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.

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.

Deep Multi-OMICs and Multi-Tissue Characterization in a Pre- and Postprandial State in Human Volunteers: The GEMM Family Study Research Design.

Cardiovascular disease (CVD) and type 2 diabetes (T2D) are increasing worldwide. This is mainly due to an unhealthy nutrition, implying that variation in CVD risk may be due to variation in the capacity to manage a nutritional load. We examined the genomic basis of postprandial metabolism. Our main purpose was to introduce the GEMM Family Study (Genetics of Metabolic Diseases in Mexico) as a multi-center study carrying out an ongoing recruitment of healthy urban adults. Each participant received a mixed meal challenge and provided a 5-hours' time course series of blood, buffy coat specimens for DNA isolation, and adipose tissue (ADT)/skeletal muscle (SKM) biopsies at fasting and 3 h after the meal. A comprehensive profiling, including metabolomic signatures in blood and transcriptomic and proteomic profiling in SKM and ADT, was performed to describe tendencies for variation in postprandial response. Our data generation methods showed preliminary trends indicating that by characterizing the dynamic properties of biomarkers with metabolic activity and analyzing multi-OMICS data it could be possible, with this methodology and research design, to identify early trends for molecular biology systems and genes involved in the fasted and fed states.

[Anthropometric parameters as predictors of insulin resistance in overweight and obese adults]. / Parámetros antropométricos como predictores de resistencia a la insulina en adultos con sobrepeso y obesidad.

OBJECTIVE: To evaluate which of the anthropometric parameters that estimate overweight and obesity are the best predictors of insulin resistance (IR) in adults from Family Medicine Unit N degrees 80 of IMSS in Morelia, Michoacán, México. DESIGN: Descriptive cross-sectional study. SETTING: Family Medicine Unit N 80 of Mexican Social Security Institute in Morelia, Michoacán, Mexico. PARTICIPANTS: A random sample of 147 adults with overweight or obesity. MAIN MEASUREMENTS: Age and sex. Anthropometrics: weight, body mass index (BMI), waist and mid arm circumference, % corporal fat; Skin folds thickness: bicipital, tricipital, subscapularis, abdominal skin folds; analyses: glucose, lipid profile, insulin; clinical: diastolic and systolic pressure, cardiovascular risk and insulin resistance by HOMA > or =2.5. RESULTS: IR was found in 41.49% of patients. ROC curves were made and the cut off point of bicipital skin fold > or =4.50mm, mid arm > or =27.50 cm were predictors of IR in 97.4%; BMI > or =25kg/m(2) was a predictor of IR in 92.3%, and by linear regression these parameters were the better predictors of IR. CONCLUSIONS: A total of 41.49% of patients were identified with IR (HOMA > or =2.5). BMI, bicipital skins fold and mid arm were the better predictors of IR. Specific studies are needed to determine the optimum cut off point of different parameters for estimating overweight and obesity in each sector in México.

[Factors associated with uncontrolled hypertension]. / Factores relacionados con el descontrol de la presión arterial.

OBJECTIVE: To assess health care characteristics for hypertensive patients and their association with uncontrolled hypertension in a primary care outpatient clinic. DESIGN: Cross-sectional.A review was conducted of 50% of 8080 (n= 4040) files. Patient, physician and primary health care clinic characteristics were recorded. RESULTS: The factors associated with uncontrolled hypertension were: age (OR, 1.43; CI95% : 1.015-1.030), BMI (OR, 1.03; CI95%: 1.02-1.05), creatinine serum levels (OR, 1.16; CI95%: 1.03-1.30), three or more different antihypertensive drugs (OR, 1.48; CI95%: 1.31-1.07), to be treated by a physician with more than 20 years of medical practice (OR, 1.21; CI95%; 1.06-1.39) or by a non-specialist physician (OR, 1.43; CI95%: 1.20-1.71) and to be treated in the morning shift (OR, 1.21; CI95%: 1.07- 1.56). CONCLUSIONS: Hypertension is well-controlled in the majority of patients. Patient-related factors are important in uncontrolled hypertension; however, health care system characteristics also play an important role.

Factores relacionados con el descontrol de la presión arterial / Factors associated with uncontrolled hypertension

Objetivo. Evaluar las características de la atención del paciente hipertenso, y su relación con el descontrol de la presión arterial, en una unidad de medicina familiar. Material y métodos. Diseño: estudio transversal. Se revisó la mitad de 8 080 (4 040) expedientes. Se registraron las características de los pacientes, los médicos tratantes y la unidad de atención. Resultados. Se encontraron como factores asociados a la hipertensión descontrolada la edad (RM, 1.43; IC95%: 1.015-1.030), IMC (RM, 1.03; IC95%: 1.02-1.05), creatinina (RM, 1.16; IC95%: 1.03-1.30), tomar tres o más fármacos antihipertensivos (RM, 1.48; IC95%: 1.31-1.07), ser atendido por un médico con más de 20 años de antigüedad (RM, 1.21; IC95%: 1.06-1.39), sin especialidad (RM, 1.43; IC95%: 1.20-1.71) y ser atendido en el turno matutino (RM, 1.21; IC95%: 1.07-1.56). Conclusiones. La presión arterial está bien controlada en la mayoría de los pacientes. En el descontrol de la presión arterial intervienen factores relacionados con el paciente mismo, pero las características del sistema de salud también tienen un papel significativo.

Objective. To assess health care characteristics for hypertensive patients and their association with uncontrolled hypertension in a primary care outpatient clinic. Material and Methods. Design: cross-sectional. A review was conducted of 50% of 8080 (n= 4040) files. Patient, physician and primary health care clinic characteristics were recorded. Results. The factors associated with uncontrolled hypertension were: age (OR, 1.43; CI95% : 1.015-1.030), BMI (OR, 1.03; CI95%: 1.02-1.05), creatinine serum levels (OR, 1.16; CI95%: 1.03-1.30), three or more different antihypertensive drugs (OR, 1.48; CI95%: 1.31-1.07), to be treated by a physician with more than 20 years of medical practice (OR, 1.21; CI95%; 1.06-1.39) or by a non-specialist physician (OR, 1.43; CI95%: 1.20-1.71) and to be treated in the morning shift (OR, 1.21; CI95%: 1.07- 1.56) Conclusions. Hypertension is well-controlled in the majority of patients. Patient-related factors are important in uncontrolled hypertension; however, health care system characteristics also play an important role.

Association between angiotensin-1 converting enzyme gene polymorphism and the metabolic syndrome in a Mexican population.

Metabolic Syndrome (MS) is recognized as a cluster of cardiovascular risk factors. All components of MS have a genetic base. Genes of the renin angiotensin system are potential candidate genes for MS. We investigated whether angiotensin converting enzyme (ACE) gene polymorphism increases susceptibility to MS as an entity in a Mexican population. In a cross-sectional study, 514 individuals were studied including 245 patients with MS and 269 subjects without MS criteria. ACE gene polymorphism was detected using PCR. MS was defined according to The National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria, except that the raised fasting plasma glucose

[Angiotensin-1 converting enzyme insertion/deletion gene polymorphism in a Mexican population with diabetic nephropathy]. / Polimorfismo inserción/deleción del gen de la enzima de conversión de la angiotensina en una población mexicana con nefropatía diabética.

BACKGROUND AND OBJECTIVE: Diabetic nephropathy is a polygenic and multifactorial disease. Studies of familial clustering and genetic predisposition suggest that genetic factors are involved. Among candidate genes, the coding for angiotensin-converting enzyme (ACE) polymorphism has been described. Our objective was to investigate the association ACE gene insertion/deletion (I/D) polymorphism with the development of diabetic nephropathy in a Mexican population. PATIENTS AND METHOD: In a cross-sectional study, we evaluated 204 patients with type 2 diabetes: 43 with incipient diabetic nephropathy, 45 with established diabetic nephropathy and 116 without diabetic nephropathy. Diabetic nephropathy was defined according the American Diabetes Association criteria. The ACE I/D gene polymorphism was detected by polymerase chain reaction. RESULTS: Patients with type 2 diabetes with both incipient diabetic nephropathy and established diabetic nephropathy significantly differed from controls with respect to variables that determined kidney damage (P<.0001) and serum lipids ( P<.01). The genotype DD was strongly associated with the development of incipient diabetic nephropathy (odds ratio [OR] adjusted = 2.83; 95% confidence interval, 1.74-4.59; P<.0001) and established diabetic nephropathy (OR adjusted = 2.95; 95% CI, 1.83-4.73; P<.0001). CONCLUSIONS: The ACE DD genotype is associated with the development of incipient diabetic nephropathy and established diabetic nephropathy in a Mexican population.