O'Neal D N, Kalfas A, Dunning P L, Christopher M J, Sawyer S D, Ward G M, Alford F P
Department of Endocrinology and Diabetes, University of Melbourne, St. Vincent's Hospital, Victoria, Australia.
J Clin Endocrinol Metab. 1994 Oct;79(4):975-83. doi: 10.1210/jcem.79.4.7962308.
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.
在10名生长激素缺乏的成年人中，研究了为期3个月的低剂量（120微克/千克·周或0.24国际单位/千克·周）重组人生长激素（rhGH）治疗对葡萄糖耐量、胰岛素分泌以及胰岛素和葡萄糖介导的葡萄糖清除的影响。在基线时以及rhGH治疗1周和3个月后进行频繁采样的静脉葡萄糖耐量试验，并采用伯格曼最小模型法进行分析，以估计葡萄糖衰减率、第一和第二阶段胰岛素分泌（phi 1和phi 2）、胰岛素的分数清除率以及葡萄糖介导和胰岛素介导的葡萄糖清除。还测量了空腹血糖、胰岛素、C肽、非酯化脂肪酸（NEFA）以及血清胆固醇和甘油三酯。将1周的数据与基线进行比较时，平均（±标准误）空腹血糖出现小幅但显著升高（4.62±0.17对5.1±0.15毫摩尔/升；P<0.01），NEFA（0.70±0.09对1.1±0.12毫摩尔/升；P<0.005），胰岛素（93.6±8.9对238.9±9.2皮摩尔/升；P<0.0001），C肽（0.32±0.13对0.66±0.13纳摩尔/升；P<0.005），phi 1（11.9±1.3对16.2±1.8皮摩尔/升·分钟/毫摩尔·升×10²）和phi 2（1.43±0.17对3.15±0.25皮摩尔/升·分钟/毫摩尔·升×10³；P<0.05）。相反，葡萄糖衰减率（1.83±0.26对1.28±0.12分钟⁻¹；P<0.05）和胰岛素介导的葡萄糖清除（0.36±0.08对0.18±0.06分钟/皮摩尔·升×10⁻⁴；P<0.005）出现相关下降。葡萄糖介导的葡萄糖清除或胰岛素的分数清除率没有变化。到3个月时，空腹胰岛素和C肽水平仍显著升高，而其他参数已恢复到基线。1周时血清胆固醇有轻微降低（5.1±0.15对4.62±0.17毫摩尔/升；P<0.01），但3个月时未持续。整个研究过程中血清甘油三酯保持不变。我们得出结论，短期低剂量rhGH治疗生长激素缺乏的成年人在1周时会诱导出一种暂时的轻度葡萄糖不耐受、高胰岛素血症、胰岛素抵抗和NEFA水平升高的状态。到3个月时，这些代谢紊乱已恢复到基线，但仍存在持续的适度高胰岛素血症。这种高胰岛素血症是否会长期持续和/或对个体产生远期有害的代谢后果，必须等待进一步研究。
