HealthDay News — Patients with prediabetes who achieve normal glucose regulation, even just one time, have a lower risk for progressing to diabetes, study data indicate.

Patients who achieved normal glucose regulation on any annual measurement during the Diabetes Prevention Program were three times as likely to achieve normal glucose regulation at follow-up as patients who remained prediabetic, Leigh Perreault, MD, from the University of Colorado in Aurora, and colleagues, reported at the American Diabetes Association meeting.

Consequently, patients who remained prediabetic after intensive lifestyle intervention had a significantly higher risk for progressing to diabetes and a significantly lower likelihood of achieving normal glucose regulation than did patients originally randomized to placebo.

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“We conclude that prediabetes is a high-risk state for diabetes, especially in patients who remain with prediabetes despite intensive lifestyle intervention,” the researchers wrote in a study published to coincide with the meeting online in Lancet.

“Reversion to normal glucose regulation, even if transient, is associated with a significantly reduced risk of future diabetes, independent of previous treatment group.”

Although previous large randomized clinical trials have shown diet, physical activity and various medications can prevent or delay diabetes onset in patients with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), the clinical significance of regression to normoglycemia is unknown.

So the researchers analyzed data from 1,990 participants in the DPP Observational Study (DPPOS) to see whether achieving normal glucose regulation reduced the risk for incident metabolic and vascular diseases, or simply reflected glucose fluctuations over time.

Participants who continued with the DPPOS follow-up were randomly assigned to intensive lifestyle intervention (n=736), metformin (n=647) and placebo (n=607).

The researchers defined prediabetes as fasting plasma glucose (FPG) of 100 to 126 mg/dL, or a two-hour plasma glucose reading of 140 to 200 mg/dL after an oral glucose tolerance test (OGTT) throughout the DPP.

Normal glucose was defined as FPG <100 mg/dL, or a two-hour glucose <140 mg/dL on at least one annual OGTT during the DPP. Diabetes was defined as FPG ≥126 mg/dL, or a two-hour glucose ≥200 mg/dL after a 75-g oral glucose challenge.

A total of 894 patients achieved normal glucose regulation at least once during DPP, and had a 56% lower risk of progression to diabetes than did the patients who remained persistently prediabetic (P<0.0001), regardless of treatment assignment, the researchers found.

The likelihood of achieving normal glucose regulation in DPPOS correlated with previous achievement of normal glucose regulation (OR,3.18; 95% CI: 2.71-3.72; P<0.0001), increased β-cell function (OR, 1.28; 95% CI: 1.18-1.39; P<0.0001), and insulin sensitivity (OR, 1.16; 95% CI: 1.08-1.25; P<0.0001). For the prediction of diabetes, increased β-cell function and insulin sensitivity had a protective effect (HR, 0.80 and 0.83, respectively).

Participants in DPP assigned to intensive lifestyle intervention who did not achieve normal glucose regulation had a 31% greater risk for diabetes (HR, 1.31; 95% CI: 1.03-1.8; P=0.0304) and a 41% lower chance for normal glucose regulation (HR, 0.59; 95% CI: 0.42-0.82; P=0.0014) than those in the placebo group.

In an accompanying editorial, Natalia Yakubovich, MD, and Hertzel C. Gerstein, MD, from the McMaster University in Hamilton, Ontario, commented that although the findings confirm the clinical relevance of regression to normoglycemia during prediabetes, further research is needed.

“Whether a reduced incidence of diabetes after regression translates into a reduced incidence of diabetes-related health consequences, such as blindness and vascular disease, is unknown, and can be assessed by ongoing follow­-up of this cohort, and by future clinical trials,” they added.


  1. Perreault L et al. Lancet. 2012; doi:10.1016/S0140- 6736(12)60525-X.
  2. Yakubovich N et al. Lancet. 2012; doi:10.1016/S0140- 6736(12)60828-9.