In these otherwise healthy subjects, serum albumin and prealbumin levels are not "markers of nutritional status." The "markers" failed to identify subjects with severe protein-calorie malnutrition until extreme starvation. That is, they failed to identify healthy individuals who would benefit from nutrition support, becoming abnormal only when starvation was already obvious. In contrast, serum albumin and prealbumin levels are known to fall promptly with injury or illness regardless of nutrient intake. They are negative acute-phase reactants. When these measures are low in sick patients, this cannot be assumed to reflect nutritional deprivation. Decisions about nutrition support should be based on evidence of meaningful benefit from this treatment rather than on assessment of "nutritional markers."

OBJECTIVESkeletal muscle protein metabolism is resistant to the anabolic action of insulin in healthy, nondiabetic older adults. This defect is associated with impaired insulin-induced vasodilation and mTORC1 signaling. We hypothesized that, in older subjects, pharmacological restoration of insulin-induced capillary recruitment would improve the response of muscle protein synthesis and anabolism to insulin.RESEARCH DESIGN AND METHODSTwelve healthy, nondiabetic older subjects (71 ± 2 years) were randomized to two groups. Subjects were studied at baseline and during local infusion in one leg of insulin alone (Control) or insulin plus sodium nitroprusside (SNP) at variable rate to double leg blood flow. We measured leg blood flow by dye dilution; muscle microvascular perfusion with contrast enhanced ultrasound; Akt/mTORC1 signaling by Western blotting; and muscle protein synthesis, amino acid, and glucose kinetics using stable isotope methodologies.RESULTSThere were no baseline differences between groups. Blood flow, muscle perfusion, phenylalanine delivery to the leg, and intracellular availability of phenylalanine increased significantly (P < 0.05) in SNP only. Akt phosphorylation increased in both groups but increased more in SNP (P < 0.05). Muscle protein synthesis and net balance (nmol · min−1 · 100 ml · leg−1) increased significantly (P < 0.05) in SNP (synthesis, 43 ± 6 to 129 ± 25; net balance, −16 ± 3 to 26 ± 12) but not in Control (synthesis, 41 ± 10 to 53 ± 8; net balance, −17 ± 3 to −2 ± 3).CONCLUSIONSPharmacological enhancement of muscle perfusion and amino acid availability during hyperinsulinemia improves the muscle protein anabolic effect of insulin in older adults.

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Endothelial-dependent vasodilation and the consequent increase in nutritive flow and mTORC1 signaling, rather than Akt signaling, are fundamental mechanisms by which insulin stimulates muscle protein synthesis in humans. Additionally, these data underscore that insulin modulates skeletal muscle proteolysis according to its effects on nutritive flow.