Regenetech Research

Type 1 Diabetes Type 1 diabetes mellitus is characterized by loss of the insulin-producing beta cells of the islets of Langerhans in the pancreas leading to a deficiency of insulin. This type of diabetes can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of the immune-mediated variety, where beta cell loss is a T-cell mediated autoimmune attack. There is no known preventive measure which can be taken against type 1 diabetes; it is about 10% of diabetes mellitus cases in North America and Europe (though this varies by geographical location), and is a higher percentage in some other areas. Most affected people are otherwise healthy and of a healthy weight when onset occurs. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. Type 1 diabetes can affect children or adults but was traditionally termed �juvenile diabetes� because it represents a majority of the diabetes cases in children. The principal treatment of type 1 diabetes, even in its earliest stages, is the delivery of artificial insulin via injection combined with careful monitoring of blood glucose levels using blood testing monitors. Without insulin, diabetic ketoacidosis often develops which may result in coma or death. Treatment emphasis is now also placed on lifestyle adjustments (diet and exercise) though these cannot reverse the progress of the disease. Apart from the common subcutaneous injections, it is also possible to deliver insulin by a pump, which allows continuous infusion of insulin 24 hours a day at preset levels, and the ability to program doses (a bolus) of insulin as needed at meal times. An inhaled form of insulin was approved by the FDA in January 2006, although it was discontinued for business reasons in October 2007. Non-insulin treatments, such as monoclonal antibodies and stem-cell based therapies, such as that developed by Regenetech, can be used to treat this type of diabetes. Type 1 diabetes is an area that can be solved, likely by production of functional implantable pancreatic tissue. A LARGE BODY OF EVIDENCE DEMOSTRATES SUPERIOR ISLET TISSUE RESULTS USING REGENETECH BIOREACTOR TECHNOLOGY EXPANSION METHODS. Type 2 Diabetes Diabetes mellitus type 2 or type 2 diabetes (formerly called non-insulin-dependent diabetes mellitus (NIDDM), or adult-onset diabetes) is a disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. While it is often initially managed by increasing exercise and dietary modification, medications are typically needed as the disease progresses. There are an estimated 23.6 million people in the U.S. (7.8% of the population) with diabetes with 17.9 million being diagnosed, 90% of whom are type 2. With prevalence rates doubling between 1990 and 2005, CDC has characterized the increase as an epidemic. Traditionally considered a disease of adults, type 2 diabetes is increasingly diagnosed in children in parallel to rising obesity rates. Unlike type 1 diabetes, there is little tendency toward ketoacidosis in type 2 diabetes, though it is not unknown. One effect that can occur is nonketonic hyperglycemia which also is quite dangerous, though it must be treated very differently. Complex and multi-factorial metabolic changes very often lead to damage and function impairment of many organs, most importantly the cardiovascular system in both types. This leads to substantially increased morbidity and mortality in both type 1 and type 2 patients, but the two have quite different origins and treatments despite the similarity in complications. Insulin resistance means that body cells do not respond appropriately when insulin is present. Unlike type 1, the insulin resistance is generally �post-receptor�, meaning it is a problem with the cells that respond to insulin rather than a problem with production of insulin. Other important contributing factors: increased hepatic glucose production (e.g., from glycogen degradation), especially at inappropriate times (typical cause is deranged insulin levels, as insulin controls this function in cells) decreased insulin-mediated glusoce transport in (primarily) muscle and adipose tissues (receptor and post-receptor defects) impaired beta-cell function�loss of early phase of insulin release in response to hyperglycemic stimuli Cancer survivors who received allogenic Hematopoietic Cell Transplantation (HCT) are 3.65 times more likely to report type 2 diabetes than their siblings. Total body irradiation (TBI) is also associated with a higher risk of developing diabetes. This is a more complex problem than type 1, but is sometimes easier to treat, especially in the early years when insulin is often still being produced internally. Type 2 may go unnoticed for years before diagnosis, since symptoms are typically milder (eg, no ketoacidosis, coma, etc) and can be sporadic. However, severe complications can result from improperly managed type 2 diabetes, including renal failure, blindness, slow healing wounds (including surgical incisions), and arterial disease, including coronary artery disease. According to CDC about 23.613 million people in the United States, or 8% of the population, have diabetes. The total prevalence of diabetes increased 13.5% from 2005-2007. Only 24% of diabetes is undiagnosed, down from 30% in 2005 and from 50% ten years ago. About 90�95% of all North American cases of diabetes are type 2, and about 20% of the population over the age of 65 has diabetes mellitus type 2. The fraction of type 2 diabetics in other parts of the world varies substantially, almost certainly for environmental and lifestyle reasons, though these are not known in detail. Diabetes affects over 150 million people worldwide and this number is expected to double by 2025. There is also a strong inheritable genetic connection in type 2 diabetes: having relatives (especially first degree) with type 2 increases risks of developing type 2 diabetes very substantially. In addition, there is also a mutation to the Islet Amyloid Polypeptide gene that results in an earlier onset, more severe, form of diabetes. About 55 percent of type 2 are obese �chronic obesity leads to increased insulin resistance that can develop into diabetes, most likely because adipose tissue (especially that in the abdomen around internal organs) is a (recently identified) source of several chemical signals to other tissues (hormones and cytokines). Other research shows that type 2 diabetes causes obesity as an effect of the changes in metabolism and other deranged cell behavior attendant on insulin resistance. Diabetes mellitus type 2 is a chronic, progressive disease that has no established cure, but does have well-established treatments which can delay or prevent entirely the formerly inevitable consequences of the condition. Often, the disease is viewed as progressive since poor management of blood sugar leads to a myriad of steadily worsening complications. However, if blood sugar is properly maintained, then the disease is effectively cured � that is, patients are at no heightened risk for neuropathy or any other high blood sugar complication. There are two main goals of treatment: reduction of mortality and concomitant morbidity (from assorted diabetic complications) preservation of quality of life The first goal can be achieved through close glycemic control (i.e., to near �normal� blood glucose levels); the reduction in severity of diabetic side effects has been very well demonstrated in several large clinical trials and is established beyond controversy. The second goal is often addressed (in developed countries) by support and care from teams of diabetic health workers (usually physician, PA, nurse, dietitian or a certified diabetic educator). Endocrinologists, family practitioners, and general internists are the physician specialties most likely to treat people with diabetes. Knowledgeable patient participation is vital to clinical success, and so patient education is a crucial aspect of this effort. Type 2 is initially treated by adjustments in diet and exercise, and by weight loss, most especially in obese patients. The amount of weight loss which improves the clinical picture is sometimes modest (2-5 kg or 4.4-11 lb); this is almost certainly due to currently poorly understood aspects of fat tissue activity, for instance chemical signaling (especially in visceral fat tissue in and around abdominal organs). In many cases, such initial efforts can substantially restore insulin sensitivity. In some cases strict diet can adequately control the glycemic levels. Treatment goals for type 2 diabetic patients are related to effective control of blood glucose, blood pressure and lipids to minimize the risk of long-term consequences associated with diabetes. The targets are: HbAlc of 6% to 7.0% Pre-prandial blood glucose: 4.0 to 6.0 mmol/L (72 to 108 mg/dl) 2-hour postprandial blood glucose: 5.0 to 8.0 mmol/L (90 to 144 mg/dl) There are several drugs available for type 2 diabetics � most are unsuitable or even dangerous for use by type 1 diabetics. They fall into several classes and are not equivalent, nor can they be simply substituted one for another. All are prescription drugs. Metformin 500mg tablets: One of the most widely used drugs now used for type 2 diabetes is the biguanide metformin; it works primarily by reducing liver release of blood glucose from glycogen stores and secondarily by provoking some increase in cellular uptake of glucose in body tissues. Both historically, and currently, the most commonly used drugs are in the Sulfonylurea group; these increase glucose stimulated insulin secretion by the pancreas and so lower blood glucose even in the face of insulin resistance. Newer drug classes include: a-glucosidase inhibitors which interfere with absorption of some glucose containing nutrients, reducing (or at least slowing) the amount of glucose absorbed Meglitinides which stimulate insulin release quickly; they can be taken with food, unlike the sulfonylureas which must be taken prior to food (sometimes some hours before, depending on the drug) Peptide analogs which work in a variety of ways: Incretin mimetics which increase insulin output from the beta cells among other effects. These includes the Glucagon-like peptide (GLP) analog, sometimes referred to as lizard spit as it was first identified in Gila monster saliva. Amylin agonist analog, which slows gastric emptying and suppresses glucagon ©2010, Regenetech, Inc.