Schalch D S, Turman N J, Marcsisin V S, Heffernan M, Guler H P
Department of Medicine, University of Wisconsin, Madison 53792.
J Clin Endocrinol Metab. 1993 Dec;77(6):1563-8. doi: 10.1210/jcem.77.6.8263142.
Recombinant human insulin-like growth factor I (rhIGF-I) lowers blood glucose, serum insulin, C-peptide, and lipid levels in healthy and diabetic animals and humans. We hypothesized that rhIGF-I might control blood glucose levels and concomitantly reduce pancreatic insulin secretion in patients with type II diabetes. If true, rhIGF-I might serve as a therapeutic agent that could mitigate some of the detrimental effects of hyperinsulinemia secondary to insulin resistance in these patients. In this study, we treated 12 patients with type II diabetes mellitus twice daily for 5 days with sc rhIGF-I in doses of 90, 120, or 160 micrograms/kg body weight. Metabolic parameters in the fasting and postprandial states were assessed during a 3-day baseline period, the rhIGF-I treatment period, and a 3-day follow-up period, respectively. Administration of rhIGF-I significantly reduced mean (+/- SD) concentrations of fasting blood glucose (12.3 +/- 4.5 to 9.1 +/- 2.6 mmol/L), serum insulin (98 +/- 52 to 56 +/- 27 pmol/L), and C-peptide (993 +/- 298 to 728 +/- 232 pmol/L). It also decreased postprandial (area under the curve) blood glucose (32.5 +/- 12.7 to 23.9 +/- 8.1 mmol/L.h), serum insulin (1102 +/- 707 to 467 +/- 332 pmol/L.h), and C-peptide (5958 +/- 2747 to 3442 +/- 1523 pmol/L.h). The administration of rhIGF-I was also associated with a small but significant reduction in serum triglycerides (6.76 +/- 3.45 to 5.32 +/- 2.59 mmol/L) and total cholesterol (6.13 +/- 1.25 to 5.66 +/- 1.20 mmol/L), 24-h creatinine clearance increased significantly (85 +/- 30 to 133 +/- 51 mL/min), and microalbuminuria was unchanged. Although rhIGF-I was reasonably well tolerated, side effects included low-grade edema, mild and mainly asymptomatic orthostatic hypotension, and bilateral temporomandibular tenderness. We conclude that short-term treatment of type II diabetic patients with rhIGF-I favorably affects metabolic control and enhances kidney function. An assessment of the risk/benefit ratio of rhIGF-I administration to this group of patients awaits extended experiments.
重组人胰岛素样生长因子I（rhIGF-I）可降低健康动物和糖尿病动物及人类的血糖、血清胰岛素、C肽和血脂水平。我们推测，rhIGF-I可能控制II型糖尿病患者的血糖水平，并同时减少胰腺胰岛素分泌。如果这一推测成立，rhIGF-I可能成为一种治疗药物，减轻这些患者因胰岛素抵抗继发的高胰岛素血症的一些有害影响。在本研究中，我们对12例II型糖尿病患者，每日皮下注射rhIGF-I两次，共5天，剂量分别为90、120或160微克/千克体重。分别在3天的基线期、rhIGF-I治疗期和3天的随访期评估空腹和餐后状态下的代谢参数。rhIGF-I的给药显著降低了空腹血糖（从12.3±4.5降至9.1±2.6毫摩尔/升）、血清胰岛素（从98±52降至56±27皮摩尔/升）和C肽（从993±298降至728±232皮摩尔/升）的平均（±标准差）浓度。它还降低了餐后（曲线下面积）血糖（从32.5±12.7降至23.9±8.1毫摩尔/升·小时）、血清胰岛素（从1102±707降至467±332皮摩尔/升·小时）和C肽（从5958±2747降至3442±1523皮摩尔/升·小时）。rhIGF-I的给药还与血清甘油三酯（从6.76±3.45降至5.32±2.59毫摩尔/升）和总胆固醇（从6.13±1.25降至5.66±1.20毫摩尔/升）的小幅但显著降低有关，24小时肌酐清除率显著增加（从85±30升至133±51毫升/分钟），微量白蛋白尿未改变。尽管rhIGF-I耐受性较好，但副作用包括轻度水肿、轻度且主要无症状的体位性低血压以及双侧颞下颌关节压痛。我们得出结论，rhIGF-I短期治疗II型糖尿病患者对代谢控制有有利影响，并增强肾功能。对该组患者使用rhIGF-I的风险/效益比评估有待进一步实验。
