Abstract
Protein energy wasting (PEW) is common in patients undergoing maintenance hemodialysis (MHD) and closely associated with poor outcomes. Insulin resistance and associated alterations in amino acid metabolism are potential pathways leading to PEW. We hypothesized that the measurement of leucine disposal during a hyperinsulinemic- euglycemic-euaminoacidemic clamp (HEAC) procedure would accurately measure the sensitivity to insulin for its actions on concomitant carbohydrate and protein metabolism in MHD patients. We examined 35 MHD patients and 17 control subjects with normal kidney function by hyperinsulinemic-euglycemic clamp (HEGC) followed by HEAC clamp procedure to obtain leucine disposal rate (LDR) along with isotope tracer methodology to assess whole body protein turnover. The glucose disposal rate (GDR) by HEGC was 5.1 ± 2.1 mg/kg/min for the MHD patients compared to 6.3 ± 3.9 mg/kg/min for the controls (p = 0.38). The LDR during HEAC was 0.09 ± 0.03 mg/kg/min for the MHD patients compared to 0.11 ± 0.05 mg/kg/min for the controls (p = 0.009). The LDR level was correlated with whole body protein synthesis (r = 0.25; p = 0.08), with whole body protein breakdown (r = -0.38 p = 0.01) and net protein balance (r = 0.85; p < 0.001) in the overall study population. Correlations remained significant in subgroup analysis. The GDR derived by HEGC and LDR correlated well in the controls (r = 0.79, p < 0.001), but less so in the MHD patients (r = 0.58, p < 0.001). Leucine disposal rate reliably measures amino acid utilization in MHD patients and controls in response to high dose insulin.
Highlights
Protein energy wasting (PEW) is common in patients undergoing maintenance hemodialysis (MHD) and closely associated with poor outcomes
We have demonstrated that insulin resistance measured by practical methods such as homeostatic model assessment (HOMA) is negatively associated with percent change with arterial plasma leucine concentrations in response to high dose insulin administration suggesting insulin mediated AA uptake into muscle or suppression of protein breakdown or both in MHD patients [9]
Of 45 MHD patients, 3 patients excluded due to active infection, 3 due to prednisone usage, 3 due to hospitalizations within last one month and one patient due to diabetes mellitus requiring insulin therapy
Summary
Protein energy wasting (PEW) is common in patients undergoing maintenance hemodialysis (MHD) and closely associated with poor outcomes. Insulin resistance and associated alterations in amino acid metabolism are potential pathways leading to PEW. We have previously shown that in MHD patients, plasma amino acid concentrations decrease during the hyperinsulinemic-euglycemic clamp (HEGC) procedure in relation to the glucose disposal rate (GDR) [9]. While these data indicate a close relationship between carbohydrate and protein metabolism in response to a hyperinsulinemic state, there remains need for examination of amino acid metabolism during the absorptive state, where the anabolic effects of insulin are substantially different compared to the post-absorptive state
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