Measurement of liver fat by MRI and its reduction by dexfenfluramine in NIDDM

Abstract

OBJECTIVE: To validate a variation of a well-established magnetic resonance imaging (MRI) technique to detect liver fat and use it to monitor liver fat changes after treatment with dexfenfluramine in men with non-insulin dependent diabetes mellitus (NIDDM). DESIGN: (a) Simple correlation study of MRI Liver Fat Index with liver biopsy results; (b) Open Study of 10 men with NIDDM treated with dexfenfluramine for 12 weeks in addition to their ‘usual’ therapy. SUBJECTS: (a) 19 patients (3F; 16M) with abnormal liver function tests undergoing liver biopsy; (b) 10 men, Body Mass Index (BMI) <30, Waist to hip ratio (WHR) >0.90 with poorly controlled NIDDM despite oral sulphonylurea therapy. MEASUREMENTS: (a) MRI liver fat; standard liver biopsy; (b) MRI visceral fat, MRI liver fat, euglycaemic clamp, plasma lipids, fasting glucose and c-peptide levels. RESULTS: In the validation group, there was a strong relationship between the MRI Liver Fat Index and histopathological assessment of the liver biopsies (r=0.87, <0.0001). During treatment with dexfenfluramine the mean Liver Fat Index reduced from 10.6±3.4 to 6.6±2.8 (P=0.05). The reduction in Liver Fat Index correlated with the reduction in visceral fat (r=0.84, P=0.001) as well as with the improvement in insulin sensitivity (r=0.62, P=0.05). Using partial correlation analysis, the relationship between the change in visceral adipose tissue and the improvement in insulin sensitivity was weaker if the Liver Fat Index was kept constant (r=0.76 decreased to r=0.56). CONCLUSIONS: In this group of subjects MRI Liver Fat Index correlated well with liver fat as seen on biopsy. The Liver Fat Index reduced after 12 weeks therapy with dexfenfluramine suggesting a role for hepatic steatosis in the complex interaction between visceral adipose tissue and insulin sensitivity.