Type 2 Diabetes Defeated

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The prevalence of type 2 diabetes mellitus is increasing at an alarming rate in the United States and around the world (1). It is a very costly disease, both monetarily and in terms of reduced quality of life (2). These costs are the consequence of the multiple debilitating chronic complications of hyperglycemia. The clinician's therapeutic goal is to avoid and mitigate these complications.

Just as the Diabetes Control and Complications Trial (DCCT) did for type 1 diabetes, the United Kingdom Prospective Diabetes Study (UKPDS) clearly demonstrated the significant benefit of improved glucose control in reducing the microvascular complications of type 2 diabetes (3). There was also a reduction in the rate of myocardial infarction (MI) among those treated with sulfonylureas or insulin, but it narrowly failed to reach statistical significance (p = 0.052). However, the epidemiological analysis including all the study individuals supported the linear relationship between glucose control and MI. Each I % decrease in HbA,c was associated with a 14% decrease in MI, a correlation that was statistically significant with a p value <0.0001 (4).

Concomitant with our recognition of the increasing public health burden of type 2 diabetes has come the growing emphasis on glucose control as the

cornerstone of the therapeutic approach to this disease. The American Diabetes Association (ADA) recommends an HbA,cgoal of 7.0% (5). Several other organizations in the United States and internationally propose even lower goals of 6.5%, and a U.S. national trial is now underway to test the value of treating to a goal of ^6.0% in type 2 diabetes.

Fortunately, many new oral medications with different mechanisms of action have become available to treat this disease (6). Progress has been made in moving our diabetes population toward the stated goals of glucose control. Yet, overall, we fail far too often. The focus must be on treating to goal.

The UKPDS helped clarify the progressive nature of type 2 diabetes. After 6 years of disease, only one-third of patients continued to have an HbA,c under 7.0% on their initially assigned treatment alone (7). Therefore, using 7.0% HbAlc as a measure of success, monotherapy failed at a rate of about 10% per year. Furthermore, this failure was shown to correlate with reduced p-cell function, or, more specifically, progressive insulin deficiency. It is clear that for many individuals with type 2 diabetes, insulin alone or in combination with oral agents will be required to treat the insulin deficiency. This will become an even greater issue in the years ahead as the number of individuals with long durations of type 2 diabetes increases. This expectation derives from the recognized relative increase in the number of younger adults being diagnosed with this form of diabetes as well as general increased longevity of our population (1).

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