Increased risk of cardiometabolic disease in normal-weight individuals with non-alcoholic fatty liver disease

Background: Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity, but there is increasing evidence that not all individuals who are overweight/obese also develop NAFLD. Currently, it is unclear whether normal-weight (Nw) individuals with NAFLD have a higher risk of cardiometabolic disease risk compared with individual sub-groups (Nw and Obesity [Ob]) of non-NAFLD. Aims: This study aimed to compare the cardiometabolic profiles, cardiovascular disease, and diabetes between Nw vs. Ob with non-NAFLD vs. NAFLD. Methods: This study utilized the Korea National Health and Nutrition Examination Surveys collected from 2019 to 2021. Individuals were stratified into Nw vs. Ob categories and further divided into non-NAFLD and NAFLD groups based on the hepatic steatosis index and liver fat score (N = 6615). Results: The prevalence of non-NAFLD Nw, non-NAFLD Ob, NAFLD Nw, and NAFLD Ob groups was 36%, 20%, 7%, and 37%, respectively. NAFLD Nw vs. non-NAFLD Ob manifests deteriorated cardiometabolic disease risk profiles and surrogate markers of insulin resistance despite having higher weight, waist circumference, and BMI. In addition, compared to non-NAFLD Nw, individuals with NAFLD Nw had a significantly higher risk of CVDs (738%, p <.001) and diabetes (408%, p <.001), with no difference between NAFLD Nw and NAFLD Ob groups. Conclusions: Cardiometabolic disease risk is more closely related to NAFLD developments than adiposity status. Therefore, not all overweight/obese individuals have a higher cardiometabolic disease risk, and NAFLD in Nw is an aggressive disease that is associated with cardiometabolic disease risk compared with Ob individuals without NAFLD.