Glycogenosis Is Associated with Measures of Insulin Resistance in Adults with Non-Alcoholic Fatty Liver Disease (NAFLD)
David E Kleiner, Cynthia Behling, Cynthia D Guy, Michael Torbenson, Matthew M Yeh, Patricia Belt, Brent A Neuschwander-Tetri, Elizabeth M Brunt. National Cancer Institute, Bethesda, MD; Sharp Hospitals, San Diego, CA; Duke University, Durham, NC; Johns Hopkins School of Medicine, Baltimore, MD; University of Washington, Seattle, WA; Johns Hopkins School of Public Health, Baltimore, MD; St. Louis University, St. Louis, MO; Washington University, St. Louis, MO
Background: Hepatocyte glycogenosis is a change in which hepatocytes fill with glycogen and acquire a glassy, pale appearance on routine stains. Glycogenosis has been identified as a dominant change in some type 1 diabetics biopsied for elevated aminotransferase levels. In this clinical situation, glycogenosis is thought to result from poor diabetic control. We have observed it in NAFLD, but its clinical and histologic associations are unknown. We sought to identify demographic, biochemical and histologic associations with glycogenosis in adults with NAFLD.
Design: Liver biopsies were blindly reviewed by the central pathology committee of the Nonalcoholic Steatohepatitis Clinical Research Network and scored as having either no (0%), focal (involving <50% of hepatocytes) or diffuse (>50% of hepatocytes) glycogenosis. This data was analyzed for associations with other histological features, age, sex, diabetes status, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), fasting glucose, fasting insulin, and homeostatic model assessment-insulin resistance (HOMA-IR). Chi-square, Fisher's exact P, and Mann-Whitney U tests were used to determine significance as appropriate.
Results: Biopsies were available on 417 patients (mean age 50 years, 61.9% female). Glycogenosis was focal in 107 and diffuse in 78 biopsies. Glycogenosis was associated with female sex, less steatosis, more ballooning injury, megamitochondria and a lower NAFLD Activity Score (NAS), all p < 0.05. Diffuse glycogenosis was seen more often in biopsies with definite NASH or without evidence of NAFLD (steatosis < 5%). There was no association with age, the diagnosis of type 2 diabetes, ALT, AST, AP or fasting glucose. Patients with any degree of glycogenosis had higher fasting insulin levels (26.8 vs 23.2 µU/mL, p=0.006) and HOMA-IR (7.9 vs 6.7, p=0.008).
Conclusions: Although not associated with type 2 diabetes, elevated glucose or aminotransferase levels, glycogenosis in patients biopsied for NAFLD was associated with higher fasting insulin and HOMA-IR levels.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 234, Wednesday Morning