Albumin and fibrinogen synthesis and insulin effect in type 2 diabetic patients with normoalbuminuria.
OBJECTIVE
Insulin stimulates albumin synthesis but inhibits that of fibrinogen in both type 1 diabetic and healthy subjects. In type 2 diabetes, fibrinogen production is increased both in the postabsorptive state and in response to hyperinsulinemia. No data exist on the rate of albumin synthesis and its response to insulin in type 2 diabetes.


METHODS
We measured fractional synthesis rates (FSRs) and absolute synthesis rates (ASRs) of both albumin and fibrinogen in postabsorptive normoalbuminuric type 2 diabetic patients at their spontaneous glucose levels (study A), as well as albumin FSR and ASR before and after a hyperinsulinemic-euglycemic euaminoacidemic clamp (study B), using leucine isotope methods.


RESULTS
In postabsorptive type 2 diabetes (study A), albumin FSR (11.2 +/- 0.9%/day) and albumin ASR (15.4 +/- 1.2 g/day) were not different from control values (albumin FSR: 9.4 +/- 0.7%/day; albumin ASR: 13.8 +/- 1.2 g/day, P > 0.1 for both). In contrast, in the type 2 diabetic subjects, both fibrinogen FSR (24.9 +/- 2.1%/day) and ASR (2.4 +/- 0.2 g/day) were greater (P < 0.025 and P < 0.007, respectively) compared with the control subjects (FSR: 18.6 +/- 1.51%/day; ASR: 1.6 +/- 0.2 g/day). Worse metabolic control in the type 2 diabetic patients was associated with hyperfibrinogenemia and increased leucine rate of appearance, whereas neither the (increased) fibrinogen ASR nor the (normal) albumin production was affected. In study B, after hyperinsulinemia (raised to approximately 860 nmol/l), albumin FSR and ASR increased by approximately 25% versus basal (P < 0.04) and to the same extent in both type 2 diabetic and control subjects.


CONCLUSIONS
In normoalbuminuric type 2 diabetic patients, postabsorptive albumin synthesis and its response to insulin were normal, whereas fibrinogen synthesis was increased, irrespective of metabolic control. Furthermore, in normoalbuminuric type 2 diabetic patients, a normal insulin sensitivity with respect to albumin production but a selective hepatic dysregulation of fibrinogen metabolism were present.
Tessari
Paolo
P
Department of Clinical and Experimental Medicine, Chair of Metabolism, Policlinico Universitario, Via Giustiniani 2, 35128 Padova, Italy. paolo.tessari@unipd.it
Kiwanuka
Edward
E
Millioni
Renato
R
Vettore
Monica
M
Puricelli
Lucia
L
Zanetti
Michela
M
Gucciardi
Antonella
A
Tosolini
Marina
M
Cogo
Paola
P
Carnielli
Virgilio
V
Tiengo
Antonio
A
Barazzoni
Rocco
R
D000328:Adult; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005340:Fibrinogen / Q000096:biosynthesis* / Q000187:drug effects; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007930:Leucine / Q000097:blood / Q000378:metabolism; D008297:Male; D012709:Serum Albumin / Q000096:biosynthesis* / Q000187:drug effects
D007004:Hypoglycemic Agents; D007328:Insulin; D012709:Serum Albumin; D005340:Fibrinogen; D005934:Glucagon; D007930:Leucine