title: Hepatic Steatosis and Insulin Resistance, But Not Steatohepatitis, Promote Atherogenic Dyslipidemia in NAFLD.
abstract: BACKGROUND
  Patients with nonalcoholic fatty liver disease (NAFLD) are at increased risk of cardiovascular disease, and atherogenic lipoproteins may play an important role.
  
  
  OBJECTIVE
  The objective of the study was to determine the contribution of the severity of steatohepatitis to atherogenic dyslipidemia in patients with NAFLD.
  
  
  METHODS
  This was a cross-sectional study.
  
  
  METHODS
  The study was conducted at a university hospital.
  
  
  METHODS
  Patients were recruited from outpatient clinics or from the general population (n = 188).
  
  
  METHODS
  Measurement of hepatic triglyceride content by magnetic resonance spectroscopy, histology (liver biopsy), metabolic profile by means of an oral glucose tolerance test, and lipoprotein analyses were performed.
  
  
  RESULTS
  Outcomes measured included standard lipids, lipoprotein subfraction analysis (apolipoprotein B/A1 levels, low-density lipoprotein (LDL) particle size/phenotype, and LDL/high-density lipoprotein subfractions), and insulin resistance.
  
  
  RESULTS
  Patients with NAFLD had severe insulin resistance, especially at the level of the adipose tissue, when compared with patients without NAFLD. Despite small differences in triglycerides and high-density lipoprotein-cholesterol, patients with NAFLD had a significantly higher plasma apolipoprotein B to apolipoprotein A1 ratio (0.66 ± 0.02 vs 0.58 ± 0.02, P = .01) and smaller LDL particle size (216.2 ± 0.7 vs 219.4 ± 1.1 Å, P = .01). Of note, these differences between patients with/without NAFLD were independent of the presence of obesity. Severity of steatohepatitis did not significantly influence the lipoprotein profile. Worse atherogenic dyslipidemia was best predicted by the degree of liver fat accumulation and adipose tissue and systemic insulin resistance.
  
  
  CONCLUSIONS
  NAFLD was associated with a worse atherogenic lipoprotein profile, regardless of similar body mass index and other clinical parameters. We speculate that this lipoprotein profile is driven mostly by liver fat content and insulin resistance and appears not to be worsened by obesity or the severity of liver disease (nonalcoholic steatohepatitis).
authors.affiliation: Divisions of Endocrinology, Diabetes, and Metabolism (F.B., P.P.S., D.B., R.L., K.C.), Gastroenterology, Hepatology, and Nutrition (A.S.), and Pathology (M.H.W.), and Pediatric Gastroenterology, Hepatology, and Nutrition (M.M.), University of Florida, Gainesville, Florida 32610; Malcom Randall Veterans Affairs Medical Center (F.B., P.P.S., D.B., R.L., A.S., M.H.W., K.C.), Gainesville, Florida 32608; Quest Diagnostics (J.J.S., A.M.B., M.J.M.), San Juan Capistrano, California 92675; Cholesterol, Genetic, and Heart Disease Institute (H.R.S.), San Mateo, California 94402; Division of Diabetes (B.O., K.C.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229.
authors.forename: Fernando
authors.initials: F
authors.lastname: Bril
authors.affiliation: Divisions of Endocrinology, Diabetes, and Metabolism (F.B., P.P.S., D.B., R.L., K.C.), Gastroenterology, Hepatology, and Nutrition (A.S.), and Pathology (M.H.W.), and Pediatric Gastroenterology, Hepatology, and Nutrition (M.M.), University of Florida, Gainesville, Florida 32610; Malcom Randall Veterans Affairs Medical Center (F.B., P.P.S., D.B., R.L., A.S., M.H.W., K.C.), Gainesville, Florida 32608; Quest Diagnostics (J.J.S., A.M.B., M.J.M.), San Juan Capistrano, California 92675; Cholesterol, Genetic, and Heart Disease Institute (H.R.S.), San Mateo, California 94402; Division of Diabetes (B.O., K.C.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229.
authors.forename: John J
authors.initials: JJ
authors.lastname: Sninsky
authors.affiliation: Divisions of Endocrinology, Diabetes, and Metabolism (F.B., P.P.S., D.B., R.L., K.C.), Gastroenterology, Hepatology, and Nutrition (A.S.), and Pathology (M.H.W.), and Pediatric Gastroenterology, Hepatology, and Nutrition (M.M.), University of Florida, Gainesville, Florida 32610; Malcom Randall Veterans Affairs Medical Center (F.B., P.P.S., D.B., R.L., A.S., M.H.W., K.C.), Gainesville, Florida 32608; Quest Diagnostics (J.J.S., A.M.B., M.J.M.), San Juan Capistrano, California 92675; Cholesterol, Genetic, and Heart Disease Institute (H.R.S.), San Mateo, California 94402; Division of Diabetes (B.O., K.C.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229.
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Baca
authors.affiliation: Divisions of Endocrinology, Diabetes, and Metabolism (F.B., P.P.S., D.B., R.L., K.C.), Gastroenterology, Hepatology, and Nutrition (A.S.), and Pathology (M.H.W.), and Pediatric Gastroenterology, Hepatology, and Nutrition (M.M.), University of Florida, Gainesville, Florida 32610; Malcom Randall Veterans Affairs Medical Center (F.B., P.P.S., D.B., R.L., A.S., M.H.W., K.C.), Gainesville, Florida 32608; Quest Diagnostics (J.J.S., A.M.B., M.J.M.), San Juan Capistrano, California 92675; Cholesterol, Genetic, and Heart Disease Institute (H.R.S.), San Mateo, California 94402; Division of Diabetes (B.O., K.C.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229.
authors.forename: H Robert
authors.initials: HR
authors.lastname: Superko
authors.affiliation: Divisions of Endocrinology, Diabetes, and Metabolism (F.B., P.P.S., D.B., R.L., K.C.), Gastroenterology, Hepatology, and Nutrition (A.S.), and Pathology (M.H.W.), and Pediatric Gastroenterology, Hepatology, and Nutrition (M.M.), University of Florida, Gainesville, Florida 32610; Malcom Randall Veterans Affairs Medical Center (F.B., P.P.S., D.B., R.L., A.S., M.H.W., K.C.), Gainesville, Florida 32608; Quest Diagnostics (J.J.S., A.M.B., M.J.M.), San Juan Capistrano, California 92675; Cholesterol, Genetic, and Heart Disease Institute (H.R.S.), San Mateo, California 94402; Division of Diabetes (B.O., K.C.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229.
authors.forename: Paola
authors.initials: P
authors.lastname: Portillo Sanchez
authors.affiliation: Divisions of Endocrinology, Diabetes, and Metabolism (F.B., P.P.S., D.B., R.L., K.C.), Gastroenterology, Hepatology, and Nutrition (A.S.), and Pathology (M.H.W.), and Pediatric Gastroenterology, Hepatology, and Nutrition (M.M.), University of Florida, Gainesville, Florida 32610; Malcom Randall Veterans Affairs Medical Center (F.B., P.P.S., D.B., R.L., A.S., M.H.W., K.C.), Gainesville, Florida 32608; Quest Diagnostics (J.J.S., A.M.B., M.J.M.), San Juan Capistrano, California 92675; Cholesterol, Genetic, and Heart Disease Institute (H.R.S.), San Mateo, California 94402; Division of Diabetes (B.O., K.C.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229.
authors.forename: Diane
authors.initials: D
authors.lastname: Biernacki
authors.affiliation: Divisions of Endocrinology, Diabetes, and Metabolism (F.B., P.P.S., D.B., R.L., K.C.), Gastroenterology, Hepatology, and Nutrition (A.S.), and Pathology (M.H.W.), and Pediatric Gastroenterology, Hepatology, and Nutrition (M.M.), University of Florida, Gainesville, Florida 32610; Malcom Randall Veterans Affairs Medical Center (F.B., P.P.S., D.B., R.L., A.S., M.H.W., K.C.), Gainesville, Florida 32608; Quest Diagnostics (J.J.S., A.M.B., M.J.M.), San Juan Capistrano, California 92675; Cholesterol, Genetic, and Heart Disease Institute (H.R.S.), San Mateo, California 94402; Division of Diabetes (B.O., K.C.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229.
authors.forename: Maryann
authors.initials: M
authors.lastname: Maximos
authors.affiliation: Divisions of Endocrinology, Diabetes, and Metabolism (F.B., P.P.S., D.B., R.L., K.C.), Gastroenterology, Hepatology, and Nutrition (A.S.), and Pathology (M.H.W.), and Pediatric Gastroenterology, Hepatology, and Nutrition (M.M.), University of Florida, Gainesville, Florida 32610; Malcom Randall Veterans Affairs Medical Center (F.B., P.P.S., D.B., R.L., A.S., M.H.W., K.C.), Gainesville, Florida 32608; Quest Diagnostics (J.J.S., A.M.B., M.J.M.), San Juan Capistrano, California 92675; Cholesterol, Genetic, and Heart Disease Institute (H.R.S.), San Mateo, California 94402; Division of Diabetes (B.O., K.C.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229.
authors.forename: Romina
authors.initials: R
authors.lastname: Lomonaco
authors.affiliation: Divisions of Endocrinology, Diabetes, and Metabolism (F.B., P.P.S., D.B., R.L., K.C.), Gastroenterology, Hepatology, and Nutrition (A.S.), and Pathology (M.H.W.), and Pediatric Gastroenterology, Hepatology, and Nutrition (M.M.), University of Florida, Gainesville, Florida 32610; Malcom Randall Veterans Affairs Medical Center (F.B., P.P.S., D.B., R.L., A.S., M.H.W., K.C.), Gainesville, Florida 32608; Quest Diagnostics (J.J.S., A.M.B., M.J.M.), San Juan Capistrano, California 92675; Cholesterol, Genetic, and Heart Disease Institute (H.R.S.), San Mateo, California 94402; Division of Diabetes (B.O., K.C.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229.
authors.forename: Beverly
authors.initials: B
authors.lastname: Orsak
authors.affiliation: Divisions of Endocrinology, Diabetes, and Metabolism (F.B., P.P.S., D.B., R.L., K.C.), Gastroenterology, Hepatology, and Nutrition (A.S.), and Pathology (M.H.W.), and Pediatric Gastroenterology, Hepatology, and Nutrition (M.M.), University of Florida, Gainesville, Florida 32610; Malcom Randall Veterans Affairs Medical Center (F.B., P.P.S., D.B., R.L., A.S., M.H.W., K.C.), Gainesville, Florida 32608; Quest Diagnostics (J.J.S., A.M.B., M.J.M.), San Juan Capistrano, California 92675; Cholesterol, Genetic, and Heart Disease Institute (H.R.S.), San Mateo, California 94402; Division of Diabetes (B.O., K.C.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229.
authors.forename: Amitabh
authors.initials: A
authors.lastname: Suman
authors.affiliation: Divisions of Endocrinology, Diabetes, and Metabolism (F.B., P.P.S., D.B., R.L., K.C.), Gastroenterology, Hepatology, and Nutrition (A.S.), and Pathology (M.H.W.), and Pediatric Gastroenterology, Hepatology, and Nutrition (M.M.), University of Florida, Gainesville, Florida 32610; Malcom Randall Veterans Affairs Medical Center (F.B., P.P.S., D.B., R.L., A.S., M.H.W., K.C.), Gainesville, Florida 32608; Quest Diagnostics (J.J.S., A.M.B., M.J.M.), San Juan Capistrano, California 92675; Cholesterol, Genetic, and Heart Disease Institute (H.R.S.), San Mateo, California 94402; Division of Diabetes (B.O., K.C.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229.
authors.forename: Michelle H
authors.initials: MH
authors.lastname: Weber
authors.affiliation: Divisions of Endocrinology, Diabetes, and Metabolism (F.B., P.P.S., D.B., R.L., K.C.), Gastroenterology, Hepatology, and Nutrition (A.S.), and Pathology (M.H.W.), and Pediatric Gastroenterology, Hepatology, and Nutrition (M.M.), University of Florida, Gainesville, Florida 32610; Malcom Randall Veterans Affairs Medical Center (F.B., P.P.S., D.B., R.L., A.S., M.H.W., K.C.), Gainesville, Florida 32608; Quest Diagnostics (J.J.S., A.M.B., M.J.M.), San Juan Capistrano, California 92675; Cholesterol, Genetic, and Heart Disease Institute (H.R.S.), San Mateo, California 94402; Division of Diabetes (B.O., K.C.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McPhaul
authors.affiliation: Divisions of Endocrinology, Diabetes, and Metabolism (F.B., P.P.S., D.B., R.L., K.C.), Gastroenterology, Hepatology, and Nutrition (A.S.), and Pathology (M.H.W.), and Pediatric Gastroenterology, Hepatology, and Nutrition (M.M.), University of Florida, Gainesville, Florida 32610; Malcom Randall Veterans Affairs Medical Center (F.B., P.P.S., D.B., R.L., A.S., M.H.W., K.C.), Gainesville, Florida 32608; Quest Diagnostics (J.J.S., A.M.B., M.J.M.), San Juan Capistrano, California 92675; Cholesterol, Genetic, and Heart Disease Institute (H.R.S.), San Mateo, California 94402; Division of Diabetes (B.O., K.C.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Cusi
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000368:Aged; D019412:Anatomy, Cross-Sectional; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D001706:Biopsy; D050171:Dyslipidemias / Q000097:blood* / Q000209:etiology* / Q000473:pathology; D005234:Fatty Liver / Q000097:blood* / Q000150:complications* / Q000473:pathology; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D008077:Lipoproteins, LDL / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000150:complications* / Q000473:pathology; D009765:Obesity / Q000097:blood / Q000150:complications; D014280:Triglycerides / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D008077:Lipoproteins, LDL; D014280:Triglycerides