Insulin Resistance is a Significant Determinant of Sarcopenia in Advanced Kidney Disease.

Maintenance hemodialysis (MHD) patients display significant nutritional abnormalities. Insulin is an anabolic hormone with direct effects on skeletal muscle (SM). We examined the anabolic actions of insulin, whole-body (WB) and SM protein turnover, in 33 MHD patients and 17 participants without kidney disease using hyperinsulinemic euglycemic euaminoacidemic (dual) clamp. Gluteal muscle biopsies were obtained before and after the dual-clamp. At baseline, WB protein synthesis and breakdown rates were similar in MHD patients. During dual-clamp, controls had higher in increase WB protein synthesis and higher suppression of WB protein breakdown compared to MHD patients resulting in statistically significantly more positive WB protein net balance (2.02 (IQR, 1.79,2.36) versus 1.68 (IQR, 1.46,1.91) mg/kg.fat free mass/min for controls versus for MHD patients, respectively, p < 0.001). At baseline, SM protein synthesis and breakdown rates were higher in MHD patients versus controls but SM net protein balance was similar between groups. During dual-clamp, SM protein synthesis increased statistically significantly more in controls compared to MHD patients (p = 0.03) whereas SM protein breakdown decreased comparably between groups. SM net protein balance was statistically significantly more positive in controls compared to MHD patients (67.3 (IQR,46.4,97.1) versus 15.4 (IQR,-83.7,64.7) μg/100 ml/min for controls MHD patients, respectively, p = 0.03). Human SM biopsy showed positive correlation between glucose and leucine disposal rates and P-AKT to AKT ratio and muscle mitochondrial markers in controls but not in MHD patients. Diminished response to anabolic actions of insulin in the stimulated setting could lead to muscle wasting in MHD patients.