The effect of 3 months of recombinant human growth hormone (GH) therapy on insulin and glucose-mediated glucose disposal and insulin secretion in GH-deficient adults: a minimal model analysis.
The effect of 3 months of low dose (120 micrograms/kg.week or 0.24 IU/kg.week) recombinant human GH (rhGH) treatment on glucose tolerance, insulin secretion, and insulin- and glucose-mediated glucose disposal was examined in 10 GH-deficient adults. The frequently sampled iv glucose tolerance test was performed at baseline and after 1 week and 3 months of rhGH therapy and analyzed by the minimal model method of Bergman to provide estimates of the glucose decay rate, first and second phase insulin secretion (phi 1 and phi 2), fractional clearance of insulin, and glucose-mediated and insulin-mediated glucose disposal. Fasting glucose, insulin, C-peptide, nonesterified fatty acids (NEFA), and serum cholesterol and triglycerides were also measured. When the 1 week data were compared to baseline, there was a small but significant rise in mean (+/- SE) fasting glucose (4.62 +/- 0.17 vs. 5.1 +/- 0.15 mmol/L; P < 0.01), NEFA (0.70 +/- 0.09 vs. 1.1 +/- 0.12 mmol/L; P < 0.005), insulin (93.6 +/- 8.9 vs. 238.9 +/- 9.2 pmol/L; P < 0.0001), C-peptide (0.32 +/- 0.13 vs. 0.66 +/- 0.13 nmol/L; P < 0.005), and phi 1 (11.9 +/- 1.3 vs. 16.2 +/- 1.8 pmol/L.min/mmol.L x 10(2)) and phi 2 (1.43 +/- 0.17 vs. 3.15 +/- 0.25 pmol/L.min/mmol.L x 10(3); P < 0.05). Conversely, there were associated decreases in glucose decay rate (1.83 +/- 0.26 vs. 1.28 +/- 0.12 min-1; P < 0.05) and insulin-mediated glucose disposal (0.36 +/- 0.08 vs. 0.18 +/- 0.06 min/pmol.L x 10(-4); P < 0.005). There was no change in glucose-mediated glucose disposal or the fractional clearance of insulin. By 3 months, fasting insulin and C-peptide levels remained significantly elevated, whereas other parameters had returned to baseline. There was a minor reduction in serum cholesterol at 1 week (5.1 +/- 0.15 vs. 4.62 +/- 0.17 mmol/L; P < 0.01), which was not maintained at 3 months. Serum triglycerides remained unchanged throughout the study. We conclude that short term low dose rhGH treatment of GH-deficient adults induces a temporary state of mild glucose intolerance, hyperinsulinemia, insulin resistance, and raised NEFA levels at 1 week. By 3 months, these metabolic disturbances had returned to baseline for a persisting modest hyperinsulinemia. Whether this hyperinsulinemia will last over the longer term and/or has distant detrimental metabolic consequences in the individual must await further studies.
Department of Endocrinology and Diabetes, University of Melbourne, St. Vincent's Hospital, Victoria, Australia.
D N
DN
O'Neal
A
A
Kalfas
P L
PL
Dunning
M J
MJ
Christopher
S D
SD
Sawyer
G M
GM
Ward
F P
FP
Alford
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D005215:Fasting; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000502:physiology*; D005951:Glucose Tolerance Test / Q000379:methods; D013006:Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000502:physiology*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use*
D001786:Blood Glucose; D007328:Insulin; D011994:Recombinant Proteins; D013006:Growth Hormone; D005947:Glucose