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.
Oxidative stress is associated with diabetes mellitus, a condition characterized by increased prevalence and progression rate of cardiovascular disease. NFE2-related factor 2 (Nrf2) is a master regulator of cellular detoxification responses and redox status. The aim of this study was to examine associations between type 2 Diabetes Mellitus (T2DM), oxidative stress and the expression of NFE2-related factor 2 (Nrf2) in a population of diabetic patients living in Juana Koslay City, San Luis, Argentina. In addition, we evaluated the functional relevance of Nrf2 by measuring the HO-1 expression among persons with type 2 diabetes. We measured clinical and biochemical parameters related to lipid metabolism and oxidative stress in a population of Type 2 Diabetes Mellitus patients (T2DM, n = 40) and controls (Co, n = 30). Compared to Co, T2DM patients had higher fasting serum glucose, glycated hemoglobin, triglycerides, total cholesterol, low-density lipoprotein cholesterol, and thiobarbituric acid reactive substances and lower high-density lipoprotein cholesterol. T2DM individuals had also higher atherogenic index and body mass index than controls. We also founded that HO-1 mRNA in whole blood was lower in T2DM than controls, suggesting that T2DM may have an altered antioxidant response to oxidative stress. Interestingly, we found reduced Nrf2 mRNA in whole blood from T2DM compared to Co. The results from this study provide novel evidence that genes associated to antioxidant defense mechanisms are markedly reduced in patients with type 2 diabetes, and that the reduction in the expression of these genes could be associated to hyperglycemia and increased levels of MDA. Linear regression analysis revealed that there was a strong and positive correlation between the changes of Nrf2 and HO-1 expression levels.
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.
Polymorphisms in the gene coding for transcription factor 7 like 2 (TCF7L2) are recognized as the strongest common genetic risk factors for Type 2 Diabetes Mellitus (T2DM) across multiple ethnicities. This study was conducted to evaluate an association between TCF7L2 variants and diabetes susceptibility in the population of Juana Koslay, San Luis, Argentina. We genotyped 2 single nucleotide polymorphisms (SNP) rs7903146 and rs12255372 in controls and diabetic subjects. Association with T2DM was found for both SNPs rs7903146 and rs12255372 in the whole sample (under a dominant genetic model, the odds ratios (OR) were 3.43, 95% CI [1.879 -6.255], p < 0.0001 and OR = 4.40, 95% CI [2.318 -8.351], p < 0.0001, respectively). The risk conferred by homozygotes is much higher than the heterozygote carriers and it is marked in case of rs7903146. The haplotype that consisted of two minor alleles (TT) or the haplotypes carrying at least one of the minor alleles at SNP rs7903146 or rs12255372 (i.e. CT or TG) were more frequent in the group of T2DM. The impact of TCF7L2 variation on T2DM risk in Juana Koslay population is compatible with that demonstrated by a range of studies conducted in various ethnic groups.
The single nucleotide polymorphism (SNP) rs4731702 in the KLF14 transcription factor gene has been associated with type 2 diabetes mellitus (T2DM) and HDL-c concentrations. The aim of the present study was to determine the distribution of KLF14 rs4731702 SNP and evaluate the association between this SNP and serum lipid profile in T2DM patients in a patient population at San Luis province, Argentina. A total of 73 volunteers (26 T2DM patients and 47 healthy age-matched controls)were genotyped for KLF14 rs4731702 SNP by Tetra Primer ARMS-PCR. The KLF14 genotypes distribution among study groups was not significantly different. In T2DM patients, there was a difference in HDL-c values and TC/HDL-c ratio, with T carriers of the rs4731702 SNP (non C/C) having higher HLD-c and lower TC/HDL-c ratio values than C/C homozygotes (p = 0.0047 and 0.0041, respectively). HDL-c levels were higher in diabetic patients, without dyslipidemia, carrying the genotype non-C/C (p = 0.023). Conversely, TC and LDL-c levels were lower in diabetic patients, without dyslipidemia, in non-C/C carriers (p < 0.001). The results of the current study showed that T2DM is characterized by dyslipidemia, and that the alterations observed in the lipoprotein might be related to lower KLF14 activity in diabetic patients as a consequence of C/C genotype and insulin resistance.
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