Tamsma J T, Beverdam F H, Leuven J A, Lemkes H H
Department of Endocrinology, University Hospital, Leiden, The Netherlands.
Diabetes. 1995 May;44(5):501-5. doi: 10.2337/diab.44.5.501.
The risk of cardiovascular morbidity and mortality is highly increased in patients with diabetic nephropathy. Postulating that the generalized vasculopathy observed in these patients may enhance transcapillary filtration of lipids and lipoproteins resulting in a more atherogenic interstitial lipid profile, we set out to analyze the composition of their interstitial fluid. We studied healthy control subjects (n = 9), normoalbuminuric insulin-dependent diabetes mellitus (IDDM) patients (n = 16), and IDDM patients with diabetic nephropathy (n = 11) matched for age, body mass index, smoking habits, duration of diabetes, and metabolic control. Interstitial fluid was collected after an overnight fast by applying mild suction (200 mmHg) to the skin. Interstitial apolipoprotein A-I (apoA-I) levels were significantly lower in patients with nephropathy (0.18 +/- 0.10 milligram [mean +/- SD]) compared with normoalbuminuric diabetic patients (0.29 +/- 0.08 milligram) and healthy control subjects (0.30 +/- 0.09 milligram). Interstitial apolipoprotein B:apoA-I ratios tended to be higher in patients with diabetic nephropathy. In these patients, normal interstitial low-density lipoprotein cholesterol concentrations were observed in the presence of lower apoA-I levels. Transcapillary filtration of apoA-I was significantly lower in patients with diabetic nephropathy. Furthermore, an altered multiple regression model explaining interstitial apoA-I levels was observed in diabetic nephropathy. In this model, transcapillary protein (IgG) filtration and serum apoA-I levels no longer explained interstitial apoA-I levels. If we assume that interstitial apoA-I is involved in reverse cholesterol transport, these data suggest a more atherogenic interstitial lipoprotein profile in IDDM patients with nephropathy.
糖尿病肾病患者发生心血管疾病发病和死亡的风险显著增加。鉴于在这些患者中观察到的全身性血管病变可能会增强脂质和脂蛋白的跨毛细血管滤过，从而导致更易致动脉粥样硬化的间质脂质谱，我们着手分析他们间质液的成分。我们研究了健康对照者（n = 9）、正常白蛋白尿的胰岛素依赖型糖尿病（IDDM）患者（n = 16）以及年龄、体重指数、吸烟习惯、糖尿病病程和代谢控制相匹配的糖尿病肾病IDDM患者（n = 11）。在禁食过夜后，通过对皮肤施加轻度负压（200 mmHg）收集间质液。与正常白蛋白尿的糖尿病患者（0.29±0.08毫克）和健康对照者（0.30±0.09毫克）相比，肾病患者的间质载脂蛋白A-I（apoA-I）水平显著降低（0.18±0.10毫克[均值±标准差]）。糖尿病肾病患者的间质载脂蛋白B:apoA-I比值往往更高。在这些患者中，在apoA-I水平较低的情况下观察到正常的间质低密度脂蛋白胆固醇浓度。糖尿病肾病患者的apoA-I跨毛细血管滤过显著降低。此外，在糖尿病肾病中观察到一个解释间质apoA-I水平的多元回归模型发生了改变。在这个模型中，跨毛细血管蛋白（IgG）滤过和血清apoA-I水平不再能解释间质apoA-I水平。如果我们假设间质apoA-I参与逆向胆固醇转运，这些数据表明肾病IDDM患者的间质脂蛋白谱更易致动脉粥样硬化。
