Replication of Integrative Data Analysis for Adipose Tissue Dysfunction, Low-Grade Inflammation, Postprandial Responses and OMICs Signatures in Symptom-Free Adults.

We previously reported preliminary characterization of adipose tissue (AT) dysfunction through the adiponectin/leptin ratio (ALR) and fasting/postprandial (F/P) gene expression in subcutaneous (SQ) adipose tissue (AT) biopsies obtained from participants in the GEMM study, a precision medicine research project. Here we present integrative data replication of previous findings from an increased number of GEMM symptom-free (SF) adults (N = 124) to improve characterization of early biomarkers for cardiovascular (CV)/immunometabolic risk in SF adults with AT dysfunction. We achieved this goal by taking advantage of the rich set of GEMM F/P 5 h time course data and three tissue samples collected at the same time and frequency on each adult participant (F/P blood, biopsies of SQAT and skeletal muscle (SKM)). We classified them with the presence/absence of AT dysfunction: low (<1) or high (>1) ALR. We also examined the presence of metabolically healthy (MH)/unhealthy (MUH) individuals through low-grade chronic subclinical inflammation (high sensitivity C-reactive protein (hsCRP)), whole body insulin sensitivity (Matsuda Index) and Metabolic Syndrome criteria in people with/without AT dysfunction. Molecular data directly measured from three tissues in a subset of participants allowed fine-scale multi-OMIC profiling of individual postprandial responses (RNA-seq in SKM and SQAT, miRNA from plasma exosomes and shotgun lipidomics in blood). Dynamic postprandial immunometabolic molecular endophenotypes were obtained to move towards a personalized, patient-defined medicine. This study offers an example of integrative translational research, which applies bench-to-bedside research to clinical medicine. Our F/P study design has the potential to characterize CV/immunometabolic early risk detection in support of precision medicine and discovery in SF individuals.

Familial hypercholesterolemia in Mexico: Initial insights from the national registry.

BACKGROUND: Familial hypercholesterolemia (FH) remains underdiagnosed and undertreated. OBJECTIVE: Report the results of the first years (2017-2019) of the Mexican FH registry. METHODS: There are 60 investigators, representing 28 federal states, participating in the registry. The variables included are in accordance with the European Atherosclerosis Society (EAS) FH recommendations. RESULTS: To date, 709 patients have been registered, only 336 patients with complete data fields are presented. The mean age is 50 (36-62) years and the average time since diagnosis is 4 (IQR: 2-16) years. Genetic testing is recorded in 26.9%. Tendon xanthomas are present in 43.2%. The prevalence of type 2 diabetes is 11.3% and that of premature CAD is 9.8%. Index cases, male gender, hypertension and smoking were associated with premature CAD. The median lipoprotein (a) level is 30.5 (IQR 10.8-80.7) mg/dl. Statins and co-administration with ezetimibe were recorded in 88.1% and 35.7% respectively. A combined treatment target (50% reduction in LDL-C and an LDL-C <100 mg/dl) was achieved by 13.7%. Associated factors were index case (OR 3.6, 95%CI 1.69-8.73, P = .002), combination therapy (OR 2.4, 95%CI 1.23-4.90, P = .011), type 2 diabetes (OR 2.8, 95%CI 1.03-7.59, P = .036) and age (OR 1.023, 95%CI 1.01-1.05, P = .033). CONCLUSION: The results confirm late diagnosis, a lower than expected prevalence and risk of ASCVD, a higher than expected prevalence of type 2 diabetes and undertreatment, with relatively few patients reaching goals. Recommendations include, the use of combination lipid lowering therapy, control of comorbid conditions and more frequent genetic testing in the future.

Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study.

Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic low-grade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders.

Effects of nonnutritive sweeteners on body weight and BMI in diverse clinical contexts: Systematic review and meta-analysis.

There is an ongoing debate about the possible influences of nonnutritive sweeteners (NNS) on body weight. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) with NNS to assess their impact on body weight. We systematically searched for RCTs at least 4 weeks in duration, evaluating the effect of NNS on body weight, both in subjects with healthy weight and in subjects with overweight/obesity at any age, and compared the effects of NNS vs caloric and noncaloric comparators. The primary outcome was the difference in body weight between NNS and comparators. Twenty studies were eligible (n = 2914). Participants consuming NNS showed significant weight/BMI differences favouring NNS compared with nonusers. Grouping by nature of comparator revealed that NNS vs placebo/no intervention and NNS vs water produced no effect. When comparing NNS vs sucrose, significant weight/BMI differences appeared favouring NNS. Consumption of NNS led to significantly negative weight/BMI differences in unrestricted energy diets, but not in weight-reduction diets. Participants with overweight/obesity and adults showed significant favourable weight/BMI differences with NNS. Data suggest that replacing sugar with NNS leads to weight reduction, particularly in participants with overweight/obesity under an unrestricted diet, information that could be utilized for evidence-based public policy decisions.

[Association between diabetes mellitus and cognitive decline in older adults. A population based study]. / Asociación de diabetes mellitus con deterioro cognitivo en adultos mayores. Estudio basado en población.

BACKGROUND: The association between diabetes and cognitive decline is already known; however, there is not much literature that document if this association is different according to gender. The aim of this study was to determine this relationship and to establish if there is a difference according to gender in older adults of Mérida, Yucatán, México. METHODS: 1293 older than sixty years old individuals without severe depression, history of psychiatric disease or stroke were included in the study. A structured survey was applied to them, including mini-mental state examination, anthropometry, capillary glucose and lipid measurements. These parameters were compared between diabetic and non-diabetic patients. The association between diabetes and cognitive decline was determined first to general population and then in each sex with logistic regression. RESULTS: Prevalence of diabetes was 27.38 %. Diabetic patients were younger (p = 0.049), with less years of formal education (p = 0.014) and with a larger waist circumference (p = 0.004) than non-diabetics. Diabetes was associated to a greater frequency of cognitive decline only in women (ß = 2.897, IC 95 % 1.428-5.877, p = 0.003). CONCLUSIONS: There is an association between diabetes and cognitive decline in women older than 60 years of age. However, there is a need of longitudinal studies that confirm these findings.

Introducción: la asociación entre diabetes y deterioro cognitivo es conocida; sin embargo, existen pocos datos respecto a si esta asociación es diferente a partir del sexo. Este estudio pretende determinar esta asociación y establecer si existe diferencia de acuerdo al sexo, en adultos mayores de Mérida, Yucatán, México. Métodos: participaron 1293 personas mayores de 60 años sin depresión grave, historia de enfermedad psiquiátrica, o evento vascular cerebral, a quienes se les aplicó una encuesta estructurada que incluyó el mini examen del estado mental, antropometría y medición capilar de glucosa y lípidos. Se compararon estos parámetros entre pacientes diabéticos y no diabéticos. Se determinó la asociación de diabetes con deterioro cognitivo mediante regresión logística para la población en general y para cada uno de los sexos. Resultados: la prevalencia de diabetes fue del 27.38 %. Los pacientes diabéticos fueron más jóvenes (p = 0.049), con menor escolaridad (p = 0.014) y con mayor circunferencia abdominal (p = 0.004) que los no diabéticos. La diabetes estuvo asociada a una mayor frecuencia de deterioro cognitivo únicamente en las mujeres (ß = 2.897, IC 95 % 1.428-5.877, p = 0.003). Conclusión: existe asociación entre diabetes y deterioro cognitivo en mujeres mayores de 60 años. Hacen falta estudios longitudinales que confirmen estos hallazgos.

Asociación entre el índice de masa corporal y el perfil de lípidos en niños y adolescentes mexicanos con obesidad: un análisis retrospectivo / Relationship between body mass index and lipid profile in obese Mexican children and adolescents: A retrospective analysis

Introducción: En México existen pocos datos referentes a la prevalencia de dislipidemia o de un perfil lipídico anormal en niños con obesidad, y su relación con el índice de masa corporal (IMC). El objetivo del estudio fue explorar esta asociación y los perfiles lipídicos más frecuentes en niños y adolescentes con obesidad. Métodos: Se realizaron mediciones antropométricas y bioquímicas en 289 niños entre 6 y 17 años de edad, y se estableció el grado de correlación de las variables lipídicas y el puntaje Z del IMC. Los pacientes se clasificaron de acuerdo con los perfiles lipídicos anormales; además, se determinó el más frecuente, y la diferencia en su frecuencia de acuerdo con el puntaje Z. Resultados: El puntaje Z del IMC demostró una correlación positiva con los niveles de colesterol total (CT) y colesterol de baja densidad (C-LDL) (r = 0.214, p <0.001 y r = 0.228, p <0.001, respectivamente). El perfil lipídico más frecuente fue el de colesterol de alta densidad bajo más hipertrigliceridemia (n= 128, 44.29%). Solamente el 16.26% de los niños fueron normolipémicos. Conclusiones: En niños con obesidad existe una correlación positiva entre el IMC y los niveles de CT y C-LDL. En estos niños, los perfiles lipídicos proaterogénicos comienzan en edades tempranas.

Background: In Mexico, data related to the prevalence of dyslipidemia or an abnormal lipid profile in obese children and its relation to body mass index (BMI) are scarce. The objective of this study is to explore this association and the most common lipid profiles in obese children and adolescents. Methods: Anthropometric and biochemical measurements were done on 289 children between the ages of 6 and 17 years, and the degree of correlation between lipid variables and BMI Z-score was established. Patients were classified according to abnormal lipid profiles. The most frequent profile was determined and the difference of their frequency according to Z-scores quartile. Results: Z-score showed a positive correlation with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels (r = 0.214, p <0.001 and 0.228, p <0.001, respectively). The most frequent lipid profile was low high-density lipoprotein cholesterol plus hypertriglyceridemia (n = 128, 44.29%). Conclusions: In obese children there is a positive correlation between BMI and TC and LDL-C levels. In these children, proatherogenic lipid profiles begin early in life.

Controversias en el diagnóstico del síndrome metabólico en poblaciones pediátricas / Controversies in diagnosis of the metabolic syndrome in pediatric population

El síndrome metabólico es el concepto clínico que integra los mecanismos mediante los cuales la acumulación de grasa intra-abdominal y la resistencia a la insulina participan en la génesis de la diabetes mellitus tipo 2, la aterosclerosis y otros procesos degenerativos (ej. deterioro cognitivo, neoplasias, esteatohepatitis no alcohólica). Su prevalencia ha aumentado en todas las sociedades occidentales; en paralelo, ha disminuido su edad de aparición, hecho que se relaciona con el aumento en la prevalencia de obesidad infantil. Sin embargo, su identificación en edades pediátricas es motivo de controversia, ya que existe poca evidencia que ligue los componentes conocidos del síndrome metabólico en adultos, con desenlaces cardiovasculares o metabólicos en la infancia o en la adolescencia. Existen varias definiciones que emplean puntos de corte y componentes distintos, situación que ocasiona confusión en su diagnóstico y tratamiento. Por otro lado, los puntos de corte de las diferentes variables del síndrome metabólico, basados en poblaciones de países desarrollados, frecuentemente no se ajustan a la realidad de los países en vías de desarrollo. Ambas situaciones dificultan la obtención de datos epidemiológicos fidedignos, respecto a la magnitud del problema. En este documento se revisan las fortalezas y debilidades de los criterios diagnósticos del síndrome metabólico en edades pediátricas.

The metabolic syndrome is a clinical concept which incorporates the phenotypic expression of intra-abdominal fat and insulin resistance under a single diagnosis. The main end points of the metabolic syndrome are well known, namely type 2 diabetes mellitus and atherosclerosis. The prevalence of the metabolic syndrome has increased in all western societies. Simultaneously, there has been a reduction in diagnosis age, probably related to the increase in prevalence of childhood obesity. However, diagnosis of the metabolic syndrome in pediatric patients has been an area of controversy. There has been little evidence connecting the known components of the metabolic syndrome in adults with either cardiovascular or metabolic end points in children and adolescents. Different definitions with distinct thresholds and components have resulted in confusion regarding diagnosis and treatment in this population. In addition, cut-off points for the components of the metabolic syndrome come from populations from developed countries; they are frequently not adjusted for populations in developing countries. Both situations complicate the possibility of obtaining accurate epidemiological data to evaluate the metabolic syndrome in the pediatric population. In this document, we discuss the strengths and weaknesses of diagnostic criteria for the metabolic syndrome when applied to children and adolescents.