Chang Yu-Hung, Lin Kun-Der, Wang Chiao-Ling, Hsieh Ming-Chia, Hsiao Pi-Jung, Shin Shyi-Jang
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Diabetes Metab Res Rev. 2008 Nov-Dec;24(8):629-34. doi: 10.1002/dmrr.894.
While some studies have reported that retinol-binding protein 4 (RBP4) might induce insulin resistance, other studies have demonstrated that the presence of albuminuria in diabetic patients and increased uric acid are related to insulin resistance. Therefore, this study attempted to further investigate the relationship among serum RBP4, serum uric acid, and the severity of albuminuria in diabetic patients.
A total of 95 type 2 diabetic patients and 16 healthy subjects participated in this study. Diabetic patients were classified into normoalbuminuria, microalbuminuria and macroalbuminuria groups according to their urine albumin-to-creatinine ratio (ACR). Serum RBP4 was measured by an enzyme-linked immunosorbent assay (ELISA).
Serum RBP4 was significantly elevated in type 2 diabetic patients with normoalbuminuria (43.4 +/- 14.9 microg/mL), microalbuminuria (57.3 +/- 24.2 microg/mL) and macroalbuminuria (64.7 +/- 27.6 microg/mL) as compared with control patients (32.6 +/- 10.0 microg/mL). Serum RBP4 was also significantly elevated in type 2 diabetic patients with microalbuminuria or macroalbuminuria as compared with the normoalbuminuric group. Serum RBP4 in diabetic subjects was positively correlated with triglycerides, uric acid and ACR, and negatively correlated with low-density lipoprotein cholesterol and estimated glomerular filtration rate (eGFR; with age and gender adjustment in each parameter). Multiple stepwise linear regression analysis showed that uric acid and eGFR remained significantly associated with serum RBP4.
Both eGFR and uric acid are significant determinants of serum RBP4, suggesting that the impaired renal clearance of early diabetic nephropathy affects RBP4 and indirectly supporting the hypothesized link among metabolic syndrome, uric acid and insulin resistance.
虽然一些研究报道视黄醇结合蛋白4(RBP4)可能诱导胰岛素抵抗,但其他研究表明糖尿病患者中蛋白尿的存在及尿酸升高与胰岛素抵抗有关。因此,本研究试图进一步探究糖尿病患者血清RBP4、血清尿酸与蛋白尿严重程度之间的关系。
共有95例2型糖尿病患者和16名健康受试者参与本研究。糖尿病患者根据尿白蛋白与肌酐比值(ACR)分为正常白蛋白尿组、微量白蛋白尿组和大量白蛋白尿组。采用酶联免疫吸附测定(ELISA)法检测血清RBP4。
与对照组患者(32.6±10.0μg/mL)相比,2型糖尿病正常白蛋白尿组(43.4±14.9μg/mL)、微量白蛋白尿组(57.3±24.2μg/mL)和大量白蛋白尿组(64.7±27.6μg/mL)的血清RBP4显著升高。与正常白蛋白尿组相比,2型糖尿病微量白蛋白尿或大量白蛋白尿患者的血清RBP4也显著升高。糖尿病受试者的血清RBP4与甘油三酯、尿酸和ACR呈正相关,与低密度脂蛋白胆固醇和估计肾小球滤过率(eGFR;各参数均经年龄和性别校正)呈负相关。多元逐步线性回归分析显示,尿酸和eGFR与血清RBP4仍显著相关。
eGFR和尿酸均是血清RBP4的重要决定因素,提示早期糖尿病肾病的肾脏清除功能受损影响RBP4,并间接支持了代谢综合征、尿酸和胰岛素抵抗之间的假设联系。