Reversing Prediabetes Without Lifestyle Change May Not Reduce Mortality Risk: Study

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Reversing prediabetes to normoglycemia over a 3-year period did not reduce overall mortality risk among a cohort of more than 45 000 Taiwanese adults, according to findings of a new study. However, the risk was attenuated among study participants who also incorporated several healthy lifestyle changes.

During median follow-up of 8 years, patients whose prediabetes was reversed did not experience significantly decreased risks for all-cause, cancer-related, or cardiovascular disease (CVD)-related death compared with those who remained in persistent prediabetes, reported Xifeng Wu, MD, PhD, of Zhejiang University in China, and colleagues in JAMA Network Open on March 28.

"Interestingly, reversion to normoglycemia combined with the adoption of healthy behaviors, such as a higher level of physical activity and no current smoking, were associated with a substantially lower risk of death and longer life expectancy," the authors wrote.

In fact, the only study participants with a significantly lower mortality risk were those who were physically active and reverted to normoglycemia or remained in a state of prediabetes compared with participants who were inactive and had persistent diabetes.

The longer life expectancy conferred by the difference was approximately 2 to 2.5 years, according to the study. The findings, the authors note, “highlight the importance of lifestyle modifications among individuals with prediabetes status."

Data gaps

Approximately 25% of individuals with prediabetes will develop type 2 diabetes (T2D) within 3 to 5 years, write Wu and colleagues. Up to 70% will progress to diabetes in their lifetime, a progression associated a higher risk of death. Findings on the association between reversion to normoglycemia and mortality risk are inconsistent, researchers add, and there is little evidence on associations between regression of prediabetes and cause-specific mortality. Moreover, there are very few studies of the role of modifiable risk factors in associations between changes in prediabetes status and risk of death.

Wu and colleagues set out 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 investigators 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.

FINDINGS

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.

Wu and co-authors noted that the results of their study "extended previous findings by confirming that the association between prediabetes and the risk of death might be explained by progression from prediabetes to diabetes." They also encourage development of “comprehensive personalized intervention strategies for lifestyle modification” in the prediabetes population.

Reference: Cao Z, Li W, Wen CP, et al. Risk of death associated with reversion from prediabetes to normoglycemia and the role of modifiable risk factors. JAMA Netw Open. Published online March 28, 2023. doi:10.1001/jamanetworkopen.2023.4989