van Dijk Peter R, Abdulle Amaal Eman, Bulthuis Marian L C, Perton Frank G, Connelly Margery A, van Goor Harry, Dullaart Robin P F
Department of Endocrinology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
Department of Internal Medicine, division vascular medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
J Clin Med. 2019 Dec 24;9(1):49. doi: 10.3390/jcm9010049.
Decreased circulating levels of free thiols (R-SH, sulfhydryl groups) reflect enhanced oxidative stress, which plays an important role in the pathogenesis of cardiometabolic diseases. Since hyperglycemia causes oxidative stress, we questioned whether plasma free thiols are altered in patients with type 2 diabetes mellitus (T2DM) without cardiovascular disease or renal function impairment. We also determined their relationship with elevated triglycerides and very low density lipoproteins (VLDL), a central feature of diabetic dyslipidemia. Fasting plasma free thiols (colorimetric method), lipoproteins, VLDL (nuclear magnetic resonance spectrometry), free fatty acids (FFA), phospholipid transfer protein (PLTP) activity and adiponectin were measured in 79 adult non-smoking T2DM subjects (HbA1c 51 ± 8 mmol/mol, no use of insulin or lipid lowering drugs), and in 89 non-smoking subjects without T2DM. Plasma free thiols were univariately correlated with glucose (r = 0.196, < 0.05), but were not decreased in T2DM subjects versus non-diabetic subjects ( = 0.31). Free thiols were higher in subjects with (663 ± 84 µmol/L) versus subjects without elevated triglycerides (619 ± 91 µmol/L; = 0.002). Age- and sex-adjusted multivariable linear regression analysis demonstrated that plasma triglycerides were positively and independently associated with free thiols (β = 0.215, = 0.004), FFA (β = 0.168, = 0.029) and PLTP activity (β = 0.228, = 0.002), inversely with adiponectin (β = -0.308, < 0.001) but not with glucose (β = 0.052, = 0.51). Notably, the positive association of free thiols with (elevated) triglycerides appeared to be particularly evident in men. Additionally, large VLDL were independently associated with free thiols (β = 0.188, = 0.029). In conclusion, circulating free thiols are not decreased in this cohort of non-smoking and generally well-controlled T2DM subjects. Paradoxically, higher triglycerides and more large VLDL particles are likely associated with higher plasma levels of thiols, reflecting lower systemic oxidative stress.
循环中游离硫醇（R-SH，巯基）水平降低反映氧化应激增强，氧化应激在心脏代谢疾病的发病机制中起重要作用。由于高血糖会导致氧化应激，我们质疑在无心血管疾病或肾功能损害的2型糖尿病（T2DM）患者中血浆游离硫醇是否发生改变。我们还确定了它们与甘油三酯升高及极低密度脂蛋白（VLDL）（糖尿病血脂异常的一个主要特征）之间的关系。对79名成年非吸烟T2DM患者（糖化血红蛋白51±8 mmol/mol，未使用胰岛素或降脂药物）和89名非吸烟非T2DM受试者测量了空腹血浆游离硫醇（比色法）、脂蛋白、VLDL（核磁共振光谱法）、游离脂肪酸（FFA）、磷脂转运蛋白（PLTP）活性和脂联素。血浆游离硫醇与血糖单变量相关（r = 0.196，P<0.05），但与非糖尿病受试者相比，T2DM患者的血浆游离硫醇并未降低（P = 0.31）。甘油三酯升高的受试者的游离硫醇水平（663±84 μmol/L）高于甘油三酯未升高的受试者（619±91 μmol/L；P = 0.002）。年龄和性别校正的多变量线性回归分析表明，血浆甘油三酯与游离硫醇呈正相关且独立相关（β = 0.215，P = 0.004）、与FFA（β = 0.168，P = 0.029）和PLTP活性（β = 0.228，P = 0.002）呈正相关，与脂联素呈负相关（β = -0.308，P<0.001），但与血糖无关（β = 0.052，P = 0.51）。值得注意的是，游离硫醇与（升高的）甘油三酯之间的正相关在男性中似乎尤为明显。此外，大颗粒VLDL与游离硫醇独立相关（β = 0.188，P = 0.029）。总之，在这个非吸烟且总体控制良好的T2DM受试者队列中，循环游离硫醇并未降低。矛盾的是，较高的甘油三酯和更多的大颗粒VLDL可能与较高的血浆硫醇水平相关，这反映了较低的全身氧化应激。
