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.
GWAS (genome-wide association studies) have associated Type 2 DiabetesMellitus with the single nucleotide polymorphism (SNPs) rs972283 (A/G) of KLF14 gene with in a global population. The most common techniques used to analyze SNPs are time consuming, multi-step process and require expensive instruments. Therefore, in order to overcome these problems, we have developed a new, rapid and cost effective T-ARMS PCR assay to genotype rs972283. However, the optimization step can be hardworking and laborious. Hence, we propose to demonstrate and discuss critical steps for its development, in a way to provide useful information. In a first step, we design and validate two specific primer pair for T-ARMS PCR. Later, the amplification conditions were optimized for DNA concentration, annealing temperature, Taq DNA polymerase units and primers concentration. The last one was considered the main interference factor for a correct amplification and appropriate band intensity. Finally, the results obtained by T-ARMS PCR were concordant with sequencing. T-ARMS PCR assay developed in our laboratory for genotyping rs972283 (A/G) of KLF14 gene is time saving and cost-effective compared to the available methods used for SNP studies.
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.
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