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Background Dyslipidemia is an important risk factor for the development of several diseases. The genetic component of hypertriglyceridemia has been studied in adults, but little is known in children. Objective The objective is to evaluate the association of two variants in APOA5 (rs662799) and APOA1 (rs5072) with triglyceride (TG) levels in Mexican children. Methods Anthropometric parameters were measured in 1559 Mexican children 5-14 years of age. DNA was isolated from blood samples. Lipid profiles and glucose concentrations were determined from serum and genotyping of rs662799, and rs5072 was performed using TaqMan® technology. Additive and dominant models adjusted for age, gender and body mass index were used to evaluate the association of these single nucleotide polymorphisms with TG levels. Results Children with high TG levels were found to have a higher body mass index and waist circumference as well as a worse lipids profile and glucose levels ( p < 0.001). Additive and dominant models demonstrated a significant association between the rs662799 and rs5072 with TG. The dominant model showed the strongest significant association (OR = 1.81; 95% CI 1.46-2.24; p = 5.40 × 10−08 for rs662799 and OR = 1.54; 95% CI 1.05-2.25; p = 2.60 × 10−02 for rs5072). Conclusion The minor alleles of rs662799 ( APOA5) and rs5072 ( APOA1) modulate TG levels in Mexican children. [ABSTRACT FROM AUTHOR]

Overstimulation of pancreatic β-cells can lead to dysfunction and death, prior to the clinical manifestations of type 2 diabetes (T2D). The excessive consumption of carbohydrates induces metabolic alterations that can affect the functions of the β-cells and cause their death. We analyzed the role of p53 in pancreatic β cell death in carbohydrate-supplemented Sprague Dawley rats. For four months, the animals received drinking water containing either 40% sucrose or 40% fructose. The glucose tolerance test was performed at week 15. Apoptosis was assessed with the TUNEL assay (TdT-mediated dUTP-nick end-labeling). Bax, p53, and insulin were assessed by Western blotting, immunofluorescence, and real-time quantitative PCR. Insulin, triacylglycerol, and serum glucose and fatty acids in pancreatic tissue were measured. Carbohydrate consumption promotes apoptosis and mobilization of p53 from the cytosol to rat pancreatic β-cell mitochondria before blood glucose rises. An increase in p53, miR-34a, and Bax mRNA was also detected (P < 0.001) in the sucrose group. As well as hypertriglyceridemia, hyperinsulinemia, glucose intolerance, insulin resistance, visceral fat accumulation, and increased pancreatic fatty acids in the sucrose group. Carbohydrate consumption increases p53 and its mobilization into β-cell mitochondria and coincides with the increased rate of apoptosis, which occurs before serum glucose levels rise., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: Obesity and type 2 diabetes mellitus are two pathologies that share metabolic abnormalities in most of the cases; however, there are differences as well. Some studies have reported that approximately 30% of obese patients have normal glucose and lipid levels in blood despite an accumulation of abdominal adipose tissue. Here, we compare the gene expression in adipose tissue of several genes associated with obesity and/or diabetes between obese patients without T2D and obese patients with T2D., Methods: Omental adipose tissue was collected during the patients elective bariatric surgery. Gene expression was determined by real-time PCR. Phenotypic variables were correlated with gene expression and 2^ -ΔΔCt relative expression analysis between groups was performed., Results: The stronger correlations in the obese without T2D or reference group was between ICAM1 and HbA1c; HP and TC and LDL while in the obese with diabetes or case group the correlation occurred between CSF1 and BMI. A correlation between HP and TC was found in the case group as well. The expression of VEGFA, CCND2, IL1R1 and PTEN was downregulated in the obese with T2D group., Conclusions: This study identified genes whose expression is different between obese subjects with and without diabetes. Those genes are related to inflammation, cholesterol transport, adipocyte differentiation/expansion and browning., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The polymorphisms rs3758391 and rs1800470 located in SIRT1 and TGF-β1 have been associated with type 2 diabetes in different populations but its functional effect is not clear. In this study, we evaluated their effect on the expression of SIRT1 and TGF-β1 in peripheral blood as well as their participation in the formation of DNA-protein complexes in a pancreas-derived cell line. It has been described that SIRT1 and TGF-β1 participate in cell growth and regulation of production and secretion of insulin in the pancreas. Anthropometric and biochemical profiles of 127 adults were measured. Genotypes for rs3758391 and rs1800470 were determined using TaqMan assays. Expression analysis of SIRT1 and TGF-β1 were performed using real-time PCR. Gene expression of these genes increased 1.8 ± 0.6- and 1.3 ± 0.6-fold in patients carrying the TT genotype of rs3758391 and rs1800470 when compared to carriers of the CC genotype. Then, we tested whether these single-nucleotide polymorphisms (SNPs) (and rs932658, which is in linkage disequilibrium with rs3758391) are located in regulatory DNA-protein binding sites by electrophoretic mobility shift assays using nuclear extract from the pancreas-derived cell line BxPC-3. The electrophoretic mobility shift assay showed no binding of nuclear proteins to DNA. In conclusion, the genotypes of rs3758391 and rs1800470 are associated with modifications in the expression of the genes SIRT1 and TGF-β1, respectively, but none of the tested SNPs are located in regulatory DNA-protein binding sites., (© 2019 John Wiley & Sons Ltd/University College London.)

The organic cation transporters OCT1 and OCT2 and the multidrug and toxin extrusion transporter MATE1, encoded by the SLC22A1, SLC22A2, and SLC47A1 genes, respectively, are responsible for the absorption of metformin in enterocytes, hepatocytes, and kidney cells. The aim of this study was to evaluate whether genetic variations in the SLC22A1, SLC22A2, and SLC47A1 genes could be associated with an altered response to metformin in patients with type 2 diabetes mellitus. A cohort study was conducted in 308 individuals with a diagnosis of type 2 diabetes mellitus of less than 3 years and who had metformin monotherapy. Three measurements of blood glycated hemoglobin (HbA 1c ) were obtained at the beginning of the study and after 6 and 12 months. Five polymorphisms were analyzed in the SLC22A1 (rs622342, rs628031, rs594709), SLC22A2 (rs316019), and SLC47A1 (rs2289669) genes by real-time polymerase chain reaction. The results showed a significant association among genotypes CC-rs622342 (β = 1.36; P < .001), AA-rs628031 (β = 0.98; P = .032), and GG-rs594709 (β = 1.21; P = .016) in the SLC22A1 gene with an increase in HbA 1c levels during the follow-up period. Additionally, a significant association was found in the CGA and CAG haplotypes with an increase in HbA 1c levels compared to the highest-frequency haplotype (AGA). In conclusion, the genetic variation in the SLC22A1 gene was significantly related to the variation of the HbA 1c levels, an important indicator of glycemic control in diabetic patients. This information may contribute to identifying patients with an altered response to metformin before starting their therapy., (© 2019, The American College of Clinical Pharmacology.)

Merkel cell tumour is a rare skin tumour of high malignancy, poor prognosis and low survival. It is characterized by its tendency to lymph node and vascular invasion and by a high percentage of locoregional recurrence in the year following surgical removal. It affects adults between 60 and 80 years of age and often occurs in the head and neck. We present the case of an 85-year-old man presenting with an ulcerated gluteal mass of 4 months' evolution. Diagnosis was by histopathological and immunohistochemical study. Early diagnosis and appropriate treatment are important to improve the prognosis of these patients., (Copyright © 2019 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background and Aims: Obesity is an important health problem worldwide and many studies have suggested a relationship between obesity and thyroid function, with controversial results. Interestingly, high TSH levels have been involved with the presence of inflammatory state and risk for developing cardiovascular diseases in hypothyroid and obese patients. The aim in this work was to determine the prevalence of hypothyroidism in patients with extreme obesity and to determine whether their TSH levels were related to increased serum levels of inflammatory and cardiovascular markers., Methods: A cross-sectional study in 101 patients with extreme obesity (BMI ≥40) was performed. Anthropometric (weight, height and waist circumference) and biochemical (fasting glucose, glycosylated hemoglobin, triglycerides, total cholesterol, LDL-C, HDL-C and insulin) parameters were measured. TSH and FT4 levels as well as clinical exploration for diagnosis of hypothyroidism were carried out. Serum concentration of IL-10, IL-6, adiponectin, resistin, leptin, ICAM-1, VCAM-1 and E-selectin were determined., Results: A high prevalence for diabetes (37.6%), prediabetes (50.5%), dyslipidemia (74.3%), hypertension (61.4%) and hypothyroidism (48.5%) was observed in patients with extreme obesity. The presence of hypothyroidism increased serum concentration of proinflammatory cytokines IL-6 and leptin and decreased the antiinflammatory cytokine adiponectin. In addition, serum TSH levels showed a correlation for waist circumference, weight, BMI, A1c, insulin, IL-6, leptin, ICAM-1 and E-selectin., Conclusion: There is a high prevalence for hypothyroidism in patients with extreme obesity. High levels of TSH contribute to elevate proinflammatory and cardiovascular risk markers, increasing the risk for development of cardiovascular diseases., (Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.)