Long-term effects of lowering postprandial glucose level on cardiovascular outcomes in early-stage diabetic patients with coronary artery disease: 10-year post-trial follow-up analysis of the DIANA study

Aims: To elucidate the long-term cardiovascular benefit of lowering postprandial hyperglycemia (PPG) in early-stage T2DM patients. Methods: This 10-year post-trial follow-up study included 243 patients from the DIANA (DIAbetes and diffuse coronary Narrowing) study, a multi-center randomized controlled trial which compared the efficacy of one-year life-style and pharmacological (voglibose/nateglinide) intervention lowering PPG on coronary atherosclerosis in 302 early-stage T2DM subjects [impaired glucose tolerance (IGT) or newly-diagnosed T2DM] (UMIN-CTRID#0000107). MACE (all-cause death, non-fatal MI or unplanned coronary revascularization) were compared in (1) three assigned therapies (life-style intervention/vogliose/nateglinide) and (2) patients with and without improvement of PPG (reversion from IGT to NGT or from DM to IGT/NGT on 75 g oral glucose tolerance test).Results: During the 10-year post-trial observational period, voglibose (HR = 1.07, 95%CI: 0.69-1.66, p = 0.74) or nateglinide (HR = 0.99, 95%CI: 0.64-1.55, p = 0.99) did not reduce MACE. Similarly, achieving the improve-ment of PPG was not associated with a reduction of MACE (HR = 0.78, 95%CI: 0.51-1.18,p = 0.25). However, in IGT subjects (n = 143), this glycemic management significantly reduced the occurrence of MACE (HR = 0.44, 95%CI: 0.23-0.86, p = 0.01), especially unplanned coronary revascularization (HR = 0.46, 95%CI: 0.22-0.94, p = 0.03).Conclusions: The early improvement of PPG significantly reduced MACE and unplanned coronary revasculari-zation in IGT subjects during the post-trial 10-year period.