Obesity-Stroke Paradox Exists in Insulin-Resistant Patients But Not Insulin Sensitive Patients

Background and Purpose- The underlying mechanisms of stroke-obesity paradox are still not fully understood. This study aims to investigate the contribution of insulin resistance to the association between body mass index and stroke outcomes. Methods- Patients with ischemic stroke without history of diabetes mellitus in the Abnormal Glucose Regulation in Patients With Acute Stroke Across-China registry were included. Overweight or obese was defined as body mass index ≥23, and the median of homeostasis model assessment-insulin resistance index was chosen as cutoff to define insulin resistance. Cox or logistic regression model was used to assess the interaction between body mass index and homeostasis model assessment-insulin resistance on 1-year prognosis (all-cause mortality and poor functional outcome defined as modified Rankin Scale score 3-6). Results- Of 1227 study participants, the median homeostasis model assessment-insulin resistance was 1.9 (interquartile range, 1.1-3.1) and 863 (70.3%) patients were classified as overweight or obese. Among insulin-resistant patients, overweight/obese patients experienced one-half of the risk of death after stroke than their low/normal weight counterparts (9.42% versus 17.69%, unadjusted hazard ratio, 0.50; 95% CI, 0.31-0.82), while among insulin-sensitive ones, no significant difference of mortality risk was found (7.58% versus 6.91%, 1.07; 0.57-1.99). Similar trends were observed for poor functional outcome. Results were similar after adjustments for confounders. There were significant interactions between body mass index and homeostasis model assessment-insulin resistance on the risks of mortality (P=0.045) and poor functional outcome (P=0.049). Conclusions- We observed the obesity paradox for mortality and functional outcome in insulin-resistant patients but did not find the obesity paradox in insulin-sensitive patients. Insulin resistance may be one of the mechanisms underlying the obesity paradox of the outcome in patients with ischemic stroke.