Effects of a diabetes-specific enteral nutrition on nutritional and immune status of diabetic, obese, and endotoxemic rats: Interest of a graded arginine supply

Objective: Obese and type 2 diabetic patients present metabolic disturbance-related alterations in nonspecific immunity, to which the decrease in their plasma arginine contributes. Although diabetes-specific formulas have been developed, they have never been tested in the context of an acute infectious situation as can be seen in intensive care unit patients. Our aim was to investigate the effects of a diabetes-specific diet enriched or not with arginine in a model of infectious stress in a diabetes and obesity situation. As a large intake of arginine may be deleterious, this amino acid was given in graded fashion. Design: Randomized, controlled experimental study. Setting: University research laboratory. Subjects: Zucker diabetic fatty rats. Interventions: Gastrostomized Zucker diabetic fatty rats were submitted to intraperitoneal lipopolysaccharide administration and fed for 7 days with either a diabetes-specific enteral nutrition without (G group, n = 7) or with graded arginine supply (1-5 g/kg/day) (GA group, n = 7) or a standard enteral nutrition (HP group, n = 10). Measurements and Main Results: Survival rate was better in G and GA groups than in the HP group. On day 7, plasma insulin to glucose ratio tended to be lower in the same G and GA groups. Macrophage tumor necrosis factor-alpha (G: 5.0 +/- 1.1 ng/2 x 10(6) cells.hr(-1); GA: 3.7 +/- 0.8 ng/2 x 10(6) cells.hr(-1); and HP: 1.7 +/- 0.6 ng/2 x 10(6) cells.hr(-1); p < .05 G vs. HP) and nitric oxide (G: 4.5 +/- 1.1 ng/2 x 10(6) cells.hr(-1); GA: 5.1 +/- 1.0 ng/2 x 10(6) cells.hr(-1); and HP: 1.0 +/- 0.5 nmol/2 x 10(6) cells.hr(-1); p < .05 G and GA vs. HP) productions were higher in the G and GA groups compared to the HP group. Macrophages from the G and GA groups exhibited increased arginine consumption. Conclusions: In diabetic obese and endotoxemic rats, a diabetes-specific formula leads to a lower mortality, a decreased insulin resistance, and an improvement in peritoneal macrophage function. Arginine supplementation has no additional effect. These data support the use of such disease-specific diets in critically ill diabetic and obese patients. (Crit Care Med 2012; 40:2423-2430)