Garay-Sevilla M E, Nava L E, Malacara J M, Wróbel K, Wróbel K, Pérez U
Instituto de Investigaciones Médicas, Universidad de Guanajuato, 20 de Enero 929, 37320 León Gto, Mexico.
Diabetes Metab Res Rev. 2000 Mar-Apr;16(2):106-13. doi: 10.1002/(sici)1520-7560(200003/04)16:2<106::aid-dmrr88>3.0.co;2-h.
Advanced glycosylation end product (AGE) formation is a major mechanism for the development of complications in diabetes, and the possible roles of insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) are not clearly established.
We examined the associations of AGEs, free IGF-I and IGFBP-3 in Type 2 diabetes mellitus (DM) patients under diverse conditions. In a cross-sectional design we studied 110 subjects (67 women and 43 men): non-diabetic controls in group 1, (n = 15) and diabetes patients as follows: group 2, without complications (n = 25); group 3, with chronic complications (n = 25); group 4, with acute or chronic infections (n = 24); group 5, hospitalized for reasons unrelated to diabetes (n = 9); group 6, with end-stage renal disease (ESRD) (n = 12). AGEs were determined by a spectrofluorometric method (HPLC). Insulin and IGFBP-3 were measured by RIA and free IGF-1 with an IRMA method.
AGEs were 13-fold higher in patients with ESRD (p<0.001), and lower in healthy individuals. Free IGF-1 was lower in the patients with complications (p = 0.017), with infections (p = 0.006) and hospitalized (p = 0.04). IGFBP-3 was higher in hospitalized patients (p=0.017). AGEs were associated with free IGF-1 (r = 0.41, p = 0.04) in the group with complications, and with HbA(1c) (r = -0.90, p = 0.002) in hospitalized patients. In the total group, free IGF-1 (r = -0.25, p = 0.008), and IGFBP-3 (r = -0.22, p = 0.021) were associated with HbA(1c).
We concluded that AGEs were markedly increased in diabetic patients with ESRD, IGF-1 was decreased in patients with infections and hospitalized, and was negatively associated with HbA(1c). IGFBP-3 was increased in hospitalized patients, with higher levels in patients with long bone fractures. A complex interaction of humoral factors may participate in the acceleration of complications of diabetes.
晚期糖基化终末产物(AGE)的形成是糖尿病并发症发生发展的主要机制,胰岛素样生长因子1(IGF-1)和IGF结合蛋白3(IGFBP-3)的潜在作用尚未明确。
我们在多种情况下研究了2型糖尿病(DM)患者中AGEs、游离IGF-I和IGFBP-3之间的关联。采用横断面设计,我们研究了110名受试者(67名女性和43名男性):第1组为非糖尿病对照组(n = 15),糖尿病患者如下:第2组,无并发症(n = 25);第3组,有慢性并发症(n = 25);第4组,有急性或慢性感染(n = 24);第5组,因与糖尿病无关的原因住院(n = 9);第6组,患有终末期肾病(ESRD)(n = 12)。采用荧光分光光度法(HPLC)测定AGEs。采用放射免疫分析法(RIA)测定胰岛素和IGFBP-3,采用免疫放射分析法(IRMA)测定游离IGF-1。
ESRD患者的AGEs水平高13倍(p<0.001),健康个体的AGEs水平较低。有并发症的患者(p = 0.017)、有感染的患者(p = 0.006)和住院患者(p = 0.04)的游离IGF-1水平较低。住院患者的IGFBP-3水平较高(p = 0.017)。在有并发症的组中,AGEs与游离IGF-1相关(r = 0.41,p = 0.04),在住院患者中,AGEs与糖化血红蛋白(HbA1c)相关(r = -0.90,p = 0.002)。在整个研究组中,游离IGF-1(r = -0.25,p = 0.008)和IGFBP-3(r = -0.22,p = 0.021)与HbA1c相关。
我们得出结论,患有ESRD的糖尿病患者中AGEs显著升高,有感染和住院的患者中IGF-1降低,且与HbA1c呈负相关。住院患者的IGFBP-3升高,长骨骨折患者的水平更高。体液因子的复杂相互作用可能参与了糖尿病并发症的加速发展。