Megan Brooks

June 09, 2012

June 9, 2012 (Philadelphia, Pennsylvania) — Regression from prediabetes to normoglycemia, even if only transient, significantly reduces the risk for future diabetes, new research shows.

The findings, from the Diabetes Prevention Program Outcomes Study (DPPOS), were presented here at the American Diabetes Association (ADA) 72nd Scientific Sessions and published online today in the Lancet.

During her presentation, study investigator Leigh Perreault, MD, from the University of Colorado in Aurora, said: "This analysis draws attention to the significant long-term reduction in diabetes risk when someone with prediabetes returns to normoglycemia, supporting a shift in the standard of care to early and aggressive glucose-lowering treatment in patients at highest risk."

Role of Regression Unclear

Several studies have shown that diabetes can be prevented or delayed in people with impaired fasting glucose or impaired glucose tolerance through diet, physical activity, and various drugs, Dr. Perreault explained. However, the clinical significance of regression from impaired glucose tolerance to normoglycemia, which has also been noted in several trials, is less well understood.

To investigate, Dr. Perreault and colleagues analyzed data on participants in the DPPOS, an ongoing observational study of participants from the DPP randomized trial.

In the DPP, overweight and obese participants with impaired glucose tolerance were randomly assigned to lifestyle intervention, metformin, or placebo. The study found that lifestyle intervention led to a 58% reduction in the development of diabetes, whereas metformin resulted in a 31% reduction.

Included in the new analysis were 1990 participants in the DPPOS with impaired glucose tolerance who returned to normoglycemia at least once during the DPP. Of these patients, 736 were in the intensive lifestyle intervention group, 647 were in the metformin group, and 607 were in the placebo group.

The investigators found that the 894 people who had at least 1 normal oral glucose tolerance test during DPP had a 56% lower relative risk of developing diabetes during passive follow-up in the DPPOS than the 1096 people who never regressed to normoglycemia during DPP, which was highly statistically significant (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.37 - 0.55; P < .0001).

Diabetes risk was reduced by 61% if normal glucose regulation was reached twice (HR, 0.39; 95% CI, 0.28 - 0.56; P < .0001) and by 67% if it was reached 3 times (HR, 0.33; 95% CI, 0.19 - 0.58; P = .0001) during the DPP.

This relationship was unaffected by treatment group assignment. "It did not matter how people got to [normal glucose regulation], the benefit was the same," Dr. Perreault told ADA session attendees. This suggests that achieving normoglycemia is more important than the method used to achieve it, with respect to lowering the risk for diabetes, she said.

"Somewhat counterintuitively," reported Dr. Perreault, people with persistent prediabetes who had been assigned to the intensive lifestyle intervention in DPP had a higher, not lower, risk of developing diabetes during DPPOS (HR, 1.31; 95% CI, 1.03 - 1.68; P = .0304).

These individuals seem "resistant to effects of lifestyle intervention, and they require greater attention," she said.

Implications for Care

Identification of regression to normoglycemia "could be an important way to stratify people into those at higher and lower risk of progression to diabetes," write the coauthors of an accompanying comment that was also published in the Lancet. "Such stratification could therefore identify individuals for whom additional treatment might be needed to prevent diabetes or to slow down disease progression," write Natalia Yakubovich, MD, and Hertzel C. Gerstein, MD, from McMaster University in Hamilton, Ontario, Canada.

In addition, "identification of the genetic, environmental, and behavioural predictors of regression might further elucidate pathophysiological mechanisms underlying diabetes development," they add.

The study was funded by the National Institutes of Health. Dr. Perreault and colleagues have disclosed no relevant financial relationships. Dr. Yakubovich disclosed grant support from Sanofi for travel expenses. Dr. Gerstein disclosed serving on scientific advisory boards for Sanofi, GlaxoSmithKline, Novo Nordisk, Roche, Merck, Novartis, Janssen, Abbott Laboratories, and AstraZeneca; trial steering committees for Bayer and Roche; receiving a grant from Lilly; and speakers' fees from Sanofi and Bayer.

American Diabetes Association (ADA) 72nd Scientific Sessions: Abstract CT-SY22. Presented June 9, 2012.

Lancet. Published online June 9, 2012. Article abstract, Comment extract