Gibson J M, Westwood M, Crosby S R, Gordon C, Holly J M, Fraser W, Anderson C, White A, Young R J
University of Manchester, Department of Medicine, Hope Hospital, Salford, United Kingdom.
J Clin Endocrinol Metab. 1995 Apr;80(4):1369-75. doi: 10.1210/jcem.80.4.7536208.
Insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) modulates the metabolic and mitogenic effects of IGFs. Although IGFBP-1 levels are abnormally high in insulin-dependent diabetes (IDDM), relatively little is known in NIDDM; conflicting data have suggested both high and low levels. We investigated whether treatment modifies IGFBP-1 levels in two groups of NIDDM patients. Study 1 examined fasting concentrations in groups of patients with NIDDM, comparable except for treatment type (sulfonylurea, n = 23; once daily insulin, n = 15; sulfonylurea plus once daily insulin, n = 14; multiple insulin injections, n = 9) and 25 nondiabetic subjects. In sulfonylurea-treated patients there were markedly reduced plasma IGFBP-1 concentrations (median, interquartile range in parentheses): control, 61.0 (36-96) micrograms/L; sulfonylureas alone, 31.5 (21-61) micrograms/L (P < 0.01); and sulfonylureas plus insulin, 31.5 (9-53) micrograms/L (P < 0.01). Once daily insulin was associated with values similar to those in the control group [62.0 (27-103) micrograms/L; P = NS], whereas IGFBP-1 levels were higher with multiple insulin injection therapy [156.0 (71-184) micrograms/L; P < 0.05]. Proinsulin levels were higher in sulfonylurea-treated patients, but there was no significant correlation between IGFBP-1 and proinsulin within any individual group. Study 2 examined the effects of treatment on the dynamics of IGFBP-1 levels between 0800-1900 h. In control subjects (n = 8), levels fell from 0800 h (mean +/- SEM, 22.4 +/- 5.2 micrograms/L) to 1000 h (14 +/- 5.2 micrograms/L), followed by a rise, more rapid after food, to a peak at 1240 h (20.6 +/- 3.7 micrograms/L). Levels then declined until 1500 h (10.7 +/- 2.9 micrograms/L), with a further postprandial peak at 1840 h (23.1 +/- 3.2 micrograms/L). Sulfonylurea therapy (n = 6) resulted in a complete loss of this pattern, with a marked fall in IGFBP-1 from 0800 h (22 +/- 2.7 micrograms/L) to less than 7 micrograms/L for the remainder of the study (area under the curve, 1150-1400 h, P < 0.001 vs. control). By contrast, in metformin-treated patients (n = 7), neither IGFBP-1 levels nor postprandial peaks were significantly different from those in the control group. Our findings suggest that in patients with NIDDM, the regulation of IGFBP-1 is markedly influenced by the choice of treatment.
胰岛素样生长因子（IGF）结合蛋白-1（IGFBP-1）可调节IGF的代谢和促有丝分裂作用。尽管在胰岛素依赖型糖尿病（IDDM）中IGFBP-1水平异常升高，但在非胰岛素依赖型糖尿病（NIDDM）中对此了解相对较少；相互矛盾的数据表明其水平有高有低。我们研究了治疗是否会改变两组NIDDM患者的IGFBP-1水平。研究1检测了NIDDM患者组的空腹浓度，这些患者除治疗类型外具有可比性（磺脲类药物治疗，n = 23；每日一次胰岛素治疗，n = 15；磺脲类药物加每日一次胰岛素治疗，n = 14；多次胰岛素注射治疗，n = 9）以及25名非糖尿病受试者。在接受磺脲类药物治疗的患者中，血浆IGFBP-1浓度显著降低（中位数，括号内为四分位数间距）：对照组，61.0（36 - 96）μg/L；单独使用磺脲类药物，31.5（21 - 61）μg/L（P < 0.01）；磺脲类药物加胰岛素，31.5（9 - 53）μg/L（P < 0.01）。每日一次胰岛素治疗的患者其数值与对照组相似[62.0（27 - 103）μg/L；P = 无显著性差异]，而多次胰岛素注射治疗时IGFBP-1水平更高[156.0（71 - 184）μg/L；P < 0.05]。接受磺脲类药物治疗的患者胰岛素原水平较高，但在任何个体组中IGFBP-1与胰岛素原之间均无显著相关性。研究2检测了0800 - 1900时治疗对IGFBP-1水平动态变化的影响。在对照组受试者（n = 8）中，水平从0800时（均值±标准误，22.4±5.2μg/L）降至1000时（14±5.2μg/L），随后升高，进食后升高更快，在1240时达到峰值（20.6±3.7μg/L）。然后水平下降直至1500时（10.7±2.9μg/L），在1840时出现进一步的餐后峰值（23.1±3.2μg/L）。磺脲类药物治疗（n = 6）导致这种模式完全消失，IGFBP-1从0800时（22±2.7μg/L）显著下降至在研究剩余时间内低于7μg/L（曲线下面积，1150 - 1400时，与对照组相比P < 0.001）。相比之下，在接受二甲双胍治疗的患者（n = 7）中，IGFBP-1水平及餐后峰值与对照组均无显著差异。我们的研究结果表明，在NIDDM患者中，IGFBP-1的调节受到治疗选择的显著影响。
