Juretić Dubravka, Motejlkova Alena, Kunović Branka, Rekić Branka, Flegar-Mestrić Zlata, Vujić Lovorka, Mesić Ranko, Lukac-Bajalo Jana, Simeon-Rudolf Vera
Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.
Acta Pharm. 2006 Mar;56(1):59-68.
The aim of this study was to determine whether the paraoxonase (PON1) status, i.e. PON1 activities and phenotypes (AA, AB and BB), and its relationship with lipid status are different in patients with type II diabetes as compared to healthy population. Diabetic group comprised 175 patients with type II diabetes mellitus (94 men and 81 women) who came to their regular control examination and took the oral glucose tolerance test. Patients with type II diabetes mellitus diagnosis for 12 years on average were on peroral antidiabetics, or insulin or diet, and 3 patients had no therapy prescribed yet. Control group comprised 114 apparently healthy individuals (28 men and 86 women) who were not on any medication. The paraoxonase activity was measured with 2.0 mmol L(-1) paraoxon in the absence and in the presence of 1.0 mol L(-1) NaCl, and with 2.0 mmol L(-1) phenylacetate. Both activities were measured spectrophotometrically at 37 degrees C in 0.1 mol L(-1) Tris-HCl buffer, pH = 8.0, containing 2.0 mmol L(-1) CaCl(2). Sera of diabetic and control subjects were assigned to the paraoxonase phenotypes on the basis of the basal paraoxonase activity distribution. We assigned 45% sera of male and 49% sera of female diabetic patients, and 64% sera of both genders of the control group to the AA low activity phenotype. There were no differences in paraoxonase activities between the gender- and phenotype-matched diabetic and control groups. Enzyme activity against the phenylacetate was higher, and phenotype-dependent, only in diabetic patients. In contrast to AA phenotype individuals, total cholesterol and LDL-cholesterol in the female diabetic group and triglyceride concentration in the male diabetic group assigned to pooled AB and BB phenotypes were higher than in the corresponding controls. It follows from PON1 phenotype distribution that less antiatherogenic paraoxonase B allele is more frequent in type II diabetes mellitus than in the healthy population. Their lipid status is more atherogenic, which could indicate a risk of premature atherosclerosis.
本研究的目的是确定与健康人群相比，2型糖尿病患者的对氧磷酶（PON1）状态，即PON1活性和表型（AA、AB和BB）及其与血脂状态的关系是否存在差异。糖尿病组包括175例2型糖尿病患者（94例男性和81例女性），他们前来进行定期复查并接受口服葡萄糖耐量试验。2型糖尿病患者平均确诊12年，正在接受口服降糖药、胰岛素治疗或饮食控制，3例患者尚未接受任何治疗。对照组包括114名明显健康的个体（28例男性和86例女性），他们未服用任何药物。在不存在和存在1.0 mol L(-1) NaCl的情况下，用2.0 mmol L(-1) 对氧磷测定对氧磷酶活性，并用2.0 mmol L(-1) 苯乙酸酯测定。两种活性均在37℃下于0.1 mol L(-1) Tris-HCl缓冲液（pH = 8.0，含有2.0 mmol L(-1) CaCl(2)）中通过分光光度法测定。根据基础对氧磷酶活性分布，将糖尿病和对照受试者的血清分为对氧磷酶表型。我们将45%的男性糖尿病患者血清和49%的女性糖尿病患者血清，以及对照组64%的男女血清归为AA低活性表型。性别和表型匹配的糖尿病组和对照组之间的对氧磷酶活性没有差异。仅在糖尿病患者中，针对苯乙酸酯的酶活性更高且与表型有关。与AA表型个体相比，合并AB和BB表型的女性糖尿病组中的总胆固醇和低密度脂蛋白胆固醇以及男性糖尿病组中的甘油三酯浓度高于相应的对照组。从PON1表型分布可以看出，抗动脉粥样硬化作用较弱的对氧磷酶B等位基因在2型糖尿病患者中比在健康人群中更常见。他们的血脂状态更具动脉粥样硬化性，这可能表明存在过早发生动脉粥样硬化的风险。
