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.

Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas.

Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p < 5 × 10-8), of which two have not been previously reported in any ancestry group. We integrated fine-mapped loci with epigenomic and transcriptomic resources to highlight potential effector genes relevant to kidney physiology and disease, and reveal key regulatory elements and pathways involved in renal function and development. We demonstrate the varying but increased predictive power offered by a multi-ancestry polygenic score for eGFR and highlight the importance of population diversity in GWASs and multi-omics resources to enhance opportunities for clinical translation for all.

Variants in the Control Region of Mitochondrial Genome Associated with type 2 Diabetes in a Cohort of Mexican Mestizos.

BACKGROUND: According to the International Diabetes Federation, Mexico is seventh place in the prevalence of type 2 diabetes (T2D) worldwide. Mitochondrial DNA variant association studies in multifactorial diseases like T2D are scarce in Mexican populations. AIM OF THE STUDY: The objective of this study was to analyze the association between 18 variants in the mtDNA control region and T2D and related metabolic traits in a Mexican mestizo population from Mexico City. METHODS: This study included 1001 participants divided into 477 cases with T2D and 524 healthy controls aged between 42 and 62 years and 18 mtDNA variants with frequencies >15%. RESULTS: Association analyses matched by age and sex showed differences in the distribution between cases and controls for variants m.315_316insC (p = 1.18 × 10-6), m.489T>C (p = 0.009), m.16362T>C (p = 0.001), and m.16519T>C (p = 0.004). The associations between T2D and variants m.315_316ins (OR = 6.13, CI = 3.42-10.97, p = 1.97 × 10-6), m.489T>C (OR = 1.45, CI = 1.00-2.11, p = 0.006), m.16362T>C (OR = 2.17, CI = 1.57-3.00, p = 0.001), and m.16519T>C (OR = 1.69, CI = 1.23-2.33, p = 0.006) were significant after performing logistic regression models adjusted for age, sex, and diastolic blood pressure. Metabolic traits in the control group through linear regressions, adjusted for age, sex and BMI, and corrected for multiple comparisons showed nominal association between glucose and variants m.263A>G (p <0.050), m.16183A>C (p <0.010), m.16189T>C (p <0.020), and m.16223C>T (p <0.024); triglycerides, and cholesterol and variant m.309_310insC (p <0.010 and p <0.050 respectively); urea, and creatinine, and variant m.315_316insC (p <0.007, and p <0.004 respectively); diastolic blood pressure and variants m.235A>G (p <0.016), m.263A>G (p <0.013), m.315_316insC (p <0.043), and m.16111C>T (p <0.022). CONCLUSION: These results demonstrate a strong association between variant m.315_316insC and T2D and a nominal association with T2D traits.

Micronutrients of the one-carbon metabolism cycle are altered in mothers and neonates by gestational diabetes and are associated with weight, height and head circumference at birth.

While several studies have previously described the levels of one-carbon metabolism-related micronutrients in women with gestational diabetes mellitus (GDM) and their neonates, the results in these literature reports have been contradictory. We hypothesized that the concentrations of micronutrients involved in the one-carbon cycle are altered in pregnant women and their neonates by GDM, and that these changes could further modify the neonatal anthropometry. Micronutrient levels were measured in 123 pregnant women with normal glucose levels (M-ND) and their neonates (N-ND), as well as in 54 pregnant women with gestational diabetes (M-GDM) and their neonates (M-GDM). Folate and vitamin B12 levels were measured via competitive ELISA, and betaine, choline, and glycine levels were measured via ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS/MS). Vitamin B12 and Glycine were found to be higher in M-GDM compared to M-ND. N-GDM had higher levels of folic acid and vitamin B12 and lower levels of betaine and choline compared to N-ND. In general, neonates presented with high concentrations of micronutrients compared to their mothers, and the fetus/maternal ratio of micronutrients was higher among the N-ND as compared to the N-GDM. Micronutrients were also variably associated with anthropometric measurements. The association of betaine with neonatal anthropometry in N-GDM is highlighted. In summary, our results implicate a potential role of GDM in altering the levels of one-carbon metabolism-related micronutrients among pregnant women and their neonates. Likewise, our results also elucidate a potential association between the concentrations of micronutrients and the weight, height, and head circumference of neonates.

Association of rs9939609-FTO with metabolic syndrome components among women from Mayan communities of Chiapas, Mexico.

BACKGROUND: Metabolic syndrome (MetS) is a complex cluster of risk factors, considered as a polygenic and multifactorial entity. The objective of this study was to determine the association of rs9939609-FTO polymorphism and MetS components in adult women of Mayan communities of Chiapas. METHODS: In a cross-sectional study, sociodemographic, anthropometric, clinical, and biochemical data were obtained from 291 adult women from three regions of Chiapas, Mexico. The prevalence of MetS and the allele and genotype frequencies of the rs9939609-FTO were estimated. Multivariate logistic regression models were used to assess the association of the single nucleotide polymorphism (SNP) with each of the MetS components. RESULTS: The MetS prevalence was 60%. We found a statistically significant association between rs9939609-FTO and hyperglycemia in the dominant model (OR 2.6; 95% CI 1.3-5.3; p = 0.007). CONCLUSIONS: Women from Mayan communities of Chiapas presented a high prevalence of MetS and a relevant association of the FTO variant with hyperglycemia. This is the first study carried out in these Mayan indigenous communities from Chiapas.

Identification of People with Diabetes Treatment through Lipids Profile Using Machine Learning Algorithms.

Diabetes incidence has been a problem, because according with the World Health Organization and the International Diabetes Federation, the number of people with this disease is increasing very fast all over the world. Diabetic treatment is important to prevent the development of several complications, also lipid profile monitoring is important. For that reason the aim of this work is the implementation of machine learning algorithms that are able to classify cases, that corresponds to patients diagnosed with diabetes that have diabetes treatment, and controls that refers to subjects who do not have diabetes treatment but some of them have diabetes, bases on lipids profile levels. Logistic regression, K-nearest neighbor, decision trees and random forest were implemented, all of them were evaluated with accuracy, sensitivity, specificity and AUC-ROC curve metrics. Artificial neural network obtain an acurracy of 0.685 and an AUC value of 0.750, logistic regression achieve an accuracy of 0.729 and an AUC value of 0.795, K-nearest neighbor gets an accuracy of 0.669 and an AUC value of 0.709, on the other hand, decision tree reached an accuracy pg 0.691 and a AUC value of 0.683, finally random forest achieve an accuracy of 0.704 and an AUC curve of 0.776. The performance of all models was statistically significant, but the best performance model for this problem corresponds to logistic regression.

Distal Symmetric Polyneuropathy Identification in Type 2 Diabetes Subjects: A Random Forest Approach.

The prevalence of diabetes mellitus is increasing worldwide, causing health and economic implications. One of the principal microvascular complications of type 2 diabetes is Distal Symmetric Polyneuropathy (DSPN), affecting 42.6% of the population in Mexico. Therefore, the purpose of this study was to find out the predictors of this complication. The dataset contained a total number of 140 subjects, including clinical and paraclinical features. A multivariate analysis was constructed using Boruta as a feature selection method and Random Forest as a classification algorithm applying the strategy of K-Folds Cross Validation and Leave One Out Cross Validation. Then, the models were evaluated through a statistical analysis based on sensitivity, specificity, area under the curve (AUC) and receiving operating characteristic (ROC) curve. The results present significant values obtained by the model with this approach, presenting 67% of AUC with only three features as predictors. It is possible to conclude that this proposed methodology can classify patients with DSPN, obtaining a preliminary computer-aided diagnosis tool for the clinical area in helping to identify the diagnosis of DSPN.

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.

Altered levels of MALAT1 and H19 derived from serum or serum exosomes associated with type-2 diabetes.

Environmental, genetic and epigenetic risk factors have been closely related to the development of type-2 diabetes (T2D). It has been reported that the expression in H19 and MALAT1 are related to metabolic diseases. To analyze the relationship between the expression of H19 and MALAT1 lncRNAs with diabetic patients. A study was conducted in subjects with T2D and nondiabetic controls, residents of Mexico City. Anthropometric measurements were made, and serum concentrations of glucose, glycosylated hemoglobin, total cholesterol, triglycerides, high- and low-density lipoprotein cholesterol were analyzed. Total RNA was extracted from serum and serum exosomes. The H19 and MALAT1 expression levels were quantified by RT-qPCR. A significant reduction in the expression of MALAT1 from serum or serum exosomes were found in patients with T2D, metabolic syndrome and low levels of HDL-c. Significant increase in H19 levels was found in diabetic subjects with poor glycemic control. Additionally, the principal component analyzes showed that serum MALAT1 expression was associated with total cholesterol and HDL-c levels, and the exosomes H19 expression was associated with waist circumference. The results obtained suggest that MALAT1 expression levels could be an epigenetic biomarker of diabetes risk or of its comorbidities.

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.

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.

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.

A trans-ancestral meta-analysis of genome-wide association studies reveals loci associated with childhood obesity.

Although hundreds of genome-wide association studies-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of 30 studies consisting of up to 13 005 cases (≥95th percentile of body mass index (BMI) achieved 2-18 years old) and 15 599 controls (consistently <50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1888 cases and 4689 controls from seven cohorts of European and North/South American ancestry. In addition to observing 18 previously implicated BMI or obesity loci, for both early and late onset, we uncovered one completely novel locus in this trans-ancestral analysis (nearest gene, METTL15). The variant was nominally associated with only the European subgroup analysis but had a consistent direction of effect in other ethnicities. We then utilized trans-ancestral Bayesian analysis to narrow down the location of the probable causal variant at each genome-wide significant signal. Of all the fine-mapped loci, we were able to narrow down the causative variant at four known loci to fewer than 10 single nucleotide polymorphisms (SNPs) (FAIM2, GNPDA2, MC4R and SEC16B loci). In conclusion, an ethnically diverse setting has enabled us to both identify an additional pediatric obesity locus and further fine-map existing loci.

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.

Identification of Diabetic Patients through Clinical and Para-Clinical Features in Mexico: An Approach Using Deep Neural Networks.

Diabetes is a chronic and noncommunicable but preventable disease that is affecting the Mexican population at worrying levels, being the first place in prevalence worldwide. Early diabetes detection has become important to prevent other health conditions that involve low organ yield until the patient death. Based on this problem, this work proposes the architecture of an Artificial Neural Network (ANN) for the automated classification of healthy patients from diabetics patients. The analysis was performed used a set of 19 para-clinical features to determine the health status of the patients. The developed model was evaluated through a statistical analysis based on the calculation of the loss function, accuracy, area under the curve (AUC) and receiving operating characteristics (ROC) curve. The results obtained present statistically significant values, with accuracy of 0.94 and AUC values of 0.98. Based on these results, it is possible to conclude that the ANN implemented in this work can classify patients with presence of diabetes from controls with significant accuracy, presenting preliminary results for the development of a diagnostic tool that can be supportive for health specialists.

[Prevalencia de complicaciones de la diabetes y comorbilidades asociadas en medicina familiar del Instituto Mexicano del Seguro Social].

Introduction: The prevalence of chronic complications and comorbidities in patients with type 2 diabetes (T2D) has increased worldwide. Objective: To compare the prevalence of complications and chronic comorbidities in patients with T2D at 36 family medicine units of five chapters of the Mexican Institute of Social Security (IMSS). Method: Complications (hypoglycemia, diabetic foot, kidney disease, retinopathy, ischemic heart disease, cerebrovascular disease and heart failure) and comorbidities (liver disease, cancer and anemia) were identified according to codes of the International Classification of Diseases, 10th Revision. Comparisons were made by chapter, age, gender and evolution time. Results: Complications and comorbidities were more common in subjects aged ≥ 62 years. Out of 297 100 patients, 34.9 % had any complication; microvascular complications (32 %) prevailed in the industrial North, whereas macrovascular complications (12.3 %) did in the rural East, and comorbidities (5 %) in southern Mexico City. Complications predominated in men (any complication, 30.2 %). Heart failure and comorbidities were more common in women (5.6 % and 4.9 %, respectively). Conclusions: T2D complications and comorbidities showed geographic and gender differences, and were greater with older age and longer evolution time. It is urgent for strategies for the prevention of complications and comorbidities to be reinforced in patients with T2D.

Introducción: La prevalencia de complicaciones crónicas y comorbilidades en pacientes con diabetes tipo 2 (DT2) se han incrementado en el mundo. Objetivo: Comparar la prevalencia de complicaciones y comorbilidades crónicas en pacientes con DT2 en 36 unidades de medicina familiar de cinco delegaciones del Instituto Mexicano del Seguro Social (IMSS). Métodos: Conforme los códigos de la Décima Revisión de la Clasificación Internacional de Enfermedades se identificaron las complicaciones (hipoglucemia, pie diabético, enfermedad renal, retinopatía, enfermedad cardiaca isquémica, enfermedad cerebrovascular y falla cardiaca) y comorbilidades (enfermedad hepática, cáncer, anemia) de DT2. Se compararon por delegación, edad, sexo y tiempo de evolución. Resultados: Las complicaciones y comorbilidades fueron más comunes en personas ≥ 62 años. De 297 100 pacientes, 34.9 % presentó cualquier complicación; microvasculares en el norte industrial (32 %), macrovasculares en el este rural (12.3 %) y comorbilidades (5 %) en el sur de la Ciudad de México; estas complicaciones predominaron en los hombres (cualquier complicación 30.2 %). La falla cardiaca y las comorbilidades fueron más comunes en mujeres (5.6 y 4.9 %). Conclusiones: Las complicaciones y comorbilidades de DT2 mostraron diferencias geográficas y de sexo y fueron mayores con la edad y el tiempo de evolución. Urge reforzar estrategias para la prevención de las complicaciones y comorbilidades en los pacientes con DT2.

Prevalencia de complicaciones de la diabetes y comorbilidades asociadas en medicina familiar del Instituto Mexicano del Seguro Social / Prevalence of complications of diabetes and associated comorbidities in family medicine of the Mexican Institute

Resumen Introducción: La prevalencia de complicaciones crónicas y comorbilidades en pacientes con diabetes tipo 2 (DT2) se han incrementado en el mundo. Objetivo: Comparar la prevalencia de complicaciones y comorbilidades crónicas en pacientes con DT2 en 36 unidades de medicina familiar de cinco delegaciones del Instituto Mexicano del Seguro Social (IMSS). Métodos: Conforme los códigos de la Décima Revisión de la Clasificación Internacional de Enfermedades se identificaron las complicaciones (hipoglucemia, pie diabético, enfermedad renal, retinopatía, enfermedad cardiaca isquémica, enfermedad cerebrovascular y falla cardiaca) y comorbilidades (enfermedad hepática, cáncer, anemia) de DT2. Se compararon por delegación, edad, sexo y tiempo de evolución. Resultados: Las complicaciones y comorbilidades fueron más comunes en personas ≥ 62 años. De 297 100 pacientes, 34.9 % presentó cualquier complicación; microvasculares en el norte industrial (32 %), macrovasculares en el este rural (12.3 %) y comorbilidades (5 %) en el sur de la Ciudad de México; estas complicaciones predominaron en los hombres (cualquier complicación 30.2 %). La falla cardiaca y las comorbilidades fueron más comunes en mujeres (5.6 y 4.9 %). Conclusiones: Las complicaciones y comorbilidades de DT2 mostraron diferencias geográficas y de sexo y fueron mayores con la edad y el tiempo de evolución. Urge reforzar estrategias para la prevención de las complicaciones y comorbilidades en los pacientes con DT2.

Abstract Introduction: The prevalence of chronic complications and comorbidities in patients with type 2 diabetes (T2D) has increased worldwide. Objective: To compare the prevalence of complications and chronic comorbidities in patients with T2D at 36 family medicine units of five chapters of the Mexican Institute of Social Security (IMSS). Method: Complications (hypoglycemia, diabetic foot, kidney disease, retinopathy, ischemic heart disease, cerebrovascular disease and heart failure) and comorbidities (liver disease, cancer and anemia) were identified according to codes of the International Classification of Diseases, 10th Revision. Comparisons were made by chapter, age, gender and evolution time. Results: Complications and comorbidities were more common in subjects aged ≥ 62 years. Out of 297 100 patients, 34.9 % had any complication; microvascular complications (32 %) prevailed in the industrial North, whereas macrovascular complications (12.3 %) did in the rural East, and comorbidities (5 %) in southern Mexico City. Complications predominated in men (any complication, 30.2 %). Heart failure and comorbidities were more common in women (5.6 % and 4.9 %, respectively). Conclusions: T2D complications and comorbidities showed geographic and gender differences, and were greater with older age and longer evolution time. It is urgent for strategies for the prevention of complications and comorbidities to be reinforced in patients with T2D.

Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies.

Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.