Abstract
BackgroundPlasma calprotectin is a potential biomarker of cardiovascular disease (CVD), insulin resistance (IR), and obesity. We examined the relationship between plasma calprotectin concentrations, CVD manifestations and the metabolic syndrome (MetS) in patients with type 2 diabetes mellitus (T2DM) in order to evaluate plasma calprotectin as a risk assessor of CVD in diabetic patients without known CVD.MethodsAn automated immunoassay for determination of plasma calprotectin was developed based on a fecal Calprotectin ELIA, and a reference range was established from 120 healthy adults. Plasma calprotectin concentrations were measured in 305 T2DM patients without known CVD. They were screened for carotid arterial disease, peripheral arterial disease (PAD), and myocardial ischemia (MI) by means of carotid artery ultrasonography, peripheral ankle and toe systolic blood pressure measurements, and myocardial perfusion scintigraphy.ResultsThe reference population had a median plasma calprotectin concentration of 2437 ng/mL (2.5-97.5% reference range: 1040–4262 ng/mL). The T2DM patients had significantly higher concentrations (3754 ng/mL, p < 0.0001), and within this group plasma calprotectin was significantly higher in patients with MetS (p < 0.0001) and also in patients with autonomic neuropathy, PAD, and MI compared with patients without (p < 0.001, p = 0.021 and p = 0.043, respectively). Plasma calprotectin was by linear regression analysis found independently associated with BMI, C-reactive protein, and HDL cholesterol. However, plasma calprotectin did not predict autonomic neuropathy, PAD, MI or CVD when these variables entered the multivariable regression analysis as separate outcome variables.ConclusionT2DM patients had higher concentrations of plasma calprotectin, which were associated with obesity, MetS status, autonomic neuropathy, PAD, and MI. However, plasma calprotectin was not an independent predictor of CVD, MI, autonomic neuropathy or PAD.Trial registration numberNCT00298844
Highlights
Plasma calprotectin is a potential biomarker of cardiovascular disease (CVD), insulin resistance (IR), and obesity
The aim of the present study was to investigate the association of plasma calprotectin levels with CVD and other complications associated with type 2 diabetes mellitus (T2DM) in a well-characterized T2DM cohort
Establishment of a reference range The one-sample Shapiro-Wilk test of normality showed that the distribution of serum calprotectin was nonGaussian (Z = 0.114, p = 0.001) and positively skewed
Summary
Plasma calprotectin is a potential biomarker of cardiovascular disease (CVD), insulin resistance (IR), and obesity. Elevated calprotectin levels have been reported to predict microvascular alterations in type 2 diabetes (T2DM) patients [7] and was found to be an early and sensitive marker of acute coronary syndrome [8] and nonfatal myocardial infarction [9]. In a screening approach among healthy individuals, increased plasma concentrations of calprotectin were found to predict the risk of future cardiovascular events [10]. Levels of plasma calprotectin appear to increase earlier than other markers of myocardial necrosis (myoglobin, creatine kinase–MB, and troponin), and high levels are associated with an increased risk of recurrent cardiovascular events [9]
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