Diabetes is a metabolic disorder that refers to the condition created by either the insufficient production or the lack of response to a key regulatory hormone of the body’s metabolism, insulin (Figure 2.1). Under normal conditions, the rise of blood glucose levels signals the release of insulin from the pancreatic beta cells into the bloodstream. This enables glucose to enter into the cells where it is either utilized to release energy or stored for future use. Reduced insulin production, or resistance to its effect, causes a condition known as hyperglycemia indicated by a build up of glucose levels in the bloodstream. This chronic rise in blood glucose is responsible for several life-threatening conditions such as heart disease, stroke, loss of vision, kidney disease, neuropathy, and degradation of extremities that can require drastic measures such as amputation.

 FIGURE 2.1. The insulin-glucagon feedback system in the hemodynamic regulation of blood glucose

There are two types of diabetes: Type I and Type 2. Type 1 diabetes occurs when the body’s immune system targets and destroys the pancreatic beta cells, abrogating insulin production. These patients are completely dependent on external sources of insulin to survive. Given the dynamic nature of the insulin-glucose balance, the therapy of Type 1 diabetics requires a highly disciplined monitoring of glucose levels, often several times a day, to monitor sudden hyper- or hypoglycemic events. Fortunately, only 5-10 per cent of diabetics fall in this category.

The vast majority of diabetics fall in the Type 2 category. This disease occurs when the pancreas is still capable of producing some insulin, but insulin dependent cells become progressively resistant to the effect of the hormone, resulting in the underutilization of blood glucose. Over a period of time, it results in the inability of the pancreas to release sufficient insulin to support the daily needs of the body’s metabolism.

The scientific community in industry and academia has been extremely active in the fight against diabetes for decades. Research has focused on two aspects of therapy: (a) insulin replacement methods and technologies and (b) non-insulin drugs that control blood glucose levels. The latter type includes drugs such as the sulfonylureas (e.g., Glucotrol®, Diabeta®, Glynase®, Micronase® and Amaryl®), meglitinides (e.g., Prandin® and Starlix®), biguanides (e.g., Glucophage® and Fortamet®), thiazolidinediones (e.g., Actos® and Avandia®), incretin mimetics (e.g., Byetta®), alpha-glucosidase inhibitors (e.g., Prandase®, Precose® and Glyset®) and dipeptidyl peptidase IV inhibitors (e.g., Januvia®).