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 mu g/kg.week or 0.24 IU/kg. we ek) recombinant human GH (rhGH) treatment on glucose tolerance, insuli n secretion, and insulin- and glucose-mediated glucose disposal was ex amined in 10 GH-deficient adults. The frequently sampled iv glucose to lerance test was performed at baseline and after 1 week and 3 months o f rhGH therapy and analyzed by the minimal model method of Bergman to provide estimates of the glucose decay rate, first and second phase in sulin secretion (Phi 1 and Phi 2), fractional clearance of insulin, an d glucose-mediated and insulin-mediated glucose disposal. Fasting gluc ose, insulin, C-peptide, nonesterified fatty acids (NEFA), and serum c holesterol 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), ins ulin (93.6 +/- 8.9 vs. 238.9 +/- 9.2 pmol/L; P(0.0001), C-peptide (0.3 2 +/- 0.13 vs. 0.66 +/- 0.13 nmol/L; P < 0.005), and Phi 1 (11.9 +/- 1 .8 vs. 16.2 +/- 1.8 pmol/L.min/mmol.L x 10(2)) and Phi 2 (1.43 +/- 0.1 7 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 u s. 1.28 +/- 0.12 min(-1); P < 0.05) and insulin-mediated glucose dispo sal (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 fracti onal clearance of insulin. By 3 months, fasting insulin and C-peptide levels remained significantly elevated, whereas other parameters had r eturned 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 th roughout the study. We conclude that short term low dose rhGH treatmen t of GH-deficient adults induces a temporary state of mild glucose int olerance, 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 hyperi nsulinemia will last over the longer term and/or has distant detriment al metabolic consequences in the individual must await further studies .