Research Article: High-molecular weight adiponectin/HOMA-IR ratio as a biomarker of metabolic syndrome in urban multiethnic Brazilian subjects

Date Published: July 26, 2017

Publisher: Public Library of Science

Author(s): Virgínia Genelhu de Abreu, Cyro José de Moraes Martins, Patricia Aguiar Cardoso de Oliveira, Emilio Antonio Francischetti, Marta Letizia Hribal.

http://doi.org/10.1371/journal.pone.0180947

Abstract

Metabolic syndrome (MetS) has an important epidemiological relevance due to its increasing prevalence and association with type 2 diabetes and cardiovascular disease. Insulin resistance is a core feature of the MetS. HOMA-IR is a robust clinical and epidemiological marker of MetS. Adiponectin is an adipokine with insulin-sensitizing and anti-inflammatory functions; its levels decrease as number of components of MetS increases. High-molecular weight adiponectin (HMWA) is the multimer responsible for the relationship of adiponectin with insulin sensitivity. HOMA-IR and HMWA are suitable candidates for MetS biomarkers. The ratio of adiponectin to HOMA-IR has been validated as a powerful index of MetS and considered a better marker of its presence, than either HOMA-IR or adiponectin alone, in selected homogeneous populations. We compared the strength of association between HMWA, HOMA-IR and HMWA/HOMA-IR ratio with MetS and its key components. Our data have shown that the median (25th, 75th percentile) of HMWA/HOMA-IR ratio was lower in subjects with MetS [0.51 (0.33, 1.31)] as compared to those without it [2.19 (1.13, 4.71)]. The correlation coefficient (r) was significantly higher for HMWA/HOMA-IR ratio as compared to HMWA for waist circumference (-0.65; -0.40, respectively); mean blood pressure (-0.27; -0.14, respectively); fasting glucose (-0.38; -0.19, respectively); HDL-cholesterol (0.44; 0.40, respectively); and triglycerides (-0.35; -0.18, respectively). In a multivariable logistic regression analysis, the HMWA/HOMA-IR ratio was a sensitive predictor for MetS, being the only marker that was significantly associated with each and all the individual components of the syndrome. These results expand on previous studies in that we used the active circulating form of adiponectin, i.e. HMWA, and represent a typical Brazilian cohort characterized by intense interethnic admixture. Thus, the HMWA/HOMA-IR ratio is a minimally invasive biomarker for MetS that could be clinically useful in prognosing patient outcome.

Partial Text

The metabolic syndrome (MetS), as defined by the Joint Interim Statement of the International Diabetes Federation (IDF), American Heart Association (AHA), National Heart, Lung and Blood Institute (NHLBI) and other international societies [1], has been considered a useful construct because its multiple components cluster with a greater than chance expectation [2]. MetS has also important epidemiological relevance due to its increasing prevalence and association with more life-threatening pathologies, including type-2 diabetes (T2DM) and cardiovascular disease (CVD) [3–6].

As described in detail before [24], we analyzed data from 200 subjects, aged 18–60 years (100 eutrophic individuals–body mass index [BMI] ≥18.5 and <25 kg/m2, and 100 obese individuals–BMI ≥30 kg/m2) recruited from the employees, students, residents and staff at the University Hospital, Rio de Janeiro State University. The Research Ethics Committee of Pedro Ernesto University Hospital, Rio de Janeiro State University approved this study without restrictions; subjects voluntarily agreed to participate and provided written informed consent. The cardiometabolic variables are given (Table 1) in the whole sample, which also compares eutrophic and obese subjects. The levels of HDL-cholesterol, HMWA and the HMWA/HOMA-IR ratio were significantly lower in obese than eutrophic subjects. However, all the other variables were significantly higher in obese subjects, except total cholesterol, which was not significantly different between the groups. MetS is a serious global issue with substantial clinical relevance and increasing prevalence. Data from the National Health and Nutrition Examination Survey (NHANES, 1999–2002) showed that 34.5% of Americans met the criteria for MetS compared with 22% in NHANES III, 1988–1994 [4,5]. Similarly, the risks of incident T2DM and CVD increased 4.6 and 1.7 fold in subjects with MetS compared with subjects without MetS [6]. We found the HMWA/HOMA-IR was more strongly associated with MetS than HMWA, and gave a better predictive power for MetS—controlled for age, gender, BMI and total cholesterol, when compared with HMWA and HOMA-IR alone. Furthermore, only the HMWA/HOMA-IR ratio showed any significant relationship with each and all the individual components of MetS. As a consequence of the epidemic of obesity, prediction of MetS is relevant because of its subsequent association with T2DM and CVD. Regarding the variables that are components of the MetS–waist circumference, blood pressure, glucose, HDL-cholesterol and triglycerides—our data show that the HMWA/HOMA-IR ratio is a sensitive predictor for MetS, being the only marker that was significantly associated with each and all the individual components of the syndrome. Thus, the HMWA/HOMA-IR ratio is a circulating and minimally invasive biomarker for MetS that could be clinically useful in prognosing patient outcome. These results expand on previous studies since they represent a typical Brazilian cohort characterized by intense interethnic admixture.   Source: http://doi.org/10.1371/journal.pone.0180947

 

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