RESUMEN
CONTEXT: Insulin is pivotal in regulating hepatic lipid synthesis, metabolism, and export. OBJECTIVE: We tested the hypothesis that intrahepatic insulin exposure is an important determinant of intrahepatocellular lipid (IHCL), taking into account regional adiposity and both glucoregulatory and antilipolytic insulin sensitivity. RESEARCH DESIGN AND METHODS: We compared 21 European males with known nonalcoholic fatty liver disease (NAFLD) with 19 healthy male controls. Insulin sensitivity, secretion, and percentage hepatic extraction were derived from iv glucose tolerance test (IVGTT) glucose, insulin, and C-peptide concentrations. Intrahepatic insulin exposure was calculated as percentage hepatic insulin extraction multiplied by basal or IVGTT insulin secretion. IHCL was quantified by proton magnetic resonance spectroscopy. Total and regional adipose tissue was measured using whole body magnetic resonance imaging. RESULTS: Percentage hepatic extraction of newly secreted insulin differed between cases with NAFLD and controls at borderline significance (median, 76 vs. 83%; P = 0.07). Cases had higher intrahepatic insulin exposure than controls, both in the basal (34 vs. 18 pmol; P = 0.0002) and glucose-stimulated states (58 vs. 24 pmol; P = 0.01). IHCL was significantly related to both basal (r(s) = 0.62; P < 0.0001) and IVGTT intrahepatic insulin exposure (r(s) = 0.47; P = 0.002). As predictors of IHCL, both basal and IVGTT intrahepatic insulin exposure were dependent on the waist-to-hip ratio and homeostasis model assessment insulin resistance, but not on magnetic resonance imaging fat measures or IVGTT insulin sensitivity. CONCLUSIONS: Men with NAFLD have higher intrahepatic insulin exposure than controls. This correlates with IHCL, but the principal determinants of IHCL were fat distribution and hepatic rather than peripheral insulin resistance.
Asunto(s)
Tejido Adiposo/fisiología , Hígado Graso/metabolismo , Insulina/metabolismo , Metabolismo de los Lípidos/fisiología , Hígado/metabolismo , Adulto , Anciano , Glucemia/metabolismo , Péptido C/sangre , Estudios de Cohortes , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/sangre , Resistencia a la Insulina/fisiología , Secreción de Insulina , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico , Adulto JovenRESUMEN
AIM: The increasing prevalence of fatty liver disease requires routine assessment methods. Proton magnetic resonance spectroscopy ((1)H MRS) is increasingly used for steatosis measurement, but due to cost, is unlikely to become a widely-used screening tool. Ultrasound is cheaper and more widely available, although subject to observer variability. Our aim was to determine the sensitivity and specificity of ultrasound against (1)H MRS, using MRS as a gold standard, for the detection and quantification of hepatic fat content. METHODS: Fifty adults participated (43 men, seven women) in this study. Hepatic steatosis was assessed by ultrasound and (1)H MRS. Images were graded by two independent radiologists to classify severity and distribution of liver fat. RESULTS: Ultrasound detected liver fat infiltration in 82% of cases measurable by (1)H MRS, while liver fat was detectable in 44% of cases graded absent by ultrasound. Ultrasound grading was subjective, with the radiologists in agreement in 53% of cases (kappa = 0.39, P = 0.002). Considerable overlap in intrahepatocellular lipid content was observed between different grades: absent (0.0-1.58%), mild (2.2-16.2%), moderate (4.9-26.7%) and severe (8.1-76.8%) steatosis. Ultrasound could not detect liver fat levels below 2% as measured by (1)H MRS Conclusion: Ultrasound is less sensitive than (1)H MRS in detecting very low levels of liver fat content, but is sensitive to fatty infiltration greater than 2%. There is a tendency of higher ultrasound grades to correlate with higher degrees of fatty infiltration, although some overlap exists. Our findings are still consistent with ultrasound being useful as a low cost screening tool.