Type 2 diabetes is a common disorder affecting nearly 17 million Americans with a high prevalence among Native Americans, Hispanics and African-Americans. The disease has a strong genetic component and tends to run in families. Approximately 90 percent of patients with type 2 diabetes in the U.S. are considered obese and sedentary. Although weight loss and regular exercise can prevent and delay the appearance of diabetes and help reduce its chronic complications, promoting and sustaining healthy lifestyle changes has proven to be very difficult in our modern society.
As obesity reaches worldwide epidemic proportions, the appearance of new cases of diabetes and early onset type 2 diabetes in youth have become major challenges for the health and scientific community.
In the early stages of type 2 diabetes, there is some residual insulin available in the pancreas of these individuals. Physicians can take advantage of this fact. By employing various oral agents, physicians can help stimulate the pancreas to secrete as much insulin as possible. Eventually however, the reserve is gone and one must resort to insulin injections, similar to the treatment for type 1 diabetes patients who perform the injections from the very beginning of their illness.
What About Enhancing Sensitivity To Hormonal Insulin?
A different strategy is to try to enhance sensitivity of the tissues in the body to the hormonal action of insulin. This approach reduces the need for insulin and the low capacity of the pancreas to produce and secrete the hormone insulin, which one would see among those with type 2 diabetes, may actually be sufficient to maintain normal blood glucose levels and other metabolic functions. As we know, performing regular physical activities is one way to reduce the need for insulin.
|  | | The Texas Diabetes Institute will soon launch a clinical study of a new exercise pill that may help reduce high blood sugars in patients with diabetes.
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For many years, we have tried to understand how the body can burn sugar during exercise in the absence of insulin. During muscle contraction, the energy required by the fibers is derived primarily from circulating glucose and fat. In the postprandial period, insulin is needed to stimulate glucose entry into muscle fibers but during exercise, the entry of glucose is insulin-independent. In other words, glucose leaves the circulation and enters the contracting muscle cells, even in the absence of the hormone insulin, which is the case with diabetes mellitus. As a result, there are falling levels of glucose in the circulating blood.
It turns out that there are some enzymes in the muscle fibers that are activated during physical activity and, as a consequence, sugar is moved easily from the circulation into the contracting muscle, even in the absence of the hormone insulin. Since these muscle enzymes are activated by pathways that do not normally require the presence of insulin, it became apparent that this natural process could be used to help reduce blood sugar levels in patients with diabetes.
There are a number of drugs that can activate these muscle enzymes and help move sugar from the blood into the muscle fibers during periods of rest. These drugs have been tested in the laboratory and in animal models. Unfortunately, only a few of these were safe enough to be developed for use in humans. However, one of these compounds, after a series of initial obligatory safety testing in animals, has reached the area of clinical investigation and is now being considered for large scale use in patients with type 2 diabetes.
A New Mechanism Of Drug Action In Controlling Blood Sugar
Hopefully, patients with type 2 diabetes who have high blood sugars can take advantage of a new “exercise pill” and be able to maintain their blood glucose control more easily. The Texas Diabetes Institute is getting ready to launch a clinical study of this drug to treat adult, obese type 2 diabetes patients who are currently using only one or no medication. According to the protocol, this new drug will be given once a day for three months.
It reduces blood sugar levels by forcing sugar entry into the muscle cells. The drug is capable of “fooling” the skeletal muscle into a “false state of intense exercise” and thus increases the demand for muscle fibers to burn sugar and fat. With this drug, muscle cells absorb the sugar from the blood (independent of the hormone insulin) and consequently cause high blood sugars in patients with diabetes to drop.
Since this represents an entirely new mechanism of drug action in the control of blood sugar levels, it is likely that this compound, if it is approved, could be used in combination with other well-known and currently available medications in the treatment of diabetes.
Using diverse drug combinations may give us a better chance of controlling blood sugar levels. The idea is to enhance our capacity to reduce blood sugar levels by using various different ways in order to safely reach goals for glucose control.
Final Notes
We are expecting some preliminary results and more data on the safety profile of this new agent before we begin the clinical trial. There is some good evidence that the proposed dose is safe. However, when the drug was taken at very high doses, some tested individuals developed acidosis, acid accumulation in the blood, which can turn into a serious illness.
Having more information on the potential side effects is clearly essential before we can start to use this new agent in patients with type 2 diabetes.
While the development of this exercise pill is still in the early stages, the potential of this new drug mechanism is encouraging. Maintaining adequate blood sugar levels is critical in preventing chronic complications and improving the quality of life in patients with diabetes. There is unequivocal evidence indicating that sustained elevated blood sugar levels are responsible for the devastating complications associated with diabetes, such as blindness, limb amputation, dialysis, heart disease and strokes.
Dr. Cersosimo is the Clinical Research Director of the Texas Diabetes Institute.
Dr. Steinberg (shown at the right) is an Assistant Professor within the Department of Orthopaedics, Podiatry Division at the University of Texas Health Science Center in San Antonio, Texas.
Editor’s Note: If you are interested in learning more about the ongoing diabetes research efforts at the Texas Diabetes Institute, please call (210) 358-7200.
For related articles, see previous Diabetes Watch columns “Educating Your Patients On Nutrition And Exercise” by Pamela M. Jensen, DPM, in the September 2002 issue (page 14) or “Taking A Closer Look At Insulin Resistance Syndrome” by Chih Yen, DPM, in the April 2002 issue (page 16) or check out the archives at www.podiatrytoday.com. |
