Diabetes occurs when the beta cells of the pancreas produce insufficient insulin to be able regulate blood sugar levels appropriately. Diabetes has no cure and is usually a life-long disease. There are several different types of diabetes, including:

• Type 1 diabetes, often called juvenile or insulin-dependent diabetes

• Type 2 diabetes, often called adult or non-insulin-dependent diabetes

• Gestational diabetes, which occurs during pregnancy

For all types of diabetes, the metabolism of carbohydrates (including sugars such as glucose), proteins, and fats is altered. Without adequate insulin, glucose builds up in the bloodstream instead of going into the cells of the body. The body is unable to use this glucose for energy despite high levels in the bloodstream. Symptoms of type 1 diabetes are usually severe and occur rapidly; without insulin treatment, death is inevitable. Even with insulin treatment, diabetics may eventually develop serious complications involving their eyes, hearts, kidneys, and blood vessels. The total number of diabetics worldwide is growing rapidly and is expected to double to over 300 million by 2025.

The cause of type 1 diabetes is the destruction of beta cells in the pancreas by a T-cell mediated autoimmune process. Consequently, the beta cells produce little or no insulin. Anti-GAD, beta cell and islet cell antibodies are markers of the autoimmune process. 100 percent of type 1 diabetes sufferers have developed autoimmune antibodies, and a significant number of type 2 patient’s exhibit autoimmunity. There is a significant therapeutic need to inhibit the autoimmune destruction of pancreatic beta cells.

Type 1 diabetes can occur at any age but usually starts in people younger than 30, and is associated with (HLA) DRB1-DQA1-DQB1 class II genotypes. Less than 10 percent of genetically susceptible individuals develop the clinical disease, suggesting an environmental trigger. The triggering environmental antigen(s) have yet to be definitively identified, but there is a growing consensus that their portal of entry is the small bowel.

It has been discovered that altered intestinal permeability frequently occurs in type 1 diabetes prior to the onset of insulin dependence. Increased permeability of the small intestine (“leaky gut”) of diabetic-prone rats precedes the onset of diabetes by more than 1 month, and accompanies the disease in humans. It is very possible that leaky gut facilitates exposure to the environmental antigens that trigger beta cell autoimmunity, and that this leak can be blocked by tight junction modulators including Alba's lead product candidate, AT-1001.