Comparing the diagnostic ability of inflammatory markers in metabolic syndrome

Highlights

• The levels of C3, leukocytes, neutrophils and lymphocytes were significantly associated with a higher prevalence of metabolic syndrome.

• Among the inflammatory markers simultaneously assessed in this study, C3 had the strongest diagnostic value in detecting metabolic syndrome.

• Developing medication targeting C3 might be effective for metabolic syndrome treatment.

Abstract

Background

Chronic low-grade inflammation contributes to the pathogenesis of the metabolic syndrome (MetS). Although some studies have demonstrated that several standard inflammatory markers provide diagnostic value for MetS, few studies have compared the diagnostic ability of various inflammatory markers. We demonstrated the diagnostic ability of several inflammatory markers in detecting MetS.

Methods

Complement component 3 (C3), C4, high-sensitivity C-reactive protein (hs-CRP), leukocyte count, neutrophil, lymphocyte and neutrophil-to-lymphocyte ratio (NLR) concentrations were measured in 6312 participants living in Tianjin, China. MetS was defined according to American Heart Association criteria. Adjusted logistic models were used to assess associations between inflammatory markers and MetS. Receiver operating characteristic (ROC) curves were performed to determine the diagnostic values of inflammatory markers for MetS.

Results

The adjusted odds ratio (95% CI) of MetS for the highest inflammatory markers (C3, leukocyte, neutrophil, lymphocyte) quintile, when compared to the lowest quintile were 2.68 (2.12–3.38), 2.53 (2.05–3.11), 1.31 (1.06–1.62) and 1.94 (1.60–2.37), respectively. ROC analysis showed that the optimal cut-off values were 101.0 mg/dl for C3 (Area under the ROC curve (AUC) = 0.68), 5.41 × 1000 cells/mm³ for leukocyte (AUC = 0.63), 3.20 × 1000 cells/mm³ for neutrophil (AUC = 0.60) and 1.82 × 1000 cells/mm³ for lymphocyte (AUC = 0.62). No significant association was observed between the other inflammatory markers and MetS.

Conclusions

Among the inflammatory markers assessed in this population, C3 has the strongest diagnostic value in detecting MetS. Further studies are encouraged to determine the efficacy of applying C3 to diagnosis and treatment in the clinical setting.

Introduction

Metabolic syndrome (MetS) is a constellation of metabolic abnormalities that includes glucose intolerance (type 2 diabetes, impaired glucose tolerance, or impaired fasting glycaemia), insulin resistance, central obesity, dyslipidemia and hypertension [1]. It is regarded as a risk factor for the development of type 2 diabetes and cardiovascular diseases [2], [3]. In most countries 20–30% of the adult population can be characterized as having MetS [4]. MetS has also become a serious public health problem, and the prevalence of MetS in mainland China was recently reported as 24.5% [5]. It is therefore of clinical and public health importance to identify high-risk individuals eligible for early intervention.

Chronic low-grade systematic inflammation seemed to be a central mechanism underlying pathophysiology of MetS [6]. Numerous studies have demonstrated a positive association between increased concentrations of high-sensitivity C-reactive protein (hs-CRP) and MetS, and it has even been proposed that adding hs-CRP as a clinical criterion for MetS [7], [8]. Leukocyte and its differential counts were directly and significantly associated with the incidence of MetS [9]. A longitudinal cohort study revealed complement component 3 (C3) and C4, the major plasma proteins of the complement pathways, were associated with the development of MetS in Chinese [10].

Although these markers have been shown to be associated with MetS, few studies have compared their diagnostic values in detecting MetS within one population. Therefore, these studies were unable to identify which biomarker had the most diagnostic value for MetS. Moreover, since inflammatory markers are closely associated with each other, previous studies have had difficulty identifying whether the associations between a single biomarker and MetS are mediated by other inflammatory markers. Therefore, the aim of this study was to evaluate and compare the diagnostic ability of various inflammatory markers for MetS in a general population in order to identify which marker was the most accurate and useful for the diagnosis of MetS. Once identified, such a marker can be used to identify individuals at higher risk for MetS who would benefit from preventive and intervention.