Nicola W, Sidhom G, El Khyat Z, Ibrahim S, Salah A, El Sayed A
Basic Medical Sciences Department, National Research Center, Cairo, Egypt.
Endocr J. 2001 Feb;48(1):25-31. doi: 10.1507/endocrj.48.25.
The renin-angiotensin system (RAS) has been unequivocally implicated as a mediator of diabetic complications. The present study was designed to evaluate the RAS in non-insulin dependent diabetic patients with diabetic nephropathy. Plasma renin activity, plasma angiotensin II and serum angiotensin-converting enzyme (ACE) activity were measured in 45 non-insulin dependent diabetes mellitus (NIDDM) patients and 15 healthy non-diabetic controls. Diabetics were subdivided into 15 normoalbuminuric NIDDM subjects, 15 NIDDM patients with microalbuminuria and 15 diabetics with macroalbuminuria. Mean plasma renin activity for macroalbuminuric diabetics (0.65+/-0.10 ng/ml/hr) was significantly reduced than the controls (1.28+/-0.37 ng/ml/hr) (P<0.001), the diabetic group with microalbuminuria (1.08+/-0.48 ng/ml/hr) (P<0.05) and normoalbuminuric patients (1.56+/-0.82 ng/ml/hr) (P<0.001). A significant negative correlation was obtained between serum creatinine and plasma renin activity (r=-0.842, p<0.001) in macroalbuminuric NIDDM patients. Plasma angiotensin II was significantly decreased in non-complicated diabetics compared to healthy controls (4.36+/-1.49 pg/ml vs 14.87+/-3.48 pg/ml respectively, p<0.001). Non-insulin dependent diabetic patients with nephropathy had significantly higher plasma angiotensin II levels (28.99+/-5.88 pg/ml) than non-complicated diabetics (p<0.001). Serum ACE activity was increased in 53.3% of NIDDM patients. All diabetic groups showed increased serum ACE activity (normoalbuminuric NIDDM 114.9+/-28.3 nmol/min/ml, microalbuminuric NIDDM 127.9+/-31.2 nmol/min/ml and macroalbuminuric NIDDM 127.0+/-29.3 nmol/min/ml) when compared to the normal control group (76.3+/-16.5 nmol/min/ml) (p<0.001). No significant difference in serum ACE activity was obtained between normoalbuminuric and nephropathic diabetics or between diabetics with and without retinopathy. No significant correlation was obtained between serum ACE activity and blood pressure, blood glucose level and duration of diabetes. Thus plasma renin activity is decreased in diabetic nephropathy and negatively correlates with serum creatinine. Plasma angiotensin II is decreased in normoalbuminuric diabetics and elevated in diabetic nephropathy. Serum ACE activity is raised in NIDDM patients with no relation to albumin excretion rate. The role of increased ACE activity in NIDDM remains to be established.
肾素-血管紧张素系统（RAS）已被明确认为是糖尿病并发症的介导因素。本研究旨在评估非胰岛素依赖型糖尿病肾病患者的RAS。对45例非胰岛素依赖型糖尿病（NIDDM）患者和15例健康非糖尿病对照者测定了血浆肾素活性、血浆血管紧张素II和血清血管紧张素转换酶（ACE）活性。糖尿病患者被分为15例正常白蛋白尿的NIDDM受试者、15例微量白蛋白尿的NIDDM患者和15例大量白蛋白尿的糖尿病患者。大量白蛋白尿糖尿病患者的平均血浆肾素活性（0.65±0.10 ng/ml/hr）显著低于对照组（1.28±0.37 ng/ml/hr）（P<0.001）、微量白蛋白尿糖尿病组（1.08±0.48 ng/ml/hr）（P<0.05）和正常白蛋白尿患者（1.56±0.82 ng/ml/hr）（P<0.001）。在大量白蛋白尿的NIDDM患者中，血清肌酐与血浆肾素活性之间存在显著负相关（r=-0.842，p<0.001）。与健康对照相比，无并发症糖尿病患者的血浆血管紧张素II显著降低（分别为4.36±1.49 pg/ml和14.87±3.48 pg/ml，p<0.001）。患有肾病的非胰岛素依赖型糖尿病患者的血浆血管紧张素II水平（28.99±5.88 pg/ml）显著高于无并发症糖尿病患者（p<0.001）。53.3%的NIDDM患者血清ACE活性升高。与正常对照组（76.3±16.5 nmol/min/ml）相比，所有糖尿病组的血清ACE活性均升高（正常白蛋白尿的NIDDM为114.9±28.3 nmol/min/ml、微量白蛋白尿的NIDDM为127.9±31.2 nmol/min/ml、大量白蛋白尿的NIDDM为127.0±29.3 nmol/min/ml）（p<0.001）。正常白蛋白尿和肾病糖尿病患者之间或有视网膜病变和无视网膜病变的糖尿病患者之间血清ACE活性无显著差异。血清ACE活性与血压、血糖水平和糖尿病病程之间无显著相关性。因此，糖尿病肾病患者的血浆肾素活性降低，且与血清肌酐呈负相关。正常白蛋白尿糖尿病患者的血浆血管紧张素II降低，而糖尿病肾病患者的血浆血管紧张素II升高。NIDDM患者血清ACE活性升高，与白蛋白排泄率无关。ACE活性升高在NIDDM中的作用尚待确定。
