DIABETES

A quick look at some of what is happening in the world of research that can affect your practice, your patients and you

The 58th Annual Scientific Sessions of the American Diabetes Association, held June 16 in Chicago, provided a few important glimpses into the future of diabetes therapy and prevention. Here are some ideas about which your diabetic patients will soon be reading:

Inhaled insulin

A collaboration of Inhale Therapeutics Systems with Pfizer has produced an insulin effective via inhalation. Similar to a metered-dose inhaler used for asthma. the collapsible, flashlight-sized aerosol system delivers a dose of insulin in dry powder form through the mouth directly to the lungs, which enters the circulation as a rapid-acting insulin.

Early clinical trials show the delivery system and formulation to be as effective as injected insulin in both type I and type II diabetes; further studies to include children over the age of 12 are scheduled to begin in November.

It is speculated that the inhaled method of delivery may be less effective and more difficult for asthmatics or other patients with compromised lung function to use.

Some promising new developments for type I

1G2, a product of Alexion Pharmaceuticals' Apogen T-Cell Therapeutics program, is a highly specific recombinant antigen designed to selectively induce autoreactive, disease-causing T-cells to undergo apoptosis (cell suicide) while preserving disease-fighting T-cells.

The immunoregulatory technology is applicable in prevention of certain autoimmune diseases, including Type I diabetes, which is caused by autoimmune destruction of pancreatic beta cells by the targeted T-cells. Studies in animal models have demonstrated 1G2's effectiveness in preventing development of the disease.

Anergen Inc.'s DiavaX is a novel, functional genomics vaccine that stimulates antibodies targeting the interaction of autoreactive white blood cells in autoimmunity to protect the diabetes-prone from the onset and progression of type I diabetes.

The vaccine utilizes Anergen's AnervaX' technology to stimulate production of anti-bodies that block T-cell activation. It contains peptides derived from the specific major histocompatibility complex molecules genetically linked to the reactive autoimmune disease, potentially blocking or down-regulating specific genetic MHC II.

Successful studies in mice prove the product's promise in transferring protection to unimmunized subjects with either treated B-cells or specific antibodies; clinical trials are expected to begin within a year.

Though replacing insulin has long been a life-saving measure in those with type I diabetes, many patients continue to experience difficulty in controlling blood glucose levels there natural hormone normally produced by pancreatic cells that is missing in people with type 1 diabetes, may be the answer.

Pramlintide. an experimental patented analog of amylin currently undergoing late- stage clinical testing, has been shown to improve glucose control and reduce the risk of diabetic complications.

In preliminary studies, pramlintide not only improved glucose control and cholesterol profiles in test subjects, but obese subjects lost weight-all without increasing the risk of hypoglycemia.

With continued studies, pramlintide promises to become the first new agent for improving metabolic control in type 1 diabetes since the insulin. Researchers are currently recruiting subjects for further clinical evaluation. Interested patients can be considered for participation by contacting Primary Physicians Research/Pittsburgh Pediatric Research, McLaughlin Run Road, Pittsburgh. Pa. 15241, (412) 2574461, ext. 128.

And for type II ...

Ergo Science reported on pre-clinical studies of its second-generation therapy for type II diabetes, Ergoset(r) (bromocriptine mesylate). and its role in improving the metabolic abnormalities associated with the disease by addressing associated abnormalities of the central nervous system.

The company's Neuroendocrine Resetting Therapy' is based on observations that distinct daily activity patterns of certain neurotransmitters are required to maintain proper glucose and lipid metabolism and that disorders in glucose and lipid metabolism develop and progress as a result of changes in these normal daily patterns of neurotransmitter activity.

Hyperactivity of CNS hypothalamic systems potentiate dyslipidemia and glucose intolerance, and Ergoset , as a potent dopamine-receptor against. has been shown to counter that hyperactivity to improve obesity, hyperglycemia, insulin resistance and pancreatic beta cell dysfunction in animal model systems. Such effects persist long after the termination of treatment, suggesting a "resetting" of a central metabolic regulation.

The FDA's Endocrinologic and Metabolic Drugs Advisory Committee, though, has recommended against approval of Ergoset pending data on durability of its effects on glycosylated hemoglobin and safety of its neuroendocrine mechanism.

Warner-Lambert Company's Rezulin (troglitazone). approved in January 1997, mains under FDA scrutiny after revised labeling in November 1997 that reflects the tendency to cause liver injury. New labeling recommended checking serum transaminase levels routinely within the first one to two months of Rezulin therapy. every three months thereafter during the first year of treatment, and periodically thereafter. Liver function tests should also be performed in the event of symptoms of liver dysfunction: nausea, vomiting, abdominal pain, fatigue, loss of appetite or dark urine.

In the NIH Diabetes Prevention Program study conducted by the National Institute of Diabetes and Digestive and Kidney Diseases, one patient of the 585 participants died with liver failure after liver transplant. Though the clinical course was complicated by extensive necrosis of the bowel and cytomegalovirus infection, drug-induced liver toxicity was ultimately blamed as the cause of death. The NIH's safety committee then dropped Rezulin(tm) from the study that is evaluating the possibilities of preventing or delaying onset of type II diabetes. Warner-Lambert is considering countering by applying for an IND to continue diabetes prevention research with Rezulin(tm).

COPYRIGHT 1998 Lebhar-Friedman, Inc.
COPYRIGHT 2000 Gale Group