Prediabetes remission linked to decades-long cardiovascular benefit

medwireNews: Achieving prediabetes remission during a lifestyle intervention may half the risk for cardiovascular death or hospitalization for heart failure for at least 20 years compared with not reaching remission, shows a post-hoc analysis of two landmark diabetes prevention trials.

“Prediabetes remission to normal glucose regulation thus emerges as a consistent, measurable, and globally applicable prevention target—one with a long-term benefit—that should be considered in future guidelines, not only for preventing type 2 diabetes but also for the primary prevention of cardiovascular morbidity and mortality in diverse populations worldwide,” write Andreas Birkenfeld (University Hospital of Tübingen, Germany) and co-authors in The Lancet Diabetes & Endocrinology.

Their findings are based on data from the US Diabetes Prevention Program Outcomes Study (DPPOS) and the Chinese DaQing Diabetes Prevention Outcomes Study (DaQingDPOS).

In DPPOS, 11.5% of 2402 participants reached remission during 1 year of intensive lifestyle intervention. Remission was defined according to American Diabetes Association criteria as fasting plasma glucose below 100 mg/dL (<5.6 mmol/L), 2-h plasma glucose below 140 mg/dL (<7.8 mmol/L), and glycated hemoglobin below 5.7% (<39 mmol/mol).

The researchers report that, during a median follow-up of 20 years, the cumulative incidence of cardiovascular death or hospitalization for heart failure was 1.7 events per 1000 person–years in DPPOS participants who reached remission compared with 4.2 events per 1000 person–years in those who did not.

After adjustment for sex, race and ethnicity, treatment assignment, age, weight, smoking status, and use of blood pressure and lipid-lowering medication, prediabetes remission was associated with a significant 53% lower risk for the composite cardiovascular outcome.

The findings were confirmed in DaQingDPOS, in which 13.3% of 540 participants reached remission after 6 years of structured lifestyle intervention (diet, exercise, or both).

In that study, cardiovascular death or hospitalization for heart failure occurred at rates of 9.5 and 17.0 cases per 1000 person–years in people with and without remission, respectively, during a median of more than 30 years of follow-up. The difference between the two groups corresponded to a significant 55% lower risk associated with remission, after adjustment for confounders.

Birkenfeld and team also carried out a meta-analysis of pooled data from the two studies, which showed that achieving remission was associated with a significant 53% lower risk for death compared with no remission.

The investigators point out that the remission rates in both DPPOS and DaQingDPOS “were rather low,” and therefore say that “it will be important in the future to determine how people not reaching remission can be amended to remission.”

They add: “Clearly, future studies will need to determine how lifestyle-based remission programmes are prioritised against, or alternatively integrated with, pharmacological or other medical approaches that might play a role in prevention strategy and policy.”

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Lancet Diabetes Endocrinol 2025; doi:10.1016/S2213-8587(25)00295-5