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Low Ghrelin Concentrations in Nonalcoholic Fatty Liver Disease Are Related to Insulin Resistance

Unit of Metabolic Diseases (G.M., R.M., N.M.), Endocrinology Unit (U.P., R.P.), Department of Internal Medicine and Gastroenterology, and Center for Applied Biomedical Research (U.P., R.D.I., R.P.), Alma Mater Studiorum, University of Bologna, I-40138 Bologna, Italy; and Gastroenterology Department (E.B., E.V., M.R.), University of Turin, Ospedale San Giovanni Battista, I-10126 Turin, Italy

Address all correspondence and requests for reprints to: Giulio Marchesini, M.D., Unit of Metabolic Disease, University of Bologna, Department of Internal Medicine and Gastroenterology, Via Massarenti, 9, I-40138 Bologna, Italy. E-mail: giulio.marchesini{at}unibo.it.

Several physiological and pathophysiological conditions, including changes in body fat, food intake, and insulin resistance, are known to be associated with variations in plasma ghrelin concentrations. We tested the hypothesis that insulin resistance exerts a primary role by measuring ghrelin in 86 patients with nonalcoholic fatty liver disease (NAFLD), a condition in which insulin resistance is relatively independent of obesity. Compared with 40 matched healthy subjects, patients with NAFLD had similar glucose levels and higher plasma insulin and insulin resistance [homeostasis model assessment (HOMA)-R index] by over 60%. Ghrelin was reduced (mean ± SD, 226 ± 72 pmol/liter in NAFLD vs. 303 ± 123 in controls; P < 0.0001). In relation to quartiles of body mass index, ghrelin progressively decreased in controls (P = 0.003), but not in patients (P = 0.926). In relation to quartiles of HOMA-R, ghrelin decreased in both groups, and significantly correlated with HOMA-R. After adjustment for age and sex, HOMA-R was the sole factor significantly associated with low ghrelin in the whole group (odds ratio, 5.79; 95% confidence interval, 2.62–12.81; P < 0.0001) and specifically in NAFLD (2.96; 1.12–7.79; P = 0.028). The study suggests that insulin resistance is a major factor controlling ghrelin levels in subjects with and without NAFLD.

This work was supported by a grant from Fondazione Cassa di Risparmio (Bologna, Italy) and by research grants from University of Bologna (Fondi Ricerca Istituzionale, 2002, COFIN).

Abbreviations: ALT, Alanine transaminase; BMI, body mass index; HDL, high-density lipoprotein; HOMA, homeostasis model assessment; ISI, insulin sensitivity index; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; OGTT, oral glucose tolerance test; OR, odds ratio; SI, sensitivity index; WHR, waist-to-hip ratio.

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