Analysis of SIRT1 genetic variants in young Mexican individuals: relationships with overweight and obesity.

The high prevalence of obesity in Mexico starting from the early stages of life is concerning and represents a major public health problem. Genetic association studies have reported that single nucleotide variants (SNVs) in SIRT1, an NAD+-dependent deacetylase that plays an important role in the regulation of metabolic cellular functions, are associated with multiple metabolic disorders and the risk of obesity. In the present study, we analyzed the effect that the SNVs rs1467568 and rs7895833 of the SIRT1 gene may have on cardiometabolic risk factors in a young adult population from Mexico. A cross-sectional study was carried out with young adults between the ages of 18 and 25 who had a body mass index (BMI) greater than 18.5 kg/m2. This study included 1122 young adults who were classified into the normal weight (n = 731), overweight group (n = 277), and obesity group (n = 114) according to BMI of whom 405 and 404 volunteers were genotyped for rs1467568 and rs7895833 respectively using TaqMan probes through allelic discrimination assays. We found that the male sex carrying the G allele of rs7895833 had slightly lower BMI levels (p = 0.009). Furthermore, subjects carrying rs1467568 (G allele) showed a 34% lower probability of presenting with hyperbetalipoproteinemia where female carrying rs1467568 had lower levels of total cholesterol (p = 0.030), triglycerides (p = 0.026) and LDL cholesterol (p = 0.013). In conclusion, these findings suggest that the presence of both SNVs could have a non-risk effect against dyslipidemia in the Mexican population.

Glycemia and associated factors in a pediatric population in Mexico.

Aims: In this study, we evaluated the association of sociodemographic, lifestyle and cardiometabolic factors with blood glucose levels in children and adolescents in Mexico. Methods: An analytical cross-sectional study of 642 children and adolescents aged 6 to 19 years from different educational centers located in municipalities of the state of San Luis Potosí, Mexico, was carried out. Pearson χ2 and Spearman correlation tests and multiple linear regression models were used to evaluate the associations of the variables with glycemia. Results: The prevalence of prediabetes was 8.0% in both sexes. Male participants were more likely to develop hyperglycemia than female participants (OR 2.7, 95% CI: 1.5-5.0). The variables associated with glucose levels were male sex, high socioeconomic status, inadequate diet, high blood pressure, and increased total cholesterol, LDL cholesterol, and triglycerides, which also explained up to 15.6% (p < 0.05) of the variability in glucose concentrations. Conclusion: The detection of sociodemographic, lifestyle and cardiometabolic factors in children and adolescents will contribute to the implementation of prevention strategies for cardiometabolic diseases, among which prediabetes is common.

Agave fructans enhance the effects of fermented milk products on obesity biomarkers: a randomised trial.

Dysbiosis has been implicated in childhood obesity. Oral intake of fermented milk containing Lacticaseibacillus casei strain Shirota preserves gut microbiota (GM) diversity in children and adults. This study was a double-blind trial involving 37 overweight or obese children aged 6-10 years. Children were followed over a 6-week intervention period in which they received different fermented milk products containing L. casei Shirota: 10 in the first group received just L. casei Shirota; 13 received L. casei Shirota with 3 g/day of inulin (L. casei+inulin); and 14 received L. casei Shirota with 3 g/day of fructans from Agave salmiana (L. casei+fructans). Principal component analysis showed the relationship between microbial abundance, GM metabolites, and other obesity-related markers. Supplementation with probiotics and synbiotics improved the HDL-cholesterol levels of overweight and obese children, although no changes in body composition were detected. We observed an increase in butyrate or propionate concentrations in the L. casei+fructans group compared to the end of the intervention (P<0.03). A diminished level of ANGPTL4 within the L. casei+fructans group (P=0.04) was also found, but no differences when lipopolysaccharide-binding protein was evaluated. The FFAR2+ cell frequency decreased between baseline and at the end of 6-week intervention in L. casei+inulin (P=0.02) and L. casei+fructans groups (P=0.04). In contrast, the percentage of CD14+FFAR3+ frequency increased in the same groups (P=0.04). The L. casei Shirota with inulin or fructans modulates GM, which improves the lipid profile and changes at a molecular level, such as expression of FFAR3 and FFAR2, ANGPTL4, propionate, and butyrate. It, therefore, could be considered an interesting therapeutic possibility for treating childhood overweight and obesity. The study was registered at ClinicalTrials.gov (ID: NCT05423015).

Uricaemia and associated health determinants in a paediatric population in Mexico.

BACKGROUND AND AIM: Uric acid (UA) is a product of the catabolism of purines, and its increase in blood may be related to the development of cardiometabolic diseases. Whether UA is the result or causal determinant of the appearance of risk factors for cardiometabolic disease is not yet known. UA levels among the young student population in San Luis Potosi have increased in recent years, which may be indicative of a serious future public health concern. Therefore, the objective of this study was to evaluate the association of sociodemographic, lifestyle and cardiometabolic determinants with UA levels in children and adolescents in San Luis Potosí. METHODS AND RESULTS: A total of 730 students (54.1% female and 45.9% male, 6-19 years old) participated in the study. The subjects attended one of five public schools located in San Luis Potosí. Venous blood samples were collected, blood serum was separated by centrifugation, and UA concentrations were measured with an automated analytical platform. UA was associated with most of the independent variables studied. It presented a positive correlation with body mass index (r = 0.363, p < 0.01). Male sex, socioeconomic status, total screen time, exercise, adequate sleep, systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol explained 23%-39% (p < 0.001) of the variability of plasma concentrations of UA in children and adolescents. CONCLUSION: Early detection of these determinants will prevent future diseases. Moreover, it will help with the implementation of preventive strategies that could improve the health of this population.

The inflammatory state of adipose tissue is not affected by the anti-inflammatory response of the A2a-adenosine system and miR-221/PTEN.

Obesity is a chronic inflammatory state with cytokines, adipokines, and miRNAs. The A2a-adenosine system decreases activation and cytokine release in immune cells. MiR-221 is upregulated in carcinogenesis and inflammatory processes, where its targets PTEN and ETS-1, negatively regulates the Akt pathway and induces the release of pro-inflammatory cytokines, respectively. However, the roles of the A2a-adenosine system and miR-221 in adipose tissue are unknown. The aim of this work was to evaluate the A2a-adenosine and miRNA pathways as immune modulators in adipose tissue. We collected aspirate of adipose tissue from patients with BMI < 25 kg/m2 (BMI < 25) and BMI ≥ 25 kg/m2 (BMI ≥ 25) who underwent liposuction; the adipose tissue was digested with collagenase, and then a Ficoll gradient was performed to obtain mononuclear cells from adipose tissue (MCAT). We evaluated the A2a levels by quantitative Retro-transcriptase Polymerase Chain Reaction (RT-qPCR) and flow cytometry and the A2a-adenosine function with a proliferation assay or cytokine levels in the presence or absence of NAD+, activators, and inhibitors of the system. We also analyzed miR-221, ETS-1 and PTEN levels by qRT-PCR. First, we detected that MCAT presented higher basal proliferation than mononuclear cells from peripheral blood; however, activation of the A2a receptor downregulated cell proliferation and cytokine release. Interestingly, while miR-221 was downregulated in MCAT from subjects with BMI ≥ 25 compared to BMI < 25, their targets ETS-1 and PTEN, were increased. In conclusion, the A2a-adenosine system is decreased in MCAT, but it maintains its function; moreover, miR-221 could participate in promoting inflammation in adipose tissue.

Amino acid profiles of young adults differ by sex, body mass index and insulin resistance.

BACKGROUND AND AIMS: An increase in plasma branched-chain amino acids is associated with a higher risk of developing type 2 diabetes and cardiovascular diseases. However, little is known about the basal plasma amino acid concentrations in young adults. Our aim was to determine the plasma amino acid profiles of young adults and to evaluate how these profiles were modified by sex, body mass index (BMI) and insulin resistance (IR). METHODS AND RESULTS: We performed a transversal study with 608 Mexican young adults aged 19.9 ± 2.4 years who were applicants to the Universidad Autónoma de San Luis Potosí. The subjects underwent a physical examination and provided a clinical history and a blood sample for biochemical, hormonal and amino acid analyses. The women had higher levels of arginine, aspartate and serine and lower levels of α-aminoadipic acid, cysteine, isoleucine, leucine, methionine, proline, tryptophan, tyrosine, urea and valine than the men. The obese subjects had higher levels of alanine, aspartate, cysteine, ornithine, phenylalanine, proline and tyrosine and lower levels of glycine, ornithine and serine than the normal weight subjects. Subjects with IR (defined as HOMA > 2.5) had higher levels of arginine, alanine, aspartate, isoleucine, leucine, phenylalanine, proline, tyrosine, taurine and valine than the subjects without IR. Furthermore, we identified two main groups in the subjects with obesity and/or IR; one group was composed of amino acids that positively correlated with the clinical, biochemical and hormonal parameters, whereas the second group exhibited negative correlations. CONCLUSION: This study demonstrates that young adults with obesity or IR have altered amino acid profiles characterized by an increase in alanine, aspartate, proline and tyrosine and a decrease in glycine.

Clinical Pharmacokinetics of Rifampin in Patients with Tuberculosis and Type 2 Diabetes Mellitus: Association with Biochemical and Immunological Parameters.

Tuberculosis (TB) remains a major public health issue due to the increasing incidence of type 2 diabetes mellitus (T2DM), which exacerbates the clinical course of TB and increases the risk of poor long-term outcomes. The aim of this study was to characterize the pharmacokinetics of rifampin (RIF) and its relationship with biochemical and immunological parameters in patients with TB and T2DM. The biochemical and immunological parameters were assessed on the same day that the pharmacokinetic evaluation of RIF was performed. Factors related to the metabolic syndrome that is characteristic of T2DM patients were not detected in the TB-T2DM group (where predominant malnutrition was present) or in the TB group. Percentages of CD8(+) T lymphocytes and NK cells were diminished in the TB and TB-T2DM patients, who had high tumor necrosis factor alpha (TNF-α) and low interleukin-17 (IL-17) levels compared to healthy volunteers. Delayed RIF absorption was observed in the TB and TB-T2DM patients; absorption was poor and slower in the latter group due to poor glycemic control. RIF clearance was also slower in the diabetic patients, thereby prolonging the mean residence time of RIF. There was a significant association between glycemic control, increased TNF-α serum concentrations, and RIF pharmacokinetics in the TB-T2DM patients. These altered metabolic and immune conditions may be factors to be considered in anti-TB therapy management when TB and T2DM are concurrently present.

Relative bioavailability of isoniazid in a fixed-dose combination product in healthy Mexican subjects.

SETTING: Subtherapeutic plasma isoniazid (INH) concentrations and the development of bacterial resistance may be attributed to poor quality and reduced bioavailability of fixed-dose combination (FDC) formulations. The bioavailability of INH from a generic and that of a branded FDC formulation had not been compared in the Mexican population. OBJECTIVE: To evaluate the bioequivalence of a generic three-drug FDC formulation (3FDC) in comparison with a 3FDC reference with doses of 300 mg INH in 20 healthy Mexican adults, and to generate data regarding the oral relative bioavailability of the drug in this population. DESIGN: A single-dose, randomised-sequence, open-label, two-period crossover study. RESULTS: Both formulations were well tolerated. The pharmacokinetic parameters of INH showed wide inter-individual variability. The average relative bioavailability calculated for maximum serum concentration area under the concentration-time curve (AUC), AUC(0-24h) and AUC(0-∞) of the test 3FDC formulation vs. the 3FDC reference were respectively 64.84% (90%CI 56.01-75.06), 59.05% (90%CI 50.27-69.36) and 57.26% (90%CI 46.93-69.84). CONCLUSIONS: The 3FDC test and reference formulations were not bioequivalent because the 90%CI for the geometric mean ratios did not meet the regulatory requirements for bioequivalence (range 80-125%) based on the rate and extent of absorption.

One-year follow-up changes in weight are associated with changes in blood pressure in young Mexican adults.

OBJECTIVE: Increasing overweight and obesity rates in Mexico have been associated with increases in mortality from cardiovascular disease (CVD). This study assessed changes in body mass index (BMI) and body weight over 1 year, and explored whether these were associated with changes in CVD risk factors of blood pressure and fasting glucose in a cohort of young Mexican adults. STUDY DESIGN: Longitudinal data were obtained from a cohort of young Mexican adults applying to college. METHODS: Data were collected from college applicants for the 2008 academic year who re-applied in 2009. In total, 795 college applicants aged 18-20 years, of both sexes (48% males and 52% females), were included in the study. The screen included height, weight, and systolic (SBP) and diastolic (DBP) blood pressure measurements plus a blood draw following an overnight fast for fasting glucose. RESULTS: At baseline, 31.8% of the participants were overweight or obese. The mean 1-year change in body weight and BMI were 0.80 kg and 0.35 kg/m(2), respectively. One-year changes in body weight and BMI were associated with increased SBP and DBP for both men and women (P < 0.05), independent of baseline BMI. A weight gain of 5% or more was positively associated with increases in blood pressure among women (P < 0.05), but not among men. A weight loss of 5% or more was associated with reductions in SBP among women. CONCLUSIONS: One-year changes in weight were associated with changes in blood pressure.