Role of Early Intervention in Preventing Progression to T2D

Zachary T. Bloomgarden, MD, MACE: We have 2 strategies for intervening at the level of prediabetes. Three, really, because initially, one has to diagnose prediabetes, which requires screening.

Although the ADA (American Diabetes Association) has come down on the side of hemoglobin A1C measurement for diagnosis, I’m rather concerned that hemoglobin A1C may overdiagnose in some situations, such as in African Americans and older individuals who tend to have a higher level of A1C for a given level of glycemia. It may underdiagnose in individuals who have more rapid erythrocyte turnover. [These individuals] tend to have a lower A1C for a given level of glycemia.

Whether one uses glycemia screening with fasting glucose, or with glucose tolerance testing, or A1C, we know that a large number of individuals in our society have prediabetes—probably twice as many as [those who] have diabetes. So, let’s say something on the order of 60 million persons. Those individuals are at variable risk of developing diabetes, depending on the severity of their hyperglycemia.

So how do we prevent diabetes? Number one, absolutely, is [through] lifestyle modification. We know that if we take individuals with prediabetes and we have them in an intensive program of diet and physical activity, we can reduce the likelihood of developing diabetes by two-thirds. That’s really something that we are rarely able to achieve with pharmacologic therapy. So, I would always work with individuals in that fashion in trying to prevent diabetes.

But, let’s say I take an individual with prediabetes based on fasting glucose. Let’s say the fasting glucose is 105, and then the next time I check it it’s 112, and the next time I check it it’s 119. Well, there’s no reason to wait until it gets up to 126 at the next measurement where they officially do have diabetes (or similarly with hemoglobin A1C). In such a case, I would use pharmacologic therapy.

Three classes of drugs have been studied and have been shown to prevent diabetes. Probably, more of the diabetes drugs would have such an effect.

Metformin reduces the likelihood of diabetes by about half as much as lifestyle intervention. Still, that’s not bad—a 30% reduction in diabetes.

The thiazolidinediones are much more potent, but they have side effects of weight gain, edema, and skeletal fractures from bone loss. So, these are probably not as desirable.

There is evidence that alpha-glucosidase inhibitors, which are not commonly used in the United States, but are widely used in some countries such as in Europe and in Asia, may actually be moderately effective in reducing the development of diabetes. [So], these are certainly options.

The glucagon-like peptide-1 (GLP-1) receptor agonists have been shown in obesity therapy trials to reduce progression from prediabetes [to diabetes], and so have a number of obesity-directed drugs, per se. So, we do have a variety of choices in preventing progression from prediabetes to diabetes.