Type 1 diabetes
As of 2009, there is no known cure for diabetes mellitus type 1.
Diabetes type 1 is caused by the destruction of enough beta cells to produce symptoms; these cells, which are found in the Islets of Langerhans in the pancreas, produce and secrete insulin, the single hormone responsible for allowing glucose to enter from the blood into cells (in addition to the hormone amylin, another hormone required for glucose homeostasis). Hence, the phrase "curing diabetes type 1" means "causing a maintenance or restoration of the endogenous ability of the body to produce insulin in response to the level of blood glucose" and cooperative operation with counterregulatory hormones.
This section deals only with approaches for curing the underlying condition of diabetes type 1, by enabling the body to endogenously, in vivo, produce insulin in response to the level of blood glucose. It does not cover other approaches, such as, for instance, closed-loop integrated glucometer/insulin pump products, which could potentially increase the quality-of-life for some who have diabetes type 1, and may by some be termed "artificial pancreas".
Encapsulation approach
A biological approach to the artificial pancreas is to implant bioengineered tissue containing islet cells, which would secrete the amounts of insulin, amylin and glucagon needed in response to sensed glucose.
When islet cells have been transplanted via the Edmonton protocol, insulin production (and glycemic control) was restored, but at the expense of continued immunosuppression drugs. Encapsulation of the islet cells in a protective coating has been developed to block the immune response to transplanted cells, which relieves the burden of immunosuppression and benefits the longevity of the transplant.[43]
One concept of the bio-artificial pancreas uses encapsulated islet cells to build an islet sheet which can be surgically implanted to function as an artificial pancreas.
This islet sheet design consists of:
* An inner mesh of fibers to provide strength for the islet sheet;
* Islet cells, encapsulated to avoid triggering a proliferating immune response, adhered to the mesh fibers;
* A semi-permeable protective layer around the sheet, to allow the diffusion of nutrients and secreted hormones;
* A protective coating, to prevent a foreign body response resulting in a fibrotic reaction which walls off the sheet and causes failure of the islet cells.
Islet sheet with encapsulation research is pressing forward with large animal studies at the present, with plans for human clinical trials within a few years.
Clinical studies underway in New Zealand by Living Cell Technologies have encapsulated pig islet cells in a seaweed derived capsule. This approach has had very positive clinical studies and is currently underway in human trials as of 2008. So far, treatment using this method of cell encapsulation has been proven safe and effective and is the first to achieve insulin independence in human trials without immunosuppressant drugs.
Islet cell regeneration
Research undertaken at the Massachusetts General Hospital between 2001 and 2003 demonstrated a protocol to reverse type 1 diabetes in non-obese diabetic mice (a frequently used animal model for type 1 diabetes mellitus). Three other institutions have had similar results, as published in the March 24, 2006 issue of Science. A fourth study by the National Institutes of Health achieved similar results, and also sheds light on the biological mechanisms involved.
Other researchers, most notably Dr. Aaron I. Vinik of the Strelitz Diabetes Research Institute of Eastern Virginia Medical School and a former colleague, Dr. Lawrence Rosenberg (now at McGill University) discovered in a protein they refer to as INGAP, which stands for Islet Neogenesis Associated Protein back in 1997. INGAP seems to be the product of a gene responsible for regenerating the islets that make insulin and other important hormones in the pancreas.
INGAP has had commercialization difficulties. Although it has appeared promising, commercial rights have changed hands repeatedly, having once been owned by Procter & Gamble Pharmaceuticals, which eventually dropped it. Rights were then acquired by GMP Companies. More recently, Kinexum Metabolics, Inc. has since sublicensed INGAP from GMP for further clinical trials. Kinexum has continued development under Dr. G. Alexander Fleming, an experienced metabolic drug developer, who headed diabetes drug review at the FDA for over a decade. As of 2008, the protein had undergone Phase 2 Human Clinical Trials, and developers were analyzing the results. At the American Diabetes Association's 68th Annual Scientific Sessions in San Francisco, Kinexum announced a Phase 2 human clinical trial with a combination therapy, consisting of DiaKine's Lisofylline (LSF) and Kinexum's INGAP peptide, which is expected to begin in late 2008. The trial will be unique in that patients who are beyond the 'newly diagnosed' period will be included in the study. Most current trials seeking to treat people with type 1 diabetes do not include those with established disease.
University of North Carolina
In September 2008, scientists from the University of North Carolina at Chapel Hill School of Medicine have announced their success in transforming cells from human skin into cells that produce insulin.
The skin cells were first transformed into stem cells and then had been differentiated into insulin-secreting cells.
However, other scientists have doubts, as the research papers fail to detail the new cells' glucose responsiveness and the amount of insulin they are capable of producing.
Gene therapy
Technology for gene therapy is advancing rapidly such that there are multiple pathways possible to support endocrine function, with potential to practically cure diabetes.
* Gene therapy can be used to manufacture insulin directly: an oral medication, consisting of viral vectors containing the insulin sequence, is digested and delivers its genes to the upper intestines. Those intestinal cells will then behave like any viral infected cell, and will reproduce the insulin protein. The virus can be controlled to infect only the cells which respond to the presence of glucose, such that insulin is produced only in the presence of high glucose levels. Due to the limited numbers of vectors delivered, very few intestinal cells would actually be impacted and would die off naturally in a few days. Therefore by varying the amount of oral medication used, the amount of insulin created by gene therapy can be increased or decreased as needed. As the insulin producing intestinal cells die off, they are boosted by additional oral medications.
* Gene therapy might eventually be used to cure the cause of beta cell destruction, thereby curing the new diabetes patient before the beta cell destruction is complete and irreversible.
* Gene therapy can be used to turn duodenum cells and duodenum adult stem cells into beta cells which produce insulin and amylin naturally. By delivering beta cell DNA to the intestine cells in the duodenum, a few intestine cells will turn into beta cells, and subsequently adult stem cells will develop into beta cells. This makes the supply of beta cells in the duodenum self replenishing, and the beta cells will produce insulin in proportional response to carbohydrates consumed.
Type 2 diabetes
Type 2 diabetes is usually first treated by increasing physical activity, and eliminating saturated fat and reducing sugar and carbohydrate intake with a goal of losing weight. These can restore insulin sensitivity even when the weight loss is modest, for example around 5 kg (10 to 15 lb), most especially when it is in abdominal fat deposits. Diets that are very low in saturated fats can reverse insulin resistance.
Testosterone replacement therapy can improve glucose tolerance and insulin sensitivity in diabetic hypogonadal men. The mechanisms by which testosterone decreases insulin resistance is under study.[64] Moreover testosterone has a protective effect on pancreatic beta cells, which is possibly exerted by androgen-receptor-mediated mechanisms and influence of inflammatory cytokines.
Recently it has been shown that a type of gastric bypass surgery can normalize blood glucose levels in 80-100% of severely obese patients with diabetes. The precise causal mechanisms are being intensively researched; its results are not simply attributable to weight loss, as the improvement in blood sugars precedes any change in body mass. This approach may become a standard treatment for some people with type 2 diabetes in the relatively near future. This surgery has the additional benefit of reducing the death rate from all causes by up to 40% in severely obese people. A small number of normal to moderately obese patients with type 2 diabetes have successfully undergone similar operations.