title: Insulin acutely increases fibrinogen production in individuals with type 2 diabetes but not in individuals without diabetes.
abstract: Fibrinogen is an acute-phase reactant and an independent cardiovascular risk factor. Insulin without amino acid replacement acutely suppressed fibrinogen production in nondiabetic and type 1 diabetic individuals. Fibrinogen production and plasma concentration increase in insulin-resistant type 2 diabetes. It is not known whether altered response to insulin contributes to hyperfibrinogenemia in type 2 diabetes. Fibrinogen fractional (FSR) and absolute (ASR) synthesis rates were measured using a leucine isotopic model in type 2 diabetic men (n = 7; age = 51 +/- 3 years; BMI = 26.7 +/- 1 kg/m(2)) compared with matched nondiabetic subjects under basal conditions and following a 4-h euglycemic-, euaminoacidemic-hyperinsulinemic clamp. Basal fibrinogen concentration (+35%, P < 0.05) and ASR (+35%, P < 0.05) were greater in the diabetic subjects. Following clamp, fibrinogen FSR and ASR were unchanged in the control subjects. In contrast, fibrinogen FSR and ASR increased by 41 and 43%, respectively (P < 0.05), in the diabetic subjects. Thus, fibrinogen production is acutely increased by insulin when euglycemia and euaminoacidemia are maintained in type 2 diabetic individuals but not in nondiabetic individuals. Enhanced fibrinogen production by insulin is likely to be a key alteration contributing to hyperfibrinogenemia and therefore cardiovascular risk in type 2 diabetes. Unchanged fibrinogen production in nondiabetic individuals suggests a role of plasma amino acids in regulating fibrinogen production in humans.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Padova, Padua, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Barazzoni
authors.forename: Edward
authors.initials: E
authors.lastname: Kiwanuka
authors.forename: Michela
authors.initials: M
authors.lastname: Zanetti
authors.forename: Michela
authors.initials: M
authors.lastname: Cristini
authors.forename: Monica
authors.initials: M
authors.lastname: Vettore
authors.forename: Paolo
authors.initials: P
authors.lastname: Tessari
mesh_terms: D000596:Amino Acids / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005340:Fibrinogen / Q000096:biosynthesis*; D005934:Glucagon / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D014280:Triglycerides / Q000097:blood
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D007328:Insulin; D014280:Triglycerides; D005340:Fibrinogen; D005934:Glucagon