The Association of Liver Fat with Inflammatory Markers in the Veterans Affairs Diabetes Trial (VADT)
Abstract Number: 1009-P
Authors: ARAMESH SAREMI, MATTHEW ALLISON, DOMINIC DITOMASSO, PING LUO, ROBERT ANDERSON, CARLOS ABRAIRA, WILLIAM DUCKWORTH, PETER D. REAVEN, Phoenix, AZ, La Jolla, CA, Hines, IL, Miami, FL
Institutions: Hines, IL; La Jolla, CA; Miami, FL; Phoenix, AZ
Results: Obesity is strongly related to the development of insulin resistance and type 2 diabetes (T2DM). It is increasingly recognized that tissue and systemic inflammation may be an important causal link between obesity and T2DM. The specific tissue location of fat and its' relevant metabolites may be particularly important as accumulation of fat in non-adipose tissue locations (i.e. “ectopic fat”), and in the liver particularly, may be uniquely proinflammatory. Computed tomography (CT) can be used to measure liver fat accumulation by comparing liver to spleen CT attenuation values (the L/S ratio). The lower the L/S ratio the greater the relative fat content with a L/S < 1 being consistent with hepatosteatosis. The aim of this study was to determine whether liver fat was associated with two inflammatory markers (CRP and adiponectin) that have been linked to the development of insulin resistance and T2DM. A total of 281 subjects (94% male) participating in the VADT, aged 40 years or older with a mean diabetes duration of 12.2 ± 8 years and HbA1c of 9.2 ± 1.3% at baseline were included. Subjects with more liver fat (L/S < 1) were significantly younger, had diabetes for fewer years, but had lower HDL cholesterol and higher triglycerides levels. There were no significant differences between groups (L/S <1 vs. L/S ≥1) in BMI, waist circumference (WC), gender, ethnicity, Hba1C levels, alcohol or medication use. Across decreasing tertiles of L/S ratio, there was a significant (p < 0.02) stepwise increase in plasma CRP and a decrease in adiponectin. In multivariate linear regression models, the L/S ratio remained significantly associated with CRP and adiponectin levels, even after adjustment for age, BMI or WC, ethnicity, duration of diabetes, lipid levels, HbA1C, and other clinical characteristics. Conclusion: In individuals with T2DM, liver fat accumulation is significantly associated with CRP and adiponectin independent of other measures of body fat or traditional risk factors. These data are consistent with the hypothesis that accumulation of ectopic fat in the liver may be an important contributor to systemic inflammation and insulin resistance.