Andrew J. Drexler, M.D.
Director, Gonda (Goldschmied) Diabetes Center, UCLA, Los Angeles.
Dr. Andrew Drexler received his M.D. from the New York University School of Medicine in 1972, completed his residency in Internal Medicine at Barnes Hospital (1975-1976) and fellowship in Endocrinology at Washington University School of Medicine (1976-1978) in St. Louis, Missouri, and spent two years at the National Institutes of Health in the Public Health Service at the Laboratory of Immunology, NIAID (1973-1975). He joined the faculty of New York University School of Medicine, as Clinical Associate Professor in 2003. He was the Director of the Diabetes Clinic in Bellevue Hospital and the Director of the Mount Sinai Diabetes Center in New York (1998-2002).
Diabetes is one of man’s oldest known diseases, having been first described in Ancient Egypt in the Ebers papyrus. However treatment of diabetes only changed in the 20th century. Prior to 1922, the best treatment for Type 1 diabetes was the Allen diet. – an extremely low-carbohydrate and low-calorie diet. The quality of life associated with this unsustainable therapy was poor and adherence only prolonged life for weeks in most cases. Dr. Allen commented that patients were rarely compliant with this diet, often smuggling in a piece of bread. Pictures of the patients from this time reveal severe wasting, only now seen in concentration camp victims and during severe famines.
Insulin, discovered in 1922 changed this. However, the initial insulin preparations were very crude and often made patients very sick. Problems existed as well with allergic reactions to either insulin or contaminants in the insulin preparations. Infections and abscesses were also common with these initial preparations. While short lived, there were initial questions about the appropriateness of insulin injections as both unnatural and dangerous. The 100% mortality of any other therapy quickly resolved these questions. Initial treatment consisted of multiple injections of what we now call Regular insulin during the day and overnight. After the initial enthusiasm abated, patients began demanding a way to prolong insulin’s action so a single injection once a day would suffice. Long-acting insulins were developed, such as protamine zinc. We now know that this advance was actually a step back, and that patients on these once daily insulin preparations had higher rates of blindness, kidney failure and nerve damage than individuals who had been treated with multiple injections. With either therapy it was unusual for patients diagnosed as children to live past 45. Furthermore their final years were often unpleasant with loss of vision and kidney failure as well as heart disease.
The current era in diabetes treatment began in the late 1970’s and early 1980’s with the introduction of hemoglobin A1c testing, patient self glucose testing, multiple daily injections and insulin pumps. These advances have permitted highly motivated patients to live longer than in the past, and in some cases without complications from the diabetes. These results, however, can only be achieved with a level of constant vigilance that is impossible for many to emulate. Even when achieved, there are significant risks associated with low blood sugar reactions that can pose a potentially lethal complication in some cases.
Current research of future diabetes treatments is focused on mechanical devices and biological approaches. The mechanical approach, or “artificial pancreas”, has many limitations because current technology cannot accurately monitor blood sugar levels and calculate how much insulin to administer. The biological approach – some method of transplanting islet cells or islet stem cells – has limitations as well. Transplants generally require immunosuppression drugs, which is a major drawback. Equally important is the absence of adequate islet cell sources for transplant. The use of non-human islet cells potentially solves this latter problem but makes the immunosuppresion complications much worse because more intense and therefore more toxic immune suppression drugs are required to prevent rejection of non-human islets. The use of stem cells may solve some of these problems, but is still far off in the future and may carry new risks that we currently don’t know.
The better fate of diabetics on the old regimen of multiple doses per day of fast-acting insulin compared with those who added NPH insulin to their treatment raises many interesting issues. I have tried using just Clear insulin to imitate the life of a type 1 diabetic in the mid-1920s and found it impossible to achieve anything other than a huge blood glucose level, primarily because the effect of short-acting insulin ran out over night. One theory about why those on the Clear insulin regimen did better than patients later taking NPH plus Clear is that the former patients experienced one or more hypoglycemic episodes every day by having nothing other than an iterated insulin bolus treatment available to them, and this may have interrupted the processes by which hyperglycemia causes vascular damage. A smoother blood sugar profile, in contrast, may have allowed these processes to continue without interruption. This explanation is inconsistent, however, with recent research, which shows that glucose homeostasis seems to be nearly as important to patient health as more normal glucose levels.
Since solid organ transplant immunosuppressive triple-therapy now quadruples the incidence of cancer among organ recipients, as well as increasing their risk for atherosclerosis, neuropathy, dyslipidemia, and liver disease — to name just a few conditions — it is obviously foolish to trade diabetes for any treatment requiring immunosuppression unless the patient already requires an organ transplant for other reasons. The shortage of human islets or pancreatic tissue for transplant further strengthens the case against this approach. Only efforts to treat diabetes by encasulated islets seem to offer reasonable hope for the immediate future.