Association of cholesteryl ester transfer protein genotypes with paraoxonase‐1 activity, lipid profile and oxidative stress in type 2 diabetes mellitus: A study in S an L uis, A rgentina

• Published in: Journal of diabetes investigation 2015-01, Vol.6 (1), p.67-77
• Main Authors: Siewert, Susana, Gonzalez, Irma Ines, Lucero, Roberto Osvaldo, Ojeda, Marta Susana
• Format: Article
• Language: English
• Subjects: Atherosclerosis; Cardiovascular disease; Catalase; Cholesterol; Cholesteryl ester transfer protein; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Dyslipidemia; Enzymatic activity; Enzymes; Gene polymorphism; Insulin; Insulin resistance; Lipid peroxidation; Lipids; Lipoproteins; Metabolism; Nitric oxide; Oxidation; Oxidative stress; Paraoxonase; Polymerase chain reaction; Proteins; Thiobarbituric acid
• ISSN: 2040-1116; 2040-1124
• DOI: 10.1111/jdi.12256

Aims/IntroductionDiabetic dyslipidemia is common in type 2 diabetes. The TaqIB polymorphism in cholesteryl ester transfer protein (CETP; B1 and B2 alleles; rs708272) is associated with changes in enzyme activity and lipid concentrations. The aim of the present study was to assess associations of CETP genotypes with lipoprotein profile, oxidant/anti‐oxidant status and the plasma activity of paraoxonase‐1 (PON‐1) in a population of diabetic patients living in San Luis, Argentina.Materials and MethodsFor oxidative stress status parameters, thiobarbituric acid‐reactive substances (TBARS) and nitric oxide (NO) levels, and catalase and PON‐1 activity were assessed in 40 patients with type 2 diabetes mellitus and 30 healthy participants. CETP polymorphism was analyzed by polymerase chain reaction‐based methods.ResultsType 2 diabetes mellitus had significantly higher concentrations of oxidative stress parameters: TBARS (P < 0.0001) and catalase activity (P < 0.0001). PON‐1 activity and NO levels were significantly lower in diabetics (P = 0.0002 and P = 0.0008, respectively). The CETP genotypes distribution among study groups was not significantly different. The B2 carriers of the TaqIB CETP polymorphism are associated with higher high‐density lipoprotein cholesterol levels and PON‐1 activity in control and type 2 diabetes mellitus patients. Linear regression analysis showed that there was a significant and positive correlation between the changes of PON‐1 activity and high‐density lipoprotein cholesterol levels in non‐B1B1 (B2 carriers) in controls (r = 0.83, P < 0.0001) and diabetic patients (r = 0.39, P = 0.0003).ConclusionsThe results of the current study show that type 2 diabetes mellitus is characterized by intense oxidative stress, and that the alterations observed in the lipoprotein profile and PON‐1 activity might be related to the higher CETP activity in diabetic patients as a consequence of insulin resistance.