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Achieving Normoglycemia, Even Once, Significantly Reduces Diabetes Risk in Patients with Prediabetes

Restoring normal glucose regulation provides long-term benefits
Value-Based Care in Cardiometabolic Health August 2012, Vol 1, No 2

Reversing prediabetes and returning to a normal state of glucose regulation, even transiently, significantly reduces future risk of developing diabetes, reported investigators from the Diabetes Prevention Program Research Group at the 2012 ADA annual meeting.

Data were analyzed from participants in the 1990 Diabetes Prevention Program who were randomized to intensive lifestyle intervention (N = 736), to metformin (N = 647), or to placebo (N = 607) and who then continued follow-up in the observational, postintervention Diabetes Prevention Program Outcomes Study (DPPOS). The primary outcome was the proportion of patients who progressed to diabetes during the DPPOS.

Patients who had at least 1 annual oral glucose tolerance test during the Diabetes Prevention Program and had normal glucose regulation (fasting plasma glucose [FPG] <100 mg/dL or a 2-hour glucose <140 mg/dL) lowered their risk for developing diabetes by 56% compared with those who continued to have prediabetes, independent of how the reduction was achieved, said principal investigator Leigh Perreault, MD, a physician in the department of endocrinology and meta­bolism, and a clinical researcher at the University of Colorado Denver School of Medicine, Aurora.

“The treatment arm did not affect the reduction in diabetes onset in DPPOS in those who reached normal glucose regulation in the Diabetes Prevention Program,” Dr Perreault noted.

Diabetes Prevention
Risk reduction was strongly associated with the number of times normal glucose regulation was achieved. Those who achieved normal glucose regulation once had a 47% reduction in the risk of progression to diabetes, those who achieved it twice had a 60.7% reduction in risk, and those who achieved it 3 times had a 66.9% reduction in risk.

Prediabetes, defined as an FPG concentration of 5.6 mmol/L to 6.9 mmol/L or 2-hour plasma glucose of 7.8 mmol/L to 11.0 mmol/L, is itself a very high risk factor for development of type 2 diabetes and carries with it the risk of diabetes complications, Dr Perreault pointed out.

Several clinical trials have shown that the incidence of diabetes can be prevented or delayed in people with prediabetes through diet, physical activity, and drugs. Together, studies have shown incidence reductions between 25% and 72%, but most participants remain with prediabetes.

Some trial results mention the 20% to 50% of participants who did not progress to diabetes and in fact regressed to normoglycemia; however, these studies offer little in the way of explaining predictive factors.

Restoring Normal Glucose Regulation
This analysis outlined 3 factors that had significant associations with the achievement of normal glucose regulation during the DPPOS:

  • Previous normal glucose regulation during the Diabetes Prevention Program
  • Increased beta-cell function
  • Insulin sensitivity.

One surprise finding was that patients from the Diabetes Prevention Program who were randomized to intensive lifestyle intervention but remained persistently prediabetic had a 31% greater risk of progressing to diabetes and a 41% lower risk of achieving normal glucose regulation during the DPPOS than did participants randomized to placebo.

This finding emphasizes a particular susceptibility for this group, who may benefit from additional interventions. These results suggest that the management strategy is unimportant, as long as the lifestyle intervention occurs early and can restore normal glucose regulation.

The analysis supports aggressive glucose-lowering treatments to achieve normal glucose levels in people with prediabetes to maximize long-term slowing or preventing the progression to diabetes.

Last modified: August 30, 2021