Janssen J A, Jacobs M L, Derkx F H, Weber R F, van der Lely A J, Lamberts S W
Department of Internal Medicine, Erasmus University, Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 1997 Sep;82(9):2809-15. doi: 10.1210/jcem.82.9.4180.
The existing literature on serum insulin-like growth factor I (IGF-I) levels in insulin-dependent diabetes mellitus (IDDM) is conflicting. Free IGF-I may have greater physiological and clinical relevance than total IGF-I. Recently, a validated method has been developed to measure free IGF-I levels in the circulation. Serum free and total IGF-I, IGF-binding protein-1 (IGFBP-1), and IGFBP-3 levels were measured in 56 insulin-treated IDDM patients and 52 healthy sex- and age-matched controls. Diabetic retinopathy was established by direct fundoscopy. In 54 IDDM patients, the glomerular filtration rate (GFR) and effective renal plasma flow were calculated from the clearance rate of [125I]iothalamate and [131I]iodohippurate sodium. Fasting free IGF-I, total IGF-I, and IGFBP-3 levels were significantly lower in IDDM patients than in age- and sex-matched healthy controls (free IGF-I, P < 0.005; total IGF-I, P < 0.001; IGFBP-3, P = 0.001), whereas IGFBP-1 levels were higher (P < 0.001). In IDDM subjects, decreases in free IGF-I, total IGF-I, and IGFBP-3 levels with age were observed (free IGF-I, r = -0.27 and P = 0.05; total IGF-I, r = -0.52 and P < 0.001; IGFBP-3, r = -0.37 and P = 0.005). Free IGF-I was inversely related to fasting glucose in IDDM subjects (r = -0.35; P = 0.01), whereas the relationship between total IGF-I and fasting glucose did not reach significance (r = -0.27; P = 0.06). Age-adjusted free IGF-I levels were significantly higher (P < 0.05) in IDDM subjects with retinopathy than in subjects without retinopathy after adjustment for age. Total IGF-I and IGFBP-3 levels were positively related to GFR (total IGF-I, r = 0.35 and P < 0.05; IGFBP-3, r = 0.28 and P < 0.05). Both of these differences lost significance after adjustment for age. Free IGF-I, total IGF-I, and IGFBP-3 levels were lower and IGFBP-1 levels were higher in insulin-treated IDDM subjects compared to those in age- and sex-matched controls. Free IGF-I, total IGF-I, and IGFBP-3 levels decreased significantly with age in IDDM subjects. Age-adjusted free IGF-I levels in subjects with diabetic retinopathy were higher than those in subjects without diabetic retinopathy. Total IGF-I and IGFBP-3 levels were positively related to GFR in IDDM subjects, but these relations were lost after adjustment for age. Measurement of serum free IGF-I levels in IDDM subjects did not have clear advantages compared to that of total IGF-I, IGFBP-1, and IGFBP-3 levels. Serum IGF-I and IGFBPs reflect their tissue concentrations to a various degree. Consequently, extrapolations concerning the pathogenetic role of the IGF/IGFBP system in the development of diabetic complications at the tissue level remain speculative.
关于胰岛素依赖型糖尿病（IDDM）患者血清胰岛素样生长因子I（IGF-I）水平的现有文献存在矛盾之处。游离IGF-I可能比总IGF-I具有更大的生理和临床相关性。最近，已开发出一种经过验证的方法来测量循环中的游离IGF-I水平。对56例接受胰岛素治疗的IDDM患者和52例年龄及性别匹配的健康对照者测定了血清游离和总IGF-I、IGF结合蛋白-1（IGFBP-1）及IGFBP-3水平。通过直接眼底镜检查确定糖尿病视网膜病变。对54例IDDM患者，根据[125I]碘肽酸盐和[131I]碘马尿酸钠的清除率计算肾小球滤过率（GFR）和有效肾血浆流量。IDDM患者的空腹游离IGF-I、总IGF-I和IGFBP-3水平显著低于年龄及性别匹配的健康对照者（游离IGF-I，P<0.005；总IGF-I，P<0.001；IGFBP-3，P = 0.001），而IGFBP-1水平较高（P<0.001）。在IDDM患者中，观察到游离IGF-I、总IGF-I和IGFBP-3水平随年龄降低（游离IGF-I，r = -0.27，P = 0.05；总IGF-I，r = -0.52，P<0.001；IGFBP-3，r = -0.37，P = 0.005）。IDDM患者中游离IGF-I与空腹血糖呈负相关（r = -0.35；P = 0.01），而总IGF-I与空腹血糖之间的关系未达到显著水平（r = -0.27；P = 0.06）。在调整年龄后，患有视网膜病变的IDDM患者经年龄校正的游离IGF-I水平显著高于无视网膜病变的患者（P<0.05）。总IGF-I和IGFBP-3水平与GFR呈正相关（总IGF-I，r = 0.35，P<0.05；IGFBP-3，r = 0.28，P<0.05）。在调整年龄后，这两种差异均失去显著性。与年龄及性别匹配的对照者相比，接受胰岛素治疗的IDDM患者的游离IGF-I、总IGF-I和IGFBP-3水平较低，而IGFBP-1水平较高。IDDM患者中游离IGF-I、总IGF-I和IGFBP-3水平随年龄显著降低。患有糖尿病视网膜病变的患者经年龄校正的游离IGF-I水平高于无糖尿病视网膜病变的患者。IDDM患者中总IGF-I和IGFBP-3水平与GFR呈正相关，但在调整年龄后这些关系消失。与测定总IGF-I、IGFBP-1和IGFBP-3水平相比，测定IDDM患者血清游离IGF-I水平并无明显优势。血清IGF-I和IGFBPs在不同程度上反映其组织浓度。因此，关于IGF/IGFBP系统在组织水平糖尿病并发症发生发展中的致病作用的推断仍具有推测性。
