CRP and adiponectin and its oligomers in the metabolic syndrome: evaluation of new laboratory-based biomarkers.

The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors, which includes abdominal obesity, hypertension, hyperglycemia, dyslipidemia, and insulin resistance.1 In the United States, 1 in 4 people has MetS, and it is associated with an increased propensity for diabetes and cardiovascular disease. Inflammation is pivotal to atherosclerosis. Recently, several lines of evidence implicate inflammation in the development of insulin resistance and MetS.2 Furthermore, abundant evidence has emerged demonstrating that high concentrations of high-sensitive C-reactive protein (hsCRP) are associated with MetS and may predict diabetes and cardiovascular events, independent of traditional risk factors. It has also been suggested that CRP may be included in the criteria for MetS.3 Concentrations of CRP predict increased cardiovascular events in MetS and diabetes.4–7 In addition, CRP concentrations correlate strongly with adiposity and insulin resistance.8–10 The adipocyte-derived hormone adiponectin is an important link among adiposity, type 2 diabetes, and cardiovascular disease.11 Circulating adiponectin concentrations are reduced in humans with obesity, type 2 diabetes, and coronary artery disease.12–14 Adiponectin-deficient mice exhibit diet-induced insulin resistance.15,16 In humans, low plasma adiponectin concentrations independently predict the development of type 2 diabetes and myocardial infarction.17,18 Hypoadiponectinemia is also associated with MetS.19 Furthermore, adiponectin concentrations have been found in a number of studies to be inversely associated with systemic inflammation, as evidenced by increased concentrations of hsCRP.20 In the circulation, adiponectin is found in 3 major forms: as trimers (low molecular weight [LMW]), as hexamers (medium molecular weight [MMW]), and as larger multimers of 12 to 18 subunits (high molecular weight [HMW]).21 HMW adiponectin, but not the MMW form, lowers blood glucose concentrations in adiponectin-deficient mice.11,21 Moreover, thiazolidinedione- and gastric bypass surgery–mediated improvements in insulin sensitivity are more closely associated with changes in HMW adiponectin than with total adiponectin concentrations.22,23 HMW adiponectin concentrations are also closely related to improvements in high-density lipoprotein cholesterol (HDL-C) following weight loss.23,24 Developing a robust biomarker that can predict MetS instead of examining individual features will be important from a population standpoint in screening, monitoring the natural history of the disease, and measuring the response to therapeutic interventions. However, the ability of HMW adiponectin to detect the presence of MetS or to predict individual MetS components has not been specifically assessed. Thus, while hsCRP concentrations are higher in MetS and adiponectin concentrations are lower in MetS and both seem to be highly relevant to the 2 major sequelae of MetS, diabetes and cardiovascular disease, existing studies have not examined the predictive power of these markers alone and/or in combination for MetS. In the present study, therefore, we tested whether CRP, adiponectin, or both HMW and LMW adiponectin/CRP ratios are valid and robust markers that predict MetS.