The Systemic Redox Status Is Maintained in Non-Smoking Type 2 Diabetic Subjects Without Cardiovascular Disease: Association with Elevated Triglycerides and Large VLDL

Abstract

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, p < 0.05), but were not decreased in T2DM subjects versus non-diabetic subjects (p = 0.31). Free thiols were higher in subjects with (663 ± 84 µmol/L) versus subjects without elevated triglycerides (619 ± 91 µmol/L; p = 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, p = 0.004), FFA (β = 0.168, p = 0.029) and PLTP activity (β = 0.228, p = 0.002), inversely with adiponectin (β = −0.308, p < 0.001) but not with glucose (β = 0.052, p = 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, p = 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.

Systemic Oxidative Stress, Aging and the Risk of Cardiovascular Events in the General Female Population

“…In line with this, lower levels of serum free thiols have been associated with elevated parameters of visceral adiposity that may increase the risk of disease development ( 39 ). The observation that patients with type 2 diabetes mellitus have significantly lower levels of free thiols also confirms findings from previous studies ( 40 , 41 ). Finally, the positive association between estimated kidney function and serum free thiols also validates previous work.…”

The Association of Oxidative and Antioxidant Potential with Cardiometabolic Risk Profile in the Group of 60- to 65-Year-Old Seniors from Central Poland

“…Concentration of free protein SH groups of blood platelets in multivariable analysis is negatively impacted by concentration of UA and presence of lipid disorders and positively impacted by plasma concentration of vWF. The obtained results are consistent with the data presented by van Dijk et al [ 55 ]. Still, the literature in this field is scarce, as is the information about the relationship between concentration of platelet protein free thiol groups and plasma concentration of vWF.…”

“…Van Dijk et al indicated such a relation, but only in bivariate analysis. In a multivariable trial, the most prominent coefficient was the concentration of triglycerides [ 55 ]. Nevertheless, the cited work compared diabetic and non-diabetic participants and hyperglycemia seems to be most harmful factor for the plasma free SH group’s balance.…”

Profoundly Disturbed Lipoproteins in Cirrhotic Patients: Role of Lipoprotein-Z, a Hepatotoxic LDL-like Lipoprotein

“…ApoA-I and apoA-II, major apolipoproteins that are carried by HDL, have been described to be decreased in cholestatic liver diseases together with impaired HL, lipoprotein lipase (LPL), and LCAT activities [ 9 , 49 ]. Hepatocytes are also able to produce protein factors involved in antioxidant defense and lipid transfer proteins, such as phospholipid transfer protein (PLTP), which affects triglyceride assembly and secretion and converts HDL in larger to smaller HDLP [ 51 , 52 , 53 , 54 , 55 ], and cholesteryl ester transfer protein (CETP) [ 52 ], which transfers cholesteryl esters from HDL towards lipoproteins of lower density. Plasma lipoproteins also tend to decrease in parenchymal liver diseases, where abnormalities in the composition of various lipoproteins depends on disturbed apolipoprotein synthesis, lipoprotein receptor abundance, and expression of enzymes involved in lipoprotein metabolism [ 1 ].…”