Mediation effect of body mass index on the association between serum magnesium level and insulin resistance in children from Mexico City.

BACKGROUND/OBJECTIVES: Reduced serum magnesium (Mg) levels have been associated with obesity, insulin resistance (IR), type 2 diabetes, and metabolic syndrome in adults. However, in the children population, the evidence is still limited. In this cross-sectional study, we aimed to analyze the association of serum Mg levels with the frequency of overweight and obesity and cardiometabolic traits in 189 schoolchildren (91 girls and 98 boys) between 6 and 12 years old from Mexico City. SUBJECTS/METHODS: Anthropometrical data were collected and biochemical parameters were measured by enzymatic colorimetric assay. Serum Mg level was analyzed by inductively coupled plasma mass spectrometry (ICP-MS). The triglyceride-glucose (TyG) index was used as a surrogate marker to evaluate IR. RESULTS: Serum Mg level was negatively associated with overweight (Odds ratio [OR] = 0.377, 95% confidence interval [CI] 0.231-0.614, p < 0.001) and obesity (OR = 0.345, 95% CI 0.202-0.589, p < 0.001). Serum Mg level resulted negatively associated with body mass index (BMI, ß = -1.16 ± 0.26, p < 0.001), BMI z-score (ß = -0.48 ± 0.10, p < 0.001) and TyG index (ß = -0.04 ± 0.04, p = 0.041). Through a mediation analysis was estimated that BMI z-score accounts for 60.5% of the negative association of serum Mg level with IR (Sobel test: z = 2.761; p = 0.005). CONCLUSION: Our results evidence that BMI z-score mediate part of the negative association of serum Mg level and IR in Mexican schoolchildren.

Overweight, Obesity, Hypertriglyceridemia, and Insulin Resistance Are Positively Associated with High Serum Copper Levels in Mexican Adults.

Recently, the role of trace elements in the pathophysiology of obesity, insulin resistance (IR), and metabolic diseases has been explored. In this cross-sectional study, we aimed to assess the association of overweight, obesity, and cardiometabolic traits with serum copper (Cu) levels in 346 Mexican adults. Serum Cu level was measured by inductively coupled plasma mass spectrometry (ICP-MS). Anthropometrical data were collected, and biochemical parameters were measured. The triglyceride-glucose (TyG) index was used as a surrogate marker to evaluate IR. Overweight and obesity status was positively associated with the serum Cu level (ß = 19.434 ± 7.309, p = 0.008). Serum Cu level was observed to have a positive association with serum triglycerides level (ß = 0.160 ± 0.045, p < 0.001) and TyG (ß = 0.001 ± 0.001, p < 0.001). Additionally, high serum Cu level was positively associated with overweight and obesity status (odds ratio [OR] = 1.9, 95% confidence interval [95% CI] 1.1-3.4, p = 0.014), hypertriglyceridemia (OR = 3.0, 95% CI 1.7-5.3, p < 0.001), and IR (OR = 2.6, 95% CI 1.4-4.6, p = 0.001). In conclusion, our results suggest that overweight, obesity, hypertriglyceridemia, and IR are positively associated with serum Cu levels in Mexican adults.

Obesity Is Associated with Oxidative Stress Markers and Antioxidant Enzyme Activity in Mexican Children.

The relationship between metabolic disorders and oxidative stress is still controversial in the child population. The present cross-sectional study aimed to analyze the associations between obesity, cardiometabolic traits, serum level of carbonylated proteins (CPs), malondialdehyde (MDA), and the enzyme activity of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in children from Mexico City (normal weight: 120; obesity: 81). Obesity resulted in being positively associated with CAT (ß = 0.05 ± 0.01, p = 5.0 × 10-3) and GPx (ß = 0.13 ± 0.01, p = 3.7 × 10-19) enzyme activity. A significant interaction between obesity and sex was observed in MDA and SOD enzymatic activity (PMDA = 0.03; PSOD = 0.04). The associations between obesity, MDA level, and SOD enzyme activity were only significant in boys (boys: PMDA = 3.0 × 10-3; PSOD = 7.0 × 10-3; girls: p ≥ 0.79). In both children with normal weight and those with obesity, CP levels were positively associated with SOD enzyme activity (PNormal-weight = 2.2 × 10-3; PObesity = 0.03). In conclusion, in Mexican children, obesity is positively associated with CAT and GPx enzyme activity, and its associations with MDA levels and SOD enzyme activity are sex-specific. Therefore, CP level is positively related to SOD enzyme activity independently of body weight.

GrimAge is elevated in older adults with mild COVID-19 an exploratory analysis.

COVID-19 has been contained; however, the side effects associated with its infection continue to be a challenge for public health, particularly for older adults. On the other hand, epigenetic status contributes to the inter-individual health status and is associated with COVID-19 severity. Nevertheless, current studies focus only on severe COVID-19. Considering that most of the worldwide population developed mild COVID-19 infection. In the present exploratory study, we aim to analyze the association of mild COVID-19 with epigenetic ages (HorvathAge, HannumAge, GrimAge, PhenoAge, SkinAge, and DNAmTL) and clinical variables obtained from a Mexican cohort of older adults. We found that all epigenetic ages significantly differ from the chronological age, but only GrimAge is elevated. Additionally, both the intrinsic epigenetic age acceleration (IEAA) and the extrinsic epigenetic age acceleration (EEAA) are accelerated in all patients. Moreover, we found that immunological estimators and DNA damage were associated with PhenoAge, SkinBloodHorvathAge, and HorvathAge, suggesting that the effects of mild COVID-19 on the epigenetic clocks are mainly associated with inflammation and immunology changes. In conclusion, our results show that the effects of mild COVID-19 on the epigenetic clock are mainly associated with the immune system and an increase in GrimAge, IEAA, and EEAA.

[From genotype to phenotype: amylase gene in childhood obesity]. / Del genotipo al fenotipo: gen de la amilasa en obesidad infantil.

Worldwide, Mexico is one of the countries with the highest rate of obesity, which is a condition considered the main risk factor for type 2 diabetes. Among the mechanisms that predispose to obesity, the interaction between food intake and genetic components has been little explored. Recently we evidenced a significant association between the copy number (CN) of AMY1A and AMY2A genes, the enzymatic activity of salivary and pancreatic amylase, and the frequency of childhood obesity in Mexico, a particular population due to the high consumption of starch in the diet and the high prevalence of obesity in children and adults. This review aims to find a better understanding of the role of amylase in obesity through a description of the evolution of the CN of its genes, the association of its enzymatic activity with obesity, and the effect of its interaction with starch intake on Mexican children. In addition, it denotes the importance of the experimental perspectives of further investigation regarding the mechanism by which amylase could regulate the abundance of oligosaccharide-fermenting bacteria and producers of short-chain fatty acids and/or branched-chain amino acids that could contribute to the alteration of the physiological processes associated with intestinal inflammation and metabolic deregulation that predispose to the development of obesity.

A nivel mundial, México es uno de los países con la tasa más alta de obesidad, un padecimiento considerado como el principal factor de riesgo de diabetes tipo 2. Dentro de los mecanismos que predisponen a la obesidad, la interacción entre la ingesta alimentaria y el componente genético ha sido poco explorada. Recientemente evidenciamos la asociación del número de copias (NC) de los genes AMY1A y AMY2A, y la actividad enzimática de amilasa salival y pancreática con la frecuencia de obesidad infantil en México, una población que se caracteriza por presentar alto consumo de almidón en la dieta y alta prevalencia de obesidad. La presente revisión busca conseguir un mejor entendimiento del papel de la amilasa en la obesidad por medio de una descripción de la evolución del NC de sus genes, la asociación de su actividad enzimática con la obesidad y el efecto de su interacción con la ingesta de almidón en niños mexicanos. Además, refiere las perspectivas experimentales que permitirían profundizar en la investigación del mecanismo por el cual la amilasa podría regular la abundancia de bacterias fermentadoras de oligosacáridos y productoras de ácidos grasos de cadena corta o aminoácidos de cadena ramificada que podrían contribuir con la alteración de los procesos fisiológicos asociados con la inflamación intestinal y la desregulación metabólica que predispone al desarrollo de obesidad.

Overweight and Obesity Are Positively Associated with Serum Copper Levels in Mexican Schoolchildren.

Due to its relationship with oxidative stress and inflammation responses, obesity and its cardiometabolic implications have been related with serum copper (Cu). Hence, we analyzed the association of overweight (OW) and obesity (OB) status and cardiometabolic traits with serum Cu level in Mexican schoolchildren. Anthropometrical data and cardiometabolic traits were analyzed in this cross-sectional study. Serum Cu level was measured by inductively coupled plasma mass spectrometry. The study involved 191 schoolchildren (93 girls and 98 boys) with a mean age of 8.054 ± 1.170 years. Children with OW and OB had higher serum Cu levels than children with normal weight (NW) (mean difference: OW vs NW = 51.85 µg dL-1, OB vs NW = 47.22 µg dL-1, p < 0.001). In a multiple linear regression model, OW and OB status were positively associated with serum Cu levels (ßOW = 49.85, 95% confidence interval (95% CI) 35.84-63.87, p < 0.001; ßOB = 44.38, 95% CI 27.70-61.05, p < 0.001). We did not identify any significant association between cardiometabolic traits and serum Cu level. In conclusion, our results show an association of the presence of OW and OB with higher serum Cu levels, for the first time in Mexican schoolchildren. However, further functional studies are needed to better understand the role of Cu in the pathophysiology of obesity.

Association of total and pancreatic serum amylase enzymatic activity with insulin resistance and the glucose and insulin responses to oral starch test in Mexican children.

BACKGROUND/OBJECTIVES: Little is known about the effect of serum amylase enzymatic activity on glucose metabolism. We investigated the association of serum amylase enzymatic activity with fasting plasma glucose, insulin resistance (IR), and the plasma glucose and insulin response to an oral starch test (OST) in Mexican children. METHODS: Anthropometric data, glucose and insulin levels, and the serum enzymatic activity of total (AMYt), salivary (AMY1), and pancreatic (AMY2) amylase were analysed in 764 children (Nnormal weight  = 427/Nobesity  = 337). After categorization into low (LA) and high (HA) AMYt, an OST with commercial white bread was performed in 39 children (Nnormal weight  = 17/Nobesity  = 22). RESULTS: A positive association between serum enzymatic activity of AMY2 and IR was observed in children with obesity (p = 0.018). Children with normal weight had lower plasma glucose and insulin response to OST than children with obesity (Pglucose  = 4.1 × 10-12 ; Pinsulin  = 2.1 × 10-15 ). Compared with the LA group, children with HA showed lower plasma glucose and insulin response to OST (Pglucose ≤ 0.040; Pinsulin ≤ 0.015). CONCLUSION: Our results suggest that AMY2 is positively associated with IR. A high level of AMYt is related to lower glucose and insulin responses to OST in Mexican children, regardless of their weight status.

The MC4R p.Ile269Asn mutation confers a high risk for type 2 diabetes in the Mexican population via obesity dependent and independent effects.

We investigated the association between the loss-of-function mutation MC4R p.Ile269Asn and T2D risk in the Mexican population. We enrolled 6929 adults [3175 T2D cases and 3754 normal glucose tolerant (NGT) controls] and 994 NGT children in the study. Anthropometric data and T2D-related quantitative traits were studied in 994 NGT children and 3754 NGT adults. The MC4R p.Ile269Asn mutation was genotyped using TaqMan. The MC4R p.Ile269Asn mutation was associated with T2D [OR = 2.00, 95% confidence interval (CI) 1.35-2.97, p = 0.00057] in Mexican adults. Additional adjustment for body-mass index (BMI) attenuated but did not remove the association (OR = 1.70, 95% CI 1.13-2.56, p = 0.011). The MC4R p.Ile269Asn mutation was associated with T2D (OR = 1.88, 95% CI 1.14-3.08, p = 0.013) in a subset of 1269 T2D cases and 1269 NGT controls matched for sex, age, and BMI. A mediation analysis estimated that BMI accounts for 22.7% of the association between MC4R p.Ile269Asn mutation and T2D risk (p = 4.55 × 10-6). An association was observed between the MC4R p.Ile269Asn mutation and BMI in NGT children and adults (children: beta = 3.731 ± 0.958, p = 0.0001; adults: beta = 2.269 ± 0.536, p = 2.3 × 10-5). In contrast, the mutation was not associated with T2D-related quantitative traits. We demonstrate that the MC4R p.Ile269Asn mutation predisposes to T2D via obesity-dependent and independent effects in the Mexican population.

AGT rs4762 is associated with diastolic blood pressure in Mexicans with diabetic nephropathy.

AIMS: Since angiotensinogen has a pivotal role in the renin-angiotensin-aldosterone system, the analysis of polymorphisms of the angiotensinogen (AGT) gene could help explain its potential involvement in hypertension and diabetic nephropathy (DN) pathogenesis. For that reason, we investigated 1) the association of AGT rs4762 with blood pressure (BP) and kidney function-related traits and 2) the interaction effect of AGT rs4762 with DN on BP and kidney function-related traits in 546 Mexican adults with type 2 diabetes (T2D). METHODS: We enrolled 546 unrelated Mexican patients with T2D (350 cases with DN and 196 controls without DN). AGT rs4762 was genotyped in all participants using TaqMan technology (effect allele: A). BP and kidney function-related traits, including serum urea and creatinine, urinary albumin, urine albumin to urine creatinine ratio (ACR), and glomerular filtration rate, were studied. DN was defined as having a previous diagnosis of T2D and an ACR ≥ 30 mg/g. The association between these parameters was investigated using logistic regression with adjustment for covariates. RESULTS: AGT rs4762 A allele was significantly associated with diastolic blood pressure (N = 546, ß = 1.243 ± 0.918, p = 0.029). A significant interaction between DN and AGT rs4762 was also observed in relation to diastolic blood pressure (DBP) (N = 546, ß = 0.930 ± 0.433, p=0.032). A follow-up analysis of simple effects particularly revealed a positive association between AGT rs4762 A allele and DBP only in patients with diabetic nephropathy (N = 350, ß = 2.837 ±â€¯1.267, p = 0.026). CONCLUSION: Our results evidence that, although AGT rs4762 is not associated with DN, the AGT rs4762 A allele is positively associated with DBP in the Mexican population with DN.

Sex/Gender Modifies the Association Between the MC4R p.Ile269Asn Mutation and Type 2 Diabetes in the Mexican Population.

CONTEXT: Studies in mice and humans suggest that melanocortin-4 receptor (MC4R) deficiency affects body weight in a sex-/gender-dependent manner. However, similar evidence for type 2 diabetes (T2D) is scarce. OBJECTIVE AND DESIGN: We investigated whether sex/gender modifies the association between the loss-of-function MC4R p.Ile269Asn mutation and T2D in 6929 Mexican adults (3175 T2D cases and 3754 normal glucose tolerance [NGT] controls). The 2003 American Diabetes Association criteria were used to define NGT and T2D. The MC4R p.Ile269Asn mutation was genotyped in all participants using TaqMan technology. RESULTS: The MC4R p.Ile269Asn mutation was associated with T2D in 6929 Mexican adults (Ncontrols = 3754, Ncases = 3175, odds ratio [OR] = 2.00, 95% confidence interval [CI], 1.35-2.97; P = 5.7 × 10-4). The MC4R p.Ile269Asn mutation had a frequency of 0.86 and 1.05% in women with NGT and T2D, and 0.78 and 1.32% in men with NGT and T2D, respectively. We identified a significant interaction between the MC4R p.Ile269Asn mutation and sex/gender on T2D risk (P = 0.049). Although a strong association between the mutation and T2D was observed in men (Ncontrols = 2418, Ncases = 1807, OR = 2.63, 95% CI, 1.62-4.28, P = 9.3 × 10-5), results were not significant in women (Ncontrols = 1336, Ncases = 1368, OR = 1.16, 95% CI, 0.60-2.26, P = 0.65). Further adjustment for body mass index in the logistic regression model did not alter the sex-/gender-specific pattern of association (men: OR = 2.22, 95% CI, 1.34-3.67, P = 0.0019; women: OR = 1.02, 95% CI, 0.51-2.02, P = 0.95). CONCLUSION: This is the first report of a male-specific association between the MC4R p.Ile269Asn loss-of-function mutation and T2D in the Mexican population.

Association of gut microbiome with fasting triglycerides, fasting insulin and obesity status in Mexican children.

BACKGROUND: The association of gut microbiota with obesity and its cardio-metabolic complications in paediatric populations is still controversial. OBJECTIVE: We investigated the association of obesity and cardio-metabolic traits with gut microbiota on 167 and 163 children with normal weight and obesity from Mexico City and Oaxaca, Mexico. METHODS: Anthropometric and biochemical traits were measured. The microbial communities were determined by high-throughput sequencing of bacterial 16S rRNA gene v3-v4 region. RESULTS: The gut microbial community structure was associated with obesity and fasting plasma insulin (FPI) in Mexico City (PObesity = 0.012, PFPI = 0.0003) and Oaxaca (PObesity = 0.034, PFPI = 0.016), and with triglycerides (TG) in Oaxaca (P = .0002). The Firmicutes/Bacteroidetes ratio was positively associated with TG in Oaxaca (P = .003). Firmicutes and Bacteroidetes phyla were positively and negatively associated with obesity (Mexico City: PFirmicutes = 0.013, PBacteroidetes = 0.009) and TG (Oaxaca: PFirmicutes = 0.002, PBacteroidetes = 0.004). In Oaxaca, Verrucomicrobia was negatively associated with obesity (P = .004). In Mexico City, the bacterial genus Fusicatenibacter, Romboutsia, Ruminococcaceae, Ruminiclostridium, Blautia, Clostridium, Anaerostipes and Intestinibacter were associated with obesity and FPI, while in Oaxaca, Bacteroides, Alistipes and Clostridium were associated with TG. CONCLUSION: The gut microbial community structure in children is associated with obesity and FPI in Mexico City, and with obesity, FPI and TG in Oaxaca.

Association of AMY1A/AMY2A copy numbers and AMY1/AMY2 serum enzymatic activity with obesity in Mexican children.

BACKGROUND: Mexican children are characterized by a high-starch intake diet and high prevalence of obesity. OBJECTIVES: To investigate the association of AMY1A/AMY2A copy numbers (CNs) and AMY1/AMY2 serum enzymatic activity with childhood obesity in up to 427 and 337 Mexican cases and controls. METHODS: Anthropometric and dietary starch intake data were collected. CN of AMY1A/AMY2A and AMY1/AMY2 serum enzymatic activity were determined using droplet digital PCR (ddPCR) and enzymatic colorimetry, respectively. An individual participant level data meta-analysis of association between AMY1A CNVs and obesity was also performed. RESULTS: A positive association between AMY1A/AMY2A CNs and their corresponding AMY1/AMY2 serum enzyme activity was observed in children with normal weight and obesity. The serum enzyme activity of AMY1 and AMY2 was negatively associated with childhood obesity risk, and the association was restricted to kids eating medium/high amount of starch (Pinteraction = .004). While no association between AMY1A and AMY2A CNs and childhood obesity was observed in our sample, we confirmed a significant association between AMY1A CN and obesity in a meta-analysis of 3100 Mexican children. CONCLUSIONS: Our data suggest that genetically determined salivary and pancreatic amylase activity can increase/decrease the risk of obesity in Mexican children, this effect being blunted by a low-starch diet.

Causal Association of Haptoglobin With Obesity in Mexican Children: A Mendelian Randomization Study.

CONTEXT: Little is known about the association between haptoglobin level and cardiometabolic traits. A previous genome-wide association study identified rs2000999 in the HP gene as the stronger genetic contributor to serum haptoglobin level in European populations. OBJECTIVE AND DESIGN: We investigated the association of HP rs2000999 with serum haptoglobin and childhood and adult obesity in up to 540/697 and 592/691 Mexican cases and controls, respectively. Anthropometric and biochemical data were collected. Serum haptoglobin was measured by an immunoturbidimetry assay. HP rs2000999 was genotyped using the TaqMan technology. Mendelian randomization analysis was performed using the Wald and inverse variance weighting methods. RESULTS: Haptoglobin level was positively associated with childhood and adult obesity. HP rs2000999 G allele was positively associated with haptoglobin level in children and adults. HP rs2000999 G allele was positively associated with childhood but not adult obesity. The association between HP rs2000999 and childhood obesity was removed after adjusting for haptoglobin level. In a Mendelian randomization analysis, haptoglobin level genetically predicted by HP rs2000999 showed a significant causal effect on childhood obesity by the Wald and inverse variance weighting methods. CONCLUSION: Our data provide evidence for the first time for a causal positive association between serum haptoglobin level and childhood obesity in the Mexican population. Our study contributes to the genetic elucidation of childhood obesity and proposes haptoglobin as an important biomarker and treatment target for obesity.

Type 2 diabetes-associated polymorphisms correlate with SIRT1 and TGF-ß1 gene expression.

The polymorphisms rs3758391 and rs1800470 located in SIRT1 and TGF-ß1 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-ß1 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-ß1 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-ß1 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-ß1, respectively, but none of the tested SNPs are located in regulatory DNA-protein binding sites.

The Melanocortin 4 Receptor p.Ile269Asn Mutation Is Associated with Childhood and Adult Obesity in Mexicans.

CONTEXT: Rare partial/complete loss-of-function mutations in the melanocortin-4 receptor (MC4R) gene are the most common cause of Mendelian obesity in European populations, but their contribution to obesity in the Mexican population is unclear. OBJECTIVE AND DESIGN: We investigated whether deleterious mutations in MC4R contribute to obesity in Mexican children and adults. RESULTS: We provide evidence that the MC4R p.Ile269Asn (rs79783591) mutation may have arisen in modern human populations from a founder event in native Mexicans. The MC4R Isoleucine 269 is perfectly conserved across 184 species, which suggests a critical role for the amino acid in MC4R activity. Four in silico tools (SIFT, PolyPhen-2, CADD, MutPred2) predicted a deleterious impact of the p.Ile269Asn substitution on MC4R function. The MC4R p.Ile269Asn mutation was associated with childhood (Ncontrols = 952, Ncases = 661, odds ratio (OR) = 3.06, 95% confidence interval (95%CI) [1.94-4.85]) and adult obesity (Ncontrols = 1445, Ncases = 2,487, OR = 2.58, 95%CI [1.52-4.39]). The frequency of the MC4R p.Ile269Asn mutation ranged from 0.52 to 0.59% and 1.53 to 1.59% in children and adults with normal weight and obesity, respectively. The MC4R p.Ile269Asn mutation co-segregated perfectly with obesity in 5 multigenerational Mexican pedigrees. While adults with obesity carrying the p.Ile269Asn mutation had higher BMI values than noncarriers, this trend was not observed in children. The MC4R p.Ile269Asn mutation accounted for a population attributable risk of 1.28% and 0.68% for childhood and adult obesity, respectively, in the Mexican population. CONCLUSION: The MC4R p.Ile269Asn mutation may have emerged as a founder mutation in native Mexicans and is associated with childhood and adult obesity in the modern Mexican population.

Correlation of HOMA-IR with BMI-for-age percentile in children and adolescents from the Soconusco region of Chiapas, Mexico / Correlación del HOMA-IR con el índice de masa corporal percentil en niños y adolescentes de la región Soconusco de Chiapas, México

Abstract Introduction: Insulin resistance (IR) is a major risk factor for developing diabetes mellitus type 2 and cardiovascular diseases. In pediatrics, morbidity and mortality associated with these diseases highlights the diagnostic importance of IR for primary care. Objective: To determine Homeostatic Model Assessment Insulin Resistance (HOMA-IR) values and their correlation with BMI-for-age percentile in children and adolescents of the Soconusco region of Chiapas, Mexico. Materials and methods: Cross-sectional study. Overweight and obesity prevalence was determined based on the Body Mass Index (BMI) percentile of112 children (5-19 years old). Glucose and fasting insulin values were quantified and used for estimation of HOMA-IR. Results: The combined prevalence of obesity and overweight was 66%, with insulin (p=0.010) and HOMA-IR (p=0.015) values higher than those of the normal weight group. The HOMA-IR values correlated positively with age (r=0.636), weight (r=0.569), height (r=0.578) and BMI percentile (r=0.198). Conclusions: In the study population, HOMA-IR has a moderately significant correlation with an increase in BMI percentile.

Resumen Introducción. La resistencia a la insulina es un factor importante en el desarrollo de diabetes mellitus tipo 2 y de enfermedades cardiovasculares. En pediatría, su morbimortalidad resalta la importancia diagnóstica con fines de atención primaria. Objetivo. Determinar los valores del homeostatic model assessment insulin resistance (HOMA-IR) y su relación con el índice de masa corporal percentil (IMCp) en niños y adolescentes de la región Soconusco, Chiapas. Materiales y métodos. Estudio transversal. Se determinó sobrepeso y obesidad por IMCp en 112 pacientes pediátricos (5-19 años); se determinaron concentraciones de glucosa y de insulina sérica para estimar el HOMA-IR. Resultados. Se encontró una prevalencia combinada de obesidad y sobrepeso de 66% con valores de insulina (p=0.010) y de HOMA-IR (p=0.015) más elevados que los del grupo de peso normal. El HOMA-IR se correlacionó positivamente con la edad (r=0.636), el peso (r=0.569), la talla (r=0.578) y el IMCp (r=0.198). Conclusión. En la población de estudio, el HOMA-IR presenta una correlación moderadamente significativa con el aumento del IMCp.

Association of rs2000999 in the haptoglobin gene with total cholesterol, HDL-C, and LDL-C levels in Mexican type 2 diabetes patients.

Recently, studies have shown significant association between the rs2000999 polymorphism in the haptoglobin-encoding gene (HP) and low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels, which are important risk factors for cardiovascular diseases. However, the association of rs2000999 with serum lipids in Latin American diabetic populations is still uncharacterized. Here, we analyzed the association of rs2000999 with TC, high-density lipoprotein cholesterol (HDL-C), and LDL-C levels in 546 Mexican adults with type 2 diabetes (T2D) and in 654 controls without T2D. In this observational case-control study we included adults from 4 centers of the Mexican Social Security Institute in Mexico City recruited from 2012 to 2015. TC, HDL-C, LDL-C, triglycerides (TG), and glucose levels were measured by an enzymatic colorimetric method. The variant rs2000999 was genotyped using TaqMan real time polymerase chain reaction. The percentage of Native-American ancestry showed a negative association with the rs2000999 A allele. In contrast, the rs2000999 A allele had a strong positive association with European ancestry, and to a lesser extent, with African ancestry. Linear regression was used to estimate the association between the variant rs2000999 and lipid concentrations, using different genetic models. Under codominant and recessive models, rs2000999 was significantly associated with TC and LDL-C levels in the T2D group and in controls without T2D. In addition, the group with T2D showed a significant association between the variant and HDL-C levels. In summary, the rs2000999 A allele in Mexican population is positively associated with the percentage of European and negatively associated with Native American ancestry. Carriers of the A allele have increased levels of TC and LDL-C, independently of T2D diagnosis, and also increased concentrations of HDL-C in the T2D sample.

Altered Glycemic Control Associated With Polymorphisms in the SLC22A1 (OCT1) Gene in a Mexican Population With Type 2 Diabetes Mellitus Treated With Metformin: A Cohort Study.

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 (HbA1c ) 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 (ß = 1.36; P < .001), AA-rs628031 (ß = 0.98; P = .032), and GG-rs594709 (ß = 1.21; P = .016) in the SLC22A1 gene with an increase in HbA1c levels during the follow-up period. Additionally, a significant association was found in the CGA and CAG haplotypes with an increase in HbA1c 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 HbA1c 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.

Interferon epsilon mRNA expression could represent a potential molecular marker in cervical cancer.

The effects of the immune system response in the malignant transformation process have been described. Molecules such as interferons are involved in such process. Interferons are small single-chained glycoproteins, involved in the first line of defense against pathogens such as viruses, bacteria, and parasites. Interferon epsilon (IFNε) is located in the 9p21.3 cytogenetic region, transcribes into a single exon mRNA. Contrary to other family members, IFNε exerts low antiviral activity. In the present work molecular alterations such as copy number variation (CNV) and expression were analyzed by available microarrays and fifty-nine cervical tissues ranging from normal to cancer and three cell lines were assessed for IFNε expression by RT-PCR, immunohistochemistry, and immunocytofluorescence. No significant CNV alterations were observed. Positive immunosignal was primarily present in the proliferative basal strata cells in the normal tissue, whereas in cervical cancer, all epithelial transformed cells were positive. The cell lines analyzed were HPV16, -18, and negative, all three cell-lines were positive for cytoplasmic protein presence. Interestingly, at the mRNA level, increased band intensity was observed, as the lesions were higher, and IFNε up-regulation in CC (P=0.0001) is reported here. Our results suggest that up-regulation is present as an independent event from single or multiple HPV infection (P=0.90). In conclusion, we suggest that IFNε mRNA up-regulation could represent a potential molecular marker in CC. Expression of IFNε might not be related to HPV infection or CNV, which could have an important role in cellular homeostasis and could influence immune related events in cervical carcinogenesis.