title: Growth hormone (GH) replacement therapy reduces serum sialic acid concentrations in adults with GH-deficiency: a double-blind placebo-controlled study.
abstract: OBJECTIVE
  Patients with adult GH-deficiency are thought to have an increased risk of cardiovascular disease. Sialic acid (SA) concentrations have been proposed as a marker of atherosclerotic disease probably related to an inflammatory response of the arterial wall. SA as a marker of cardiovascular disease in adult GH-deficiency and its relation to changes in fasting lipid profile and hormone concentrations have not yet been investigated.
  
  
  METHODS
  We performed a randomised, double-blind placebo-controlled study in 18 patients with adult GH-deficiency before and after 3 months GH replacement therapy (0.036 U/kg/d; GH-treated group: 6 females, 3 males; age: 47.3 +/- 5.4 years., mean +/- SEM; placebo-group: 5 females, 4 males; mean age 50.2 +/- 4.7). In addition, SA concentrations were measured in 18 sex and age matched healthy control subjects.
  
  
  METHODS
  Blood samples were obtained after an overnight fast. Serum SA, triglycerides and cholesterol were measured using enzymatic methods. Lipoprotein classes were separated by ultracentrifugation. Insulin and IGF-I were determined by radioimmunoassay, HbA1C was measured by anion exchange liquid chromatography.
  
  
  RESULTS
  SA concentrations of the patients with adult GH-deficiency were not significantly different compared to the control group (GH-deficient group: 2.29 +/- 0.02 mmol/l, mean +/- SEM vs. control group: 2.09 +/- 0.13 mmol/l, P = 0.25). Before GH replacement therapy SA concentrations correlated positively with the patients age (r = 0.45; P < 0.04) and fasting insulin concentrations (r = 0.5; P < 0.03) but not with fasting lipid profile. GH replacement therapy significantly increased IGF-I (GH: + 27 +/- 2.6 vs. placebo: + 1.0 +/- 0.8 nmol/l, P < 0.001) and fasting insulin concentrations (GH: + 71.9 +/- 8.0 vs. placebo: + 19.6 +/- 22.6 pmol/l, P < 0.04) compared to placebo therapy. SA concentrations (GH: - 0.41 +/- 0.15 vs. placebo: - 0.01 +/- 0.12 mmol/l, P < 0.05), total cholesterol (GH: - 0.71 +/- 0.16 vs. placebo: 0.23 +/- 0.21 mmol/l, P < 0.003) and LDL-cholesterol (- 0.71 +/- 0.14 vs. placebo: - 0.12 +/- 0.21 mmol/l P < 0.04) significantly decreased after GH replacement therapy compared to placebo therapy. No significant correlation between changes in SA concentrations and changes in lipid profile were observed following GH replacement therapy.
  
  
  CONCLUSIONS
  These results suggest that, firstly, GH replacement therapy may have a beneficial effect on the pathogenesis of atherosclerosis despite the increase in insulin concentrations, a surrogate marker of insulin resistance, secondly, the proposed beneficial effect of GH on the atherosclerotic process is likely to be multifactorial and cannot only be explained by changes in lipid profile and finally, SA might be a useful marker for the process of atherosclerotic disease in interventional studies.
authors.affiliation: Department of Medicine, St Thomas Hospital (UMDS), London, UK. Emmanuel.Christ@hcuge.ch
authors.forename: E R
authors.initials: ER
authors.lastname: Christ
authors.forename: M H
authors.initials: MH
authors.lastname: Cummings
authors.forename: P J
authors.initials: PJ
authors.lastname: Lumb
authors.forename: M A
authors.initials: MA
authors.lastname: Crook
authors.forename: P H
authors.initials: PH
authors.lastname: Sönksen
authors.forename: D L
authors.initials: DL
authors.lastname: Russell-Jones
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000172:deficiency* / Q000627:therapeutic use*; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000627:therapeutic use; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid / Q000097:blood*; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; D007328:Insulin; D014280:Triglycerides; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D002784:Cholesterol; D019158:N-Acetylneuraminic Acid