We read with great interest the article by Gastaldelli et al.1 Their analyses were based on the RISC (relationship between insulin sensitivity and cardiovascular disease risk) Study, an ongoing prospective project aiming to evaluate the possible relation between insulin resistance (IR) and cardiovascular risk in a clinically healthy European Caucasian population, free of diabetes, hypertension, and cardiovascular diseases. The authors also evaluated the associations among fatty liver, IR, carotid intima media thickness (IMT), and risk of coronary heart disease. Although their results provided additional data to this area of active investigation, several issues deserve further discussion.
First, FLI (Fatty Liver Index), an algorithm on the basis of body mass index, waist circumference, triglycerides, and gamma-glutamyl transferase, was used to identify fatty liver.2 However, this index was constructed to predict ultrasonographic fatty liver after excluding subjects with hepatitis B virus or hepatitis C virus infection and limited by the inherent flaws of ultrasound, such as operator dependent interpretation, reduced sensitivity in the morbidly obese, and inability to precisely quantify hepatic fat content and detect small amounts of fatty infiltration.3 The index is conceptually insulin-related; however, insulin level is not included in the index because it is not routinely measured.2 Therefore, the use of FLI in their analyses cannot avoid the confounding error of insulin resistance. Taken together, their findings may only indicate a significant association between carotid IMT, risks of coronary heart disease, and insulin resistance but not fatty liver. To show an association with fatty liver, the authors should conduct a subgroup analysis with patients who are free of insulin resistance.
Second, alanine aminotransferase (ALT) elevation is an independent predictor of nonalcoholic steatohepatitis,4 and ALT level is also independently associated with insulin resistance.5 Our recent data further showed that ALT level is proportionally associated with the risk of carotid IMT in subjects with fatty liver.6 Although the authors already identified a difference in ALT levels among the three groups, further subgroup analyses to evaluate the effects of ALT level on these associations would be more informative.