Olde Tyme Medicine: Diabetes

ThenHumans were most likely afflicted with diabetes long before it was first documented on ancient Egyptian papyrus 3,500 years ago. It was already an ancient disease when Aretaeus of Cappadocia described the ravages the disease wrought on the human body, “a melting down of the flesh and limbs into urine.” And it was most certainly an ancient disease in 1899 when a debate between Joseph von Mering and Oskar Minkowski led to a canine pancreatectomy and the connection between the ensuing polyuria and diabetes. And still it was a little over 20 years later, when Canadian orthopedist Frederick Banting and medical student Charles Best were able to isolate a pancreatic extract and purify it with the help of biochemist James Collip, that the first human being in history, a 14-year-old boy, was administered insulin therapy for the treatment of diabetes (http://www.fasebj.org/cgi/content/full/16/14/1853e).

Now

Discovery of the existence of type 2 diabetes by British researcher Harry Himsworth during his studies on insulin sensitivity during the 1930s pushed diabetes treatment into the modern age. Himsworth hypothesized that type 2 diabetics suffered from a decreased sensitivity to insulin. But his theory was not proved correct until the 1960s when Drs. Rosalyn Yalow and Solomon Berson developed the radioimmunoassay, a tool still in use today that allows for the measurement of minute quantities of hormones circulating in an individual’s bloodstream, in this case, insulin (http://www.fasebj.org/cgi/content/full/16/14/1853e). The blood glucose monitor was first patented on September 14, 1971, nearly two years after its invention, by Tom Clemens. It was called the Ames Reflectance Meter and was designed to read Dextrostix, the first dry reagent blood sugar test, made available in 1965 (http://www.bayercarediabetes.com/720.htm; http://www.diabetesmonitor.com/arm.htm). Dean Kamen—known prominently for his other invention, the Segway—was also working in the early 70s on an invention that garners him much less fame, but has had a decidedly greater impact on society. While a college undergraduate, Kamen invented the AutoSyringe, an automatic infusion pump that led to the development of wearable insulin pumps.

Tomorrow

Despite growing technology (smaller and more accurate insulin pumps are now available, monitoring can be done without pricking a fingertip, software exists that can categorize blood glucose data and transmit it from a patient’s home to a physician’s office), insulin injection was first pioneered some 70 years ago and insulin pump technology is coming up on its 40th birthday. One reason diabetic patients have trouble controlling their blood glucose levels is the inconvenience of frequent testing and injections, which advancements in therapeutic management have sought to minimize. Oral therapies are one option, but many would be surprised to know that metformin, the most popular anti-diabetic drug in the United States, has been commercially available in Europe since 1959; the drug gained FDA approval in 1995.

Another oral therapy recently approved by the FDA is inhaled insulin. Approved in January 2006, inhaled insulin is a fast and easy method of delivery that eliminates traditional barriers to management. And yet, as with any new breakthrough, researchers expect complications down the road. After indications that inhaled insulin results in minor decreases in lung capacity, experts believe that long-term risks of inhaled insulin’s use may outweigh the short-term benefits.

The most promising diabetes development, however, is a hockey-puck-sized, three-part, man-made organ ("artificial pancreas") that will combine an insulin pump, glucose monitor, and a computer algorithm to regulate blood glucose levels in real-time.

Early results from a major human clinical trial of the artificial pancreas in France demonstrate the pitfalls and the promises of the technology in its infant stage. The sensor was able to accurately measure blood glucose levels 95% of the time when compared with results of fingerstick tests, and blood glucose levels were maintained in the normal range 50% of the time compared with 25% for patients who used fingerstick values to tune insulin delivery from the pump. Incidence of hypoglycemia dropped to below 5%. On the downside, the blood glucose sensors stopped working after an average of six months in the body, and while the artificial pancreas increased the percentage of patients with blood glucose levels in a normal range, those patients still did not have accurate levels for 50% of the time, leading researchers to conclude that the algorithm used to calculate insulin levels needs to be adjusted.

BeyondThe ideal cure for any major disease is to restore to the body its ability to function, as it was intended, in a normal and healthy fashion. For diabetic patients, this would involve returning to the body its ability to properly produce and use insulin. Islet cells transplanted according to the Edmonton Protocol have been shown to restore insulin production and glycemic control, but at the expense of immunosuppression. To combat this, bio-engineered tissues containing islet cells with a protective coating against immune system response have been tested in animal studies, and are currently in pre-clinical development (http://en.wikipedia.org/wiki/Artificial_pancreas; http://www.isletmedical.com/pages/company_research.htm; http://www.isletmedical.com/pages/trials_participation.htm).

Gene therapy has been identified for numerous potential cures including programming viral vectors to infect specific cells with DNA, causing them to produce insulin (http://en.wikipedia.org/wiki/Artificial_pancreas; http://www.liebertonline.com/doi/abs/10.1089/dia.2005.7.549); curing the cause of beta cell destruction, and in turn diabetes (http://en.wikipedia.org/wiki/Artificial_pancreas; http://www.hopkinsbayview.org/healthcarenews06/060605diabetes.html); and turning duodenum cells and duodenum adult stem cells into beta cells which would produce insulin and amylin naturally (http://en.wikipedia.org/wiki/Artificial_pancreas; http://www.surgery.ubc.ca/presentarch/PedDiabetes04.pdf).

Stem cells were recently identified as a potential treatment for type 1 diabetes in a study published in the January 22 issue of the Proceedings of the National Academy of Sciences. Investigators discovered that cells passed from mother to diabetic child—a phenomenon known as maternal microchimerism—can differentiate into islet beta cells that produce insulin; female islet beta cells were found in male pancreatic tissue. Additionally, greater amounts of maternal DNA were found in type 1 children and adolescents than healthy siblings, suggesting that the maternal DNA is involved in the repairing of damaged tissue. Researchers believe that maternal stem cells could be harvested and used to treat diabetic children, and would have an edge over donated islet cells because of they would already be a partial genetic match (http://www.fhcrc.org/about/ne/news/2007/01/22/diabetes.html).

Bradley Schmidt is a freelance writer and a frequent contributor to MDNG.