title: Circulating fibroblast growth factor-21 is elevated in impaired glucose tolerance and type 2 diabetes and correlates with muscle and hepatic insulin resistance.
abstract: OBJECTIVE Fibroblast growth factor (FGF)-21 is highly expressed in the liver and regulates hepatic glucose production and lipid metabolism in rodents. However, its role in the pathogenesis of type 2 diabetes in humans remains to be defined. The aim of this study was to quantitate circulating plasma FGF-21 levels and examine their relationship with insulin sensitivity in subjects with varying degrees of obesity and glucose tolerance. RESEARCH DESIGN AND METHODS Forty-one subjects (8 lean with normal glucose tolerance [NGT], 9 obese with NGT, 12 with impaired fasting glucose [IFG]/impaired glucose tolerance [IGT], and 12 type 2 diabetic subjects) received an oral glucose tolerance test (OGTT) and a hyperinsulinemic-euglycemic clamp (80 mU/m(2) per min) combined with 3-[(3)H] glucose infusion. RESULTS Subjects with type 2 diabetes, subjects with IGT, and obese subjects with NGT were insulin resistant compared with lean subjects with NGT. Plasma FGF-21 levels progressively increased from 3.9 +/- 0.3 ng/ml in lean subjects with NGT to 4.9 +/- 0.2 in obese subjects with NGT to 5.2 +/- 0.2 in subjects with IGT and to 5.3 +/- 0.2 in type 2 diabetic subjects. FGF-21 levels correlated inversely with whole-body (primarily reflects muscle) insulin sensitivity (r = -0.421, P = 0.007) and directly with the hepatic insulin resistance index (r = 0.344, P = 0.034). FGF-21 levels also correlated with measures of glycemia (fasting plasma glucose [r = 0.312, P = 0.05], 2-h plasma glucose [r = 0.414, P = 0.01], and A1C [r = 0.325, P = 0.04]). CONCLUSIONS Plasma FGF-21 levels are increased in insulin-resistant states and correlate with hepatic and whole-body (muscle) insulin resistance. FGF-21 may play a role in pathogenesis of hepatic and whole-body insulin resistance in type 2 diabetes.
authors.affiliation: Division of Diabetes, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Alberto O
authors.initials: AO
authors.lastname: Chavez
authors.forename: Marjorie
authors.initials: M
authors.lastname: Molina-Carrion
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Abdul-Ghani
authors.forename: Franco
authors.initials: F
authors.lastname: Folli
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Defronzo
authors.forename: Devjit
authors.initials: D
authors.lastname: Tripathy
mesh_terms: D000328:Adult; D001794:Blood Pressure; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D005346:Fibroblast Growth Factors / Q000097:blood*; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000097:blood* / Q000503:physiopathology; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000503:physiopathology*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009765:Obesity / Q000097:blood / Q000503:physiopathology; D012016:Reference Values
chemical_list: C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors