Effects of dietary protein restriction on albumin and fibrinogen synthesis in macroalbuminuric type 2 diabetic patients

Aims/hypothesis: Diabetic nephropathy is associated with hypoalbuminaemia and hyperfibrinogenaemia. A low-protein diet has been recommended in patients with diabetic nephropathy, but its effects on albumin and fibrinogen synthesis are unknown. Methods: We compared the effects of a normal (NPD; 1.38 ± 0.08 g kg-1 day-1) or low (LPD; 0.81 ± 0.04 g kg-1 day-1) -protein diet on endogenous leucine flux (ELF), albumin and fibrinogen synthesis (l-[5,5,5,-2H 3]leucine infusion), and markers of inflammation in nine type 2 diabetic patients with macroalbuminuria. Six healthy participants on NPD served as control participants. Results: In comparison with healthy participants, type 2 diabetic patients on an NPD had similar ELF, reduced serum albumin (38 ± 1.1 vs 42 ± 0.8 g/l; p < 0.05), similar fractional synthesis rates (FSR) and absolute synthesis rates (ASR) of albumin, and both increased plasma fibrinogen concentration [10.7 ± 0.6 vs 7.2 ± 0.5 μmol/l (3.64 ± 0.22 vs 2.45 ± 0.18 g/l); p < 0.05] and fibrinogen ASR [11.03 ± 1.17 vs 6.0 ± 1.8 μmol 1.73 m-2 day -1 (3.7 ± 0.4 vs 1.9 ± 0.3 g 1.73 m-2 day-1); p < 0.01]. After LPD, type 2 diabetic patients had the following changes in comparison with NPD: reduced proteinuria (2.74 ± 0.4 vs 4.51 ± 0.8 g/day; p < 0.05), ELF (1.93 ± 0.08 vs 2.11 ± 0.08 μmol kg-1 min-1; p < 0.05) and total fibrinogen pool; increased serum albumin (42 ± 1 vs 38 ± 1 g/l; p < 0.01) and albumin ASR (14.1 ± 1 vs 9.9 ± 1 g 1.73 m -2 day-1; p < 0.05); and reduced plasma IL-6 levels, which were correlated with albumin ASR (r = -0.749; p < 0.05). Conclusions/interpretation: LPD in type 2 diabetic patients with diabetic nephropathy reduces low-grade inflammatory state, proteinuria, albuminuria, whole-body proteolysis and ASR of fibrinogen, while increasing albumin FSR, ASR and serum concentration. ISRCTN ID no: CCT-NAPN-16911 © 2007 Springer-Verlag.