IMPAIRED GLUCOSE TOLERANCE IN PATIENTS WITH NON ALCOHOLIC FATTY LIVER DISEASE - A PRELIMINARY ANALYSIS

Krikor Kichian, Alice Gerhardt, Klaus Gutfreund, Larry Jewell,Mang Ma, Leanne Mulesa, Winnie W Wong, Vincent G Bain

BACKGROUND: Recent investigations have demonstrated a clear association between insulin resistance and the development of non alcoholic fatty liver disease (NAFLD). Only a minority of patients with NAFLD develop progressive fibrosis and cirrhosis, but at present there is no way of identifying these patients early in their course. We are conducting a prospective study to determine predictors of disease severity in NAFLD and report here our preliminary data on insulin resistance.
METHODS: Eight patients presenting with persistently elevated levels of alanine transaminase (ALT) and with negative blood work for other liver diseases including viral hepatitis were included in the study. After verifying a history of minimal or no alcohol intake and obtaining informed consent all patients underwent a liver biopsy to confirm the diagnosis of NAFLD and to assess the degree of steatohepatitis. Subjects then had a two-hour oral glucose tolerance test (75 mg of glucose), and glucose, insulin, and C peptide levels were measured at 30, 60, 90 and 120 minutes. Insulin resistance was estimated by the homeostatic model assessment (HOMA).
RESULTS: The median age of the 8 patients was 47.7 (30-67 yr) with 4 females and 4 males. The median level of ALT was 68.2 (47-90) and all patients had a body mass index (BMI) above 28 with a median BMI of 35.6. Five patients had impaired glucose tolerance (IGT defined as fasting glucose of less then 6.9 mmol/L with a two hour plasma glucose between 7.6 and 11 mmol/L). Two patients had normal glucose tolerance (NGT) and 1 had diabetes. Two of five patients with IGT had steatohepatitis while the other three had only steatosis on biopsy. NGT was seen in one patient with steatohepatitits and one with only steatosis. The patient with diabetes had a biopsy significant for bridging fibrosis. The average insulin resistance index (4.19 ± 1.54 vs 4.4 ± 2.38) as well as the fasting insulin levels (18.2 ± 5.6 vs 18.7 ± 10.7) was elevated to the same degree in patients with steatohepatitis and those with only steatosis.
CONCLUSION: These preliminary results demonstrate that IGT and insulin resistance is prevalent in patients with NAFLD, however we have not demonstrated their use as markers of disease severity.