Prediabetes is associated with increased risk of early mortality and cardiac diseases, as well as heart failure. Insulin resistance plays a major role in these risks. Lifestyle modifications can prevent type 2 diabetes and improve cholesterol and blood pressure. However, long-term studies have not shown benefits for the prevention of major death or heart problems. This led to uncertainty regarding the current clinical prevention methods. An emerging approach focuses on achieving remission of prediabetes by returning high blood sugar to a normal level. Evidence like the prediabetes lifestyle intervention study (PLIS) and the diabetes prevention program outcome study (DPPOS) studies demonstrate that achieving remission provides lasting metabolic benefits and improves insulin sensitivity, as well as lowering the incidence of diabetes. A recent study published in The Lancet Diabetes & Endocrinology aimed to evaluate whether remission also reduces heart failure hospitalization or cardiovascular death over many years.
In this post-hoc observational analysis, data were collected from the two major long-term diabetes prevention clinical trials: the Chinese DaQing diabetes prevention outcome study (DaQingDPOS) and the US DPPOS. Remission was estimated after 6 years of lifestyle changes in DaQingDPOS and at one year in DPPOS, with sensitivity analyses through World Health Organization (WHO)/ International Diabetes Federation (IDF) thresholds.
The primary outcome in both clinical studies was hospitalization due to heart failure and death due to cardiovascular diseases. The secondary outcomes were all-cause mortality, hospitalization for heart failure, and cardiovascular death, as well as major adverse cardiovascular event (MACE), including non-fatal or fatal stroke, myocardial infarction, hospitalized heart failure, all-cause mortality rates, or sudden death. Kaplan-Meier curves, Cox models, chi-square, and Wilcoxon statistical methods were used in this analysis.
A total of 2402 individuals were included in the DPPOS study. The participants in the DPPOS trial were followed from the starting period to the phase 3 trial (July 31, 1996, to February 23, 2020). In DPPOS, after one year of intervention, 275 participants (median age = 47.9 [42.1 to 54.4] years) achieved remission compared to 2127 participants (median age = 51.5 [44.9 to 58.9] years) who did not achieve remission with p < 0.0001. Median follow-up period for the primary endpoint was similar between the remission (20.3 years) and non-remission (20.0 years) groups. The primary event rate was found to be lower in the remission group (1.74/1000 person (95% confidence interval [CI]: 0.87 to 3.48) compared to the non-remission group (4.17, 95% CI: 3.55 to 4.89). Remission reduced risk with a crude hazard ratio of 0.41 (95% CI: 0.20 to 0.84) and an adjusted HR of 0.47 (95% CI: 0.23 to 0.97). Extended MACE rates were found to be 6.23 vs 9.95/1000 person-years with p = 0.016, and mortality rates were 6.05 vs 9.18/1000 person-years with p = 0.033.
A total of 540 individuals were included in the DaQingDPOS trial, in which 72 participants (median age = 49.0 [44.5 to 57.5] years) reached remission, and 468 did not reach remission (median age = 51.0 [44.0 to 57.0] years) after 6 years, with p = 0.743. In DaQingDPOS, the median follow-up period was more than 30 years. Remission also reduced mortality risk and cardiovascular events risk, like the DPPOS trial. Composite event rates were 9.5 vs 17.0 per 1000 person-years (p = 0.021) with adjusted hazard ratio (HR) of 0.49 (95% CI: 0.28 to 0.84). Mortality (event rate = 16.4 vs 26.8 HR = 0.55 [95% CI: 0.36 to 0.84], p = 0.006) and MACE (27.0 vs 45.9, HR = 0.54 [95% CI = 0.38 to 0.77], p = 0.001) were similarly reduced.
This study’s limitations include a post-hoc design, a baseline difference between groups, low remission rates, and limited estimation of cardiovascular events.
In conclusion, this analysis highlights that prediabetes remission to normal glucose levels consistently reduces the risks of cardiovascular deaths and heart failure hospitalization, as well as mortality risk. These findings suggest remission is a valuable global prevention strategy for cardiovascular diseases and diabetes.
Reference: Vazquez Arreola E, Gong Q, Hanson RL, et al. Prediabetes remission and cardiovascular morbidity and mortality: post-hoc analyses from the Diabetes Prevention Program Outcome study and the DaQing Diabetes Prevention Outcome study. Lancet Diabetes Endocrinol. 2025. doi:10.1016/S2213-8587(25)00295-5
