Pakistan Pharmacists Association  

Regaining Normal Glucose Function in Patients With Prediabetes


Study Summary

The Diabetes Prevention Program (DPP) was a randomized clinical trial involving 3234 volunteers at high risk for diabetes. All participants had impaired glucose tolerance (IGT), defined as having a fasting plasma glucose level of 5.3-6.9 mmol/L and attaining a 2-hour glucose of 7.8-11.0 mmol/L during a 75-g oral glucose tolerance test. The study discussed here evaluated a subgroup of participants who also had impaired fasting glucose (IFG), defined by the American Diabetes Association as a baseline fasting glucose of > 5.6 mmol/L and < 7.0 mmol/L.

Regression from this combined IFG/IGT state to normal glucose regulation (NGR) (fasting glucose < 5.6 mmol/L and 2-hour glucose < 7.8 mmol/L) was the primary outcome measure, and regression to isolated IFG or isolated IGT was the secondary outcome measure. In addition, the study sought to identify predictors for regression to NGR, isolated IFG, or isolated IGT within each treatment group (intensive lifestyle modification or metformin vs placebo) using Cox regression analyses.

At the first annual examination, 16.5% of the 2528 study participants had had regression to NGR. Of those who still had combined IFG/IGT, another 8% had regression to NGR at year 2, and among the remaining volunteers who still had IFG/IGT, another 4.4% had regression by year 3. Thus, a total of 600 (23.7%) participants had regression to NGR within 3 years. Lower baseline fasting and lower 2-hour glucose predicted regression to NGR, as did younger age and a greater insulin secretion to the oral glucose load. The intensive lifestyle intervention group was twice as likely to have regression as the placebo group (hazard ratio 2.05; 95% confidence interval 1.66-2.53), but the trend toward greater regression in the metformin group was not statistically significant (hazard ratio 1.25; 95% confidence interval 0.99-1.58). Greater weight loss also had a significant and independent effect on regression to NGR (hazard ratio 1.34; 95% confidence interval 1.21-1.49).


No one would argue that preventing progression to diabetes is a worthwhile pursuit. However, even in subdiabetic states of IFG and IGT, the microvascular and macrovascular complications generally associated with diabetes are more common than in patients with NGR. As the investigators of the current study point out, "true diabetes prevention likely resides in the restoration of NGR rather than in the maintenance of a high-risk state, such as pre-diabetes." Therefore, it is encouraging to note that nearly one quarter of the study participants achieved NGR within the 3-year study window. Over half of those patients did so in the first year, so for the most part, those who succeed in having NGR restored will do so relatively quickly.

One important finding was that if NGR is to be regained, it will likely occur through healthy eating and exercise and that this effect is probably independent of weight loss. However, it is important to remember that the DPP was a clinical trial of healthy volunteers who received a structured intervention. Whether these findings can translate to clinical practice needs further study.

In addition, as noted by the study authors, some factors associated with restoration of NGR are not modifiable. In particular, younger age and greater insulin secretion, which is likely also age related, are not reversible, as much as we might like them to be. Still, it was older DPP participants who had the greatest success achieving intensive lifestyle goals and subsequently the greatest reduction in diabetes incidence. If younger patients can more easily attain NGR, then perhaps a less structured intervention (more like what they would receive in clinical practice) will be equally effective.