A systematic review of biobanks in Latin America: Strengths and limitations for biomedical research.

Biobanks are valuable tools for developing and applying scientific research and international cooperation through the collection of biological materials and their associated data. Systematic research following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines was conducted in late 2022 in PubMed and Scopus, and generated 17 articles to be reviewed in depth and critically assessed using the Critical Appraisal Skills Programme Checklist due to the limited available data; 12 relevant health organizations and government websites outside of peer-reviewed journals were also included. Our research identified 44 biobanks in Latin America. In general, there is a lack of regulation and legislation guaranteeing the stored materials' quality and institutional collaboration. We believe a consensus needs to be reached regarding the terminology and definitions used for biobanks. The design for informed consent should also be agreed upon to ensure the privacy of the data shared among institutions. In conclusion, in Latin America, there is a clear need for government support in creating specific procedures for biobanks and providing further support for existing biobanks.

Performance of the enhanced Sampson-NIH equation for VLDL-C and LDL-C in a population with familial combined hyperlipidemia.

INTRODUCTION: Low-density cholesterol (LDL-C) has long been estimated by the Friedewald formula (F-LDL-C); however, this method underestimates LDL-C in patients with hypertriglyceridemia (HTG) or low LDL-C levels. The Martin (M-LDL-C) and Sampson (S-LDL-C) formulas partially resolve these limitations. Recently, Sampson et al. developed a new equation (eS-VLDL-C) that includes ApoB. This new equation could be particularly useful in FCHL, which is characterized by the predominance of triglyceride-rich VLDL and a discordance between LDL-C and ApoB. METHODS: Very low-density lipoproteins (VLDL-C) was measured in 336 patients with FCHL by sequential ultracentrifugation. LDL-C was estimated by subtracting VLDL-C, estimated by the different equations, from non-HDL cholesterol. Spearman correlations, R2, mean squared error (RMSE), and bias were used to compare the accuracy of the different equations. Concordance of the estimated LDL-C values with LDL-C thresholds and ApoB was also assessed by their kappa coefficients and ROC analysis. RESULTS: Overall population had a mean age of 47 years, and 61.5% were women. 19.5% had type 2 diabetes, hypertension was present in 20.8%, and only 12.2% were on statin treatment. Both S-LDL-C and eS-LDL-C performed similarly, and better than M-LDL-C and F-LDL-C. In Bland-Altman analysis, eS-LDL-C showed the lowest bias, better performance in HTG, and better concordance with LDL-C treatment goals compared to other formulas (e.g. ρ: 0.87, 95% CI 0.84-0.89). CONCLUSIONS: LDL-S and LDL-eS equations estimate the concentration of LDL-C with greater accuracy than other formulas. The LDL-eS has best performance in estimating LDL-C with lower RMSE than other formulas.

The health system and access to treatment in patients with cervical cancer in Mexico.

Cervical cancer (CC) is tightly related to a low Human Development Index. Mexico is an upper-middle-income country with 126 million inhabitants, and its public health system aims to provide universal health coverage. Currently, employment-based social insurance covers approximately 60% of the population, and the scope of the remaining 40% is on course via the "IMSS-Bienestar" Institute. However, the annual government spending on health remains at 3% of the Gross Domestic Product, which is well below the 6% recommended by the Organization for Economic Cooperation and Development. CC is the second in incidence and mortality among women. Regarding primary prevention with the Human Papilloma Virus-vaccine, the current coverage for girls aged 9 to 14 years is only around 7%. Among secondary prevention with screening, the program is yet to cover the total number of women at risk; nevertheless, the age-standardized CC mortality rate has decreased from 12 per 100,000 women in 1979 to 5.7 per 100,000 women in 2020 due in part to increased screening coverage. Still, around two-thirds of patients present with locally advanced disease at diagnosis. Data from our country demonstrate that even socially disadvantaged CC patients achieve "standard" survival outcomes if treatment is granted. Nevertheless, there is a shortage in almost every aspect regarding CC treatment, including oncologists, chemotherapy units, medical physicists, radiation technicians, and both teletherapy and brachytherapy facilities. In conclusion, advances in the public health system in Mexico are urgently required to achieve CC control and reduce the mortality from this neoplasia that mainly targets socially disadvantaged women.

Arterial Stiffness and HbA1c: Association Mediated by Insulin Resistance in Hispanic Adults.

Arterial stiffness may be associated with glucose metabolism parameters, such as HbA1c, mainly via insulin resistance. We aimed to investigate the association between arterial stiffness and HbA1c and explore the mediator effect of insulin resistance. In this cross-sectional study, arterial stiffness (pulse-wave velocity; PWV), HbA1c, and insulin resistance (METS-IR) were determined in Hispanic adults. In addition to sex and age, various biochemical measurements (glucose, lipid profile, etc.) and adipose tissue (fat mass and visceral fat mass) were considered as potential confounding variables. A multivariate regression analysis shows that HbA1c is associated with PWV, even after adjusting for several confounding variables. Importantly, the results show that insulin resistance mediated 17.9% of the effect of HbA1c over PWV. In conclusion, HbA1c may be a potential resource for predicting arterial stiffness due to the influence of insulin resistance in Hispanic subjects.

Identification of Glucose and Insulin Patterns during A 5-H Glucose Tolerance Test and Association with Cardiometabolic Risk Factors

ABSTRACT 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.

Identification of glucose and insulin patterns during A 5-H glucose tolerance test and association with cardiometabolic risk factors.

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.

Total body water and sicca symptoms in primary Sjögren's syndrome.

OBJECTIVES: To evaluated the total body water (TBW) among patients with primary Sjögren's syndrome (pSS) and assess its correlation with the severity of oral and ocular sicca symptoms, and some objective sicca variables. METHODS: We included 85 patients and 85 controls matched by sex, age, and body mass index (BMI). We assessed the Schirmer-I test and the non-stimulated whole salivary flow (NSWSF). We evaluated ocular and oral symptoms during the past 15 days using a 0-10 visual analogue scale (VAS) (highest score=worst symptoms). We obtained the TBW by bioelectric impedance analysis. RESULTS: 80% were women (mean age 54.8 years and mean disease duration 11.5 years). TBW was similar in pSS and controls (46.8±4.6 vs. 46.9±4.5, p=0.88). TBW correlated with age (ρ=-0.25, p=0.02), disease duration (ρ=-0.30, p=0.005), BMI (ρ=-0.78, p=0.001) and ocular VAS scale (ρ=-0.28, p=0.01); but not with NSWSF, Schirmer test or oral VAS scale. When comparing patients in the lowest TBW percentile (≤25%) with the remaining patients, the former group was older, had longer disease duration, higher BMI, lower frequency of anti-Ro/SSA and antinuclear antibodies, and higher ocular VAS scores. In the multivariate analysis, the ocular VAS score (OR 1.88, 95% CI 1.08-3.2, p=0.02) and the BMI 1.92 (OR 1.4, 95% CI 1.4-2.66, p=0.0001) remained associated with a lower TBW percentage. CONCLUSIONS: Patients with pSS had similar TBW percentages to control subjects. However, lower TBW percentages in the pSS were associated with higher BMI and also with the most severe ocular symptoms.

Guía de práctica clínica mexicana para el diagnóstico y tratamiento de las dislipidemias y enfermedad cardiovascular aterosclerótica.

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. BACKGROUND: Cardiovascular diseases are the leading cause of mortality worldwide and Mexico is no exception. The epidemiological data obtained in 1990 showed that cardiovascular diseases represented 19.8% of all causes of death in our country. This figure increased significantly to 25.5% for 2015. Some national surveys suggest that more than 60% of the adult population has at least one risk factor for cardiovascular disease (obesity or overweight, hypertension, smoking, diabetes, dyslipidemias). On the other hand, data from the Pan American Health Organization have linked the process of atherosclerosis as the first cause of premature death, significantly reducing life expectancy, which has enormous social repercussions. OBJECTIVE: This document constitutes the Clinical Practice Guide (CPG) prepared at the initiative of the Mexican Society of Cardiology in collaboration with the Mexican Society of Nutrition and Endocrinology, AC, National Association of Cardiologists of Mexico, AC, Mexican Association for the Prevention of Atherosclerosis and its Complications, AC, National Normative Committee of General Medicine, AC, National College of Geriatric Medicine, AC, College of Internal Medicine of Mexico, AC, Mexican Society of Angiology and Vascular and Endovenous Surgery, AC, Mexican Institute of Research Nephrological, AC and the Mexican Academy of Neurology, A.C.; with the methodological support of the Ibero-American Agency for the Development and Evaluation of Health Technologies, in order to establish recommendations based on the best available evidence and agreed upon by an interdisciplinary group of experts. The objective of this document is to provide evidence-based recommendations to help decision makers in the diagnosis and treatment of dyslipidemias in our country. MATERIAL AND METHODS: This document complies with international quality standards, such as those described by the Institute of Medicine of the USA, the Institute of Clinical Excellence of Great Britain, the Scottish Intercollegiate Guideline Network and the Guidelines International Network. A multidisciplinary group of clinical experts and methodologists with experience in systematic reviews of the literature and the development of clinical practice guidelines was formed. A scope document was agreed upon, relevant clinical questions were established, the best available evidence critically evaluated in systematic literature reviews was exhaustively identified, and clinical recommendations were developed. The modified Delphi Panel methodology was used to achieve an adequate level of consensus in each of the recommendations contained in this CPG. RESULTS: 23 clinical questions were agreed upon which gave rise to their respective clinical recommendations. CONCLUSIONS: We consider that this document contributes to better clinical decision-making and becomes a point of reference for clinicians and patients in the management of dyslipidemias and this contributes to reducing the morbidity and mortality derived from atherosclerotic cardiovascular events in our country.

Autoimmune Thyroid Disease in Primary Sjögren's Syndrome: Real-life Screening Practice and Clinical Outcomes.

BACKGROUND: Notwithstanding the frequent coexistence of autoimmune thyroid disease (ATD) and primary Sjögren's Syndrome (SS), it is still unknown how often this association is studied along with its clinical impact. OBJECTIVE: This study aimed to describe real-world screening practices for ATD in patients with SS and evaluate clinical outcomes of patients with both diagnoses using validated activity and chronicity indexes. METHODS: It is a retrospective study of 223 patients with SS attending a tertiary referral center. Patients were under rheumatology surveillance and might have attended other clinics, including internal medicine and/or endocrinology. We registered glandular and extraglandular features, serology and scored the activity (ESSDAI) and the accrual damage (SSDDI) indexes. We also identified any thyroid function tests (TFT) performed, anti-thyroid antibodies, images, and histological thyroid examinations. A single endocrinologist reviewed all data. RESULTS: One hundred forty-nine patients had at least one set of TFT. Younger age was associated with a lack of screening (OR 0.98, 95 % CI 0.95-0.99, p=0.01). Sixty-nine patients had thyroid disease, with the most common diagnosis being ATD (n=24). Patients with ATD had a lower prevalence of Ro/SSA and anti-La/SSB antibodies but similar cumulative SS activity and damage scores. CONCLUSION: At least one-third of our patients were not screened for thyroid disease, with these patients being the youngest. Thyroid disorders were found in about 40 % of patients with SS, with ATD being the most common. Having SS/ATD did not confer more disease activity or damage accrual. These results highlight the importance of making treating physicians aware of screening for thyroid disease in this population.

Effectiveness of Concomitant Chemoradiotherapy with Gemcitabine in Locally Advanced Cervical Cancer Patients with Comorbidities.

PURPOSE: The standard treatment for locally advanced cervical cancer (LACC) is concomitant chemoradiotherapy with cisplatin (CDDP) followed by brachytherapy. The presence of comorbidities are risk factors for nephrotoxicity and are associated with lower survival. Gemcitabine is a radiosensitizing drug that has shown efficacy and safety in this context. The effectiveness of concomitant chemoradiotherapy with gemcitabine was evaluated versus cisplatin in LACC patients with comorbidities and preserved renal function. MATERIALS AND METHODS: An observational, longitudinal and paired study was carried out that included patients treated between February 2003 and December 2015. The primary objectives were to evaluate response rates, progression-free survival, and overall survival; the secondary objectives were to evaluate toxicity and renal function. RESULTS: Sixty-three patients treated with gemcitabine at 300 mg/m2 weekly and 126 patients treated with CDDP 40 mg/m2 weekly were included. There were no significant differences in response rates and survival rates. Treatment with cisplatin presented a higher frequency of hematological toxicities, while gemcitabine presented a higher frequency of gastrointestinal toxicities. A decrease in glomerular filtration rate (GFR; baseline vs. 1-year post-treatment) was observed in the cisplatin group (p=0.002), while not in the gemcitabine group (p=0.667). In a multivariate analysis, it is observed that only CDDP correlates with the decrease in GFR (hazard ratio, 2.42; p=0.012). CONCLUSION: In LACC patients with comorbidities, gemcitabine and CDDP show the same efficacy, with different toxicity profiles. Treatment with cisplatin is associated with a significant decrease in GFR during follow-up, compared to treatment with gemcitabine that does not decrease it.

Guía de práctica clínica mexicana para el diagnóstico y tratamiento de las dislipidemias y enfermedad cardiovascular aterosclerótica / Mexican clinical practice guideline for the diagnosis and treatment of dyslipidemias and atherosclerotic cardiovascular disease

resumen está disponible en el texto completo

Abstract Background: Cardiovascular diseases are the leading cause of mortality worldwide and Mexico is no exception. The epidemiological data obtained in 1990 showed that cardiovascular diseases represented 19.8% of all causes of death in our country. This figure increased significantly to 25.5% for 2015. Some national surveys suggest that more than 60% of the adult population has at least one risk factor for cardiovascular disease (obesity or overweight, hypertension, smoking, diabetes, dyslipidemias). On the other hand, data from the Pan American Health Organization have linked the process of atherosclerosis as the first cause of premature death, significantly reducing life expectancy, which has enormous social repercussions. Objective: This document constitutes the Clinical Practice Guide (CPG) prepared at the initiative of the Mexican Society of Cardiology in collaboration with the Mexican Society of Nutrition and Endocrinology, AC, National Association of Cardiologists of Mexico, AC, Mexican Association for the Prevention of Atherosclerosis and its Complications, AC, National Normative Committee of General Medicine, AC, National College of Geriatric Medicine, AC, College of Internal Medicine of Mexico, AC, Mexican Society of Angiology and Vascular and Endovenous Surgery, AC, Mexican Institute of Research Nephrological, AC and the Mexican Academy of Neurology, A.C.; with the methodological support of the Ibero-American Agency for the Development and Evaluation of Health Technologies, in order to establish recommendations based on the best available evidence and agreed upon by an interdisciplinary group of experts. The objective of this document is to provide evidence-based recommendations to help decision makers in the diagnosis and treatment of dyslipidemias in our country. Material and methods: This document complies with international quality standards, such as those described by the Institute of Medicine of the USA, the Institute of Clinical Excellence of Great Britain, the Scottish Intercollegiate Guideline Network and the Guidelines International Network. A multidisciplinary group of clinical experts and methodologists with experience in systematic reviews of the literature and the development of clinical practice guidelines was formed. A scope document was agreed upon, relevant clinical questions were established, the best available evidence critically evaluated in systematic literature reviews was exhaustively identified, and clinical recommendations were developed. The modified Delphi Panel methodology was used to achieve an adequate level of consensus in each of the recommendations contained in this CPG. Results: 23 clinical questions were agreed upon which gave rise to their respective clinical recommendations. Conclusions: We consider that this document contributes to better clinical decision-making and becomes a point of reference for clinicians and patients in the management of dyslipidemias and this contributes to reducing the morbidity and mortality derived from atherosclerotic cardiovascular events in our country.

Biochemical and Hematological Relationship with the Evaluation of Autonomic Dysfunction by Heart Rate Recovery in Patients with Asthma and Type 2 Diabetes.

There are several methods to assess the function of the autonomic nervous system. Among them, heart rate recovery (HRR) is an accepted, easy, low-cost technique. Different pathological conditions have been related to the development of autonomic dysfunction. Our study aimed to evaluate the relationship between HRR and HRR-derived parameters in ambulatory patients with asthma or type 2 diabetes followed at the National Institutes of Health in Mexico City. A total of 78 participants, 50 women and, 28 men were enrolled; anthropometric, respiratory evaluations, and fasting blood samples were taken before participants performed a 6-min walking test (6MWT). Abnormal HRR was defined as a drop of ≤8 and ≤11 beats/min at 1 or 2 min and correlated negatively with basal oxygen saturation at 1 min. Heart rate at 1 min, correlated negatively with final oxygen saturation (p < 0.01). Statistically significant negative correlations were also observed between red cell count and white blood cell count and HOMA-IR with a p < 0.01. Since discrete hematological but significant changes correlated with HRR and HRR-derived parameters, we consider that these measures are helpful in clinical settings to identify subclinical autonomic dysfunction that permits us to prevent or anticipate chronic and fatal clinical outcomes.

Primary Barriers of Adherence to a Structured Nutritional Intervention in Patients with Dyslipidemia.

PURPOSE: To describe the primary barriers to adequately adhering to a structured nutritional intervention. PATIENTS AND METHODS: A total of 106 participants diagnosed with dyslipidemia and without a medical nutrition therapeutic plan were included in this two-year study conducted at the INCMNSZ dyslipidemia clinic in Mexico City. All patients were treated with the same structured strategies, including three face-to-face visits and two telephone follow-up visits. Diet plan adherence was evaluated at each site visit through a 3-day or 24-h food recall. RESULTS: Barriers to adhere to the nutritional intervention were: lack of time to prepare their meals (23%), eating outside the home (19%), unwillingness to change dietary patterns (14%), and lack of information about a correct diet for dyslipidemias (14%). All barriers decreased significantly at the end of the intervention. Female gender, current smoking, and following a plan of more than 1500 kcal (R2 = 0.18 and p-value = 0.004) were associated with good diet adherence. Participants showed good levels of adherence to total caloric intake at visit 2 and 3, reporting 104.7% and 95.4%, respectively. Adherence to macronutrient intake varied from 65.1% to 126%, with difficulties in adhering to recommended carbohydrate and fat consumption being more notable. CONCLUSION: The study findings confirm that a structured nutritional intervention is effective in reducing barriers and improving dietary adherence and metabolic control in patients with dyslipidemias. Health providers must identify barriers to adherence early on to design interventions that reduce these barriers and improve adherence.

Comparative assessment of LDL-C and VLDL-C estimation in familial combined hyperlipidemia using Sampson's, Martin's and Friedewald's equations.

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 (< 70 and < 100 mg/dL) and Apo B (< 80 and < 65 mg/dL) thresholds were assessed. RESULTS: Sampson's equation was more accurate (RMSE 11.21 mg/dL; R2 = 0.88) compared to Martin's (RMSE 13.15 mg/dL; R2 = 0.875) and the Friedewald's equation (RMSE 13.7 mg/dL; R2 = 0.869). When assessing performance according to LDL-C, Sampson's had highest correlation and lowest RMSE compared to other equations (RMSE 19.99 mg/dL; R2 = 0.840). Comparing performance strength across triglyceride levels, Sampson's showed consistently improved correlations compared to Martin's and Friedewald's formulas for increasing triglycerides and for the FCHL phenotype of mixed dyslipidemia. Sampson's also had improved concordance with treatment goals. CONCLUSIONS: In FCHL, VLDL-C and LDL-C estimation using Sampson's formula showed higher concordance with lipid targets assessed using VLDL-C obtained by ultracentrifugation compared with Friedewald's and Martin's equations. Implementation of Sampson's formula could improve treatment monitoring in FCHL.

Natural course of metabolically healthy phenotype and risk of developing Cardiometabolic diseases: a three years follow-up study.

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.

Familial hypertriglyceridemia: an entity with distinguishable features from other causes of hypertriglyceridemia.

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 < 0.001). The polygenic set of SNPs, accounted for 1.78% of the variance in triglyceride levels in FHTG and 6.73% in CHTG. CONCLUSIONS: The clinical and genetic differences observed between FHTG and CHTG supports the notion that FHTG is a unique entity, distinguishable from other causes of hypertriglyceridemia by the higher concentrations of insulin, FGF-21, ANGPTL3, apo A-II and lower levels of apo B. We propose the inclusion of these parameters as useful markers for differentiating FHTG from other causes of hypertriglyceridemia.

Association between insulin resistance and arterial stiffness in Mexican patients without type 2 diabetes.

BACKGROUND: Central aortic arterial stiffness (CAAS) is an independent cardiovascular risk factor. Insulin resistance (IR) contributes to CAAS-associated risk. OBJECTIVE: To evaluate the association between IR and CAAS in a Mexican population without diabetes. METHODS: IR was estimated with Homeostatic Model Assessment 2-Insulin Resistance (HOMA2-IR) and other surrogate markers (Metabolic score for IR [METS-IR], Quantitative Insulin Sensitivity Check Index [QUICKI], triglycerides/glucose index [TyG], TyG*body mass index [TyG*BMI] and triglycerides/high-density lipoprotein cholesterol ratio [TG/HDL-C]). CAAS was evaluated using carotid-femoral pulse wave velocity analysis (PWVcf) and the standardized augmentation index (AI-75). Bivariate correlations were made between surrogate markers and PWVcf. Increased CAAS was defined as PWVcf above the 90th percentile. Thresholds and area under the curve (AUC) were obtained for each surrogate marker in order to evaluate their performance in estimating increased CAAS. RESULTS: Three hundred and fifty-eight patients were included. A correlation was found between HOMA2-IR and PWVcf; this correlation was replicated with other surrogate markers. METS-IR and TyG*BMI had the highest degree of correlation with PWVcf. When adjustments were made for covariates, the correlations with TyG*BMI, METS-IR, HOMA2-IR and QUICKI maintained significance. HOMA2-IR showed the strongest correlation with AI-75. METS-IR and TyG showed the best AUC. Patients with prediabetes had the highest PWVcf. CONCLUSIONS: The relationship between IR and CAAS is present before the onset of diabetes; this association may entail higher cardiovascular risk.

ANTECEDENTES: La rigidez arterial central aórtica (RACA) es un factor de riesgo cardiovascular independiente. La resistencia a la insulina (RI) contribuye al riesgo asociado a RACA. OBJETIVO: Evaluar la asociación entre RI y RACA en una población mexicana sin diabetes. MÉTODOS: La RI se estimó con HOMA2-IR y (Homeostatic Model Assessment 2-Insulin Resistance) otros subrogados (METS-IR [Metabolic score for IR], QUICKI [Quantitative Insulin Sensitivity Check Index], TyG [ratio triglicéridos/glucosa], TyG*IMC [TyG*índice de masa corporal] y TG/HDL [ratio TG/lipoproteínas de alta densidad]). Se evaluó la RACA mediante el análisis de velocidad de onda del pulso carotídeo-femoral (VOPcf) y el índice de aumentación estandarizado (AI-75). Se realizaron correlaciones bivariante entre los subrogados y la VOPcf. RACA aumentada se definió como VOPcf arriba del percentil 90. Se obtuvieron puntos de corte y área bajo la curva (ABC) para cada subrogado para estimar RACA aumentada. RESULTADOS: Se incluyó 358 pacientes. Se encontró una correlación entre HOMA2-IR y VOPcf; esta correlación se replicó con los subrogados. METS-IR y TyG*IMC tuvieron el mayor grado de correlación con VOPcf. Al ajustar, las correlaciones con TyG*IMC, METS-IR, HOMA2-IR y QUICKI mantuvieron significancia. La correlación con AI-75 fue mayor para HOMA2-IR. METS-IR y TyG mostraron la mejor ABC. Los pacientes con prediabetes tuvieron mayor VOPcf. CONCLUSIONES: La relación entre la RI y la RACA está presente desde etapas no diabéticas; esta asociación puede conllevar mayor riesgo cardiovascular.

Omega-3 and omega-6 fatty acids in primary Sjögren's syndrome: clinical meaning and association with inflammation.

OBJECTIVES: Lipid mediators derived from polyunsaturated fatty acids (FA), have been related to inflammation and immune response regulation. Herein we evaluated the intake and serum levels of ω-3 and ω-6 FA among patients with primary Sjögren's syndrome (pSS), and correlated with ocular/oral sicca symptoms, disease activity and a panel of chemokines/cytokines. METHODS: We included 108 patients and 100 controls. Dietary information was obtained from a food questionnaire of one-day reminder and processed using a nutritional software. Among the SS group, we measured serum ω-3 (α-linolenic acid [α-LN], eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA]) and ω-6 (linoleic acid [LA], arachidonic acid [AA]) by gas chromatography flame ionization. We scored the ESSDAI, ESPRI, Schirmer-I test and NSWSF. In a subsample, we assessed the OSDI, ophthalmologic staining scores and measured CXCL8, CXCL10, CCL2, IL-22 and IL-21 in saliva, and CXCL8, CXCL10, CCL2 and CXCL9 in tears by Luminometry. RESULTS: ω-3 and ω-6 intake was lower in SS patients than controls, and did not correlate with serum levels. We found a negative correlation between α-LN and the OSDI and ESSDAI, as well as DHA and ESSDAI. In tears, AA positively correlated with CXCL9, whereas in saliva, α-LN, DHA and the ω3 sum negatively correlated with CCL2. We observed a negative correlation between the ω6 sum and IL-21. CONCLUSIONS: pSS patients had deficient omega intake. Lower ocular symptoms, ESSDAI scores and salivary CCL2 correlated with higher ω-3 levels, possible suggesting a role in chronic inflammation. Further studies are warranted to deepen in the knowledge of this association.

Clinical characterization of data-driven diabetes subgroups in Mexicans using a reproducible machine learning approach.

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.