Getting prediabetes patients to regain glucose control as early as possible provides the best shot at preventing disease progression, regardless of whether it is achieved through lifestyle interventions or drug therapy, according to the latest analysis from the landmark Diabetes Prevention Program.
In fact, even a transient reversion to normal glucose regulation was associated with a significantly reduced risk of diabetes among participants in the DPP, a major randomized trial comparing weight loss and dietary changes with drug therapy for preventing the onset of type 2 diabetes.
Compared with 1,096 participants in that multicenter trial who consistently had prediabetes, the risk of diabetes was 56% lower (hazard ratio, 0.44) among 894 individuals who had returned to normal glucose regulation during the intervention period, according to findings from the Diabetes Prevention Program Outcomes Study (DPPOS), an ongoing postintervention observational study, Dr. Leigh Perreault of the University of Colorado, Aurora, and her colleagues reported online in the June 9 Lancet.
"Diabetes risk reduction was strongly associated with the number of times normal glucose regulation was achieved. Specifically, diabetes risk was reduced 47% in DPPOS if normal glucose regulation was attained only once (HR, 0.53); 61% if it was reached twice (HR,0.39); and 67% if it was reached three times (HR, 0.33)," the investigators said (Lancet 2012 June 9 [doi:10.106/S0140-6736(12)60525-X]).
At baseline, all 3,234 participants were at risk for developing diabetes. They were randomized to receive lifestyle interventions, metformin treatment, or placebo, and were followed for a median of 3.2 years during the intervention.
The current analysis, at a median follow-up of 5.7 years, shows that the reduced risk for diabetes among those subjects who returned to normal glucose regulation during the intervention was not affected by group assignment, the investigators said.
Factors associated with increased diabetes risk during DPPOS included age younger than 45 years (HR, 1.47), and African American ethnic origin (HR, 1.77).
"Paradoxically, increased weight loss during DPP adversely affected diabetes risk (HR, 1.26) in DPPOS independent of previous treatment," the investigators also noted, adding that this was "probably because of the high rate of weight regain in DPPOS with associated adverse effects on diabetes risk."
High body mass index at the beginning of DPPOS also related to diabetes risk during DPPOS follow-up (HR, 1.14). Higher beta-cell function and insulin sensitivity were protective (HR, 0.80 and 0.83, respectively).
Those who consistently had prediabetes during DPP – despite intensive lifestyle interventions – had an increased risk of developing diabetes during DPPOS, compared with those who didn’t have prediabetes and who were in the placebo group (HR, 1.31).
"Although there is widespread consensus that diabetes prevention is crucially important, there is less agreement with respect to the particular intervention," the investigators noted. "Results from the present analysis would contend that the strategy is unimportant as long as the intervention is early (when someone has prediabetes) and can restore normal glucose regulation, even if transiently."
The findings also suggest that maintenance of prediabetes despite intensive lifestyle modification represents a high-risk state that may warrant additional interventions, she and her colleagues said.
"Together, these data serve as essential clinical information to support early and aggressive measures for long-term prevention of diabetes in people at risk," they concluded.
This study was funded by the National Institutes of Health. The authors reported having no relevant financial conflicts.