Effects of GH on urea, glucose and lipid metabolism, and insulin sensitivity during fasting in GH-deficient patients

Fasting-related states of distress pose major health problems, and growth hormone (GH) plays a key role in this context. The present study was designed to assess the effects of GH on substrate metabolism and insulin sensitivity during short-term fasting. Six GH-deficient adults underwent 42.5 h of fasting on two occasions, with and without concomitant GH replacement. Palmitate and urea fluxes were measured with the steady-state isotope dilution technique after infusion of [9,10-³H]palmitate and [¹³C]urea. During fasting with GH replacement, palmitate concentrations and fluxes increased by 50% [palmitate: 378 ± 42 (GH) vs. 244 ± 12 μmol/l, P < 0.05; palmitate: 412 ± 58 (GH) vs. 276 ± 42 μM, P = 0.05], and urea turnover and excretion decreased by 30-35% [urea rate of appearance: 336 ± 22 (GH) vs. 439 ± 43 μmol·kg ^-1·h^-1, P < 0.01; urea excretion: 445 ± 43 (GH) vs. 602 ± 74 mmol/24 h, P < 0.05]. Insulin sensitivity (determined by a euglycemic hyperinsulinemic clamp) was significantly decreased [M value: 1.26 ± 0.06 (GH) vs. 2.07 ± 0.22 mg·kg ^-1·min^-1, P < 0.01] during fasting with GH replacement. In conclusion, continued GH replacement during fasting in GH-deficient adults decreases insulin sensitivity, increases lipid utilization, and conserves protein.