161-OR: Prediabetes Remission and Cardiovascular Mortality and Morbidity

Introduction and Objective: Lifestyle interventions (LI) are effective in preventing T2D in people with prediabetes. Whether this approach also reduces cardiovascular (CV) death and heart failure (CHF) in people with prediabetes is matter of debate. We tested the hypothesis whether remission of prediabetes to normal glucose regulation (NGR; FPG<5.6 mmol/l, 2-h glucose OGTT <7.8 mmol/l, HbA1c <39 mmol/mol) reduces CV complications in people with prediabetes. Methods: In the Diabetes Prevention Program Outcomes Study (DPPOS) Phase 3 from the NIDDK repository from all three treatment arms (LI, metformin, placebo) with data for up to 21 years of follow-up were analyzed. Participants were separated into responders (i.e. remission to NGR) and non-responders (non-remission to NGR) based on the response at year 1 of the DPP intervention. Outcomes included 1) a composite of CV death and hospitalization for CHF and 2) extended MACE (CV events/death, arterial revascularization, hosp. for CHF or unstable angina, diagnosis of coronary heart disease or silent myocardial infarction). Results: Of 2427 participants, 278 (11%) were responders and 2149 (89%) non-responders at year 1. At baseline, BMI was 32.3kg/m2 (IQR: 28.7, 37.0) in responders and 32.5Kg/m2 (28.8, 37.1) in non-responders, and was reduced to 30.1kg/m2 (26.6, 34.2) and 31.4kg/m2 (27.7, 36.2; both p<0.01), respectively. In total, 93 of 278 (33.5 %) responders were diagnosed with T2D during DPPOS phase 3 compared to 1215 of 2149 (56.5 %) non-responders (p<0.001). During a mean observation time of 21 years and after adjustment for available risk factors, including baseline body weight, age, development of T2D, randomization assignment and medication, responders had lower relative risk (RR) for the composite endpoint of CV death and CHF (RR=0.43 (95 % CI: 0.21, 0.90); p=0.02) and for extended MACE (RR=0.60 (0.41, 0.89) p=0.01) than non-responders. Conclusion: LI-induced prediabetes remission markedly reduced CV morbidity and mortality in people with prediabetes. Disclosure E. Vazquez Arreola: None. R.L. Hanson: None. A. Sandforth: None. L. Sandforth: None. S. Katzenstein: None. N. Stefan: Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim. Consultant; Lilly Diabetes. Speaker's Bureau; Lilly Diabetes. Consultant; Pfizer Inc. Speaker's Bureau; Sanofi. Research Support; Sanofi. Speaker's Bureau; Novo Nordisk, GlaxoSmithKline plc. Consultant; GlaxoSmithKline plc. H. Preissl: None. N. Marx: Speaker's Bureau; Abbott, Amgen Inc, AstraZeneca. Advisory Panel; AstraZeneca. Speaker's Bureau; Bayer Pharmaceuticals, Inc. Advisory Panel; Bayer Pharmaceuticals, Inc. Speaker's Bureau; Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Daiichi Sankyo. Advisory Panel; Merck Sharp & Dohme Corp. Speaker's Bureau; Novo Nordisk. Advisory Panel; Novo Nordisk. Speaker's Bureau; Sanofi. Advisory Panel; Sanofi. Speaker's Bureau; Lilly Diabetes. R. Jumpertz von Schwartzenberg: None. A.L. Birkenfeld: None. Funding Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). German Federal Ministry for Education and Research (01GI0925) via the German Center for Diabetes Research (DZD e.V.)