Background Endothelial vascular function, an independent risk factor for cardiovascular disease, is impaired by insulin resistance. Nonalcoholic steatohepatitis (NASH) is associated with insulin resistance. However, the effect of NASH on endothelial function, either direct or via insulin resistance, is unknown.
Hypothesis NASH impairs endothelial function either directly or as a consequence of insulin resistance (IR). To test this hypothesis, we assessed endothelial function as well as insulin sensitivity in subjects with biopsy-proven NASH and BMI-matched controls.
Materials and Methods We studied four biopsy-proven NASH and four control subjects matched for age, gender, and BMI. We assessed lipid parameters by standard procedures and insulin sensitivity using the euglycemic hyperinsulinemic clamp technique. We determined endothelial vascular function by measuring changes in leg blood flow (LBF) in response to graded intrafemoral arterial infusion of the endothelium dependent vasodilator methacholine (MCh). Results are expressed as mean ± SEM in NASH vs controls and compared using an unpaired t-test.
Results Total cholesterol was 224 ± 36 vs 177 ± 42 mg/dL NASH and controls, respectively (p = .05). LDL cholesterol was 151 ± 30 and 103 ± 29 mg/dL NASH and controls, respectively (p = .05). Triglyceride and HDL cholesterol levels did not differ between groups. Glucose disposal rates (insulin sensitivity) were 3.9 ± 1.3 and 6.2 ± 1.9 mg/kg/min NASH and controls, respectively (p = ns). Maximal increments in LBF in response to intra-arterial Mch, expressed as a percentage of baseline, were 34 ± 17 vs 193 ± 58% in NASH and controls, respectively (p = .05).
Conclusions NASH is associated with endothelial dysfunction over and above that associated with the obesity of NASH. Whether the endothelial dysfunction is attributable to the elevated LDL cholesterol levels, the differences in insulin sensitivity, or the intrinsic process of NASH itself requires further work and investigation.
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