We read with great interest the article by Park et al. (1) on the associations of body weight changes with major cardiovascular events in patients with type 2 diabetes. Using data from the Korean National Health Insurance Service Database, the authors included subjects with type 2 diabetes (N = 1,522,241) who underwent health examinations twice in a 2-year interval between 2009 and 2012 and were followed until December 2018. Based on a two-stage design, the authors found that both weight loss and weight gain of >5% within a 2-year interval were associated with an increased risk of major cardiovascular events.
The authors discussed with surprise that severe weight loss was associated with increased risks of cardiovascular events and all-cause mortality. However, the results are not surprising after checking the clinical characteristics of participants in Table 1 of the article by Park et al. (1). Participants in the severe weight loss group had the highest prevalence of chronic obstructive pulmonary disease and cancer (nearly twice high as those in the stable weight group for cancer: 9.5% vs. 4.8%). Patients with type 2 diabetes with such comorbid diseases were more likely to experience unintentional weight loss and worse health outcomes (2). Although comorbidity status, including chronic obstructive pulmonary disease and cancer, has been statistically adjusted for in multivariable Cox models (yes vs. no), it may be insufficient to control for varying degrees of severity and duration. With such a large dataset, we believe that the authors were able to perform subgroup analyses by comorbidity status to reduce residual confounding. Moreover, sensitivity analyses by excluding participants with multiple morbidities may also help to examine the robustness of the findings.
Observational studies, even including a large number of subjects with a long-term follow-up period, cannot be the alternative for trials to settle the intentional effect of weight loss in patients with type 2 diabetes, because it is hard to distinguish between intentional and unintentional weight loss (3). The current findings indicate that care should be taken when severe body weight change is observed during routine visits, whereas actions should not be precluded from patients with type 2 diabetes who want to lose weight.
See accompanying article, p. e188.
Duality of Interest. No potential conflicts of interest relevant to this article were reported.