Lam K S, Pang R W, Wat M S, Lauder I J, Janus E D
Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong.
Nephrol Dial Transplant. 1996 Nov;11(11):2229-36. doi: 10.1093/oxfordjournals.ndt.a027141.
This study was conducted to determine whether circulating levels of lipoprotein (a), an independent risk factor of macrovascular disease, are increased in non-insulin-dependent diabetes mellitus (NIDDM) patients with microalbuminuria who have an increased risk of cardiovascular mortality. Apolipoprotein (a) [apo(a)] levels and phenotypes, and other circulating lipid levels were determined in 227 Chinese NIDDM patients with varying stages of diabetic nephropathy. None was on lipid-lowering therapy. Apo(a) levels in normoalbuminuric (geometric mean 166 U/L; 95% confidence intervals 137, 200; n = 105) and microalbuminuric patients (162; 132, 209; n = 77) were similar to values in controls (166; 143, 193, n = 168). Albuminuric patients, however, had higher apo(a) levels than both normoalbuminuric patients and controls (242; 184, 317; n = 45; P < 0.05). The overall size range of the apo(a) phenotypes and the frequency of having at least one small isoform, i.e. < 700 kDa, were similar among the four groups of subjects. A positive correlation was found between log apo(a) and log plasma creatinine levels (P < 0.01). Compared to normoalbuminuric patients, both microalbuminuric and albuminuric patients were older (P < 0.01) and had higher HbA1c (P < 0.01), greater BMI (P < 0.05) and longer disease duration (P < 0.05) compared to normoalbuminuric patients. Nevertheless, using multiple linear regression analysis, it was found that the presence of nephropathy conferred an independent influence on increasing total cholesterol (P < 0.001), triglyceride (P < 0.001) and apoB (P < 0.01), and decreasing HDL cholesterol (P < 0.05) levels even when only the normoalbuminuric and microalbuminuric groups were analysed. The prevalence of macrovascular disease was significantly increased in microalbuminuric and albuminuric patients (45.1 and 48.7% respectively vs 20.2% in normoalbuminuric patients, P < 0.01). It is concluded that circulating apo(a) levels were not increased in Chinese NIDDM patients with microalbuminuria. However, atherogenic changes in other lipid and lipoprotein levels may contribute to an increased risk of macrovascular disease in these patients.
本研究旨在确定脂蛋白(a)（一种大血管疾病的独立危险因素）在心血管死亡风险增加的非胰岛素依赖型糖尿病（NIDDM）微量白蛋白尿患者中的循环水平是否升高。对227例处于不同糖尿病肾病阶段的中国NIDDM患者测定了载脂蛋白(a)[apo(a)]水平和表型以及其他循环脂质水平。所有患者均未接受降脂治疗。正常白蛋白尿患者（几何均数166 U/L；95%可信区间137, 200；n = 105）和微量白蛋白尿患者（162；132, 209；n = 77）的apo(a)水平与对照组（166；143, 193, n = 168）相似。然而，白蛋白尿患者的apo(a)水平高于正常白蛋白尿患者和对照组（242；184, 317；n = 45；P < 0.05）。四组受试者中apo(a)表型的总体大小范围以及至少有一种小异构体（即< 700 kDa）的频率相似。发现log apo(a)与log血浆肌酐水平之间呈正相关（P < 0.01）。与正常白蛋白尿患者相比，微量白蛋白尿和白蛋白尿患者年龄更大（P < 0.01），糖化血红蛋白更高（P < 0.01），体重指数更大（P < 0.05），病程更长（P < 0.05）。然而，使用多元线性回归分析发现，即使仅分析正常白蛋白尿组和微量白蛋白尿组，肾病的存在对总胆固醇升高（P < 0.001）、甘油三酯升高（P < 0.001）和载脂蛋白B升高（P < 0.01）以及高密度脂蛋白胆固醇降低（P < 0.05）具有独立影响。微量白蛋白尿和白蛋白尿患者大血管疾病的患病率显著升高（分别为45.1%和48.7%，而正常白蛋白尿患者为20.2%，P < 0.01）。结论是，中国NIDDM微量白蛋白尿患者的循环apo(a)水平并未升高。然而，其他脂质和脂蛋白水平的致动脉粥样硬化变化可能导致这些患者大血管疾病风险增加。
