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Abstract Plasmatic uric acid (UA) has been inconsistently associated with diabetic retinopathy (DR). Specific sight-threatening stages of DR have not been studied for their association with UA. Cross-sectional, comparative study. Between 2014 and 2018 we recruited 210 Mexican individuals > 18 years-old with type 2 diabetes (T2D). Clinical, ophthalmological and biochemical assessment was performed with standardized funduscopic examination. Certified readers classified DR stages. The association between DR and UA was assessed by multiple logistic regression analysis, calculating odds ratios (OR) and 95% CI, after adjustment for covariates. Two hundred and ten patients were included, 41 (19.5%) had referable DR. Subjects with referable (severe or worse) DR had longer diabetes duration, 22 (15–28) vs 15 (8–20) years (P

Background: Adipose tissue excess is associated with adverse health outcomes, including type 2 diabetes. Body mass index (BMI) is used to evaluate obesity but is inaccurate as it does not account for muscle mass, bone density, and fat distribution. Accurate measurement of adipose tissue through dual-energy X-ray absorptiometry (DXA) and computed axial tomography (CT) is crucial for managing and monitoring adiposity-related diseases. Still, these are not easily accessible in most hospitals in Mexico. Bioelectrical impedance analysis (BIA) is non-invasive and low-cost but may not be reliable in conditions affecting the body’s hydration status, like diabetes. Objectives: To assess fat mass concordance between BIA and DXA in Hispanic-American adults with type 2 diabetes mellitus (T2DM). Methods: Cross-sectional study of a non-probabilistic sample of subjects over 18 years with type 2 diabetes. We used DXA as the reference method. Results: We evaluated the accuracy of FM estimation through BIA and DXA in 309 subjects with type 2 diabetes. Results showed a trend of overestimating the diagnosis of obesity using BIA, especially in individuals with a higher fat mass index (FMI). At the group level, we found BIA accurate; however, at the individual level, it is not. The bias between the 2 methods showed a statistically significant overestimation of body fat by BIA (P ⩽ .01) in both sexes. BIA demonstrated high precision in estimating fat mass. We were able to provide a correction factor of 0.55 kg in men. Conclusion: BIA is inaccurate compared to DXA for body composition assessment in patients with diabetes. Inaccurate measurements can result in misclassification. However, BIA is precise for body composition assessment in patients with diabetes, so it is reliable for tracking patient progress over time.

Introduction The burden of multimorbidity is recognised increasingly in low- and middle-income countries (LMICs), creating a strong emphasis on the need for effective evidence-based interventions. Core outcome sets (COS) appropriate for the study of multimorbidity in LMICs do not presently exist. These are required to standardise reporting and contribute to a consistent and cohesive evidence-base to inform policy and practice. We describe the development of two COS for intervention trials aimed at preventing and treating multimorbidity in adults in LMICs.Methods To generate a comprehensive list of relevant prevention and treatment outcomes, we conducted a systematic review and qualitative interviews with people with multimorbidity and their caregivers living in LMICs. We then used a modified two-round Delphi process to identify outcomes most important to four stakeholder groups (people with multimorbidity/caregivers, multimorbidity researchers, healthcare professionals and policymakers) with representation from 33 countries. Consensus meetings were used to reach agreement on the two final COS. Registration: https://www.comet-initiative.org/Studies/Details/1580.Results The systematic review and qualitative interviews identified 24 outcomes for prevention and 49 for treatment of multimorbidity. An additional 12 prevention and 6 treatment outcomes were added from Delphi round 1. Delphi round 2 surveys were completed by 95 of 132 round 1 participants (72.0%) for prevention and 95 of 133 (71.4%) participants for treatment outcomes. Consensus meetings agreed four outcomes for the prevention COS: (1) adverse events, (2) development of new comorbidity, (3) health risk behaviour and (4) quality of life; and four for the treatment COS: (1) adherence to treatment, (2) adverse events, (3) out-of-pocket expenditure and (4) quality of life.Conclusion Following established guidelines, we developed two COS for trials of interventions for multimorbidity prevention and treatment, specific to adults in LMIC contexts. We recommend their inclusion in future trials to meaningfully advance the field of multimorbidity research in LMICs.PROSPERO registration number CRD42020197293.

Abstract Background Pirfenidone has demonstrated significant anti‐inflammatory and antifibrotic effects in both animal models and some clinical trials. Its potential for antifibrotic activity positions it as a promising candidate for the treatment of various fibrotic diseases. Pirfenidone exerts several pleiotropic and anti‐inflammatory effects through different molecular pathways, attenuating multiple inflammatory processes, including the secretion of pro‐inflammatory cytokines, apoptosis, and fibroblast activation. Objective To present the current evidence of pirfenidone's effects on several fibrotic diseases, with a focus on its potential as a therapeutic option for managing chronic fibrotic conditions. Findings Pirfenidone has been extensively studied for idiopathic pulmonary fibrosis, showing a favorable impact and forming part of the current treatment regimen for this disease. Additionally, pirfenidone appears to have beneficial effects on similar fibrotic diseases such as interstitial lung disease, myocardial fibrosis, glomerulopathies, aberrant skin scarring, chronic liver disease, and other fibrotic disorders. Conclusion Given the increasing incidence of chronic fibrotic conditions, pirfenidone emerges as a potential therapeutic option for these patients. However, further clinical trials are necessary to confirm its therapeutic efficacy in various fibrotic diseases. This review aims to highlight the current evidence of pirfenidone's effects in multiple fibrotic conditions.

Aims: To assess the prevalence and risk factors for chronic kidney disease (CKD) among adults with type 2 diabetes within primary care. Methods: This cross-sectional study evaluated 1319 individuals receiving standard care across 26 primary units from July 2017 to January 2023. The estimated glomerular filtration rate (eGFR) and albuminuria were used for the diagnosis of CKD. CKD was defined by eGFR values of

Background: Arterial stiffness [assessed with pulse wave velocity (PWV)] can predict atherosclerotic cardiovascular disease. Objective: To evaluate arterial stiffness in patients with familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCHL). Methods: Patients were paired with a healthy control group and arterial stiffness was measured using carotid femoral PWV. Linear regression models were used to assess the relationship between PWV and clinical status. Results: The participants included 99 (50.0%) controls, 73 (36.8%) FH, and 26 (13.2%) FCHL. There was no significant difference in PWV among the three groups. The FCHL group had a numerically higher augmentation index (AIX75%) compared to the FH group. The FH group had an increased likelihood (OR: 2.450, 95% CI: 1.151-5.338; p = 0.021) of a decreased Buckberg subendocardial viability ratio (SERV) index, suggesting low coronary blood flow. Conclusions: This pilot study provides initial insights into subclinical atherosclerosis in primary dyslipidemias. Patients with FCHL had greater arterial stiffness compared to the other groups. Studies with a larger number of participants, ideally statin-free, are necessary to confirm findings.

Mexican Afro-descendant is a population poorly studied in many aspects, between them the infectious diseases that they suffer. This population is mainly found in the country’s Pacific (Oaxaca and Guerrero states) and Atlantic (Veracruz) coast. In these regions, a diversity of triatomine vectors of the Chagas disease is found. Also, all the genotypes of Trypanosoma cruzi DTUs have been reported. That is why the present study aimed to study the presence of antibodies against T. cruzi and cardiac pathology associated with the Chagas disease in the Mexican Afro-descendant population of Guerrero and Oaxaca. ELISA, Western blot, and recombinant antigen’s ELISA were used to evaluate the seropositivity of these communities. Furthermore, an electrocardiographic study and evaluation of risk factors associated with T. cruzi infection in the Oaxaca and Guerrero populations were conducted. 26.77% of the analyzed population was positive for two serological tests. These percentages are higher than the previously reported for the mestizo population in similar studies. Electrocardiographic results showed cardiac disorder associated with the Chagas disease in the population. Also, risk factors were identified associated with the men’s activities in the outdoor working areas.

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.

Abstract Background The prevention of type 2 diabetes is challenging due to the variable effects of risk factors at an individual level. Data-driven methods could be useful to detect more homogeneous groups based on risk factor variability. The aim of this study was to derive characteristic phenotypes using cluster analysis of common risk factors and to assess their utility to stratify the risk of type 2 diabetes. Methods Data on 7317 diabetes-free adults from Sweden were used in the main analysis and on 2332 diabetes-free adults from Mexico for external validation. Clusters were based on sex, family history of diabetes, educational attainment, fasting blood glucose and insulin levels, estimated insulin resistance and β-cell function, systolic and diastolic blood pressure, and BMI. The risk of type 2 diabetes was assessed using Cox proportional hazards models. The predictive accuracy and long-term stability of the clusters were then compared to different definitions of prediabetes. Results Six risk phenotypes were identified independently in both cohorts: very low-risk (VLR), low-risk low β-cell function (LRLB), low-risk high β-cell function (LRHB), high-risk high blood pressure (HRHBP), high-risk β-cell failure (HRBF), and high-risk insulin-resistant (HRIR). Compared to the LRHB cluster, the VLR and LRLB clusters showed a lower risk, while the HRHBP, HRBF, and HRIR clusters showed a higher risk of developing type 2 diabetes. The high-risk clusters, as a group, had a better predictive accuracy than prediabetes and adequate stability after 20 years. Conclusions Phenotypes derived using cluster analysis were useful in stratifying the risk of type 2 diabetes among diabetes-free adults in two independent cohorts. These results could be used to develop more precise public health interventions.

Background: The implementation of the “Step by Step” educational program to reduce diabetic foot events has reported favorable results in several countries. Objective: To describe the implementation process of the program to reduce diabetic foot amputations in Mexico and the application of essential indicators for monitoring. Materials and methods: From June 2018 to October 2022, basic and advanced courses on the prevention and treatment of diabetic foot were taught. Health professionals attended and reported the actions they carried out 1 year later. In a clinical center, the essential indicators were recorded during 5 years of follow-up in foot care. Results: Ninety-two health-care professionals were trained in face-toface mode and 638 in virtual mode. Fifty-two replicas of courses were reported, with a record of 1,379 attendees. Sixteen sites sent their actions, being the most frequent the review of > 80% of patients, standardization of evaluation procedures and registration of indicators in files, courses for nursing staff and patients, and preparation of didactic material. In the Center of Comprehensive Care for the Patient with Diabetes, 14 indicators were implemented, and in 5 years no diabetic foot amputation has been reported. Conclusion: It is feasible to implement an educational strategy for the prevention of timely care of the diabetic foot to reduce the rate of amputations in our environment.

Introduction: Diabetes is a worldwide public health problem. In Mexico, diabetes was the third leading cause of death in the total population in 2020. The indigenous people in Mexico are approximately 6%. This study aims to estimate the trends in diabetes prevalence from 2000 to 2018 in the group of Mexican indigenous language speakers and to analyze the main sociodemographic (e.g., age, educational and socioeconomic level, and the urbanicity of the area of residence) and clinical (e.g., age of diabetes onset, years with diabetes, and BMI) characteristics of this group. Methods: This cross-sectional study included participants aged ≥20 years from 4 National Health Surveys, 2000–2018. We presented the analyses for indigenous and nonindigenous strata. Logistic models adjusted were used to estimate the trend of diabetes in the study period. Results: We found a significant increase in the prevalence of diabetes in the indigenous group. This trend in the ORs was maintained when adjusting for age, sex, waist circumference, and area of residence. For the study period, the prevalence change in diagnosed diabetes in the indigenous group was greater than that in the nonindigenous group (OR=6.4, 95% CI=4.1, 8.8 and OR=3.3, 95% CI=2.5, 4.1, respectively). We also found a significant prevalence change in undiagnosed diabetes for the indigenous group (OR=7.7, 95% CI=1.3, 14.6). Conclusions: In contrast to the results in nonindigenous populations, our main result reveals an increasing probability of being diabetic in the indigenous population from 2006 to 2018. It is necessary to clarify the origin of the accelerated change in diabetes prevalence among the indigenous population in Mexico.

Introduction: Roux-en-Y gastric bypass substantially alters the gut microbial composition which could be associated with the metabolic improvements seen after surgery. Few studies have been conducted in Latin American populations, such as Mexico where obesity prevalence is above 30% in the adult population. Thus, the aim of this study was to characterize the changes in gut microbiota structure in a Mexican cohort before and after Roux-en-Y gastric bypass and to explore whether surgery-related changes in the microbial community were associated with weight loss. Methods: Biological samples from patients who underwent Roux-en-Y gastric bypass were examined before and 12 months after surgery. Fecal microbiota characterization was performed through 16S rRNA sequencing. Results: Twenty patients who underwent Roux-en-Y gastric bypass showed a median excess weight loss of 66.8% 12 months after surgery. Surgery increased alpha diversity estimates (Chao, Shannon index and observed operational taxonomic units (OTUs), p

Background and Aims: Metabolic-associated fatty liver disease (MAFLD) is a leading cause of chronic liver disease. Nowadays, the prevalence of MAFLD in Mexico is unknown with no screening point-of-care tools. We aimed to estimate the prevalence of MAFLD in Mexico and to develop a score for MAFLD screening. Methods: We conducted a cross-sectional study in 5 Mexican states, including adult subjects evaluated in checkup campaigns. Subjects underwent a liver ultrasound to look for hepatic steatosis. Based on the most clinically relevant variables associated with MAFLD, we developed the MAFLD-screening score (MAFLD-S). Discrimination and calibration of the score were evaluated using the area under the ROC curve and observed vs predicted plots, respectively. Results: We included 3357 participants (60% female, mean age 47 ± 12 years). Fifty-two percent had hepatic steatosis, and 47% met MAFLD criteria. Subjects with MAFLD were older (48 ± 11 vs 45 ± 13 years, P < .001), were more frequently males (43% vs 36%, P < .001), and had a higher body mass index (31.6 + 4.9 vs 25.6 + 3.8 kg/m2, P < .001) than subjects without MAFLD. The MAFLD-S includes age, body mass index, gender, diabetes, hypertension, and dyslipidemia and has an area under the curve of 0.852, 95% CI = 0.828–0.877, with a sensitivity of 78.8% and a specificity of 82.8% for the optimal cutoff. Using data from the National Health and Nutrition Survey 2018–2019, we predicted a MAFLD national prevalence of 49.6%. Conclusion: Nearly half of the Mexican population has MAFLD, representing a present and future challenge. With external validation, the MAFLD-S could be a valuable and practical screening tool.

Objective. To examine trends in the prevalence of metabolic syndrome (MS) and its components. Materials and methods. Data from 27 800 Mexican adults who participated in Ensanut 2006, 2012, 2016 and 2018 were analyzed. Linear regression was used across each Ensanut period to assess temporal linear trends in the prevalence of MS. Logistic regression models were obtained to calculate the percentage change, p-value for the trend and the association between the presence of MS and the risk of developing type 2 diabetes mellitus (T2DM) over 10 years using the Finnish Diabetes Risk Score (FINDRISC) and cardiovascular disease (CVD) using Globorisk. Results. The prevalence of MS in Mexican adults according to the harmonized definition was: 40.2, 57.3, 59.99 and 56.31%, in 2006, 2012, 2016 and 2018 respectively (p for trend

Objective. To estimate the prevalence of diabetes (diagnosed and undiagnosed), glycemic control in Mexico, and its associated factors. Materials and methods. We used data from Ensanut 2018 (n=12 648) and 2020 (n=2 309). We defined diabetes as fasting glucose ≥126 mg/dl or HbA1c≥6.5% or previously diagnosed; glycemic control was defined as HbA1c

Introduction Diabetic peripheral neuropathy (DPN) causes morbidity and affects the quality of life. Before diabetes diagnosis, neuropathic damage may be present. Sudoscan provides accurate measurement of the sudomotor function. This study aimed to assess the abnormalities detected by Sudoscan, offered estimates of DPN prevalence, and investigated the relationship between metabolic and clinical parameters. Additionally, we evaluated the diagnostic accuracy of the Sudoscan compared with monofilament and tuning fork tests for detecting DPN.Research design and methods Cross-sectional descriptive study including patients with type 2 diabetes for

Abstract Arterial hypertension is a major global health problem. It is the main risk factor for preventable death and the leading cause of premature death in the world. This study aims to describe the changes in hypertension-related mortality in Mexico between 1998 and 2018. Using death certificates and national population public data sets, a total of 335,863 deaths due to hypertension were found in Mexico, disaggregated by sex and age, during the time period covered in this study. An age-period-cohort analysis was conducted to show trends in hypertension mortality rates. Mortality due to hypertension in Mexico affects more women than men. In the most recent cohorts, the risk of dying from hypertension is two times higher in men compared to women. Hypertensive kidney disease is found to be the main underlying cause, with an average increase throughout the period studied. Our results indicate that mortality rates due to hypertension continue to grow and point to an alarming trend of mortality shifting towards younger ages, with sex-based disparities in absolute numbers and in changing trends.

Introduction Disentangling the specific factors that regulate glycemia from prediabetes to normoglycemia could improve type 2 diabetes prevention strategies. Metabolomics provides substantial insights into the biological understanding of environmental factors such as diet. This study aimed to identify metabolomic markers of regression to normoglycemia in the context of a lifestyle intervention (LSI) in individuals with prediabetes.Research design and methods We conducted a single-arm intervention study with 24 weeks of follow-up. Eligible study participants had at least one prediabetes criteria according to the American Diabetes Association guidelines, and body mass index between 25 and 45 kg/m2. LSI refers to a hypocaloric diet and >150 min of physical activity per week. Regression to normoglycemia (RNGR) was defined as achieving hemoglobin A1c (HbA1c)

Background: Insulin resistance is key in the pathogenesis of the metabolic syndrome and cardiovascular disease. Objective: We aimed to identify glucose and insulin patterns after a 5-h oral glucose tolerance test (OGTT) in individuals without diabetes and to explore cardiometabolic risk factors, beta-cell function, and insulin sensitivity in each pattern. Methods: We analyzed the 5-h OGTT in a tertiary healthcare center. We identified classes using latent class trajectory analysis and evaluated their association with cardiometabolic risk factors, beta-cell function, and insulin sensitivity surrogates by multinomial logistic regression analysis. Results: We included 1088 5-h OGTT performed between 2013 and 2020 and identified four classes. Class one was associated with normal insulin sensitivity and secretion. Class two showed hyperglycemia, dysinsulinism, and a high-risk cardiometabolic profile (obesity, hypertriglyceridemia, and low high-density lipoprotein [HDL] cholesterol). Class three included older individuals, a higher proportion of males, and a greater prevalence of hypertension, hyperglycemia, hyperinsulinemia, and postprandial hypoglycemia. Finally, class four showed hyperglycemia, dysinsulinism, and hyperinsulinemia; this class had the worst cardiometabolic profile (a high proportion of males, greater age, hypertension, obesity, hypertriglyceridemia, and low HDL cholesterol, p < 0.001 vs. other classes). Conclusions: The latent class analysis approach allows the identification of groups with an adverse cardiometabolic risk factor, and who might benefit from frequent follow-ups and timely multidisciplinary interventions.

Tuberculosis (TB) associated with diabetes mellitus (DM) is a growing problem, particularly in low- and medium-resource countries. We conducted an open-label, parallel-group, randomized, and controlled trial in a tertiary care center in Mexico City to assess TB preventive treatment (TPT) with isoniazid (INH) or rifampicin (RIF) in people with type 2 DM. Participants were assigned six months of INH 300 mg/day plus pyridoxine 75 mg or three months of RIF 600 mg/day. The primary outcomes were adverse events resulting in permanent treatment cessation and considered possibly or probably related to study drugs. We included 130 subjects, 68 randomized to INH and 62 to RIF. We prematurely halted the study based on recommendations of the Adverse Event Safety Panel. There was no difference between arms in the overall frequency of adverse events. However, the INH group had significantly more permanent treatment interruptions due to grade 2 recurrent or grade 3 or 4 hepatoxicity. In comparison, the RIF arm had more treatment interruptions due to grade 3 or 4 gastrointestinal intolerance. TPT using INH or RIF is not safe enough to be considered a universal indication to patients with type 2 DM and TB infection. These results underline the need to search for alternative TB preventions with better safety profiles for type 2 DM patients.

Abstract Background LCAT (lecithin-cholesterol acyltransferase) deficiency is characterized by two distinct phenotypes, familial LCAT deficiency (FLD) and Fish Eye disease (FED). This is the first systematic review evaluating the ethnic distribution of LCAT deficiency, with particular emphasis on Latin America and the discussion of three Mexican-Mestizo probands. Methods A systematic review was conducted following the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis) Statement in Pubmed and SciELO. Articles which described subjects with LCAT deficiency syndromes and an assessment of the ethnic group to which the subject pertained, were included. Results The systematic review revealed 215 cases (154 FLD, 41 FED and 20 unclassified) pertaining to 33 ethnic/racial groups. There was no association between genetic alteration and ethnicity. The mean age of diagnosis was 42 ± 16.5 years, with fish eye disease identified later than familial LCAT deficiency (55 ± 13.8 vs. 41 ± 14.7 years respectively). The prevalence of premature coronary heart disease was significantly greater in FED vs. FLD. In Latin America, 48 cases of LCAT deficiency have been published from six countries (Argentina (1 unclassified), Brazil (38 FLD), Chile (1 FLD), Columbia (1 FLD), Ecuador (1 FLD) and Mexico (4 FLD, 1 FED and 1 unclassified). Of the Mexican probands, one showed a novel LCAT mutation. Conclusions The systematic review shows that LCAT deficiency syndromes are clinically and genetically heterogeneous. No association was confirmed between ethnicity and LCAT mutation. There was a significantly greater risk of premature coronary artery disease in fish eye disease compared to familial LCAT deficiency. In FLD, the emphasis should be in preventing both cardiovascular disease and the progression of renal disease, while in FED, cardiovascular risk management should be the priority. The LCAT mutations discussed in this article are the only ones reported in the Mexican- Amerindian population.

Abstract Background We investigated pathogenic DYRK1B variants causative of abdominal obesity-metabolic syndrome 3 (AOMS3) in a group of patients originally diagnosed with type 2 diabetes. All DYRK1B exons were analyzed in a sample of 509 unrelated adults with type 2 diabetes and 459 controls, all belonging to the DMS1 SIGMA-cohort (ExAC). We performed in silico analysis on missense variants using Variant Effect Predictor software. To evaluate co-segregation, predicted pathogenic variants were genotyped in other family members. We performed molecular dynamics analysis for the co-segregating variants. Results After filtering, Mendelian genotypes were confirmed in two probands bearing two novel variants, p.Arg252His and p.Lys68Gln. Both variants co-segregated with the AOMS3 phenotype in classic dominant autosomal inheritance with full penetrance. In silico analysis revealed impairment of the DYRK1B protein function by both variants. For the first time, we describe age-dependent variable expressivity of this entity, with central obesity and insulin resistance apparent in childhood; morbid obesity, severe hypertriglyceridemia, and labile type 2 diabetes appearing before 40 years of age; and hypertension emerging in the fifth decade of life. We also report the two youngest individuals suffering from AOMS3. Conclusions Monogenic forms of metabolic diseases could be misdiagnosed and should be suspected in families with several affected members and early-onset metabolic phenotypes that are difficult to control. Early diagnostic strategies and medical interventions, even before symptoms or complications appear, could be useful.

Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants.

Abstract Background Sampson et al. developed a novel method to estimate very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) in the setting of hypertriglyceridemia. Familial Combined Hyperlipidemia (FCHL) is a common primary dyslipidemia in which lipoprotein composition interferes with LDL-C estimation. This study aimed to evaluate performance of LDL-C using this new method (LDL-S) compared with LDL-C estimated by Friedewald’s and Martin eq. (LDL-F, LDL-M) in FCHL. Methods Data were collected from 340 subjects with confirmed FCHL. Concordance for VLDL-C measured by ultracentrifugation and LDL-C estimated using these measures compared to Sampson’s, Martin’s and Friedewald’s equations was performed using correlation coefficients, root mean squared error (RMSE) and bias. Also, concordance of misclassified metrics according to LDL-C (

La diabetes tipo 2 frecuentemente se acompaña de comorbilidades que requieren la prescripción de otros fármacos, además de aquellos dirigidos al control glucémico. Para el abordaje y tratamiento integral es recomendable contar con algoritmos terapéuticos de condiciones metabólicas, de tensión arterial y en la salud mental de los pacientes. En el escrito se muestran matrices de decisión para el tratamiento farmacológico de hiperglucemia, hipertensión arterial sistémica, hiperlipidemia, hiperuricemia y trastornos psiquiátricos no psicóticos. Estos algoritmos son de aplicación en la práctica clínica cotidiana.

Globally, we are failing to meet numerous nutritional, health, and environmental targets linked to food. Defining food composition in its full chemical and quantitative diversity is central to data-driven decision making for supporting nutrition and sustainable diets. “Foodomics”—the application of omics-technology to characterize and quantify biomolecules to improve wellbeing—has the potential to comprehensively elucidate what is in food, how this composition varies across the food system, and how diet composition as an ensemble of foods guides outcomes for nutrition, health, and sustainability. Here, we outline: (i) challenges of evaluating food composition; (ii) state-of-the-art omics technology and innovations for the analysis of food; and (iii) application of foodomics as a complementary data-driven approach to revolutionize nutrition and sustainable diets. Featuring efforts of the Periodic Table of Food Initiative, a participatory effort to create a globally shared foodomics platform, we conclude with recommendations to accelerate foodomics in ways that strengthen the capacity of scientists and benefit all people.

Abstract Background Whether the metabolically healthy obese (MHO) phenotype is a single, stable or a transitional, fluctuating state is currently unknown. The Mexican-Mestizo population has a genetic predisposition for the development of type 2 diabetes (T2D) and other cardiometabolic complications. Little is known about the natural history of metabolic health in this population. The aim of this study was to analyze the transitions over time among individuals with different degrees of metabolic health and body mass index, and evaluate the incidence of cardiometabolic outcomes according to phenotype. Methods The study population consisted of a metabolic syndrome cohort with at least 3 years of follow up. Participants were apparently-healthy urban Mexican adults ≥20 years with a body mass index (BMI) ≥20 kg/m2. Metabolically healthy phenotype was defined using the criteria of the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) metabolic syndrome criteria and the subjects were stratified into 4 groups according to their BMI and metabolic health. For cardiometabolic outcomes we estimated the incidence of cardiometabolic outcomes and standardized them per 1, 000 person-years of follow-up. Finally, to evaluate the risk for transition and development of cardiometabolic outcomes, we fitted Cox Proportional Hazard regression models. Results Amongst the 5541 subjects, 54.2% were classified as metabolically healthy and 45.8% as unhealthy. The MHO prevalence was 39.3%. Up to a third of the population changed from their initial category to another and the higher transition rate was observed in MHO (42.9%). We also found several novel factors associated to transition to metabolically unhealthy phenotype; socioeconomic status, number of pregnancies, a high carbohydrate intake, history of obesity and consumption of sweetened beverages. Similarly, visceral adipose tissue (VAT) was a main predictor of transition; loss of VAT ≥5% was associated with reversion from metabolically unhealthy to metabolically healthy phenotype (hazard ratio (HR) 1.545, 95%CI 1.266–1.886). Finally, we observed higher incidence rates and risk of incident T2D and hypertension in the metabolically unhealthy obesity (MUHO) and metabolically unhealthy lean (MUHL) phenotypes compared to MHO. Conclusions Metabolic health is a dynamic and continuous process, at high risk of transition to metabolically unhealthy phenotypes over time. It is imperative to establish effective processes in primary care to prevent such transitions.

Abstract Background Familial hypertriglyceridemia (FHTG) is a partially characterized primary dyslipidemia which is frequently confused with other forms hypertriglyceridemia. The aim of this work is to search for specific features that can help physicians recognize this disease. Methods This study included 84 FHTG cases, 728 subjects with common mild-to-moderate hypertriglyceridemia (CHTG) and 609 normotriglyceridemic controls. All subjects underwent genetic, clinical and biochemical assessments. A set of 53 single nucleotide polymorphisms (SNPs) previously associated with triglycerides levels, as well as 37 rare variants within the five main genes associated with hypertriglyceridemia (i.e. LPL, APOC2, APOA5, LMF1 and GPIHBP1) were analyzed. A panel of endocrine regulatory proteins associated with triglycerides homeostasis were compared between the FHTG and CHTG groups. Results Apolipoprotein B, fibroblast growth factor 21(FGF-21), angiopoietin-like proteins 3 (ANGPTL3) and apolipoprotein A-II concentrations, were independent components of a model to detect FHTG compared with CHTG (AUC 0.948, 95%CI 0.901–0.970, 98.5% sensitivity, 92.2% specificity, P

Objetivo. Presentar el perfil de la población de 20 años o más que acude a realizarse una prueba de detección de diabetes y de hipertensión. Material y métodos. Con información de la Encuesta Nacional de Salud y Nutrición 2018-19, se obtuvieron dos modelos de regresión logística múltiple con variables asociadas con la detección de diabetes e hipertensión. Se generaron perfiles basados en combinaciones de las variables incluidas en el modelo. Se graficaron los incrementos de las probabilidades de acuerdo con los perfiles. Resultados. La población cuyas probabilidades predichas son las más altas para acudir a detección corresponde a adultos con antecedente familiar de la enfermedad, con comorbilidad asociada y estilos de vida poco saludables. Conclusiones. El sistema de salud debe buscar personas con el mayor riesgo de desarrollar o tener diabetes e hipertensión sin diagnóstico, mediante cuestionarios de riesgo tipo score. A esta población se les deberán hacer estudios de tamizaje y, en su caso, diagnósticos.

The term “triglyceride-rich lipoproteins” (TRLs) includes chylomicrons and their remnants, very low-density lipoproteins (VLDL), and intermediate-density lipoproteins (IDL). In this manuscript, the mechanisms by which atherogenic TRLs contribute to the formation of atheroma plaques are reviewed. Cholesterol from TRLs that can be retained in the subendothelial space (i.e., remnants, DLs, and small VLDLs) contributes to the genesis of atherosclerosis. Triglycerides of atherogenic TRLs induce inflammation of the arterial wall. Mechanisms that explain the involvement of TRLs in atherosclerosis are the generation of pro-atherogenic changes in high-density lipoproteins and low-density lipoproteins, accumulation of TRLs in plasma, and their passage to the subendothelial space where they cause endothelial dysfunction and inflammation of the vascular wall. Furthermore, plasma accumulation of TRLs causes hyperviscosity and a procoagulant state. Finally, this manuscript summarizes the controversial aspects of the clinical approach and the treatment of cases with dyslipidemia explained by atherogenic TRLs.

The human body is a complex system maintained in homeostasis thanks to the interactions between multiple physiological regulation systems. When faced with physical or biological perturbations, this system must react by keeping a balance between adaptability and robustness. The SARS-COV-2 virus infection poses an immune system challenge that tests the organism’s homeostatic response. Notably, the elderly and men are particularly vulnerable to severe disease, poor outcomes, and death. Mexico seems to have more infected young men than anywhere else. The goal of this study is to determine the differences in the relationships that link physiological variables that characterize the elderly and men, and those that characterize fatal outcomes in young men. To accomplish this, we examined a database of patients with moderate to severe COVID-19 (471 men and 277 women) registered at the “Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán” in March 2020. The sample was stratified by outcome, age, and sex. Physiological networks were built using 67 physiological variables (vital signs, anthropometric, hematic, biochemical, and tomographic variables) recorded upon hospital admission. Individual variables and system behavior were examined by descriptive statistics, differences between groups, principal component analysis, and network analysis. We show how topological network properties, particularly clustering coefficient, become disrupted in disease. Finally, anthropometric, metabolic, inflammatory, and pulmonary cluster interaction characterize the deceased young male group.

Abstract Background The type 2 diabetes (T2D) specific dementia-risk score (DSDRS) was developed to evaluate dementia risk in older adults with T2D. T2D-related factors have been shown increase the risk of age-related conditions, which might also increase dementia risk. Here, we investigate the associations of DSDRS with frailty, disability, quality of life (QoL) and cognition in community-dwelling older adults with T2D. Methods We included 257 community-dwelling older adults with T2D to evaluate the association between DSDRS and Mini-mental state examination (MMSE), Isaac’s set-test (IST), clock drawing test (CDT), quality of life (SF-36), risk of malnutrition (Mini-Nutritional Assessment or MNA), as well as frailty, Katz’ and Lawton-Brody scores. We also assessed the phenotype and correlates of high-estimated dementia risk by assessing individuals with DSDRS >75th age-specific percentiles. Results Mean age of participants was 78.0 ± 6.2 years. DSDRS showed a significant correlation with MMSE test, IST, CDT, SF-36, MNA, Lawton-Brody and Katz scores, and an increasing number of frailty components. DSDRS was higher among frail, pre-frail, and subjects with limited ADL and IADL (p 75th age-specific percentiles had lower education, MMSE, IST, SF-36, MNA, Katz, Lawton-Brody, and higher frailty scores. High-estimated 10-year dementia risk was associated with ADL and IADL disability, frailty and risk of malnutrition. When assessing individual components of DSDRS, T2D-related microvascular complications were associated to all outcome measures. Conclusion The DSDRS is associated with frailty, disability, malnutrition and lower cognitive performance. These findings support that T2D-related factors have significant burden on functional status, QoL, disability and dementia risk.

Objetivo. Describir la submuestra de adultos para el análisis de biomarcadores de enfermedades crónicas, así como los tamaños de muestra (n) y la representatividad de las mismas en la Encuesta Nacional de Salud y Nutrición 2016. Material y métodos. Se calculó una submuestra con representati­vidad nacional para la obtención de sangre, suero y orina en adultos. Se comparó la prevalencia de variables de interés para las submuestras. Resultados. Las n obtenidas de suero y orina fueron de 4 000 y 3 782 adultos con al menos un valor en algún marcador bioquímico sérico y marcadores de orina, respectivamente. Esta n varió con el agrupamiento de marcadores y selección por horas de ayuno. No se observa­ron diferencias en la distribución de las variables de interés entre las muestras de hogar, sangre y orina. Conclusión. Los datos ponderados de las submuestras de marcadores en orina, suero y sangre son comparables con la muestra total de adultos de la encuesta. Los datos de las submuestras permiti­rán monitorear la distribución de enfermedades crónicas en México, incluidas las alteraciones en función hepática, renal, y consumo de sodio.

Objective. To describe in a national sample 1) the preva­lence, awareness, treatment and control of dyslipidemias 2) the prevalence of dyslipidemias through previous national surveys. Materials and methods. We analyzed data of the National Health and Nutrition Survey 2012, a represen­tative cross-sectional study. Serum samples of 9 566 adults ≥20 years old with fasting ≥8 hours were analyzed for lipid fractions. Age-adjusted prevalences were calculated, by so­ciodemographic variables. Prevalence of awareness, treatment and control was estimated. A description of the dyslipidemia prevalence reported in previous surveys is reported. Re­sults. Hypoalphalipoproteinemia and elevated LDL-C are the most prevalent dyslipidemias in Mexican adults. One in four adults had hypercholesterolemia at the moment of the interview without previous diagnosis. Awareness, treatment and control of dyslipidemia were 12.6, 3.7 and 3.1%, respec­tively. Conclusions. Dyslipidemias are the most prevalent risk factor for cardiovascular diseases in Mexico. Public poli­cies to increase awareness, access to therapy and sustained control are urgently needed.

Current Genome-Wide Association Studies (GWAS) rely on genotype imputation to increase statistical power, improve fine-mapping of association signals, and facilitate meta-analyses. Due to the complex demographic history of Latin America and the lack of balanced representation of Native American genomes in current imputation panels, the discovery of locally relevant disease variants is likely to be missed, limiting the scope and impact of biomedical research in these populations. Therefore, the necessity of better diversity representation in genomic databases is a scientific imperative. Here, we expand the 1,000 Genomes reference panel (1KGP) with 134 Native American genomes (1KGP + NAT) to assess imputation performance in Latin American individuals of mixed ancestry. Our panel increased the number of SNPs above the GWAS quality threshold, thus improving statistical power for association studies in the region. It also increased imputation accuracy, particularly in low-frequency variants segregating in Native American ancestry tracts. The improvement is subtle but consistent across countries and proportional to the number of genomes added from local source populations. To project the potential improvement with a higher number of reference genomes, we performed simulations and found that at least 3,000 Native American genomes are needed to equal the imputation performance of variants in European ancestry tracts. This reflects the concerning imbalance of diversity in current references and highlights the contribution of our work to reducing it while complementing efforts to improve global equity in genomic research.

IntroductionCoronavirus disease (COVID-19) is a global pandemic. Vitamin D deficiency has been associated with susceptibility to infectious disease. In this study, the association between COVID-19 outcomes and vitamin D levels in patients attending a COVID-19 reference center in Mexico City are examined.MethodsConsecutive patients with confirmed COVID-19 were evaluated. All patients underwent clinical evaluation and follow-up, laboratory measurements and a thoracic computerized tomography, including the measurement of epicardial fat thickness. Low vitamin D was defined as levels

Background: Trials evaluating safety and efficacy of tocilizumab in coronavirus disease 19 (COVID-19) show contradictory results. Objective: The objective of the study was to evaluate the effect of tocilizumab in hospital mortality among patients with severe COVID-19 in a third-level medical center. Methods: This prospective cohort study included patients with severe and critical COVID-19. Primary outcome was death during hospitalization. Secondary outcomes included invasive mechanical ventilation (IMV), days on IMV, ventilator-free days (VFDs), length of hospital stay (LOS), and development of hospitalacquired infections (HAIs). Bivariate, multivariate, and propensity score matching analysis were performed. Results: During the study period, 99/794 (12%) patients received tocilizumab. Male patients, health care workers, and patients with increased inflammatory markers received tocilizumab more frequently. No difference in hospital mortality was observed between groups (34% vs. 34%, p = 0.98). Tocilizumab was not independently associated with mortality. No significant treatment effects were observed in propensity score analysis. IMV was more frequent (46% vs. 11%, p < 0.01) and LOS was longer (12 vs. 7 days, p < 0.01) in the tocilizumab group, reflecting increased severity. Although HAIs were more frequent in the tocilizumab group (22% vs. 10%, p < 0.01), no difference was seen after adjusting for IMV (38% vs. 40%, p = 0.86). Conclusions: In our study, tocilizumab was not associated with decreased hospital mortality among patients with severe COVID-19.

Antecedentes: Las enfermedades cardiovasculares son la principal causa mundial de mortalidad y México no es la excepción. Los datos epidemiológicos obtenidos en 1990 mostraron que los padecimientos cardiovasculares representaron el 19.8% de todas las causas de muerte en nuestro país; esta cifra se incrementó de manera significativa a un 25.5% para 2015. Diversas encuestas nacionales sugieren que más del 60% de la población adulta tiene al menos un factor de riesgo para padecer enfermedades cardiovasculares (obesidad o sobrepeso, hipertensión, tabaquismo, diabetes, dislipidemias). Por otro lado, datos de la Organización Panamericana de la Salud han relacionado el proceso de aterosclerosis como la primer causa de muerte prematura, reduciendo la expectativa de vida de manera sensible, lo que tiene una enorme repercusión social. Objetivo: Este documento constituye la guía de práctica clínica (GPC) elaborada por iniciativa de la Sociedad Mexicana de Cardiología en colaboración con la Sociedad Mexicana de Nutrición y Endocrinología, A.C., Asociación Nacional de Cardiólogos de México, A.C., Asociación Mexicana para la Prevención de la Aterosclerosis y sus Complicaciones, A.C., Comité Normativo Nacional de Medicina General, A.C., Colegio Nacional de Medicina Geriátrica, A.C., Colegio de Medicina Interna de México, A.C., Sociedad Mexicana de Angiología y Cirugía Vascular y Endovenosa, A.C., Instituto Mexicano de Investigaciones Nefrológicas, A.C. y la Academia Mexicana de Neurología, A.C.; con el apoyo metodológico de la Agencia Iberoamericana de Desarrollo y Evaluación de Tecnologías en Salud, con la finalidad de establecer recomendaciones basadas en la mejor evidencia disponible y consensuadas por un grupo interdisciplinario de expertos. El objetivo de este documento es el de brindar recomendaciones basadas en evidencia para ayudar a los tomadores de decisión en el diagnóstico y tratamiento de las dislipidemias en nuestro país. Material y métodos: Este documento cumple con estándares internacionales de calidad, como los descritos por el Instituto de Medicina de EE.UU., el Instituto de Excelencia Clínica de Gran Bretaña, la Red Colegiada para el Desarrollo de Guías de Escocia y la Red Internacional de Guías de Práctica Clínica. Se integró un grupo multidisciplinario de expertos clínicos y metodólogos con experiencia en revisiones sistemáticas de la literatura y el desarrollo de guías de práctica clínica. Se consensuó un documento de alcances, se establecieron las preguntas clínicas relevantes, se identificó de manera exhaustiva la mejor evidencia disponible evaluada críticamente en revisiones sistemáticas de la literatura y se desarrollaron las recomendaciones clínicas. Se utilizó la metodología de Panel Delphi modificado para lograr un nivel de consenso adecuado en cada una de las recomendaciones contenidas en esta GPC. Resultados: Se consensuaron 23 preguntas clínicas que dieron origen a sus respectivas recomendaciones clínicas. Conclusiones: Esperamos que este documento contribuya a la mejor toma de decisiones clínicas y se convierta en un punto de referencia para los clínicos y pacientes en el manejo de las dislipidemias y esto contribuya a disminuir la morbilidad y mortalidad derivada de los eventos cardiovasculares ateroscleróticos en nuestro país.

Objective. To estimate the prevalence of total, diagnosed and undiagnosed diabetes, and the prevalence of poor glyce­mic control in Mexico, and its associated factors. Materials and methods. Data from 3 700 adult participants were analysed in the 2016 National Health and Nutrition Survey. Diabetes prevalences were estimated with population weights, and the factors associated with total diabetes and poor glycemic control with Poisson regression models. Results The total prevalence of diabetes was 13.7% (9.5% diagnosed, 4.1% undiagnosed); 68.2% of people with diagnosed diabetes presented poor glycemic control. Longer disease duration, living in the centre or south of the country and being treated in pharmacies were associated with poor glycemic control. Being treated in a social security system was associated with better glycemic control. Conclusion. Multisectoral efforts are needed to strengthen screening, timely diagnosis and disease control, considering differences by region and type of health service.

Objective. To characterize medical care and self-care actions in a population with diabetes in locations smaller than 100 000 inhabitants. Materials and methods. With information from the Encuesta Nacional de Salud y Nutrición 100k (Ensanut 100k), two logistic regression models were obtained: not performing five basic actions in the last consultation and not taking priority self-care actions. Results. Having low schooling, belonging to the low economic stratum, and speaking indigenous language, increase the probability of not taking self-care actions. On the contrary, as age increases, the chances of self-care are reduced by 3%. Belonging to an indigenous household and the low tercile, increases the chances that health personnel will not perform the five basic actions during the consultation. Conclusion. It is essential that a diabetes control program be established that includes patient education and update courses for medical staff.

ABSTRACT: Background: Estimates of the burden of cardio-metabolic risk factors in Latin America and the Caribbean (LAC) rely on relative risks (RRs) from non-LAC countries. Whether these RRs apply to LAC remains unknown. Methods: We pooled LAC cohorts. We estimated RRs per unit of exposure to body mass index (BMI), systolic blood pressure (SBP), fasting plasma glucose (FPG), total cholesterol (TC) and non-HDL cholesterol on fatal (31 cohorts, n=168,287) and non-fatal (13 cohorts, n=27,554) cardiovascular diseases, adjusting for regression dilution bias. We used these RRs and national data on mean risk factor levels to estimate the number of cardiovascular deaths attributable to non-optimal levels of each risk factor. Results: Our RRs for SBP, FPG and TC were like those observed in cohorts conducted in high-income countries; however, for BMI, our RRs were consistently smaller in people below 75 years of age. Across risk factors, we observed smaller RRs among older ages. Non-optimal SBP was responsible for the largest number of attributable cardiovascular deaths ranging from 38 per 100,000 women and 54 men in Peru, to 261 (Dominica, women) and 282 (Guyana, men). For non-HDL cholesterol, the lowest attributable rate was for women in Peru (21) and men in Guatemala (25), and the largest in men (158) and women (142) from Guyana. Interpretation: RRs for BMI from studies conducted in high-income countries may overestimate disease burden metrics in LAC; conversely, RRs for SBP, FPG and TC from LAC cohorts are similar to those estimated from cohorts in high-income countries. Funding: Wellcome Trust (214185/Z/18/Z)

Background: Diabetes educators are an important element in the multidisciplinary treatment team of diabetes. Diabetes education interventions are recommended throughout the course of the disease since they have a favorable impact in glucose control. Objective: The objective of the study was to evaluate the baseline status and at follow-up of patients participating in diabetes education sessions. Methods: Retrospective cohort study based on the review of clinical records of patients from a National Health Institute in Mexico. A total of 153 subjects that attended individual sessions were included in the study. Changes were assessed in 48 participants that had a second evaluation. The outcomes included clinical, anthropometric, and biochemical parameters, along with variables related to diabetes education. Results: The knowledge about tools for diabetes self-management was poor. Significant changes were found in different components that promote self-management of diabetes including knowing glycemic targets, performing an adequate insulin injection, and practicing self-monitoring of blood glucose. Conclusions: The knowledge of patients with diabetes about their disease is inadequate. Interventions related to diabetes education could promote better adherence to self-care behaviors in patients with diabetes.

Introduction To assess the cost-effectiveness of a multidisciplinary and comprehensive innovative diabetes care program (CAIPaDi) versus usual treatment in public health institutions.Research design and methods Using a cost-effectiveness analysis, we compared the CAIPaDi program versus usual treatment given in Mexican public health institutions. The analysis was based on the IQVIA Core Diabetes Model, a validated simulation model used to estimate long-term clinical outcomes. Data were prospectively obtained from the CAIPaDi program and from public databases and published papers. Health outcomes were expressed in terms of life-years gained and quality-adjusted life years (QALYs). Health and economic outcomes were estimated from a public perspective and discounted at 5% per year over a 20-year horizon. Costs are reported in US dollars (US$) of 2019. A probabilistic sensitivity analysis was performed using life-years gained and QALYs.Results The CAIPaDi costs on average US$559 (95% CI: −$879 to −$239) less than the usual treatment (95% CI: −$879 to −$239) and produced a difference in mean life-years gained (0.48, 95% CI: 0.45 to 0.52) and mean QALYs (1.43, 95% CI: 1.40 to 1.46). The cost-effectiveness ratio resulted in a saving per life-year gained of −US$1155 (95% CI: −$1962 to −$460). Mean differences in QALYs resulted in a saving per QALY of −US$735 (95% CI: −$1193 to −$305). Probabilistic sensitivity analysis proved the results are robust on both life-years gained and QALYs.Conclusions CAIPaDi has a better cost-effectiveness ratio than the usual therapy in Mexican public health institutions.

Introduction Previous reports in European populations demonstrated the existence of five data-driven adult-onset diabetes subgroups. Here, we use self-normalizing neural networks (SNNN) to improve reproducibility of these data-driven diabetes subgroups in Mexican cohorts to extend its application to more diverse settings.Research design and methods We trained SNNN and compared it with k-means clustering to classify diabetes subgroups in a multiethnic and representative population-based National Health and Nutrition Examination Survey (NHANES) datasets with all available measures (training sample: NHANES-III, n=1132; validation sample: NHANES 1999–2006, n=626). SNNN models were then applied to four Mexican cohorts (SIGMA-UIEM, n=1521; Metabolic Syndrome cohort, n=6144; ENSANUT 2016, n=614 and CAIPaDi, n=1608) to characterize diabetes subgroups in Mexicans according to treatment response, risk for chronic complications and risk factors for the incidence of each subgroup.Results SNNN yielded four reproducible clinical profiles (obesity related, insulin deficient, insulin resistant, age related) in NHANES and Mexican cohorts even without C-peptide measurements. We observed in a population-based survey a high prevalence of the insulin-deficient form (41.25%, 95% CI 41.02% to 41.48%), followed by obesity-related (33.60%, 95% CI 33.40% to 33.79%), age-related (14.72%, 95% CI 14.63% to 14.82%) and severe insulin-resistant groups. A significant association was found between the SLC16A11 diabetes risk variant and the obesity-related subgroup (OR 1.42, 95% CI 1.10 to 1.83, p=0.008). Among incident cases, we observed a greater incidence of mild obesity-related diabetes (n=149, 45.0%). In a diabetes outpatient clinic cohort, we observed increased 1-year risk (HR 1.59, 95% CI 1.01 to 2.51) and 2-year risk (HR 1.94, 95% CI 1.13 to 3.31) for incident retinopathy in the insulin-deficient group and decreased 2-year diabetic retinopathy risk for the obesity-related subgroup (HR 0.49, 95% CI 0.27 to 0.89).Conclusions Diabetes subgroup phenotypes are reproducible using SNNN; our algorithm is available as web-based tool. Application of these models allowed for better characterization of diabetes subgroups and risk factors in Mexicans that could have clinical applications.

El pie diabético es una complicación incapacitante de gran impacto individual, familiar, social y económico. Se han realizado varios esfuerzos en países latinoamericanos para reducir la incidencia de hospitalizaciones y amputaciones por esta condición. El abordaje de los aspectos educativos constituye la base para su prevención. Los programas de entrenamiento preventivo dirigidos a profesionales de la salud, pacientes y familiares han mostrado reducir la aparición de úlceras en pie y amputación. Dichos programas han generado importante material para profesionales de la salud y pacientes basados en la práctica clínica con la finalidad de disminuir los factores de riesgo y cuidar el pie del paciente con diabetes. En el abordaje del tratamiento de diabetes, el manejo integral y multidisciplinario incluye necesariamente la atención del pie de personas con diabetes. Con la implementación de estos modelos, es factible la revisión y tratamiento oportuno a una mayor proporción de pacientes. Con estas estrategias se ha logrado reducir la incidencia de las complicaciones en pies. Sin embargo, aún se requiere fortalecer y difundir el concepto de reducir al máximo las amputaciones por pie diabético.

Within human physiology, systemic interactions couple physiological variables to maintain homeostasis. These interactions change according to health status and are modified by factors such as age and sex. For several physiological processes, sex-based distinctions in normal physiology are present and defined in isolation. However, new methodologies are indispensable to analyze system-wide properties and interactions with the objective of exploring differences between sexes. Here we propose a new method to construct complex inferential networks from a normalization using the clinical criteria for health of physiological variables, and the correlations between anthropometric and blood tests biomarkers of 198 healthy young participants (117 women, 81 men, from 18 to 27 years old). Physiological networks of men have less correlations, displayed higher modularity, higher small-world index, but were more vulnerable to directed attacks, whereas networks of women were more resilient. The networks of both men and women displayed sex-specific connections that are consistent with the literature. Additionally, we carried out a time-series study on heart rate variability (HRV) using Physionet’s Fantasia database. Autocorrelation of HRV, variance, and Poincare’s plots, as a measure of variability, are statistically significant higher in young men and statistically significant different from young women. These differences are attenuated in older men and women, that have similar HRV distributions. The network approach revealed differences in the association of variables related to glucose homeostasis, nitrogen balance, kidney function, and fat depots. The clusters of physiological variables and their roles within the network remained similar regardless of sex. Both methodologies show a higher number of associations between variables in the physiological system of women, implying redundant mechanisms of control and simultaneously showing that these systems display less variability in time than those of men, constituting a more resilient system.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.