Changing attitudes: Diabetes is progressive

The specifics are left to the individual physician

(Editor’s Note: The following is a commentary from Diabetes Management’s consulting editor, Ralph Hall, MD, emeritus professor of medicine, School of Medicine, University of Missouri-Kansas City. Hall will be presenting a session on this subject at the American Diabetes Association scientific sessions in San Diego in June.)

The UKPDS (United Kingdom Prospective Diabetes Study) dramatically demonstrated the progressive nature of Type 2 diabetes. Patients in each arm of this 10-year-plus study had gradually increasing HbA_1c determinations, and the vast majority of patients who started out on monotherapy eventually required another oral drug or insulin. Many patients had evidence of beta cell failure and required insulin.

In truth, diabetes is almost inevitably a progressive disease in those who are not managed vigorously.

The earliest phase of Type 2 diabetes in many patients who are obese is manifested by insulin resistance with blood glucose levels that don’t quite reach levels that are considered diagnostic of diabetes.

The early phase of insulin release may be blunted, and the post-prandial blood glucose rises despite increased release of insulin by the beta cell. At this time, diet and exercise may suffice to bring glucose levels back into the normal range.

Diet and exercise still important

In fact, diet and vigorous exercise are still the best forms of treatment at every stage of the disease. However, most patients are not able to lose enough weight or exercise adequately and as a result, will eventually need oral therapy or insulin. Traditionally, monotherapy with a sulfonylurea has been started at this point.

Now, however, there are a number of alternative oral drugs that lower blood glucose by a variety of mechanisms other than stimulating the beta cells to secrete insulin.

There are many questions left for the individual physician to answer:

1. Is there a particular agent that will lower the blood glucose and prolong the life of the beta cell either by decreasing insulin resistance or preventing further weight gain in this patient?

2. Further, will this approach lower the number of cardiovascular complications?

3. Some investigators believe that metformin is the drug of choice in overweight patients when monotherapy is started. What then is the next choice if another agent is eventually needed?

4. Do we now have any data to support a choice or are we left with a decision based on what therapy is likely to lead to the best compliance, i.e. a pill that has to be taken once a day or several times per day. Or will we simply choose on the basis of cost?

There is preliminary evidence that the various stages can be prolonged based on whether patients maintain good control on metformin and tolazamide.

If clinicians control the blood lipids, hypertension and other risk factors, both macrovascular and microvascular disease can be markedly reduced.