Body weight changes in patients with type 2 diabetes and a recent acute coronary syndrome: an analysis from the EXAMINE trial

Abstract

Background Patients with type 2 diabetes (T2D) may experience frequent body weight changes over time. The prognostic impact of these weight changes (gains or losses) requires further study. Aims To study the associations between changes in body weight (intentional or unintentional) with subsequent outcomes. Methods The EXAMINE trial included 5380 patients with T2D and a recent acute coronary syndrome, who were randomized to alogliptin or placebo. Time-updated Cox models and mixed effects models were used to test the associations between changes in body weight and subsequent outcomes over a median follow-up of 1.6 (1.0–2.1) years. Results During the post-randomization follow-up period, 1044 patients (19.4%) experienced a weight loss ≥ 5% of baseline weight, 2677 (49.8%) had a stable weight, and 1659 (30.8%) had a ≥ 5 % weight gain. Patients with weight loss were more frequently women and had more co-morbid conditions. In contrast, patients who gained ≥ 5% weight were more frequently men with less co-morbid conditions. A weight loss ≥ 5% was independently associated with a higher risk of subsequent adverse outcomes, including all-cause mortality: adjusted HR (95% CI) = 1.79 (1.33–2.42), P < 0.001. Similar associations were found for cardiovascular mortality, the composite of cardiovascular mortality or heart failure hospitalization, and the primary outcome. A weight gain ≥ 5% was independently associated with an increase in the risk of subsequent cardiovascular mortality or heart failure hospitalization only: adjusted HR (95% CI) = 1.34 (1.02–1.76), P = 0.033. Conclusions In patients with T2D who had a recent ACS/MI, a ≥ 5% loss of body weight was associated with a higher risk of subsequent cardiovascular events and mortality.

Association of magnitude of weight loss and weight variability with mortality and major cardiovascular events among individuals with type 2 diabetes mellitus: a systematic review and meta-analysis

“…Ten studies [ 9 , 11 , 18 , 22 , 24 , 28 , 31 – 34 ] excluded individuals with pre-existing CV comorbidities. One study [ 19 ] included T2DM patients with a recent acute coronary syndrome. Ten studies [ 8 , 9 , 11 , 12 , 18 , 20 – 23 , 35 ] used a more than 2-year weight change interval to make sure that the change in weight was sustained.…”

“…Among the 18 studies that investigated the association between weight loss and risk of all-cause mortality (outcomes are presented in Additional file 2 : Table S3), 14 studies[ 8 – 12 , 19 – 21 , 23 , 27 , 29 , 32 , 35 , 38 ] found that weight loss was associated with an increased risk of all-cause mortality (HR [95% CI] ranging from 1.21 [1.03–1.41] to 5.6 [3.96–7.91]). Other 3 studies [ 7 , 28 , 31 ] found no association between weight loss and mortality.…”

“…Six studies [ 8 – 12 , 19 ] with a total of 207,901 participants were pooled for the analysis of relation between magnitude of weight loss and all-cause mortality (Fig. 2 ).…”

“…Eight studies reported the association between weight loss and a composite of CVD events (outcomes are presented in Additional file 2 : Table S4). Three of them [ 8 , 19 , 31 ] found that weight loss was associated with composite of CVD events (HR [95% CI] ranging from 1.31 [1.02–1.68] to 2.14 [1.15–1.86]). In the ADDITION-Cambridge trial [ 7 ], moderate weight loss was associated with a decreased risk of CVD events for (HR 0.52, 95% CI 0.32–0.86).…”

“…Eight studies analyzed the relationship between weight loss and CV mortality. Four of these studies [ 8 , 11 , 19 , 20 ] reported an increased risk of CV mortality (HR [95% CI] ranging from 1.175 [1.020–1.353] to 2.76 [1.87–4.09]). The other 3 studies [ 21 , 23 , 28 ] found no significant association between weight loss and CV mortality.…”