Obesity has reached epidemic proportions in the past decade and represents one of the confounding factors associated with the MS and T2DM [19,30] (figure 1).

Hyperuricemia has been associated with increasing body mass index (BMI) in recent studies and are even apparent in the adolescent youth [30-33].

Leptin levels are elevated and associated with insulin resistance in MS and early T2DM. Bedir A et al. have recently discussed the role of leptin as possibly being a regulator of serum uric acid (SUA) concentrations in humans and even suggested that leptin might be one of the possible candidates for the missing link between obesity and hyperuricemia [34]. Furthermore, hypertriglyceridemia and free fatty acids are related to hyperuricemia independently of obesity and central body fat distribution [30,33] (table 1: (T): Triglyceride toxicity and (F): Free fatty acid toxicity).

Hyperglycemia: Impaired glucose tolerance: Type 2 Daibetes Mellitus (T2DM)

Glucotoxicity places an additional burden of redox stress on the arterial vessel wall and capillary endothelium. Hyperglycemia induces both an oxidative stress (glucose autoxidation and advanced glycosylation endproducts (AGE) – ROS oxidation products) and a reductive stress through pseudohypoxia with the accumulation of NADH and NAD(P)H in the vascular intima [19,35,36].

This redox stress consumes the natural occurring local antioxidants such as: SOD, GPX, and catalase (table 4). Once these local intimal antioxidants are depleted uric acid can undergo the paradoxical antioxidant – prooxidant switch or the urate redox shuttle [37,38]


A direct relation between homocysteine levels and serum uric acid (SUA) levels is known to occur in patients with atherosclerosis. Not only do these two track together (possibly reflecting an underlying elevated tension of redox stress) but also may be synergistic in creating an elevated tension of redox stress, especially in the rupture prone, vulnerable atherosclerotic plaque with depletion of local occurring antioxidants [39-41] (figure 1).

Atherosclerosis and Atheroscleropathy

Non-diabetic atherosclerosis and atheroscleropathy (accelerated atherosclerosis associated with MS, prediabetes, and T2DM) are each impacted with the elevation of uric acid [42,43].

Prothrombotic milieu

In MS and T2DM there is an observed increased thrombogenecity, hyperactive platelets, increased PAI-1 (resulting in impaired fibrinolysis), and increased fibrinogen in the atherosclerotic milieu associated with the dysfunctional endothelial cell. Additionally, the vulnerable atherosclerotic plaque includes increased tissue factor, which increases the potential for thrombus formation when the plaque ruptures and exposes its contents to the lumen [19,42,43].