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.

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.

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.

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.

Impact of Lipids and Vascular Damage on Early Atherosclerosis in Adolescents with Parental Premature Coronary Artery Disease.

AIM: To assess the relationship of cardiovascular risk factors (CRFs) with carotid intima media thickness (IMT) in adolescents with a parental history of premature coronary artery disease (PCAD). METHODS: This cross-sectional study included 50 healthy adolescents, aged 14-18 years, both sexes, with a parental history of PCAD, that were compared to 50 controls without this history. Questionnaires regarding information of CRFs were applied. Blood chemistry analyses, included lipid profile, lipoprotein (a), low density lipoprotein (LDL) susceptibility to oxidation, and inflammatory cytokine levels. The IMT was evaluated by ultrasound. RESULTS: The mean age of all participants was 15.9 years. Anthropometric measurements, blood pressure, and lipid profile were similar in both groups. However, the parental history of PCAD group exhibited lower high density lipoprotein cholesterol concentrations, shorter LDL particle oxidation time, and higher lipoprotein (a) levels compared to the control group. IMT was significantly higher in adolescents with a parental history of PCAD compared to controls, (0.53 ± 0.04 mm vs 0.47 ± 0.02 mm, p = 0.001). Among adolescents with a parental history of PCAD, those with ≥ 3 CRFs had significantly higher IMT values (0.56 mm) than those with < 3 CRFs (0.52 mm) and controls (0.48 mm). Multivariable analyses identified that systolic blood pressure and parental history of PCAD explained 26.8% and 16.1% of the variation in IMT. Furthermore, body mass index, LDL-C, ApoB-100, triglycerides and lipoprotein (a) interact with blood pressure levels to explain the IMT values. CONCLUSION: Adolescents with a parental history of PCAD had higher IMT values than the control group, primary explained by systolic blood pressure and the parental inheritance. Adolescents with parental history of PCAD and ≥ 3 CRFs exhibited the highest IMT values. Notably, lipids and systolic blood pressure jointly contribute to explain IMT in these adolescents.

Glycemic control and high-density lipoprotein characteristics in adolescents with type 1 diabetes.

BACKGROUND: Recent evidence suggests that high-density lipoprotein (HDL) physicochemical characteristics and functional capacity may be more important that HDL-C levels in predicting coronary heart disease. There is little data regarding HDL subclasses distribution in youth with type 1 diabetes. OBJECTIVE: To assess the relationships between glycemic control and HDL subclasses distribution, composition, and function in adolescents with type 1 diabetes. METHODS: This cross-sectional study included 52 adolescents with type 1 diabetes aged 12-16 years and 43 age-matched non-diabetic controls. Patients were divided into two groups: one in fair control [hemoglobin A1c (HbA1c) < 9.6%] and the second group with poor glycemic control (HbA1c ≥ 9.6%). In all participants, we determined HDL subclasses distribution, composition, and the ability of plasma and of isolated HDL to promote cellular cholesterol efflux. Levels of soluble adhesion molecules were also measured. RESULTS: Although both groups of patients and the control group had similar HDL-C levels, linear regression analyses showed that compared with non-diabetic subjects, the poor control group had a lower proportion of HDL2b subclass (p = 0.029), triglyceride enriched (p = 0.045), and cholesteryl ester depleted (p = 0.028) HDL particles. Despite these HDL changes, cholesterol efflux was comparable among the three groups. The poor control group also had significantly higher intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 plasma concentrations. CONCLUSIONS: In adolescents with type 1 diabetes, poor glycemic control is associated with abnormalities in HDL subclasses distribution and HDL lipid composition, however, in spite of these HDL changes, the ability of HDL to promote cholesterol efflux remains comparable to that of healthy subjects.

Cardiovascular autonomic responses during head-up tilt test in newly diagnosed type 2 diabetes.

BACKGROUND: Autonomic dysfunction is commonly observed in patients with long-standing type 2 diabetes. Previous studies have confirmed the value of both subjectively assessed symptoms and objective measurements of autonomic nervous system function in diagnosing cardiovascular autonomic neuropathy. However, the head-up tilt test (HUTT) has been rarely used to investigate cardiovascular autonomic responses in subjects with high risk of newly diagnosed type 2 diabetes (nT2D). OBJECTIVE: To evaluate autonomic cardiovascular responses through passive orthostatic challenge along the diabetes continuum. METHODS: The study population was stratified as normoglycemic (n = 16), prediabetes (n = 20), and nT2D (n = 20). The prevalence of orthostatic intolerance and autonomic cardiovascular responses was evaluated with the Task Force Monitor during a 30-min passive HUTT. Spectral indices of heart rate and blood pressure variability and baroreceptor effectiveness index (BEI) were calculated through the HUTT. BEI was obtained by the sequence method. RESULTS: There were no differences in the prevalence of orthostatic intolerance or in the indices of heart rate and blood pressure variability among the three groups of study. The BEI was attenuated in the nT2D group in supine rest and throughout HUTT compared with normoglycemic and prediabetes groups. The multivariable linear regression analysis showed that BEI was associated with fasting glucose (ß = - 0.52, p < 0.001) and HbA1c (ß = - 0.57, p  < 0.001) independently of cardiovascular risk factors. CONCLUSION: Cardiovascular autonomic neuropathy, expressed as blunted BEI, is the only abnormal autonomic nervous test detected in nT2D, and it was independently associated with fasting glucose and HbA1c values.

Uric acid is associated with morpho-functional adipose tissue markers in apparently healthy subjects.

BACKGROUND: Studies have focused on the search of novel biomarkers that allow to easily identify dysfunctional adipose tissue (AT). Uric acid (UA) could be produced and reabsorbed by AT. It has been suggested that the increases of UA concentrations participates in AT dysfunction. We investigated the association of UA with morpho-functional adipose tissue markers in apparently healthy subjects. METHODS: Forty apparently healthy individuals were included. Dietary habits and anthropometrical features were evaluated. Circulating concentrations of UA, adiponectin, leptin, and plasminogen activator inhibitor-1 (PAI-1) were quantified. Periumbilical subcutaneous AT samples were obtained and adipocyte number, adipocyte area, and macrophages content were assessed. RESULTS: The present study included 40 healthy subjects (67% women) with an average age of 57 ± 9 y, BMI of 26 ± 4 (kg/m2). UA showed a significant association with the number and mean area of adipocytes, macrophages number, adiponectin, and PAI-1. Although UA was independently associated with the number and mean area of adipocytes, macrophages number, adiponectin into the adjusted multivariable model. CONCLUSION: UA concentrations are associated with morpho-functional adipose tissue markers. Our results underscore the importance of UA as one earlier instigator of adipose tissue dysfunction in subjects without metabolic abnormalities.

Effect of dietary chia supplementation on glucose metabolism and adipose tissue function markers in non-alcoholic fatty liver disease subjects.

Introduction: Background: adipose tissue dysfunction is a key factor for diabetes and non-alcoholic fatty liver disease (NAFLD) development. Chia (Salvia hispanica) is an abundant source of omega-3 fatty acids, antioxidants, and fiber which could improve adipose tissue functionality. Aim: to analyze the effect of an isocaloric chia-supplemented diet on glucose metabolism, adipose tissue inflammation, and endothelial function markers in patients with NAFLD and early stages of diabetes. Methods: in 32 patients with previous NAFLD diagnosis, without known diabetes, the effect of a diet supplemented with ground chia (25 g/day/8 weeks) was evaluated. Visceral (VAF) and liver fat, plasma lipids, fatty acids, and cytokine profiles, oral glucose tolerance test (OGTT), insulinogenic index (IGI30), insulin disposition index (DIO), and endothelial progenitor cells (EPC) were analyzed. Before and after eight weeks of diet supplementation. Results: chia supplementation promoted increases in plasma alpha-linolenic acid (75 %) and fiber consumption (55 %), and a higher number of EPC (+126 %). Basal OGTT showed that nine patients had normal OGTT, 17 pre-diabetes, and six newly diagnosed diabetes. In patients with diabetes, chia favored a healthier adipose tissue (VAF -7 %, NAFLD -100 %, adiponectin +47 %, resistin -30 %, IL-6 -44 %, IL-1ß -22 %) and upturn glucose metabolism through the improvement of beta-cell function (IGI30 +50 %, DIO +66 %). Conclusions: dietary supplementation with 25 g/day of ground chia may promote a healthier adipose tissue and improve pancreatic ß-cell and endothelial function. Among patients with early metabolic abnormalities, phytochemical properties of chia may retard diabetes progression and advanced stages of liver damage.

Introducción: Antecedentes: la disfunción del tejido adiposo es un factor clave para el desarrollo de diabetes e hígado graso no alcohólico (HGNA). La chía (Salvia hispanica) es una fuente abundante de ácidos grasos omega-3, antioxidantes y fibra, que podrían mejorar la funcionalidad del tejido adiposo. Objetivo: analizar el efecto de una dieta isocalórica suplementada con chía sobre el metabolismo de glucosa y los marcadores de inflamación del tejido adiposo y de función endotelial en pacientes con HGNA y etapas tempranas de diabetes. Métodos: en 32 pacientes con diagnóstico previo de HGNA, pero sin diabetes conocida, se evaluó el efecto de una dieta suplementada con chía molida (25 g/día) sobre la grasa visceral (GAV) y hepática, el perfil de lípidos, los ácidos grasos y las citoquinas en plasma, la prueba de tolerancia oral a la glucosa (OGTT), el índice insulinogénico (IGI30), el índice de disposición de insulina (DIO) y las células progenitoras endoteliales (EPC), antes y después de ocho semanas de suplementación. Resultados: la suplementación con chía promovió aumentos en el consumo de ácido alfa-linolénico en plasma (75 %) y fibra de alta viscosidad (55 %) y un mayor número de EPC (+126 %). La OGTT basal mostró que nueve pacientes tenían curva normal, 17 tenían prediabetes y seis, diabetes de recién diagnóstico. En los pacientes con diabetes, la chía favoreció un tejido adiposo más sano (GAV -7 %, NAFLD -100 %, adiponectina +47 %, resistina -30 %, IL-6 -44 %, IL-1ß -22 %) y un aumento del metabolismo de la glucosa a través de la mejora de la función de las células beta (IGI30 +50 %, DIO +66 %). Conclusiones: la suplementación de la dieta con 25 g/día de chía molida puede promover un tejido adiposo más saludable y mejorar la función endotelial y de las células ß pancreáticas. Entre los pacientes con anomalías metabólicas tempranas, las propiedades fitoquímicas de la chía pueden retrasar la progresión de la diabetes y el desarrollo de etapas avanzadas de daño hepático.

Dysfunctional adiposity index as a marker of adipose tissue morpho-functional abnormalities and metabolic disorders in apparently healthy subjects.

Compared to body mass index, waist circumference (WC), and adiposity measurements, adipose tissue (AT) morpho-functionality evaluations are better predictors of cardiometabolic abnormalities (CA). The present study establishes a dysfunctional adiposity index (DAI) as an early marker of CA based on adipocytes morpho-functional abnormalities. DAI was established in 340 subjects without cardiovascular risk factors selected from a cross-sectional study (n=1600). Then, DAI was calculated in 36 healthy subjects who underwent subcutaneous AT biopsy. The correlation of DAI with adipocyte morphology (size/number) and functionality (adiponectin/leptin ratio) was analyzed. The DAI cut-off point was identified and its independent association with CA was determined in 1418 subjects from the cross-sectional study. The constant parameters to calculate the DAI were [WC/[22.79+[2.68*BMI]]]*[triglycerides (TG, mmol/L)/1.37]*[1.19/high density lipoprotein-cholesterol (HDL-C, mmol/L)] for males, and [WC/[24.02+[2.37*BMI]]]*[TG(mmol/L)/1.32]*[1.43/HDL-C(mmol/L)] for females. DAI correlated with adipocytes mean area, adipocyte number and adiponectin/leptin ratio. DAI ≥1.065 was independently associated with diabetes, non-alcoholic fatty liver disease, subclinical atherosclerosis, and hypertension. The present study highlights that DAI is associated with early CA independently of adiposity and other risk factors. Since DAI is obtained using accessible parameters, it can be easily incorporated into clinical practice for early identification of AT abnormalities in apparently healthy subjects.

Metabolic control achievement in a population with premature coronary artery disease: results of the genetics of atherosclerotic disease study.

BACKGROUND AND AIMS: To the best of our knowledge, no studies have investigated the metabolic control of patients with premature coronary artery disease (CAD). The present study analyzes the metabolic control, defined as the simultaneous target in blood pressure, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol and hemoglobin A1c, as well as the factors associated with its achievement in patients with premature CAD. METHODS: The study included 1206 patients with CAD diagnosed before the age of 55 and 65 years in men and women, respectively. Sociodemographic, clinical and biochemical data were collected to know the prevalence of cardiovascular risk factors, including individual components of metabolic control plus smoking cessation and body mass index (BMI) <25 kg/m2. Non-strict and strict targets were used to evaluate metabolic control. RESULTS: Participants were 54 ± 8 years old, 19.7% were women and had a median CAD evolution of 2.4 years. Non-strict and strict metabolic control was achieved by 18.4% and 6.2% of patients, respectively. Moreover, 79.8% and 67.6% met a composite of three or more cardiovascular risk factor goals using both criteria. BMI <25 kg/m2 was independently associated with 1.734 (95% confidence interval: 1.207-2.492) and 2.541 (95% confidence interval: 1.608-4.014) higher probabilities to meet non-strict or strict metabolic control. CONCLUSION: Our results show that 18.4% and 6.2% of subjects with premature CAD achieved non-strict and strict metabolic control, respectively. BMI <25 kg/m2 was found to be associated with the achievement of metabolic control. Multidisciplinary strategies including healthy lifestyle changes and pharmacological therapies could decrease the socioeconomic and clinical impact of premature CAD.