Reversing Prediabetes Alone Doesn’t Cut Mortality Risk

Reversing prediabetes was not associated with a lower mortality risk, according to a Taiwanese cohort study of more than 45,000 adults.

Over 8 years of median follow-up, patients who reversed their condition to a state of normoglycemia didn’t experience a significantly lower risk for all-cause, cancer-related, or cardiovascular-related death compared with those who remained in persistent prediabetes, reported Xifeng Wu, MD, PhD, of Zhejiang University in China, and colleagues.

“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 JAMA Network Open. “These findings highlight the importance of lifestyle modifications among individuals with prediabetes status.”

Across multiple analyses looking at modifiable risk factors and all-cause mortality, the only groups with a significantly lower risk were patients who were physically active and either reversed their prediabetes (HR 0.72, 95% CI 0.59-0.87) or remained in a state of prediabetes (HR 0.77, 95% CI 0.66-0.90), with both groups compared with inactive individuals with persistent diabetes. These differences translated to roughly a 2- to 2.5-year longer life expectancy.

Physically active individuals were clocking 7.50 or more metabolic equivalent of task (MET) hours per week, while inactive individuals were getting less than 3.75 MET hours per week. No benefit was seen for individuals who were “moderately” active (3.75-7.49 MET hours per week). Though it depends on someone’s body weight, a brisk walk can typically range from 3 to 6 METs, according to the CDC.

While individuals with obesity didn’t see a significant death protection by reversing prediabetes (HR 1.10, 95% CI 0.82-1.49) compared with those of normal weight with persistent prediabetes, those who stayed in a prediabetic state with obesity carried an excess risk for death (HR 1.33, 95% CI 1.10-1.62).

And normoglycemia still couldn’t offset the risks that came with smoking, as current smokers carried a similar 60-61% higher mortality risk whether they had achieved normoglycemia or remained in persistent prediabetes when compared with never smokers with persistent prediabetes. This translated to roughly 3 to 3.5 years less of life expectancy for the current smokers.

This pattern was not seen with alcohol drinkers, though.

The 45,782-person population-based cohort study gathered data from the Taiwan MJ Cohort Study, which recruited participants from 1996 to 2007. In the entirely Asian cohort, 63% were men, and average age was 44.6 years.

Within the first 3 years after study enrollment, 3.9% progressed to full-blown type 2 diabetes, while 37.2% reversed back to normoglycemia. Over the median 8-year follow-up period, 1,528 deaths occurred, including 671 from cancer and 308 from cardiovascular disease.

Not surprisingly, those who progressed to full-blown type 2 diabetes over the 3-year period had a higher risk for all-cause and cardiovascular-related mortality than those who persistently stayed in the prediabetic state:

• All-cause mortality: HR 1.50 (95% CI 1.25-1.79)
• Cardiovascular-related mortality: HR 1.61 (95% CI 1.12-2.33)

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.”

Diabetes status was ranked according to fasting plasma glucose level by American Diabetes Association criteria: normoglycemia (<100 mg/dL), prediabetes (100-125 mg/dL), diabetes (≥126 mg/dL). All were measured with overnight fasting blood samples taken in the morning.