Risk of Death Associated With Reversion From Prediabetes to Normoglycemia and the Role of Modifiable Risk Factors

Abstract

ImportanceIndividuals with prediabetes have a higher risk of death than healthy individuals. However, previous findings have suggested that individuals with reversion from prediabetes to normoglycemia may not have a lower risk of death compared with individuals with persistent prediabetes.ObjectivesTo investigate the associations between changes in prediabetes status and risk of death and to elucidate the roles of modifiable risk factors in these associations.Design, Setting, and ParticipantsThis population-based prospective cohort study used data from 45 782 participants with prediabetes from the Taiwan MJ Cohort Study who were recruited between January 1, 1996, and December 31, 2007. Participants were followed up from the second clinical visit to December 31, 2011, with a median (IQR) follow-up of 8 (5-12) years. 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. Cox proportional hazards regression models were used to examine the associations between changes in prediabetes status at baseline (ie, the second clinical visit) and risk of death. Data analysis was performed between September 18, 2021, and October 24, 2022.Main Outcomes and MeasuresAll-cause mortality, cardiovascular disease (CVD)–related mortality, and cancer-related mortality.ResultsOf 45 782 participants with prediabetes (62.9% male; 100% Asian; mean [SD] age, 44.6 [12.8] years), 1786 (3.9%) developed diabetes and 17 021 (37.2%) reverted to normoglycemia. Progression from prediabetes to diabetes within a 3-year period was associated with higher risks of all-cause death (hazard ratio [HR], 1.50; 95% CI, 1.25-1.79) and CVD-related death (HR, 1.61; 95% CI, 1.12-2.33) compared with persistent prediabetes, while reversion to normoglycemia was not associated with a lower risk of all-cause death (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). Among individuals who were physically active, reversion to normoglycemia was associated with a lower risk of all-cause death (HR, 0.72; 95% CI, 0.59-0.87) compared with those with persistent prediabetes who were physically inactive. Among individuals with obesity, risk of death varied between those who experienced reversion to normoglycemia (HR, 1.10; 95% CI, 0.82-1.49) and those who had persistent prediabetes (HR, 1.33; 95% CI, 1.10-1.62).Conclusions and RelevanceIn 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.

Physical Activity, Cardiovascular Status, Mortality, and Prediabetes in Hispanic and Non-Hispanic Adults

“…Study limitations included our inability to capture progression to diabetes as an intermediary end point due to lack of intercurrent diabetes assessments prior to events. In a study of 45 782 Asian individuals with prediabetes, at any given level of PA, progression to diabetes was a leading predictor of mortality . As with the Da Qing study, more benefit in the prediabetes group may occur after longer follow-up .…”

Pros and cons of live kidney donation in prediabetics: A critical review and way forward

“…Physical activity is of utmost important in prediabetics. A recent study showed that conversion of euglycemia along with physically activity was associated with a lower risk of death compared with persistent PD and physical inactivity[ 133 ]. Keeping these facts in mind, it is important to fully educate prediabetic kidney donors about physical activity prior to donation.…”

Should Prediabetes be Treated Pharmacologically?

“…Even assuming that all the individuals who died had developed diabetes before doing so (highly unlikely), 64% of those still living would not have developed diabetes. Furthermore, a mean of one-third, with a wide range of 13–69% depending on the diagnostic criteria used to diagnose prediabetes and euglycemia, returned to normal glucose regulation over time [ 10 , 14 ].…”

“…The presence of prediabetes did not affect the clinical outcomes of patients who experienced an acute coronary syndrome, such as acute pulmonary edema, length of hospital stay, 28-day readmission rates, recurrence or CVD mortality, compared to those with normal HbA1c levels [ 16 ]. In individuals with IGT, the risk of CVD mortality was the same whether they returned to normal glucose regulation or not [ 14 ].…”

“…Data from prior publications are included in this commentary and are acknowledged in references [ 1 – 5 , 7 – 9 , 11 – 14 , 16 – 28 , 30 , 33 – 41 , and 43 ].…”