Attman P O, Knight-Gibson C, Tavella M, Samuelsson O, Alaupovic P
Department of Nephrology, Sahlgrenska University Hospital, University of Göteborg, Sweden.
Nephrol Dial Transplant. 1998 Nov;13(11):2833-41. doi: 10.1093/ndt/13.11.2833.
Diabetic nephropathy (DN) is a common cause of chronic renal failure (CRF). Patients with DN have abnormal lipoprotein metabolism that can be influenced by both the impairment of renal function and the metabolic control of diabetes. The aim of the study was to explore the specific compositional lipoprotein abnormalities in patients with insulin-dependent DN in comparison with diabetic patients without nephropathy and non-diabetic CRF patients.
The lipid and apolipoprotein (apo) composition of major lipoprotein density classes was determined in 20 patients with insulin-dependent diabetes mellitus and nephropathy and compared with that in seven diabetic patients without nephropathy, 20 patients with non-diabetic CRF, and nine healthy control subjects. Lipoproteins isolated by preparative ultracentrifugation were very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL).
Patients with DN had a plasma lipid and apolipoprotein profile characteristic of renal dyslipoproteinaemia with increased concentrations of triglycerides and cholesterol, reduced levels of apoA-I and apoA-II and increased levels of apoB, apoC-II, apoC-III and apoE. These changes were more pronounced in diabetic than in non-diabetic patients with comparable degrees of renal failure. All density classes were characterized by abnormal concentration and composition of some lipid and apolipoprotein constituents. DN patients had a more than four-fold increase of VLDL mass, a three-fold increase of IDL mass, and a significant reduction of HDL mass compared to control subjects. They also had significantly higher concentrations of apoB, apoC-peptides and apoE particularly in VLDL and IDL, and to some extent in LDL. In HDL, DN patients had lower cholesterol, apoA-I, apoA-II and apoC-II levels than controls. The major compositional change in DN patients was a significant increase in the relative content of apoC-peptides in IDL and LDL. The lipoprotein abnormalities were more pronounced in patients with high HbA1c values. In addition, lower GFR and increased proteinuria were associated with higher concentrations of triglycerides and apoC peptides in VLDL, IDL, and LDL in DN patients.
The results indicate that patients with DN share the characteristic features of dyslipidaemia of CRF with accumulation of intact or partially delipidized apoB-containing lipoproteins enriched in apoC-peptides and apoE, which are present not only in VLDL and IDL but also in LDL density range. The alterations are more marked in DN than in nondiabetic CRF patients reflecting the additional impact of metabolic control. Increased levels of these lipoproteins may represent risk factors for the accelerated development of atherosclerotic vascular disease in these patients.
糖尿病肾病（DN）是慢性肾衰竭（CRF）的常见病因。DN患者存在脂蛋白代谢异常，这可能受到肾功能损害和糖尿病代谢控制的双重影响。本研究的目的是探讨胰岛素依赖型DN患者与无肾病的糖尿病患者及非糖尿病CRF患者相比，特定组成的脂蛋白异常情况。
测定了20例胰岛素依赖型糖尿病肾病患者主要脂蛋白密度类别的脂质和载脂蛋白（apo）组成，并与7例无肾病的糖尿病患者、20例非糖尿病CRF患者及9例健康对照者进行比较。通过制备性超速离心分离的脂蛋白有极低密度脂蛋白（VLDL）、中间密度脂蛋白（IDL）、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）。
DN患者具有肾性血脂异常血症的血浆脂质和载脂蛋白谱特征，甘油三酯和胆固醇浓度升高，apoA-I和apoA-II水平降低，apoB、apoC-II、apoC-III和apoE水平升高。在具有相当程度肾衰竭的患者中，这些变化在糖尿病患者中比在非糖尿病患者中更明显。所有密度类别的一些脂质和载脂蛋白成分的浓度和组成均异常。与对照组相比，DN患者的VLDL质量增加了四倍多，IDL质量增加了三倍，HDL质量显著降低。他们的apoB、apoC肽和apoE浓度也显著更高，特别是在VLDL和IDL中，在某种程度上在LDL中也是如此。在HDL中，DN患者的胆固醇、apoA-I、apoA-II和apoC-II水平低于对照组。DN患者的主要组成变化是IDL和LDL中apoC肽的相对含量显著增加。在HbA1c值高的患者中，脂蛋白异常更明显。此外，较低的肾小球滤过率（GFR）和蛋白尿增加与DN患者VLDL、IDL和LDL中甘油三酯和apoC肽的较高浓度相关。
结果表明，DN患者具有CRF血脂异常的特征，完整或部分脱脂的富含apoC肽和apoE的含apoB脂蛋白蓄积，这些脂蛋白不仅存在于VLDL和IDL中，也存在于LDL密度范围内。这些改变在DN患者中比在非糖尿病CRF患者中更明显，反映了代谢控制的额外影响。这些脂蛋白水平的升高可能代表这些患者动脉粥样硬化性血管疾病加速发展的危险因素。
