Association of cholesteryl ester transfer protein genotypes with paraoxonase-1 activity, lipid profile and oxidative stress in type 2 diabetes mellitus: A study in San Luis, Argentina.

AIMS/INTRODUCTION: Diabetic 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 METHODS: For 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. RESULTS: Type 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). CONCLUSIONS: The 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.

Reduced blood nrf-2 mRNA in local overweight boys at risk of metabolic complications: a study in San Luis City, San Luis, Argentina.

BACKGROUND: Childhood overweight (OW) is a matter of public health concern because of its long-term impact on adulthood health. NF-E2-related factor 2 (Nrf-2) regulates the antioxidant/lipogenic response to a sustained positive energy balance that prevails during weight gain. Here we aimed at studying a possible link between OW and Nrf-2-dependent antioxidant/lipogenic response in a local population of boys at risk of metabolic complications. METHODS: We measured clinical and biochemical parameters related to lipid metabolism, oxidative stress, and metabolic syndrome in a population of OW boys [body mass index (BMI) percentile ≥85(th) and <95(th), n=22] and normal weight boys (NW; BMI percentile<85(th), n=27) from San Luis City, San Luis, Argentina. RESULTS: Compared to NW, OW boys had lower insulin sensitivity, an altered plasma lipid profile, and increased markers of oxidative stress and inflammatory fatty acids. OW boys also had a higher atherogenic index and peripheral insulin resistance than NW boys. We also found that glutathione peroxidase activity and the reduced glutathione to oxidized glutathione ratio were lower in OW boys than NW boys, suggesting that OW boys may have an altered antioxidant response to oxidative stress. Finally, Nrf-2 expression negatively correlated with metabolic syndrome parameters in OW boys. CONCLUSIONS: Our data suggest that OW boys have a reduced antioxidant and lipogenic response to a positive energy balance, resulting in oxidative stress, insulin resistance, and risk of developing metabolic complications. Our data also provide a rationale for nutritional interventions aimed at restoring Nrf-2 expression to reduce the risk of metabolic complications in OW boys.

Impact of metabolic syndrome risk factors in first-degree relatives of type 2 diabetic patients.

OBJECTIVE: Family members of patients with an established diagnosis of type 2 diabetes mellitus (T2DM) are theoretically at risk of having the metabolic syndrome (MetS). A sample of these family members was studied from a population in a small township in Argentina, which has a high prevalence of T2DM. METHODS: We examined the clinical and metabolic characteristics of 132 first-degree relatives of T2DM patients (FDR) and 112 age-matched controls. The subjects were categorized according to the International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria for MetS. RESULTS: The prevalence of MetS in the FDR group was 34.8 (IDF) and 26.5% (NCEP-ATPIII) respectively, which was significantly different to the prevalence in controls (p < 0.025). According to IDF criteria, the most prevalent factors among FDR subjects with MetS were low HDL-cholesterol (87%) followed by hypertriglyceridemia (69.5%). In the MetS group, which ranged between 20-29 years old (36%), the major risk factor in women was a low HDL-cholesterol serum level. In the MetS group, which ranged between 30-39 years old (44.4%), the most important risk factor in men was hypertriglyceridemia. CONCLUSION: This study revealed that the prevalence of MetS is high in young FDR adults, who need urgent preventive treatment, including lifestyle changes. The risk of developing T2DM is five times higher in non-diabetic people with MetS than in those without the syndrome.