U-Shaped Associations Between Body Weight Changes and Major Cardiovascular Events in Type 2 Diabetes Mellitus: A Longitudinal Follow-up Study of Over 1.5 Million Nationwide Cohort

<b>Objective</b>: Despite the benefits of weight loss on metabolic profiles in patients with type 2 diabetes mellitus (T2DM), its association with myocardial infarction (MI), ischemic stroke (IS), atrial fibrillation (AF), heart failure (HF), and all-cause death, remains elusive. <p><b>Research Design and Methods: </b>Using the National Database, we screened subjects who underwent general health check-ups twice in a 2-year interval between 2009 and 2012. After identifying 1,522,241 T2DM patients without previous history of MI, IS, AF, and HF, we followed them up until December 2018. Patients were stratified according to the magnitude of weight changes between two general health check-ups: ≤-10%, -10 to ≤-5%, -5 to ≤5%, 5 to ≤10%, and >10%.</p> <p><b>Results: </b>During the follow-up (median 7.0 years),<b> </b>32,106 cases of MI, 44,406 cases of IS, 34,935 cases of AF, 68,745 cases of HF, and 84,635 all-cause deaths occurred. Patients with weight changes of -5 to ≤5% showed the lowest risk of each cardiovascular event. Both directions of weight change were associated with an increased cardiovascular risk. Stepwise increases in the risks of MI, IS, AF, HF, and all-cause death were noted with progressive weight gain (all P<.0001). Similarly, the more weight loss occurred, the higher the cardiovascular risks observed (all P<.0001). The U-shaped associations were consistently observed in both univariate and multivariate analyses. Explorative subgroup analyses also consistently showed a U-shaped association.</p> <p><b>Conclusion</b>: Both weight loss and gain beyond 5% within a 2-year interval were associated with an increased risk of major cardiovascular events in patients with T2DM. </p>