Nipping Prediabetes Reduces Risk for Disease Advancement

Gregory A. Nichols, PhD


August 31, 2012

Effect of Regression From Prediabetes to Normal Glucose Regulation on Long-Term Reduction in Diabetes Risk: Results From the Diabetes Prevention Program Outcomes Study

Perreault L, Pan Q, Mather KJ, Watson KE, Hamman RF, Kahn SE; Diabetes Prevention Program Research Group
Lancet. 2012;379:2243-2251

Study Summary

The latest study from the Diabetes Prevention Program Outcomes Study (DPPOS), an ongoing observational study of participants from the Diabetes Prevention Program (DPP) randomized trial, compared long-term diabetes risk in participants who achieved normal glucose regulation (fasting plasma glucose level < 100 mg/dL and a 2-hour plasma glucose level < 140 mg/dL) during the DPP with those who had persistent prediabetes. Participants who met the criteria for diabetes during the DPP were excluded.

The investigators compared diabetes incidence overall and stratified by DPP treatment group. They also examined insulin secretion and insulin sensitivity during the DPP and the DPPOS, again comparing persons who attained normal glucose regulation at least once with those who had persistent dysglycemia.

A total of 1990 DPPOS participants were studied (736 from the DPP lifestyle intervention group, 647 from the metformin group, and 607 from the placebo group). Participants who achieved normal glucose regulation at least once during the DPP had a 56% reduced risk for progression to diabetes during the DPPOS. Furthermore, diabetes risk was reduced 47% in DPPOS if normal glucose regulation was attained only once, but 61% if it was reached twice and 67% if it was reached 3 times. Previous randomization group in the DPP did not affect risk reduction in the DPPOS in participants who attained normal glucose regulation.

Attainment of normal glucose regulation during the DPP strongly predicted achievement of normal glucose regulation during the DPPOS and was unaffected by previous treatment group. Compared with participants who had sustained prediabetes, those who attained normal glucose regulation experienced greater insulin secretion (corrected insulin response) during both the DPP and the DPPOS, but insulin sensitivity was substantially greater only during the DPP.


The current study is fascinating because it suggests that the key to diabetes prevention is not how the disease is prevented, but whether an individual is able to restore normal glucose regulation, even briefly. The DPP was one of several studies that demonstrated that onset of type 2 diabetes could prevented or delayed with lifestyle modification or pharmacotherapy.[1,2,3,4,5,6,7] All of these studies were conducted in participants at high risk for diabetes because of impaired glucose tolerance.

The idea of briefly restoring normal glucose regulation is consistent with the concept of "beta-cell rest" that is believed to protect beta cells from exhaustion and death.[8] Indeed, the authors noted that their findings suggest that preservation of beta-cell function seems to be more closely related to long-term prevention of diabetes than is insulin sensitivity.

The findings from the Diabetes Prevention Program Research Group study are also consistent with other studies showing that it is possible to reverse newly diagnosed diabetes with early intensive therapy,[9] and that the type of therapy is not a factor in remission.[10] In any case, the take-away message is that the goal of treatment of early hyperglycemic therapy, before or after reaching the threshold for diabetes, should be the restoration of normal glucose regulation -- by any means necessary.

One caveat is that it remains unclear whether preventing diabetes also prevents its complications. That is the final and perhaps most important piece of the puzzle.



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