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. RESEARCH DESIGN AND 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