Daily Dose: Reversion from Prediabetes to Normoglycemia & Mortality Risk

Patient Care brings primary care clinicians a lot of medical news every day—it’s easy to miss an important study. The Daily Dose provides a concise summary of one of the website's leading stories you may not have seen.

On March 29, 2023, we reported on a study published in JAMA Network Open that aimed to examine more closely the link between prediabetes status changes and mortality risk and to explore the impact of modifiable risk factors in these associations.

The study

Researchers tapped data from the Taiwan MJ cohort study, which enrolled more than a half million persons undergoing standardized medical screening between 1996 and 2007. The final all-Asian cohort numbered 45 782 individuals with prediabetes. Mean age was 44.6 years and 63% were men. Participants were categorized into 3 groups according to changes in their prediabetes status within a 3-year period after initial enrollment: reversion to normoglycemia, persistent prediabetes, and progression to diabetes.

The results

Within the first 3 years after enrollment, 3.9% of participants developed T2D and 37.2% reverted back to normoglycemia. There were 1528 deaths over the median follow-up period of 8 years; of those, 671 were from cancer and 308 from CVD.

In adjusted models for the 3-year period, those who progressed to frank T2D had a 50% (hazard ratio [HR], 1.50; 95% CI, 1.25-1.79) higher risk of death from any cause and a 61% (HR, 1.61; 95% CI, 1.12-2.33) higher risk of death from CVD. Reversion to normoglycemia compared with persistent prediabetes, however, was not associated with a lower risk of death from any cause (HR, 0.99; 95% CI, 0.88-1.10), cancer-related death (HR, 0.91; 95% CI, 0.77-1.08),or CVD-related death (HR, 0.97; 95% CI, 0.75-1.25).

Physical activity. Compared with individuals with persistent prediabetes who were inactive, the HRs of all-cause death among individuals who returned to a normal glycemic state were 0.72 (95% CI, 0.59-0.87) for those who were active and 1.01 (95% CI, 0.86-1.19) for those who were inactive. The risk of all-cause mortality among participants whose prediabetes progressed to T2D varied based on level of activity.

Obesity. Among individuals with obesity, reversing prediabetes to normoglycemia was not associated with a significantly lower risk of death (HR 1.10, 95% CI 0.82-1.49) when compared with normal weight participants with persistent prediabetes. However, participants with obesity who remained in a state of persistent prediabetes were at an increased risk of death (HR 1.33, 95% CI 1.10-1.62).

Smoking. Current smokers who reverted to normoglycemia were at a 60% greater risk of call-cause death (HR, 1.60; 95% CI, 1.31-1.96) vs those who remained in persistent prediabetes who never smoked. When the researchers compared individuals with persistent diabetes who never smoked to those who reverted to normoglycemia from prediabetes, both groups, if currently smoking, saw a similar decrease in life expectancy of 3.6 years.

Note from authors

"In this cohort study, although reversion from prediabetes to normoglycemia within a 3-year period did not mitigate the overall risk of death compared with persistent prediabetes, risk of death associated with reversion to normoglycemia varied based on whether individuals were physically active or had obesity. These findings highlight the importance of lifestyle modification among those with prediabetes status."

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