The dysfunctional adiposity index is a clinical surrogate of pericardial fat in adults without premature CVD: A sub-analysis of the GEA Mexican study control group.

BACKGROUND AND AIM: The Dysfunctional Adiposity Index (DAI) is a clinical surrogate for evaluating adipose tissue functionality and cardiometabolic health. However, its association with Pericardial Fat Volume (PFV) has not been tested. The aim of this study was to evaluate DAI- PFV association, stratified by type 2 diabetes (T2D) status, and identify DAI thresholds for detecting increased PFV among patients without premature CVD. METHODS AND RESULTS: Participants from the GEA-Mexican study underwent a computed tomography scan to measure PFV. Adjusted logistic regression analyses tested the association between DAI and PFV. AUROC curves evaluated DAI's ability to identify elevated PFV (≥57.57 cm³), and the Youden method determined DAI thresholds, along with diagnostic metrics. The study analyzed 997 participants (women: 55%; mean age: 54 ± 9 years; median PFV: 42 cm³ [IQR: 29-58]), with a 13% prevalence of T2D. DAI was positively associated with elevated PFV (OR: 1.33, 95% CI: 1.07-1.70), which was more pronounced among subjects with T2D (OR: 3.01, 95% CI: 1.41-6.40). DAI thresholds were established for all participants (>1.176), individuals without T2D (>1.003), and with T2D (>1.936), yielding sensitivities of 71%, 81%, and 57%, and specificities of 48%, 38%, and 75%, respectively. The adjusted logistic regression tied DAI thresholds to a 1.68-fold elevation in PFV for all, 2.06-fold for those without T2D, and 6.81-fold for those with T2D. CONCLUSION: DAI was positively associated with increased PFV, particularly among participants with T2D. Established DAI thresholds demonstrated good diagnostic values for detecting increased PFV. DAI could serve as an accessible marker to identify PF in clinical settings.

Visceral adipose tissue is an independent predictor and mediator of the progression of coronary calcification: a prospective sub-analysis of the GEA study.

BACKGROUND: Coronary artery calcium (CAC) improves cardiovascular event prediction. Visceral adipose tissue (VAT) is a cardiometabolic risk factor that may directly or through its related comorbidities determine the obesity-related risk. A clinical VAT estimator could allow an efficient evaluation of obesity-related risk. We aimed to analyze the effect of VAT and its related cardiometabolic risk factors on CAC progression. METHODS: CAC was quantified at baseline and after 5 years by computed tomography (CT), determining its progression. VAT and pericardial fat were measured by CT and estimated by a clinical surrogate (METS-VF). Considered cardiometabolic risk factors were: peripheral insulin resistance (IR), HOMA-IR, adipose tissue IR (ADIPO-IR), and adiponectin. Factors independently associated to CAC progression were analyzed by adjusted Cox proportional hazard models, including statin use and ASCVD risk score as covariates. We performed interaction and mediation models to propose possible pathways for CAC progression. RESULTS: The study included 862 adults (53 ± 9 years, 53% women), incidence CAC progression rate: 30.2 (95% CI 25.3-35.8)/1000 person-years. VAT (HR: 1.004, 95% CI 1.001-1.007, p < 0.01) and METS-VF (HR: 1.001, 95% CI 1.0-1.001, p < 0.05) independently predicted CAC progression. VAT-associated CAC progression risk was evident among low-risk ASCVD subjects, and attenuated among medium-high-risk subjects, suggesting that traditional risk factors overcome adiposity in the latter. VAT mediates 51.8% (95% CI 44.5-58.8%) of the effect attributable to IR together with adipose tissue dysfunction on CAC progression. CONCLUSIONS: This study supports the hypothesis that VAT is a mediator of the risk conferred by subcutaneous adipose tissue dysfunction. METS-VF is an efficient clinical surrogate that could facilitate the identification of at-risk adiposity subjects in daily clinical practice.

Adipose tissue dysfunction serum markers are associated with high density lipoprotein size and glycation in the early stages of type 2 diabetes.

BACKGROUND: High-density lipoproteins (HDLs) have antiatherogenic properties related to their chemical structure. Adipose tissue (AT) influences HDL reverse cholesterol transport and plasma HDL cholesterol levels. However, whether AT dysfunction affects HDL subpopulations and their glycation in early type 2 diabetes (T2D) is still unknown. OBJECTIVE: To investigate the association of inflammation and AT dysfunction serum markers with the size and glycation of HDLs in normoglycemic, prediabetes, and T2D subjects. METHODS: We assessed HDL particle size and advanced glycation end-product (AGE) content in HDLs isolated from normoglycemic (n = 17), prediabetes (n = 17), and recently T2D-diagnosed (n = 18) subjects. Insulin, adiponectin, and plasminogen activator inhibitor 1 (PAI-1) were determined using the Bio-Rad Multiplex Platform, and free fatty acids (FFAs) and high sensitivity C-reactive protein (hs-CRP) were determined by standard procedures. The AT insulin resistance (ATIR) index and ATIR/adiponectin and adiponectin/leptin ratios were calculated. RESULTS: HDL was progressively smaller (nm) and enriched with AGE (mg-BSA-AGE/mg protein) according to the glucose categories: 8.49 and 7.5 in normoglycemic subjects, 8.44 and 12.4 in prediabetic subjects, and 8.32 and 14.3 in T2D subjects (P = 0.033 and P = 0.009 for size and AGE, respectively). In multivariable regression analysis, the ATIR/adiponectin ratio was inversely associated with HDL size (ß = -0.257, P = 0.046), and the ATIR ratio was directly associated with HDL glycation (ß = 0.387, P = 0.036). In contrast, adiponectin and the adiponectin/leptin ratio were not associated with alterations in HDL particles. Furthermore, HDL size was associated with resistin (ß = -0.348, P = 0.007) and PAI-1 (ß = -0.324, P = 0.004). HDL and AGE were related to insulin concentrations (ß = 0.458, P = 0.015). Analyses were adjusted for age, sex, body mass index, triglycerides, and HDL-cholesterol. CONCLUSION: HDL size was significantly associated with the ATIR/adiponectin ratio and inflammation, whereas glycation was more strongly related to the ATIR index. These findings have important implications for the management and prevention of cardiovascular disease in T2D patients.

Self-reported dietary omega-3 polyunsaturated fatty acids are associated with adipose tissue markers and glucose metabolism in apparently healthy subjects.

BACKGROUND: Plasminogen activator inhibitor 1 (PAI-1) and resistin are associated with dysfunctional adipose tissue (AT)-related metabolic complications. The role of dietary eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids in this relationship is unknown. AIM: To investigate the association of EPA and DHA with PAI-1 and resistin, as well as the role of this association on the glucose metabolism of apparently healthy subjects. SUBJECTS AND METHODS: Thirty-six healthy individuals were included. Validated food frequency questionnaires were used to analyse dietary habits. Inflammatory and glucose metabolism markers were quantified. Subcutaneous AT samples were obtained, and adipocyte number, area, and macrophage content were assessed. RESULTS: In 36 subjects aged 56 ± 8 years and with a body mass index of 26 ± 4 kg/m2, logEPA, and logDHA showed significant association with logresistin and a marginal association with PAI-1. Adipocyte number, area, and lognumber of macrophages per adipocyte significantly correlated with PAI-1 but not with logresistin. Although logEPA and logDHA were independently associated with loginsulin, loginsulin resistance, and C-Peptide, the addition of logresistin, but not of PAI-1, into the multivariable model, abolished the associations. CONCLUSIONS: EPA and DHA could modulate glucose metabolism across AT functional states. Our data indicate that this association is independent of other metabolic risk factors.

Participation of white adipose tissue dysfunction on circulating HDL cholesterol and HDL particle size in apparently healthy humans.

OBJECTIVE: To use the combined presence of the elevated insulin resistance index in adipose tissue (Adipo-IR) and low values of adiponectin as a marker of dysfunctional adipose tissue, and to analyze its possible association with low values of high-density lipoprotein cholesterol (HDL-C) and small size of HDL particles. RESEARCH DESIGN AND METHODS: The analysis included 253 subjects with functional adipose tissue and 253 with dysfunctional adipose tissue, considering similar gender, age, and body mass index (BMI). Adipo-IR was considered when index values (free fatty acids × insulin concentrations) were ≥75th percentile. Low levels of adiponectin were considered when concentration in serum was <25th percentile (determined by ELISA). HDL size was estimated by a quantitative validated equation. Small HDL size was considered when values were <25th percentile. RESULTS: When comparing subjects with functional adipose tissue with those of dysfunctional adipose tissue, the latter had a higher prevalence of low HDL-C (51.4% vs. 64.0%; p = 0.004) and small HDL (56.9% vs. 67.6%; p = 0.009). Multivariate analysis indicated that independently from other metabolic risk factors, dysfunction of adipose tissue is significantly associated with low HDL-C (OR: 1.624 [CI 95%: 1.100-2.397]) and small HDL (OR: 1.462 [CI 95%: 1.000-2.139]). Adding BMI, waist circumference, and subcutaneous or visceral adipose tissue did not modify the association. CONCLUSIONS: Dysfunction of adipose tissue is associated with a 65 and 50% higher probability of having low HDL-C and small HDL. Identification of dysfunctional adipose tissue could be a useful tool in the clinical setting to prevent the cardiometabolic risk independently from adiposity.

Effects of fatty liver on the size and composition of high-density lipoprotein cholesterol subpopulations in adolescents with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is an emerging disease in the pediatric population. The association between T2DM and non-alcoholic fatty liver disease (NAFLD) has been described. Recent evidence suggests that sizes and composition of high-density lipoprotein (HDL) may be more important that HDL-C levels in predicting coronary heart disease. There is not data regarding the HDL subclasses distribution and composition in T2DM youths with NAFLD. METHODS: This cross-sectional study included 47 adolescents with T2DM and 23 non-diabetic controls of both sexes aged 10 to 18 years. The presence of NAFLD was determined estimated proton density fat fraction (PDFF) by magnetic resonance by spectroscopy. We compared the HDL subclasses distribution (HDL2b, HDL2a, HDL3a HDL3b and HDL3c) and the HDL chemical composition (total protein, triglyceride, phospholipid, cholesteryl esters, and free cholesterol) between the groups of adolescents with T2DM and the control group. RESULTS: Patients with T2DM and NAFLD had a significantly lower proportion HDL2b (P = .040) and a higher proportion of HDL3c (P = .035); higher proportion of TG (P = .032) and a lower CE (P = .002) and FC (P < .001). A negative association was observed between PDFF and the percentages of HDL2b (r2 = -0.341, P = .004) and the average particle size (r2 = -0.327, P = .05), and a positive association with HDL3c subpopulations (r2 = 0.327, P = .015); about composition inside HDL particle, a positive association with PDFF and the TG (r2 = 0.299, P = .013) and negative with CE (r2 = -0.265, P = .030). CONCLUSIONS: In adolescents diagnosed with T2DM, the presence of NAFLD is associated with abnormalities in the distribution of HDL subpopulations and the lipid composition of HDL particles.

Chia (Salvia hispanica)-supplemented diet ameliorates non-alcoholic fatty liver disease and its metabolic abnormalities in humans.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a public health problem lacking an approved pharmacological treatment. Omega-3 fatty acids have shown to reverse NAFLD. Chia is a seed rich in α-linolenic acid (ALA), antioxidants, and fiber; therefore, it could be useful to treat NAFLD. METHODS: In a single arm experimental design study, the effect of 25 g/day of milled chia was assessed in 25 patients with NAFLD. After two weeks of dietary stabilization (basal condition) and eight weeks of a chia-supplemented isocaloric diet, liver:spleen attenuation index and visceral abdominal fat (VAF) were measured by computed tomography. Lipids, lipoproteins, free fatty acids (FFA), and ALA plasma concentrations were also determined. RESULTS: Dietary chia supplementation induced an increase in plasma ALA concentration (75%) and dietary fiber (55%) consumption. After chia supplementation, VAF (9%), body weight (1.4%), total cholesterol (2.5%), non-high density lipoprotein cholesterol (3.2%), and circulating FFA (8%) decreased. Furthermore, NAFLD regressed in 52% of the treated patients (P < 0.05 for all). CONCLUSIONS: The results of the present study show that 25 g/day of milled chia ameliorates NAFLD. Chia is an accessible vegetal source of omega-3 fatty acids, antioxidants, and fiber, which could have the potential to prevent metabolic abnormalities in NAFLD patients. Considering that there is no pharmacological treatment approved for NAFLD, the findings of the present study suggest that a chia-supplemented diet could be an innovative alternative to control this disease. RETROSPECTIVELY REGISTERED: https://clinicaltrials.gov/show/NCT03942822.

Determinación del estado nutricional mediante el ángulo de fase en pacientes en hemodiálisis.

INTRODUCTION: Multi-frequency bio-impedance analysis (BIA) accurately evaluates body composition. OBJECTIVE: To assess nutritional status and its relationship with body mass index (BMI) or with BIA-obtained phase angle in patients with end-stage renal disease (ESRD) on hemodialysis. METHOD: BMI, BIA and dialysis malnutrition score (DMS) were assessed in 99 patients on hemodialysis (43.6 ± 17.2 years of age, 58.8% males). Multivariate linear regression analysis was used to determine BMI and phase angle independent associations with DMS. RESULTS: Malnutrition risk (DMS > 13) showed a gradual increase among patients with normal BMI and phase angle (44.4%), low BMI (45.8%), low phase angle (64.0%), and in those with both parameters at abnormal ranges (68.0%). The phase angle was the only variable that was independently associated with patient nutritional status (standardized coefficient beta -0.372, p < 0.001), accounting for 13.8% of DMS variation. CONCLUSION: Phase angle is inversely and independently associated with malnutrition risk in patients with ESRD, which suggests that BIA-assessed body composition might be better than BMI in the clinical assessment of patients with ESRD.

INTRODUCCIÓN: La bioimpedancia eléctrica multifrecuencia (BIE) evalúa con precisión la composición corporal. OBJETIVO: Investigar el estado nutricional y su relación con el índice de masa corporal (IMC) o el ángulo fase obtenido por BIE en pacientes con enfermedad renal terminal (ERT) en hemodiálisis. MÉTODO: En 99 pacientes en hemodiálisis (43.6 ± 17.2 años, 58.8 % varones) se evaluó IMC, BIE y puntuación de desnutrición (DMS, Dialysis Malnutrition Score). La independencia de las asociaciones del IMC y el ángulo fase con el DMS se determinó con regresión lineal múltiple. RESULTADOS: El riesgo de desnutrición (DMS > 13) se incrementó gradualmente entre los sujetos con IMC y ángulo fase normales (44.4 %), IMC bajo (45.8 %), ángulo fase bajo (64.0 %) y en aquellos con ambos parámetros anormales (68.0 %). El ángulo fase fue la única variable asociada independientemente con el estado nutricional de los pacientes (coeficiente beta estandarizado −0.372, p < 0.001), lo que explicó 13.8 % de la variación en el DMS. CONCLUSIONES: El ángulo fase se asocia inversa e independientemente con el riesgo de desnutrición en pacientes con ERT, lo que sugiere que la composición corporal evaluada por BIE pudiera ser mejor que el IMC en la valoración clínica de pacientes con esta enfermedad.

Vitamin D Deficiency is not Associated with Fatty Liver in a Mexican Population.

INTRODUCTION AND AIM: Association of vitamin D deficiency (VDD) with fatty liver (FL) disease is controversial. The purpose of this study was to analyze the association of VDD with FL. MATERIAL AND METHODS: Cross-sectional study. Data on cardiovascular risk factors, medications, alcohol intake, smoking, diet, and physical activity were obtained. Biochemical, anthropometric, and blood pressure variables were measured. The 25-hydroxyvitamin D (25(OH)D) was quantified through chemoluminescence. The presence of FL, defined as a liver/spleen attenuation index lower than 1.0, was identified through computed axial tomography (CAT). RESULTS: The study included 1,467 subjects (49.7% men) with a mean age of 53.3 ± 9.3 years and BMI of 28.3 ± 4.0 kg/m2. Only 11% had optimum values of vitamin D, and 25(OH)D concentration was lower in participants with FL. Multivariate logistic regression models, adjusted for age, gender, BMI, sampling season, glucose, total cholesterol, triglycerides, HOMA-IR, hs-CRP, ALT, AST, and elevated VAT, revealed an association between FL and vitamin D (VD) insufficiency (RM 1.61 [0.99-2.61]) and with VDD (RM 1.68 [1.02-2.77]); however, statistical significance was lost when including caloric consumption and physical activity in the model. CONCLUSIONS: In Mexican adults, deficient VD concentration and FL were not independently associated of caloric consumption and physical activity.

The UCP2 -866G/A, Ala55Val and UCP3 -55C/T polymorphisms are associated with premature coronary artery disease and cardiovascular risk factors in Mexican population.

We examined the role of UCP gene polymorphisms as susceptibility markers for premature coronary artery disease (pCAD). The UCP2 Ala55Val (C/T rs660339), UCP2 -866G/A (rs659366), and UCP3 -55C/T (rs1800849) polymorphisms were genotyped in 948 patients with pCAD, and 763 controls. The distribution of the UCP2 A55V (C/T rs660339) and UCP3 -55 (rs1800849) was similar in patients and controls. However, under a recessive model, the UCP2 -866 (rs659366) A allele was associated with increased risk of developing pCAD (OR = 1.43, Pc = 0.003). On the other hand, patients with pCAD and UCP2 A55V (rs660339) TT showed high levels of visceral abdominal fat (VAF) (Pc = 0.002), low levels of subcutaneous abdominal fat (SAF) (Pc = 0.001) and high VAT/SAT ratio (Pc < 0.001). Also, patients with UCP2 -866 (rs659366) AA showed increased levels of VAF (Pc = 0.003), low levels of SAF (Pc = 0.001) and a high VAT/SAT ratio (Pc = 0.002), whereas patients with the UCP3 -55 (rs1800849) TT presented high levels of VAF (Pc = 0.002). The results suggest the association of the UCP2 -866 (rs659366) polymorphism with risk of developing pCAD. Some polymorphisms were associated with abdominal fat levels and cardiovascular risk factors.

Type 2 Diabetes Mellitus is Associated with Carotid Artery Plaques in Patients with Premature Coronary Heart Disease.

BACKGROUND: In subjects without a history of coronary heart disease (CHD), type 2 diabetes mellitus (T2DM) is associated with carotid artery plaques (CAP), which is a better marker than high carotid intima-media thickness (hCIMT) for predicting first or recurrent cardiovascular events. OBJECTIVE: The objective of this study is to analyze the association of T2DM with CAP and hCIMT in premature CHD patients. METHODS: Premature CHD was considered before the age of 55 years in men and before 65 in women. T2DM was defined according to the American Diabetes Association criteria. CAP was defined as a focal structure encroaching the arterial lumen by at least 50% of the surrounding IMT value or with a thickness > 1.5 mm. RESULTS: Among 1196 patients (CHD duration 1.5 years [interquartile range: 0.4-5.6]), 37.2% had T2DM, and 97.8% were on antihypertensive, 94.4% on lipid-lowering, and 97.3% on anti-aggregate treatment. hCIMT prevalence was similar in patients with or without T2DM, whereas CAP prevalence was higher among T2DM patients (17.7% vs. 30.9%; p < 0.001). T2DM showed association with CAP, independently of CHD evolution and glycemic control (odds ratio: 1.57; 95% confidence interval: 1.09-2.26). CONCLUSIONS: T2DM has an independent association with CAP. Early detection of recurrent cardiovascular events, with CAP identification, could be useful to prevent complications in patients with CHD.

Association of vitamin D deficiency with coronary artery disease in Mexican population: Genetics of atherosclerotic disease (GEA) study. / Deficiencia de vitamina D y su asociación con enfermedad arterial coronaria en población mexicana: estudio Genético de la Enfermedad Aterosclerosa.

Objective: To investigate the independent association between vitamin D deficiency (VDD) and coronary artery disease (CAD) in Mexican adult population. Method: Matched case-control study. Data cardiovascular on risk factors, medication use, physical activity, alcohol use, smoking and vitamin D consumption were obtained. Biochemical variables, anthropometric and blood pressure were measured. 25(OH)D was quantified by chemiluminescence. Results: We studied 250 patients with established CAD and 250 age-gender-body mass index (BMI) matched control subjects, with a mean age of 53 ± 6.1 years and BMI of 28 ± 3.5 kg/m2. Deficiency of 25(OH)D was significantly higher in the control group (21.2 vs. 16%). Multiple logistic regression analysis did not show association between VDD and CAD (OR: 1.37 [0.08-23.2]). Multiple linear regression analysis also showed that statin use (b = 2.2; p = 0.004) and no alcohol use (b = -1.8; p = 0.03) significantly increased 25(OH)D levels. Conclusions: No independent association between VDD and the presence of coronary artery disease was found in Mexican adult population. The results suggest that treatment with statins and absence of alcohol consumption, might be the explanation for the higher concentrations of 25(OH)D observed in patients with CAD.

Serum magnesium is inversely associated with coronary artery calcification in the Genetics of Atherosclerotic Disease (GEA) study.

BACKGROUND: Serum magnesium is inversely associated to coronary artery calcification (CAC) in patients with chronic kidney disease. There is little information on this association in a general healthy population. OBJECTIVE: The aim of this study was to examine the cross-sectional association of serum magnesium levels with CAC. METHODS: We included 1276 Mexican-mestizo subjects (50 % women), aged 30-75 years, free of symptomatic cardiovascular disease. CAC was quantified by multidetector computed tomography using the method described by Agatston. Cross-sectional associations of serum magnesium with cardiometabolic factors and subclinical atherosclerosis defined as a CAC score > 0, were examined in logistic regression models adjusted for age, sex, education, smoking status, body mass index, systolic blood pressure, physical activity, elevated abdominal visceral tissue, fasting insulin and glucose, alcohol consumption, menopausal status (women only), low (LDL-C) and high density lipoprotein cholesterol (HDL-C), triglycerides, diuretic use, type 2 diabetes mellitus (DM2), and family history of DM2. RESULTS: After full adjustment, subjects in the highest quartile of serum magnesium had 48 % lower odds of hypertension (p = 0.028), 69 % lower odds of DM2 (p = 0.003), and 42 % lower odds of CAC score > 0 (p = 0.016) compared to those with the lowest serum magnesium. The analyses also showed that a 0.17 mg/dL (1SD) increment in serum magnesium was independently associated with 16 % lower CAC (OR 0.84, 95 % CI 0.724-0.986). CONCLUSIONS: In a sample of Mexican-mestizo subjects, low serum magnesium was independently associated to higher prevalence not only of hypertension and DM2, but also to coronary artery calcification, which is a marker of atherosclerosis and a predictor of cardiovascular morbidity and mortality.

Microalbuminuria and its Association with Subclinical Atherosclerosis in the Mexican Mestizo population: the GEA study.

BACKGROUND: Microalbuminuria is an early marker of atherosclerosis. Ethnic differences for both conditions have been reported. We studied microalbuminuria prevalence and its association with coronary artery calcification as an early atherosclerosis marker in a Mexican-Mestizo population free of diabetes and hypertension (healthy), as well as in hypertensive and diabetic subjects. METHODS: In 1,472 adults (53.3 ± 9.4 years old, 50.3% women), anthropometric measurements, fasting blood glucose, and lipid profile were determined. A spot urine sample was used to quantify the albumin-to-creatinine ratio and to define microalbuminuria (20-200 mg/g in men, and 30-300 mg/g in women). A coronary artery calcification score was obtained by electron-beam computed tomography and subclinical atherosclerosis was defined as a score > 0. RESULTS: Overall microalbuminuria prevalence was 9.3% (5.4% in healthy, 11.6% in obese, 12% in hypertensive, and 25% in diabetic subjects). Compared to "healthy" subjects without microalbuminuria, those with microalbuminuria had a ∼3-fold higher prevalence of coronary artery calcification > 0, while normal-high albumin-to-creatinine ratio (OR: 1.8; p < 0.05) and microalbuminuria (OR: 2.6; p < 0.001) was independently associated with coronary artery calcification > 0 only among diabetic subjects. CONCLUSIONS: Microalbuminuria and high-normal albumin-to-creatinine ratio were independently associated with subclinical atherosclerosis, suggesting that they may confer a higher risk of future cardiovascular events.

Role of adiponectin and free fatty acids on the association between abdominal visceral fat and insulin resistance.

BACKGROUND: Experimental studies have shown that high free fatty acid (FFA) and low adiponectin (ADIPO) levels are involved in the mechanisms by which adiposity promotes insulin resistance (IR). However, no previous clinical studies have simultaneously analysed the relative contribution of FFA and ADIPO levels on the relation of abdominal visceral fat (AVF) with insulin resistance. OBJECTIVE: To analyse the contribution of low ADIPO (adiponectin < =p25th: 8.67 µg/mL in women and 5.30 µg/mL in men), and high FFAs (FFAs > =p75th: 0.745 mEq/L in women and 0.60 mEq/L in men) to the association of high AVF (AVF > =p75th: 127 cm2 in women; 152.7 cm2 in men) with insulin resistance (HOMA-IR > =75th: 3.58 in women and 3.12 in men), in non-diabetic subjects. MATERIAL AND METHODS: A cross-sectional analysis was performed including 1217 control participants of the Genetics of Atherosclerotic Disease study (GEA). Clinical, tomographic and biochemical parameters were measured in all participants. Logistic regression models were used to assess the association of high AVF with IR stratifying according to gender, and to normal or low ADIPO and normal or high FFA serum levels. RESULTS: In comparison to referent group, in men low ADIPO unlike high FFA increased the risk of IR. Females with normal AVF and low ADIPO, or high AVF and normal ADIPO had aprox 3 folds risk of IR (OR [IC95%]: 3.7 [2.1-6.6], p < 0.001, and 3.4 [2.0-5.7], p < 0.001; respectively). The risk increased to 7.6 [4.2-13.8], p < 0.001 when high AVF and low ADIPO were present. Irrespective of AVF, the effect of low ADIPO on IR was higher than that seen for high FFA. Besides, our results suggest an additive effect of high AVF, high FFA and low ADIPO on the IR prevalence. CONCLUSIONS: The present study provides novel and important information about the combined effect of high AVF and low ADIPO on the risk of IR. Furthermore, our data suggest that the effect of low adiponectin levels on the high AVF-IR association is stronger than that observed for high FFA, suggesting that adiponectin could be used as biomarker to identify subjects at high risk for T2DM and CAD.

Hepatic lipase (LIPC) C-514T gene polymorphism is associated with cardiometabolic parameters and cardiovascular risk factors but not with fatty liver in Mexican population.

The aim of the present study was to evaluate the role of the C-514T (rs1800588) gene polymorphism of the hepatic lipase (LIPC) as susceptibility marker for fatty liver in the Mexican population. The polymorphism was genotyped by 5' exonuclease TaqMan assays in a group of 1468 subjects (980 with and 488 without fatty liver) belonging to the Genetics of Atherosclerotic Disease (GEA) Mexican Study. Anthropometric and biochemical measurements were performed on all individuals. The polymorphism was not associated with fatty liver, however, under dominant model, the TT genotype was associated with increased levels of triglycerides (P=0.0002), apolipoprotein A1 (P=0.015), triglycerides/HDL-cholesterol index (P=0.046) and increased frequency of type 2 diabetes mellitus (P=0.045). On the other hand, the same genotype was associated with the presence of small LDLs (P=0.003). The risk analysis showed that under a dominant model, the LIPC C-514T polymorphism was associated with increased risk of type 2 diabetes (OR=1.42, P=0.029), hypertriglyceridemia (OR=1.36, P=0.006), and coronary artery calcification (CAC)≥1 (OR=1.44, P=0.015) and decreased risk of hypoalphalipoproteinemia (OR=0.78, P=0.036). The results suggest that the LIPC C-154T polymorphism is associated with cardiometabolic parameters and cardiovascular risk factors but not with fatty liver in Mexican population. The association detected with CAC indicates that this polymorphism could be a marker for subclinical atherosclerosis.

Fatty liver and abdominal fat relationships with high C-reactive protein in adults without coronary heart disease.

BACKGROUND AND RATIONALE: Fatty liver (FL) and abdominal visceral fat (AVF) are strongly associated with systemic inflammation, however, it has not been defined if each one is independently involved, and if the insulin resistance is associated. To investigate if FL, AVF and insulin resistance are independently or additively associated with the high-sensitivity C-reactive protein (hs-CRP) in subjects without coronary artery disease we included 491 men and 553 women. MATERIAL AND METHODS: All had anthropometric and plasma biochemical measurements, FL and AVF assessments by computed tomography. RESULTS: The FL prevalence was 35.6% in men and 28.0% in women, p < 0.01. The prevalence of obesity, metabolic syndrome and homeostasis model assessment of insulin resistance (HOMA-IR) was significantly higher in FL compared to non FL subjects. FL and AVF accounted for 21 and 17%, respectively, to hs-CRP plasma levels. FL, AVF ≥ P75 and HOMA-IR ≥ P75 were independently and additively associated with plasma hs-CRP. The risk of hs-CRP ≥ 3 mg/L increased progressively in men from 1.36 (0.5-3.86) through 3.58 (1.32-9.7) in those with 1 or 3 factors respectively. In women from 2.25 (1.2-4.2) to 4.67 (2.3-9.4), respectively. In conclusion, both the FL and hs-CRP ≥ 3 mg/L occur in 1 of every 3 non CAD subjects. In men, FL and AVF ≥ P75 were associated with 3.6 times the risk of hs-CRP ≥ 3 mg/L, while in women, these factors were independently and additively associated with a 4.7 times higher risk of systemic inflammation.

Self-perceived stress is associated with adiposity and atherosclerosis. The GEA Study.

BACKGROUND: A growing body of evidence suggests that psychological stress is an independent cardiovascular risk factor. Obesity prevalence shows accelerating trends worldwide, and is known to be associated with a range of comorbidities and survival. The aim of this study was to assess the relationship between self-perceived psychological stress with parameters of adiposity, metabolic syndrome, and subclinical atherosclerosis in Mexican participants. METHODS: Metabolic Syndrome was defined using the Adult Treatment Panel III criteria, obesity was defined as BMI >30, subclinical atherosclerosis disease was determined by computed tomography, and carotid intima media thickness was determined by ultrasonography. Self-perceived psychological stress was assessed using a single-item questionnaire. RESULTS: A total of 1243 control subjects were included in the sample, mean age 54.2 ± 9 years old; the prevalence of chronic self-perceived psychological stress (>5 years) was 10.13 %, female gender (62.7 %), obesity prevalence (48.4 %), and self-reporting sedentary lifestyle (56.3 %). The chronic stressed cohort presented higher subcutaneous abdominal fat content (285 vs 319 cm(2)), and carotid intima media thickness (0.63 vs 0.66 mm; p < 0.01 for both). However, after adjustment for lifestyle/social covariates (Model 1) and biological mediators (Model 2), chronic self-perceived stress was independently associated with obesity in men (OR 2.85, 95 % CI 1.51 - 5.40) and carotid atherosclerosis in women (OR 2.262, 95 % CI 1.47 - 4.67; p < 0.01 for both). CONCLUSION: Our study suggests that self-reported chronic stress is an independent risk factor for obesity in men. In addition, carotid atherosclerosis was also found to be an independent risk factor in women in a Mexican population sample.

Association of fatty liver with cardiovascular risk factors and subclinical atherosclerosis in a Mexican population.

INTRODUCTION: Individuals with fatty liver (FL) have an increased risk of coronary artery disease (CAD) probably due to its association with cardiometabolic risk factors (CMRF). OBJECTIVE: To know the prevalence of FL and analyze its association with CMRF and subclinical atherosclerosis, in a sample of Mexican Mestizo population. MATERIAL AND METHODS: This study included 846 subjects from the Genetic of Atherosclerosis Disease (GEA) study (53 ± 9 years, 50.7% women) without diabetes and no personal or family history of premature CAD. Blood samples were taken for measurements of lipids profile, uric acid, and insulin. The presence of FL was identified by computed tomography. Carotid intima media thickness (CIMT) was measured by B mode ultrasound, using the > 75 percentile as cutoff value to define subclinical atherosclerosis. RESULTS: The general prevalence of FL was 32.4%. In men, FL was associated with hyperuricemia, whereas in women, hyperuricemia, low level of high density lipoprotein cholesterol, and metabolic syndrome were the factors associated with this hepatic alteration. In women, FL was associated with a 66% higher probability of having high CIMT, independently of age, hypertension, dyslipidemia, and waist circumference, but not of HOMA-IR. CONCLUSIONS: In women, FL was associated with the presence of subclinical atherosclerosis independently of traditional CMRF. Our study suggests that, in women, insulin resistance could be a mediator of metabolic abnormalities and of subclinical atherosclerosis.

[Dietary patterns and physical activity in the mexican population: association with fatty liver]. / Patrones dietarios y de actividad física en población mexicana: asociación con hígado graso.

INTRODUCTION: Non-alcoholic fatty liver (FL) has a high prevalence and is associated with clinical conditions such as dyslipidemia, arterial hypertension, diabetes, and coronary artery disease. OBJECTIVE: To investigate the association of physical activity (PA) and nutritional factors on the presence of FL, and to analyze the association of the energy intake/energy expenditure (EI/EE) index with FL. METHODS: We studied 786 nondiabetic subjects without a history of hepatic or cardiovascular disease, and alcohol consumption < 20 g/d. Diet and PA were assessed using standardized questionnaires, and visceral abdominal fat (VAF) and liver fat by tomography. The energy intake/energy expenditure (EI/EE) index effect on the presence on FL was analyzed. RESULTS: No macronutrient was associated with FL. After adjusting for age, gender, VAF, and total kilocalories, PA significantly reduced the risk of FL (OR: 0.86; 95% CI: 0.74-0.99; p = 0.03). In logistic regression analysis adjusted for confounding factors, the EI/EE index was associated with the presence of FL (OR: 1.69; 95% CI: 1.02-2.82; p = 0.04). CONCLUSION: These results suggest that independent of macronutrient composition, a high hypercaloric diet with physical inactivity favours the development of fatty liver.