Effects of seven years of GH-replacement therapy on insulin sensitivity in GH-deficient adults.
The few trials in GH-deficient (GHD) adults that have investigated the long-term effects of GH-replacement therapy on insulin sensitivity have shown conflicting results. In this study, insulin sensitivity was determined using the hyperinsulinemic, euglycemic clamp technique in 11 GHD adults at baseline and after 6 months, 1 yr, 2 yr, and 7 yr of GH-replacement therapy. Furthermore, insulin sensitivity in the GHD patients was compared with that in 11 matched control subjects at baseline and with that in 11 other matched controls at study end. The mean initial GH dose was 1.10 mg/d. The dose was gradually lowered; and after 7 yr, the mean dose was 0.61 mg/d. A sustained reduction in body fat and a sustained increase in fat-free mass were observed. Serum high-density lipoprotein-cholesterol (HDL-C) increased, and serum low-density lipoprotein-cholesterol (LDL-C) decreased, after 7 yr of treatment. Fasting blood glucose was transiently increased during the first year of GH replacement. The glucose infusion rate/body weight (GIR/BW), as measured using the hyperinsulinemic, euglycemic clamp technique, was unaltered during GH-replacement therapy. The comparisons with the control subjects revealed that GIR/BW in the GHD patients was 45% of that in the control subjects at baseline; whereas, at study end, the GIR/BW was 71% of that in the control subjects (P = 0.06 vs. baseline). This could suggest that GH-replacement therapy may prevent the age-related decline in insulin sensitivity in GHD patients.
Svensson
Johan
J
Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. johan.svensson@medic.gu.se
Fowelin
Jesper
J
Landin
Kerstin
K
Bengtsson
Bengt-Ake
BA
Johansson
Jan-Ove
JO
D000328:Adult; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000008:administration & dosage; D013006:Growth Hormone / Q000008:administration & dosage / Q000627:therapeutic use*; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008055:Lipids / Q000097:blood; D008297:Male; D008659:Metabolic Diseases / Q000188:drug therapy / Q000503:physiopathology; D008875:Middle Aged; D012016:Reference Values
D005230:Fatty Acids, Nonesterified; D008055:Lipids; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D005947:Glucose