title: Nonalcoholic Steatohepatitis (NASH) Is Associated with a Decline in Pancreatic Beta Cell (β-Cell) Function.
abstract: 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 β-cell function.
  
  
  OBJECTIVE
  To evaluate the pancreatic β-cell function in NAFLD using the homeostatic model assessment-β (HOMA-β) and β-cell index (BI).
  
  
  METHODS
  HOMA-β was measured in ninety-nine non-diabetic 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-β compared to both lean and obese controls (43.1 vs. 9 vs. 22.1 %, respectively, P < 0.05). HOMA-β was directly related to serum alkaline phosphate, total bilirubin, and weight and inversely related to age. There was no difference in HOMA-β between subjects with NAFL and NASH. Subjects with NASH had lower β-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-β was directly associated with fibrosis stage.
  
  
  CONCLUSIONS
  NASH is associated with strained pancreatic β-cell function in non-diabetic subjects. Future studies are necessary to evaluate the temporal relationship between β-cell function and hepatic histology.
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, MCV Box 980342, Richmond, VA, 23298-0342, USA, mssiddiqui@mcvh-vcu.edu.
authors.forename: Mohammad S
authors.initials: MS
authors.lastname: Siddiqui
authors.forename: Kai L
authors.initials: KL
authors.lastname: Cheang
authors.forename: Velimir A
authors.initials: VA
authors.lastname: Luketic
authors.forename: Sherry
authors.initials: S
authors.lastname: Boyett
authors.forename: Michael O
authors.initials: MO
authors.lastname: Idowu
authors.forename: Kavish
authors.initials: K
authors.lastname: Patidar
authors.forename: Puneet
authors.initials: P
authors.lastname: Puri
authors.forename: Scott
authors.initials: S
authors.lastname: Matherly
authors.forename: Richard T
authors.initials: RT
authors.lastname: Stravitz
authors.forename: Richard K
authors.initials: RK
authors.lastname: Sterling
authors.forename: Arun J
authors.initials: AJ
authors.lastname: Sanyal
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000503:physiopathology*