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AACE: Ralph A. DeFronzo, MD — Diabetes Prevention Supports More Aggressive and Earlier Intervention

May 9, 2013

Dr. DeFronzo presented the "Diabetes Update – 2013," focusing on preventing diabetes….

Dr. Ralph A DeFronzo from the University of Texas Health Science Center in San Antonio, made a case for treating patients with impaired glucose tolerance to prevent or delay conversion to type 2 diabetes.


Dr. DeFronzo, who is Director of the Diabetes Research Unit at UTHSC began his presentation with a current review of the exploding statistics on the number of Americans with impaired glucose tolerance and the costs associated with it — particularly the costs in dollars and quality of life associated with microvascular complications.

He stated that the key to reducing the risk of patients with impaired glucose tolerance going on to meet the definition of type 2 diabetes is preserving beta cell function. And the key to preserving beta cell function is earlier intervention than what we do now.

To make his case for early intervention, Dr. DeFronzo reviewed extensive data from multiple studies – beginning with a look at lifestyle interventions.

"There’s no doubt – when you look at diabetes prevention – if you can get people to lose weight and exercise on a regular basis, lifestyle intervention is great therapy," he stated. "The issue is not whether diet and exercise works. It works. The issue is can you get people to do it on a long-term basis. I think it’s time to face reality. The reality is, it doesn’t work long term."

However, Dr. DeFronzo went on to demonstrate how pharmaceutical treatment can preserve beta cell function and dramatically reduce the risk of developing type 2 diabetes in patients with impaired glucose tolerance.

He reviewed several studies that looked at the use of TZD’s in patients with impaired glucose tolerance.

"What you can see, in all of these studies — whatever TZD you look at — is although the initial drop in A1c may vary, whatever the initial drop, it’s maintained," Dr. DeFronzo said. "You have durability of control over a long period of time…. If you know nothing else, and I told you that I gave you a drug that dropped your A1c and you asked why that happened, there’s only one answer. We preserved beta cell function. If you don’t stop beta cell failure, you will not stabilize A1c."

He said the literature on the TZD’s consistently shows a 50 to 70 percent improvement in reducing the conversion rate of impaired glucose tolerance to type 2 diabetes.

However, given legal battles surrounding some of the TZD’s, Dr. DeFronzo said their use is on the decline. Although he uses TZDs in his patients, he said he believes the use of incretin hormones will increase going forward.

"Although we have less data on the incretin hormones, in my opinion the data are so impressive that these drugs will eventually become the drugs of choice," he said.

In addition to augmenting insulin secretion in patients with elevated blood sugar, the GLP1 analogs help prevent type 2 diabetes by replenishing beta cell insulin stores and by preventing beta cell exhaustion, Dr. DeFronzo said.

As an example of the dramatic results seen with incretin therapies, Dr. DeFronzo shared results from a little-known study evaluating liraglutide’s effect on beta cells in obese patients.

"Sixty-one percent of people lost more than 5 percent of their body weight," he said. "This would be sufficient to get the drug approved as weight-loss drug by the FDA. Nineteen percent lost more than 10 percent of their body weight. But look at this… ninety percent of the people with prediabetes returned to normal glucose tolerance. That’s even better than what you’d see with a TZD. Looking at metabolic syndrome, there was a 60 percent decrease."

Given the ability of these therapies to prevent the progression to type 2 diabetes, Dr. DeFronzo said it was clear that earlier intervention makes sense financially and in terms of quality of life for patients.

AACE Meeting, May 2, 2013