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

Abstract

Aims/hypothesis Diabetic nephropathy is associated with hypoalbuminaemia and hyperfibrinogenaemia. A lowprotein 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,-2 H 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-16911Keywords Absolute synthesis . Albumin . Diabetic nephropathy . Fibrinogen . Fractional synthesis . Leucine . Low-grade inflammation . Low-protein diet . Macroalbuminuria . Type 2 diabetes Abbreviations ASR absolute synthesis rate CRP C-reactive protein ELF endogenous leucine flux FSR fractional synthesis rate KIC α-ketoisocaproic acid LPD low-protein diet Diabetologia (2008) 51:21-28

Repeated quantitative measurements of De Novo synthesis of albumin and fibrinogen

“…The assessment of the fibrinogen synthesis rate in the present study is a needed addition to the small number of publications detailing the de novo synthesis of fibrinogen in humans [7, 8, 19, 22, 23, 32–34]. The quantitative values of our results are in agreement with these prior publications.…”

Protein Nutrition and Malnutrition in CKD and ESRD

“…Limiting protein waste products can lead to less uremic toxin elaboration and less toxin-induced inflammation. The positive effects of moderate dietary protein restriction on inflammatory state (IL-6) have been shown in proteinuric diabetic patients [161]. The intestinal source of inflammation can be minimized by preventing dysbiosis through increasing dietary fiber, appropriate treatment of constipation in addition to an adequate dietary provision of protein and energy.…”

Effect of a Low-Protein Diet Supplemented with Ketoacids on Skeletal Muscle Atrophy and Autophagy in Rats with Type 2 Diabetic Nephropathy

“…Thus, the treatment strategies for renal failure, including the use of protein-restricted diets [1], have gained increased interest for the treatment of patients with diabetic nephropathy. Despite the few studies that suggest that protein intake restriction fails to improve renal prognosis in type 1 or type 2 diabetic patients with incipient or overt nephropathy[2] and confers renoprotection[3], several findings have demonstrated that a low-protein diet preserves renal function and structure in animal models [4] and in type 2 diabetic patients with macroalbuminuria[5] and improves disease prognosis[6], low-grade inflammation and proteinuria[7] and depressive symptoms[8]. However, there has been increasing concern regarding the risk of the subsequent development of malnutrition due to these diets.…”