Nonalcoholic Steatohepatitis (NASH) Is Associated with a Decline in Pancreatic Beta Cell (β-Cell) Function

Background Nonalcoholic fatty liver disease (NAFLD) represents a histological spectrum ranging from benign hepatic steatosis (NAFL) to nonalcoholic steatohepatitis (NASH). NAFLD is closely associated with insulin resistance (IR), and although the role of IR in NAFLD has been an area of intense investigation, there are limited data on pancreatic beta-cell function. Aim To evaluate the pancreatic beta-cell function in NAFLD using the homeostatic model assessment-beta (HOMA-beta) and beta-cell index (BI). Methods HOMA-beta was measured in ninety-nine nondiabetic subjects with histologically confirmed NAFLD and compared to lean (age-and gender-matched) and obese (age-, gender-, and BMI-matched) controls. Using the values from an oral glucose tolerance test, BI was compared in 31 non-diabetic, non-cirrhotic subjects with NASH and gender- and BMI-matched controls. Results The subjects with NAFLD had higher HOMA-beta compared to both lean and obese controls (43.1 vs. 9 vs. 22.1 %, respectively, P < 0.05). HOMA-beta was directly related to serum alkaline phosphate, total bilirubin, and weight and inversely related to age. There was no difference in HOMA-beta between subjects with NAFL and NASH. Subjects with NASH had lower beta-cell function as measured by a lower BI (2.09 +/- 1.64 vs. 7.74 +/- 25.12; P = 0.04). In patients with NASH, BI was inversely associated with fibrosis independent of age, BMI, and serum ALT levels. In contrast, HOMA-beta was directly associated with fibrosis stage. Conclusion NASH is associated with strained pancreatic beta-cell function in non-diabetic subjects. Future studies are necessary to evaluate the temporal relationship between beta-cell function and hepatic histology.