Obesity and weight loss are inversely related to mortality and cardiovascular outcome in prediabetes and type 2 diabetes: data from the ORIGIN trial

Aims The association of body weight and weight change with mortality and cardiovascular (CV) outcome in patients with diabetes mellitus (DM) is not clearly established. We assessed the relationship between weight, weight change, and outcomes in patients with established CV risk factors and type 2 DM or pre-diabetes. Methods and results A total of 12 521 participants from the ORIGIN trial were grouped in BMI categories of low body weight [body mass index (BMI)<22 kg/m(2)] normal (22-24.9), overweight (25-29.9), obesity Grades 1-3 (30-34.9, 35-39.9, >= 40kg/m(2), respectively). Outcome variables included total and CV mortality and composite outcomes of CV death, non-fatal stroke, or myocardial infarction plus revascularization or heart failure hospitalization. Follow-up was 6.2years (interquartile range 5.8-6.7years). After multivariable adjustment, lowest risks were seen in patients with overweight and mild obesity for total mortality [overweight: hazard ratio (HR) 0.80 (95% confidence interval (CI) 0.69-0.91); obesity Grade 1: HR 0.82 (0.71-0.95), both P<0.01)] and CV mortality [overweight: HR 0.79 (0.66-0.94); obesity Grade 1: 0.79 (0.65-0.95), all compared to patients with normal BMI, P<0.05]. Obesity of any severity was not associated with higher mortality. Low body weight was related to higher mortality [HR 1.28 (1.02-1.61); CV mortality: HR 1.34 (1.01-1.79), P<0.05]. A continued 2-year weight loss was associated with higher risk of mortality [HR 1.32 (1.18-1.46), P<0.0001] and CV mortality [HR 1.18 (1.02-1.35), compared to patients without weight loss, P<0.05]. In turn, weight gain was not related to any adverse outcome. Conclusion Obesity in patients with DM or pre-diabetes and CV risk profile was not associated with higher mortality or adverse CV outcome. The lowest mortality risk was seen in patients with overweight and moderate obesity (BMI 25-35kg/m(2)). Weight loss was an independent risk factor for higher mortality compared to no weight loss.