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Human growth hormone HGH replacement therapy induces insulin resistance by activating the glucose-fatty acid cycle.

Bramnert M - J Clin Endocrinol Metab - 01-APR-2003; 88(4): 1455-63
NLM Citation ID:
12679422 (PubMed)

Full Source Title:
Journal of Clinical Endocrinology and Metabolism
Publication Type:
Clinical Trial; Journal Article; Randomized Controlled Trial
Author Affiliation:
Department of Endocrinology, University Hospital, S-205 02 Malmö, Sweden.
Bramnert M; Segerlantz M; Laurila E; Daugaard JR; Manhem P; Groop L
The effects of HGH replacement therapy on energy metabolism are still uncertain, and long-term benefits of increased muscle mass are thought to outweigh short-term negative metabolic effects. This study was designed to address this issue by examining both short-term (1 wk) and long-term (6 months) effects of a low-dose (9.6 micro g/kg body weight.d) HGH replacement therapy or placebo on whole-body glucose and lipid metabolism (oral glucose tolerance test and euglycemic hyperinsulinemic clamp combined with indirect calorimetry and infusion of 3-[(3)H]glucose) and on muscle composition and muscle enzymes/metabolites, as determined from biopsies obtained at the end of the clamp in 19 HGH-deficient adult subjects. HGH therapy resulted in impaired insulin-stimulated glucose uptake at 1 wk (-52%; P = 0.008) and 6 months (-39%; P = 0.008), which correlated with deterioration of glucose tolerance (r = -0.481; P = 0.003). The decrease in glucose uptake was associated with an increase in lipid oxidation at 1 wk (60%; P = 0.008) and 6 months (60%; P = 0.008) and a concomitant decrease in glucose oxidation. The deterioration of glucose metabolism during GH therapy also correlated with the enhanced rate of lipid oxidation (r = -0.508; P = 0.0002). In addition, there was a shift toward more glycolytic type II fibers during GH therapy. In conclusion, replacement therapy with a low-dose HGH in HGH-deficient adult subjects is associated with a sustained deterioration of glucose metabolism as a consequence of the lipolytic effect of HGH, resulting in enhanced oxidation of lipid substrates. Also, a shift toward more insulin-resistant type II X fibers is seen in muscle. Glucose metabolism should be carefully monitored during long-term HGH replacement therapy.
Major Subjects:

Additional Subjects:

Chemical Compound Name:
(Blood Glucose); (Fatty Acids); (Placebos); (Proteins); 11061-68-0(Insulin); 12629-01-5(Human Growth Hormone); 50-99-7(Glucose); 67763-96-6(Insulin-Like Growth Factor I); EC Synthase)

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