Bulum Tomislav, Duvnjak Lea, Prkacin Ingrid
Sveucilisna Klinika za dijabetes, endokrinologiju i bolesti metabolizma Vuk Vrhovac, Zagreb, Hrvatska.
Acta Med Croatica. 2011;65(3):243-50.
Lipoproteins may contribute to diabetic nephropathy. Although elevated total HDL cholesterol levels have been shown to protect from coronary artery disease and nephropathy in many studies, HDL can be subdivided into at least two major subclasses, which are thought to differ in the ability to protect against atherosclerosis. The objective of this study was to determine the relationship between serum lipids and HDL subclasses with albuminuria in patients with type 1 diabetes.
We analyzed lipid profiles of 259 patients with type 1 diabetes and normal thyroid function. Patients were classified as normoalbuminuric (albumin excretion rate < 30 mg/24 h, n = 215) and microalbuminuric (albumin excretion rate 30-300 mg/24 h, n = 44) in at least two urine collections. None showed signs of adrenal, thyroid, renal or cardiovascular disease, or received drugs, apart from insulin, that could attenuate glucose metabolism, serum lipids or renal function. Total, LDL, HDL, HDL2, HDL3, VLDL cholesterol and triglycerides were measured by an enzymatic colorimetric method and urinary albumin concentration was determined by an immunoturbidimetric assay.
Patients with microalbuminuria had higher levels of total cholesterol (5.07 vs. 5.02 mmol/L, Mann Whitney=6874, P = 0.666), LDL cholesterol (2.81 vs. 2.80 mmol/L, Mann Whitney = 6964, P = 0.778), VLDL cholesterol (0.57 vs. 0.48 mmol/L, Mann Whitney = 6268, P = 0.151) and triglycerides (1.27 vs. 1.08 mmol/L, Mann Whitney = 6283, P = 0.158), and lower levels of HDL cholesterol (1.68 vs. 1.73 mmol/L, Mann Whitney = 6501, P = 0.293) and HDL3 cholesterol (1.15 vs. 1.16 mmol/L, Mann Whitney = 6991, P = 0.812); however, these differences were not statistically significant. In contrast, HDL2 cholesterol levels were significantly lower in those who had microalbuminuria compared with those who had normoalbuminuria (0.50 vs. 0.57 mmol/L, Mann Whitney = 5600, P = 0.01).
Microalbuminuria is the earliest clinical indicator of diabetic nephropathy. Clustering of coronary artery disease with nephropathy has been shown previously in patients with type 1 diabetes. Specific effects of HDL subclasses on cardiovascular disease have also been observed, i.e. a protective effect of large HDL subfractions (HDL2) and an increased risk for small HDL particles (HDL3). Results of the present study showed that lower levels of HDL2 cholesterol were associated with microalbuminuria in patients with type 1 diabetes. Whether higher HDL2 cholesterol levels may be protective against the development of microalbuminuria in patients with type 1 diabetes can only be determined in long-term studies.
脂蛋白可能与糖尿病肾病有关。尽管在许多研究中已表明，总高密度脂蛋白胆固醇（HDL-C）水平升高可预防冠状动脉疾病和肾病，但HDL可至少细分为两个主要亚类，它们在预防动脉粥样硬化的能力方面被认为有所不同。本研究的目的是确定1型糖尿病患者血清脂质和HDL亚类与蛋白尿之间的关系。
我们分析了259例甲状腺功能正常的1型糖尿病患者的血脂谱。在至少两次尿液收集过程中，将患者分为正常白蛋白尿组（白蛋白排泄率<30mg/24h，n = 215）和微量白蛋白尿组（白蛋白排泄率30 - 300mg/24h，n = 44）。除胰岛素外，所有患者均未表现出肾上腺、甲状腺、肾脏或心血管疾病的迹象，也未接受可能减弱糖代谢、血清脂质或肾功能的药物治疗。采用酶比色法测量总胆固醇、低密度脂蛋白胆固醇（LDL-C）、HDL-C、HDL2-C、HDL3-C、极低密度脂蛋白胆固醇（VLDL-C）和甘油三酯，并采用免疫比浊法测定尿白蛋白浓度。
微量白蛋白尿患者的总胆固醇（5.07对5.02mmol/L，曼-惠特尼检验=6874，P = 0.666）、LDL-C（2.81对2.80mmol/L，曼-惠特尼检验=6964，P = 0.778）、VLDL-C（0.57对0.48mmol/L，曼-惠特尼检验=6268，P = 0.151）和甘油三酯（1.27对1.08mmol/L，曼-惠特尼检验=6283，P = 0.158）水平较高，而HDL-C（1.68对1.73mmol/L，曼-惠特尼检验=6501，P = 0.293）和HDL3-C（1.15对1.16mmol/L，曼-惠特尼检验=6991，P = 0.812）水平较低；然而，这些差异无统计学意义。相比之下，微量白蛋白尿患者的HDL2-C水平显著低于正常白蛋白尿患者（0.50对0.57mmol/L，曼-惠特尼检验=5600，P = 0.01）。
微量白蛋白尿是糖尿病肾病最早的临床指标。先前在1型糖尿病患者中已显示冠状动脉疾病与肾病的聚集现象。也已观察到HDL亚类对心血管疾病的特定影响，即大HDL亚组分（HDL2）的保护作用和小HDL颗粒（HDL3）风险增加。本研究结果表明，1型糖尿病患者中较低的HDL2-C水平与微量白蛋白尿有关。HDL2-C水平升高是否可预防1型糖尿病患者微量白蛋白尿的发生，只能在长期研究中确定。
