Liver fat, statin use, and incident diabetes: The Multi-Ethnic Study of Atherosclerosis

Background and aims: To balance competing cardiovascular benefits and metabolic risks of statins, markers of type 2 diabetes (T2D) susceptibility are needed. We sought to define a competing risk/benefit of statin therapy on T2D and cardiovascular disease (CVD) events using liver attenuation and coronary artery calcification (CAC). Methods and results: 3153 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA) without CVD, T2D/impaired fasting glucose, or baseline statin therapy had CT imaging for CAC and hepatic attenuation (hepatic steatosis). Cox models and rates of CVD and T2D were calculated to assess the role of liver attenuation in T2D and the relative risks/benefits of statins on CVD and T2D. 216 T2D cases were diagnosed at median 9.1 years follow-up. High liver fat and statin therapy were associated with diabetes (HR 2.06 [95%CI 1.52-2.79, P < 0.0001] and 2.01 [95%CI 1.46-2.77, P < 0.0001], respectively), after multivariable adjustment. With low liver fat and CAC = 0, the number needed to treat (NNT) for statin to prevent one CVD event (NNT 218) was higher than the number needed to harm (NNH) with an incident case of T2D (NNH 68). Conversely, those with CAC >100 and low liver fat were more likely to benefit from statins for CVD reduction (NNT 29) relative to T2D risk (NNH 67). Among those with CAC >100 and fatty liver, incremental reduction in CVD with statins (NNT 40) was less than incremental risk increase for T2D (NNH 24). Conclusions: Liver fat is associated with incident T2D and stratifies competing metabolic/CVD risks with statin therapy. Hepatic fat may inform T2D surveillance and lipid therapeutic strategies.