Prediabetes remission and cardiovascular morbidity and mortality: post-hoc analyses from the Diabetes Prevention...

Prediabetes is associated with increased risk of cardiovascular disease and heart failure. Multicomponent lifestyle interventions, including diet and physical activity targeting weight loss are recommended for prediabetes management, although their long-term impact on cardiovascular outcomes remains unclear. Reaching prediabetes remission by restoring normal glucose regulation has been shown to profoundly reduce future type 2 diabetes risk outlasting the time of lifestyle intervention. We aimed to investigate whether prediabetes remission is associated with a lower incidence of cardiovascular death or hospitalisation for heart failure compared with non-remission, with a long-term legacy effect.

Post-hoc analyses were performed from two landmark diabetes prevention trials, the US Diabetes Prevention Program Outcomes Study (DPPOS) and the Chinese DaQing Diabetes Prevention Outcomes Study (DaQingDPOS). Remission was assessed using the American Diabetes Association criteria after 1 year (DPPOS) or 6 years (DaQingDPOS) of intervention. The primary endpoint was cardiovascular death or hospitalisation for heart failure over 20 and 30 years, respectively. In DPPOS, inverse probability of treatment weighting adjusted for baseline differences. A unifying meta-analysis was calculated across both data sets for the primary endpoint and all-cause mortality.

For DPPOS, follow-up time is reported from the start of the original Diabetes Prevention Program trial, July 31, 1996, to the end of DPPOS phase 3, Feb 23, 2020. In total, 2402 participants were included in DPPOS and 540 in DaQingDPOS. In DPPOS, 275 (11·5%) of 2402 participants reached remission after 1 year of intervention compared with 2127 (88·5%) of 2402 not reaching remission. In DPPOS, after a median follow-up of 20 years, the event rate for cardiovascular death or hospitalisation of heart failure was 1·74 (95% CI 0·87-3·48) per 1000 person-years in participants who reached remission versus 4·17 (95% CI 3·55-4·89) in those without remission (p=0·013) with a fully adjusted hazard ratio of 0·41 (95% CI 0·20-0·84; p=0·014). Results remained robust after adjustment, were confirmed in DaQingDPOS (primary endpoint: HR 0·49 [95% CI 0·28-0·84]; p=0·010), and were supported by a pooled meta-analysis. Results were stable when analysing the composite endpoint in those reaching remission at least once during follow-up, with a HR of 0·43 (0·29-0·63; p<0·0001).

Reaching prediatbetes remission is linked to a decades-long benefit, halving the risk of cardiovascular death or hospitalisation for heart failure in diverse populations. Targeting remission might represent a new approach to cardiovascular prevention.

German Center for Diabetes Research via the German Federal Ministry of Research, Technology and Space; Ministry of Science, Research, and the Arts Baden-Württemberg; Helmholtz Munich; the Helmholtz Young Investigators Groups funding programme; the Cluster of Excellence EXC-2124; and the German Research Foundation (DFG). For DaQing: Centers for Disease Control and Prevention, WHO, the China-Japan Friendship Hospital, and Da Qing First Hospital and Fuwai Hospital, Chinese Academy of Medical Sciences. For DPPOS: National Institute of Diabetes and Digestive and Kidney Diseases.

For the German and Chinese translation of the abstract see Supplementary Materials section.