Abstract P207: Nonalcoholic Fatty Liver Disease Interacts With Diabetes Increasing The Risk Of Atherosclerosis In The Family Heart Study
Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and type 2 diabetes (T2D), which are risk factors for atherosclerosis. However, it is not clear whether NAFLD has an independent contribution to atherosclerosis. The burden of calcification in the coronary artery (CAC) can be measured by computed tomography (CT) and is a measure of atherosclerosis. CT measured liver attenuation (in Hounsfield Units) is inversely related to the amount of fat in the liver (FL), while elevated alanine aminotransferse (ALT, in U/L) levels indicate hepatic damage and is often used as a marker of NAFLD. We investigated whether NAFLD, defined by FL and ALT levels, is a significant predictor of the presence of CAC independent of insulin resistance (HOMA-IR: fasting glucose* fasting insulin/22.5) and overall obesity (BMI, kg/m2) in 2,550 European-American individuals. We employed a linear mixed model to account for the non-independence of family members, and included age, age2, sex, current cigarette smoking (yes/no), alcohol intake (yes/no) and clinical center in each model. Heavy drinkers (men: ≥ 21 drinks/week, women: ≥ 14 drinks/week) and subjects who tested positive for hepatitis-C antibodies were excluded from the analyses. In the multivariate model including FL, ALT, BMI, HOMA-IR, and T2D, neither FL nor ALT was associated with CAC; while BMI (p< 0.0001), HOMA-IR (p= 0.0150) and T2D (p= 0.0008) were significant. Also, we employed a similar multivariate regression model separately in subjects without T2D (not taking hypoglycemic medications and/or fasting glucose <126 ml/dL) and with T2D (but excluding subject taking insulin medication). In subjects without T2D, we found that ALT (p=0.0385, OR=1.126, 95% CI:1.006–1.260) was a significant predictor of CAC together with BMI (p< 0.0001) and HOMA-IR (p= 0.0082). In subjects with T2D, ALT (p=0.0376, OR= 0.590, 95% CI:0.361–0.964) was a significant predictor of CAC but not FL, BMI or HOMA-IR which may reflect the effect of other T2D medication. Further, we investigated whether T2D interacts with ALT modifying the risk of CAC independent of BMI and HOMA-IR. In the combined T2D and non-T2D subsets, we included the interaction term (T2D*ALT) in the multivariate model and found significant association of CAC with T2D*ALT (p= 0.0018, OR= 0.555, 95% CI: 0.0384–0.802), ALT (p= 0.0315, OR= 1.134, 95% CI: 1.011–1.271), and T2D (p=0.0001), together with BMI (p<0.0001) and HOMA-IR (p= 0.0156). In summary, we found that: (i) the association of NAFLD steatosis (FL) with CAC is mediated by overall obesity (BMI) and insulin resistance (HOMA-IR); (ii) ALT, indicating hepatic damage, is a significant predictor of atherosclerosis independent of BMI and HOMA-IR; and (iii) having hepatic damage along with T2D augments the risk of atherosclerosis.
- © 2012 by American Heart Association, Inc.