Fibrinogen kinetics and protein turnover in obese non-diabetic males: effects of insulin.
BACKGROUND
Although hyperfibrinogenemia and insulin resistance are common in obesity and diabetes mellitus, the impact of obesity per se on fibrinogen turnover and the insulin effects on fibrinogen and protein kinetics is unknown.


METHODS
We measured fibrinogen and albumin fractional (FSR) and absolute (ASR) synthesis rates, as well as protein turnover, in non-diabetic, obese and in control male subjects both before and following an euglycemic, euaminoacidemic, hyperinsulinemic clamp, using L-[(2)H(3)]-Leucine isotope infusion.


RESULTS
In the obese, basal fibrinogen concentrations was approximately 25% greater (p < 0.035), and fibrinogen pool approximately 45% greater (p < 0.005), than in controls. Both FSR and ASR of fibrinogen were similar to control values. With hyperinsulinemia, although fibrinogen FSR and ASR were not significantly modified with respect to baseline in either group, fibrinogen ASR resulted to be approximately 50% greater in the obese than in controls (p < 0.015). Hyperinsulinemia equally stimulated albumin synthesis and suppressed leucine appearance from endogenous proteolysis in both groups. Amino acid clearance was also similar. In the obese, the insulin-mediated glucose disposal was approximately 50% lower (p < 0.03) than in controls, and it was inversely correlated with fibrinogen ASR during the clamp in both groups (r = - 0.58).


CONCLUSIONS
In obese, non-diabetic males, post absorptive fibrinogen production is normal. Whole-body amino acid disposal, basal and insulin-responsive protein degradation, and albumin synthesis are also normal. However, the greater fibrinogen ASR in the obese with hyperinsulinemia, and the inverse relationship between insulin sensitivity and clamp fibrinogen production, suggest a role for hyperinsulinemia and/or insulin resistance on fibrinogen production in obesity.
Tessari
P
P
Department of Clinical and Experimental Medicine, Chair of Metabolism, Policlinico Universitario, via Giustiniani 2, Padua, Italy. paolo.tessari@unipd.it
Cosma
A
A
Vettore
M
M
Millioni
R
R
Puricelli
L
L
Cogo
P
P
Cecchet
D
D
Carnielli
V
V
Kiwanuka
E
E
D000328:Adult; D000596:Amino Acids / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D015992:Body Mass Index; D001830:Body Surface Area; D002097:C-Reactive Protein / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D005340:Fibrinogen / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D012016:Reference Values; D018180:Thrombomodulin / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D000596:Amino Acids; D001786:Blood Glucose; D007328:Insulin; D015850:Interleukin-6; D018180:Thrombomodulin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D005340:Fibrinogen; D002097:C-Reactive Protein; D002784:Cholesterol