Cocoa, glucose tolerance, and insulin signaling: cardiometabolic protection.

Experimental and clinical evidence reported that some polyphenol-rich natural products may offer opportunities for the prevention and treatment of type 2 diabetes, due to their biological properties. Natural products have been suggested to modulate carbohydrate metabolism by various mechanisms, such as restoring β-cell integrity and physiology and enhancing insulin-releasing activity and glucose uptake. Endothelium is fundamental in regulating arterial function, whereas insulin resistance plays a pivotal role in pathophysiological mechanisms of prediabetic and diabetic states. Glucose and insulin actions in the skeletal muscle are improved by insulin-dependent production of nitric oxide, favoring capillary recruitment, vasodilatation, and increased blood flow. Endothelial dysfunction, with decreased nitric oxide bioavailability, is a critical step in the development of atherosclerosis. Furthermore, insulin resistance has been described, at least in part, to negatively affect endothelial function. Consistent with this, conditions of insulin resistance are usually linked to endothelial dysfunction, and the exposure of the endothelial cells to cardiovascular risk factors such as hypertension, dyslipidemia, and hyperglycemia is associated with reduced nitric oxide bioavailability, resulting in impaired endothelial-dependent vasodilatation. Moreover, endothelial dysfunction has been described as an independent predictor of cardiovascular risk and events. Cocoa and cocoa flavonoids may positively affect the pathophysiological mechanisms involved in insulin resistance and endothelial dysfunction with possible benefits in the prevention of cardiometabolic diseases.