title: Fatty liver is associated with insulin resistance, risk of coronary heart disease, and early atherosclerosis in a large European population.
abstract: Patients with fatty liver (FL) disease have a high risk of developing diabetes and cardiovascular diseases. The aim was to evaluate the association between FL, insulin resistance (IR), coronary heart disease (CHD) risk, and early atherosclerosis in a large European population (RISC Study). In 1,307 nondiabetic subjects (age 30-60 years) recruited at 19 centers, we evaluated liver enzymes, lipids, insulin sensitivity (by euglycemic-hyperinsulinemic clamp), glucose tolerance (by 75 g oral glucose tolerance test), carotid atherosclerosis as intima media thickness (IMT), CHD risk by the Framingham Heart study prediction score, and physical activity (by accelerometer). The presence of FL was estimated using the fatty liver index (FLI; >60, likelihood >78% presence FL; FLI <20 likelihood >91% absence of FL). Subjects were divided into three groups: G1: FLI <20 (n = 608); G3: FLI >60 (n = 234), G2: intermediate group (n = 465). Compared to G1, G3 included more men (70% versus 24%) and people with impaired glucose tolerance (23% versus 5%). IMT increased with FLI (G3 = 0.64 +/- 0.08 versus G1 = 0.58 +/- 0.08 mm, P < 0.0001). FLI was associated with increased CHD risk (r = 0.48), low-density lipoprotein cholesterol (r = 0.33), alanine aminotransferase (r = 0.48), aspartate aminotransferase (r = 0.25), systolic blood pressure (r = 0.39) and IMT (r = 0.30), and reduced insulin sensitivity (r = -0.43), high-density lipoprotein cholesterol (r = -0.50), adiponectin (r = -0.42), and physical activity (r = -0.16, all P < 0.0001). The correlations hold also in multivariate analysis after adjusting for age, gender, and recruiting center.
  
  
  CONCLUSIONS
  In middle-age nondiabetic subjects, increased IMT, CHD risk, and reduced insulin sensitivity are associated with high values of FLI.
authors.affiliation: Fondazione Toscana G. Monasterio and Institute of Clinical Physiology, Consiglio Nazionale delle Ricerche (CNR) Pisa, Pisa, Italy. amalia@ifc.cnr.it
authors.forename: Amalia
authors.initials: A
authors.lastname: Gastaldelli
authors.forename: Michaela
authors.initials: M
authors.lastname: Kozakova
authors.forename: Kurt
authors.initials: K
authors.lastname: Højlund
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: Angela
authors.initials: A
authors.lastname: Favuzzi
authors.forename: Asimina
authors.initials: A
authors.lastname: Mitrakou
authors.forename: Beverley
authors.initials: B
authors.lastname: Balkau
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000453:epidemiology*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging; D003327:Coronary Disease / Q000453:epidemiology*; D005060:Europe / Q000453:epidemiology; D005234:Fatty Liver / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D014463:Ultrasonography