Abstract
Context: Data on metabolic effects of Growth Hormone (GH) derived from studies using GH suppression by pharmacological agents may not reflect selective actions. Objective: To evaluate the effects of GH antagonism on glucose and lipid metabolism using pegvisomant, a selective GH receptor antagonist in patients with type 1 diabetes (T1D). Design & participants: In a randomised, placebo-controlled, crossover study, 10 young adults with T1D were evaluated at baseline, and after 4 weeks of treatment with either 10mg of pegvisomant or placebo. The assessments included an overnight euglycaemic steady state followed by a hyperinsulinaemic euglycaemic clamp, and employed glucose and glycerol cold stable isotopes. Outcome measures: Hepatic and peripheral insulin sensitivity (IS), lipid turnover and intramyocellular lipid (IMCL) Results: Compared with placebo, pegvisomant treatment resulted in lower IGF-I levels (p<0.001). During the overnight steady state, insulin requirements for euglycaemia (p=0.019), insulin levels (p=0.008) and glucose production rates (Ra) (p=0.033) were reduced. During the clamp study, glucose infusion rates (p=0.031) increased, glucose Ra (p=0.015) decreased whilst glucose disposal rates were unchanged. Free fatty acids (FFA) levels were similar during the steady state, but were lower during the clamp (p=0.040) following pegvisomant. Soleus muscle IMCL decreased following treatment (p=0.024), however no change in tibialis anterior muscle was observed. Conclusions: The study demonstrates that GH antagonism in T1D results in improved hepatic IS. Lack of consistent changes in FFA may suggest a direct effect of GH on IS. Unchanged peripheral IS despite reductions in IMCL indicate that GH induced alterations in IMCL may not be causally linked to glucose metabolism.