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,-2H3]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 micromol/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 micromol 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 micromol 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.