathy is still debated. We tested the regulation of both systemic and myocardial ADN and the relationship with AMP-activated protein kinase (AMPK) activity in a swine model of non-ischemic dilated cardiomyopathy. Methods and results Cardiac tissue was collected from seven instrumented adult male minipigs by pacing the left ventricular (LV) free wall (180 beats/min, 3 weeks), both from pacing (PS) and opposite sites (OS), and from five controls. Circulating ADN levels were inversely related to global and regional cardiac function. Myocardial ADN in PS was down-regulated compared to control (p < 0.05), yet ADN receptor 1 was significantly up-regulated (p < 0.05). No modifications of AMPK were observed in either region of the failing heart. Similarly, myocardial mRNA levels of PPARγ, PPARα, TNFα, iNOS were unchanged compared to controls. Conclusions Paradoxically, circulating ADN did not show any cardioprotective effect, confirming its role as negative prognostic biomarker of heart failure. Myocardial ADN was reduced in PS compared to control in an AMPK-independent fashion, suggesting the occurrence of novel mechanisms by which reduced cardiac ADN levels may regionally mediate the decline of cardiac function.
    Cardiovascular Diabetology 11/2012; 11(1):143. DOI:10.1186/1475-2840-11-143 · 4.02 Impact Factor
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