Jain S K, McVie R, Jaramillo J J, Chen Y
Department of Pediatrics, Louisiana State University School of Medicine, Shreveport 71130, USA.
Free Radic Biol Med. 1998 Jan 1;24(1):175-81. doi: 10.1016/s0891-5849(97)00213-x.
The reason for the disproportionately higher level of vascular disease in patients with diabetes is not known. Oxidative modification of low-density lipoproteins has been implicated in impaired cholesterol uptake and its deposition in the arterial wall and atherosclerosis. The present study has examined the effects of hyperketonemia, glycemic control and duration of diabetes on the in vitro oxidative susceptibility to Cu++ of low-density lipoprotein (LDL) + very low-density lipoprotein (VLDL) from 34 Type-I diabetic patients without any clinical sign of vascular disease and 22 age-matched normal individuals. LDL + VLDL was isolated from plasma using a micro-affinity column. LDL + VLDL isolated from diabetic patients and age-matched normal individuals was treated with 25 mM CuCl2 for 1.5, 3 and 5 h. The ketone bodies acetoacetate (AA) and beta-hydroxybutyrate (BHB), as well as glycated hemoglobin (HbA1), were measured in the blood by standard methods. There was no difference in the in vitro oxidative susceptibility of LDL + VLDL at all time periods between Type-I diabetics (n = 34) and age-matched normal individuals (n = 22). However, among diabetics, when patients were separated into normoketonemic (NK) and hyperketonemic (HK) groups, in vitro oxidation of LDL + VLDL at 1.5 h from hyperketonemic diabetics was a 69% greater (p < .02) compared with that of normoketonemic diabetics and 80% greater (p < .02) compared with that of normal individuals. There was a significant correlation (r = 0.38, p < .03) between the in vitro oxidation of LDL + VLDL at 1.5 h and AA levels in diabetic patients. The level of in vitro oxidizability of LDL + VLDL did not have any correlation with levels of BHB (r = 0.20, p > .26), HbA1 (r = 0, p > .99), glucose (r = 0.06, p > .75) or duration of diabetes (r = 0.15, p > .40) in diabetic patients. In vitro incubation of normal plasma with AA resulted in an increase in the Cu + induced lipid peroxidation of LDL + VLDL. This study suggests that frequent episodes of ketosis and elevated levels of AA constitute a risk factor for the oxidative modification of low-density lipoproteins and development of vascular disease in diabetic patients.
糖尿病患者血管疾病水平异常升高的原因尚不清楚。低密度脂蛋白的氧化修饰与胆固醇摄取受损及其在动脉壁和动脉粥样硬化中的沉积有关。本研究检测了高酮血症、血糖控制和糖尿病病程对34例无任何血管疾病临床症状的I型糖尿病患者及22例年龄匹配的正常个体的低密度脂蛋白（LDL）+极低密度脂蛋白（VLDL）体外对Cu++氧化敏感性的影响。使用微亲和柱从血浆中分离LDL+VLDL。将从糖尿病患者和年龄匹配的正常个体中分离出的LDL+VLDL用25 mM CuCl2处理1.5、3和5小时。通过标准方法检测血液中的酮体乙酰乙酸（AA）和β-羟基丁酸（BHB）以及糖化血红蛋白（HbA1）。I型糖尿病患者（n=34）和年龄匹配的正常个体（n=22）在所有时间段内LDL+VLDL的体外氧化敏感性均无差异。然而，在糖尿病患者中，当将患者分为正常酮血症（NK）组和高酮血症（HK）组时，高酮血症糖尿病患者1.5小时时LDL+VLDL的体外氧化比正常酮血症糖尿病患者高69%（p<.02），比正常个体高80%（p<.02）。糖尿病患者中，1.5小时时LDL+VLDL的体外氧化与AA水平之间存在显著相关性（r=0.38，p<.03）。糖尿病患者中，LDL+VLDL的体外氧化水平与BHB水平（r=0.20，p>.26）、HbA1水平（r=0，p>.99）、血糖水平（r=0.06，p>.75）或糖尿病病程（r=0.15，p>.40）均无相关性。正常血浆与AA体外孵育导致Cu+诱导的LDL+VLDL脂质过氧化增加。本研究表明，频繁的酮症发作和AA水平升高是糖尿病患者低密度脂蛋白氧化修饰和血管疾病发生的危险因素。
