Luis E. Simental-Mendía

Obesity and inflammation: epidemiology, risk factors, and markers of inflammation.

Obesity is a public health problem that has reached epidemic proportions with an increasing worldwide prevalence. The global emergence of obesity increases the risk of developing chronic metabolic disorders. Thus, it is an economic issue that increased the costs of the comorbidities associated. Moreover, in recent years, it has been demonstrated that obesity is associated with chronic systemic inflammation, this status is conditioned by the innate immune system activation in adipose tissue that promotes an increase in the production and release of pro-inflammatory cytokines that contribute to the triggering of the systemic acute-phase response which is characterized by elevation of acute-phase protein levels. On this regard, low-grade chronic inflammation is a characteristic of various chronic diseases such as metabolic syndrome, cardiovascular disease, diabetes, hypertension, non-alcoholic fatty liver disease, and some cancers, among others, which are also characterized by obesity condition. Thus, a growing body of evidence supports the important role that is played by the inflammatory response in obesity condition and the pathogenesis of chronic diseases related.

The Product of Triglycerides and Glucose, a Simple Measure of Insulin Sensitivity. Comparison with the Euglycemic-Hyperinsulinemic Clamp

CONTEXT To meet the worldwide challenge of emerging diabetes, accessible and inexpensive tests to identify insulin resistance are needed. OBJECTIVE To evaluate the sensitivity and specificity of the product of fasting, we compared the triglycerides and glucose (TyG) index, a simple measure of insulin resistance, with the euglycemic-hyperinsulinemic clamp test. DESIGN AND SETTING We conducted a cross-sectional study of the general population and outpatients of the Internal Medicine Department at the Medical Unit of High Specialty of the Specialty Hospital at the West National Medical Center in Guadalajara, Mexico. PATIENTS Eleven nonobese healthy subjects, 34 obese normal glucose tolerance individuals, 22 subjects with prediabetes, and 32 diabetic patients participated in the study. INTERVENTION We performed a euglycemic-hyperinsulinemic clamp test. MAIN OUTCOME MEASURES Sensitivity and specificity of the TyG index [Ln(fasting triglycerides) (mg/dl) x fasting glucose (mg/dl)/2] were measured, as well as the area under the curve of the receiver operating characteristic scatter plot and the correlation between the TyG index and the total glucose metabolism (M) rates. RESULTS Pearsons correlation coefficient between the TyG index and M rates was -0.681 (P < 0.005). Correlation between the TyG index and M rates was similar between men (-0.740) and women (-0.730), nonobese (-0.705) and obese (-0.710), and nondiabetic (-0.670) and diabetic (-0.690) individuals. The best value of the TyG index for diagnosis of insulin resistance was 4.68, which showed the highest sensitivity (96.5%) and specificity (85.0%; area under the curve + 0.858). CONCLUSIONS The TyG index has high sensitivity and specificity, suggesting that it could be useful for identification of subjects with decreased insulin sensitivity.

The Product of Fasting Glucose and Triglycerides As Surrogate for Identifying Insulin Resistance in Apparently Healthy Subjects

BACKGROUND Because the insulin test is expensive and is not available in most laboratories in the cities of undeveloped countries, we tested whether the product of fasting triglycerides and glucose levels (TyG) is a surrogate for estimating insulin resistance compared with the homeostasis model assessment of insulin resistance (HOMA-IR) index. METHODS We performed a population-based cross-sectional study. Sampling strategy was based on a randomized two-stage cluster sampling procedure. Only apparently healthy subjects, men and nonpregnant women aged 18-65 years, with newly diagnosed impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or IFG + IGT were enrolled. Renal disease, malignancy, and diabetes were exclusion criteria. Sensitivity, specificity, predictive values, and the probability of disease given a positive test were calculated. The optimal TyG index for estimating insulin resistance was established using a receiver operating characteristic scatter plot analysis. RESULTS A total of 748 apparently healthy subjects aged 41.4 +/- 11.2 years were enrolled. Insulin resistance was identified in 241 (32.2%) subjects (HOMA-IR index 4.4 +/- 1.6). New diagnoses of IFG, IGT, and IFG + IGT were established in 145 (19.4%), 54 (7.2%), and 75 (10.0%) individuals. respectively. The best TyG index for diagnosis of insulin resistance was Ln 4.65, which showed the highest sensitivity (84.0%) and specificity (45.0%) values. The positive and negative predictive values were 81.1% and 84.8%, and the probability of disease, given a positive test, was 60.5%. CONCLUSIONS The TyG index could be useful as surrogate to identify insulin resistance in apparently healthy subjects.

Curcumin downregulates human tumor necrosis factor-α levels: A systematic review and meta-analysis ofrandomized controlled trials

BACKGROUND Tumor necrosis factor-α (TNF-α) is a key inflammatory mediator and its reduction is a therapeutic target in several inflammatory diseases. Curcumin, a bioactive polyphenol from turmeric, has been shown in several preclinical studies to block TNF-α effectively. However, clinical evidence has not been fully conclusive. OBJECTIVE The aim of the present meta-analysis was to evaluate the efficacy of curcumin supplementation on circulating levels of TNF-α in randomized controlled trials (RCTs). METHODS The search included PubMed-Medline, Scopus, Web of Science and Google Scholar databases by up to September 21, 2015, to identify RCTs investigating the impact of curcumin on circulating TNF-α concentration. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics. Meta-regression and leave-one-out sensitivity analyses were performed to assess the modifiers of treatment response. RESULTS Eight RCTs comprising nine treatment arms were finally selected for the meta-analysis. There was a significant reduction of circulating TNF-α concentrations following curcumin supplementation (WMD: -4.69pg/mL, 95% CI: -7.10, -2.28, p<0.001). This effect size was robust in sensitivity analysis. Meta-regression did not suggest any significant association between the circulating TNF-α-lowering effects of curcumin with either dose or duration (slope: 0.197; 95% CI: -1.73, 2.12; p=0.841) of treatment. CONCLUSION This meta-analysis of RCTs suggested a significant effect of curcumin in lowering circulating TNF-α concentration.

Curcumin Lowers Serum Lipids and Uric Acid in Subjects With Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial.

Background: Nonalcoholic fatty liver disease (NAFLD) is one of the most common hepatic diseases in the general adult population. Dyslipidemia, hyperuricemia, and insulin resistance are common risk factors and accompanying features of NAFLD. Curcumin is a dietary natural product with beneficial metabolic effects relevant to the treatment of NAFLD. Aim: To assess the effects of curcumin on metabolic profile in subjects with NAFLD. Methods: Patients diagnosed with NAFLD (grades 1–3; according to liver sonography) were randomly assigned to curcumin (1000 mg/d in 2 divided doses) (n = 50) or control (n = 52) group for a period of 8 weeks. All patients received dietary and lifestyle advises before the start of trial. Anthropometric measurements, lipid profile, glucose, insulin, glycated hemoglobin, and uric acid concentrations were measured at baseline and after 8 weeks of follow-up. Results: Eighty-seven subjects (n = 44 and 43 in the curcumin and control group, respectively) completed the trial. Supplementation with curcumin was associated with a reduction in serum levels of total cholesterol (P < 0.001), low-density lipoprotein cholesterol (P < 0.001), triglycerides (P < 0.001), non–high-density lipoprotein cholesterol (P < 0.001), and uric acid (P < 0.001), whereas serum levels of high-density lipoprotein cholesterol and glucose control parameters remained unaltered. Curcumin was safe and well tolerated during this study. Conclusion: Results of the present trial suggest that curcumin supplementation reduces serum lipids and uric acid concentrations in patients with NAFLD.

Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post-hoc analysis of a randomized controlled trial.

BACKGROUND Cytokines are involved in the development of metabolic abnormalities that may result in metabolic syndrome (MetS). Since curcumin has shown anti-inflammatory properties, the aim of this study was to evaluate the effect of curcumin supplementation on serum cytokines concentrations in subjects with MetS. METHODS This study was a post-hoc analysis of a randomized controlled trial in which males and females with diagnosis of MetS, according to the criteria defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines, were studied. Subjects who met the inclusion criteria were randomly assigned to either curcumin (daily dose of 1g/day) or a matched placebo for a period of 8 weeks. RESULTS One hundred and seventeen subjects were assigned to either curcumin (n=59) or placebo (n=58) groups. Within-group analysis revealed significant reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 following curcumin supplementation (p<0.001). In the placebo group, serum levels of TGF-β were decreased (p=0.003) but those of IL-6 (p=0.735), TNF-α (p=0.138) and MCP-1 (p=0.832) remained unaltered by the end of study. Between-group comparison suggested significantly greater reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 in the curcumin versus placebo group (p<0.001). Apart from IL-6, changes in other parameters remained statistically significant after adjustment for potential confounders including changes in serum lipids and glucose levels, and baseline serum concentration of the cytokines. CONCLUSION Results of the present study suggest that curcumin supplementation significantly decreases serum concentrations of pro-inflammatory cytokines in subjects with MetS.

Effect of curcumin on circulating interleukin-6 concentrations: A systematic review and meta-analysis of randomized controlled trials.

The aim of this meta-analysis was to evaluate the efficacy of curcuminoids supplementation on circulating concentrations of IL-6 in randomized controlled trials (RCTs). The search included PubMed-Medline, Scopus, Web of Science and Google Scholar databases by up to November 01, 2015, to identify RCTs investigating the impact of curcuminoids on circulating IL-6 concentrations. Nine RCTs comprising 10 treatment arms were found to be eligible for the meta-analysis. There was a significant reduction of circulating IL-6 concentrations following curcuminoids supplementation (WMD: -0.60pg/mL, 95% CI: -1.06, -0.14, p=0.011). Meta-regression did not suggest any significant association between the circulating IL-6 lowering effects of curcuminoids with either dose or duration of treatment. There was a significant association between the IL-6-lowering activity of curcumin and baseline IL-6 concentration (slope: -0.51; 95% CI: -0.80, -0.23; p=0.005). This meta-analysis of RCTs suggested a significant effect of curcumin in lowering circulating IL-6 concentrations. This effect appears to be more evident in patients with higher degrees of systemic inflammation.

The effects of a nutraceutical combination on plasma lipids and glucose: A systematic review and meta-analysis of randomized controlled trials.

Dyslipidemia and hyperglycemia are associated with an increased risk of ischemic cardiovascular disease. Positive effects of a nutraceutical combination comprising red yeast rice, berberine, policosanol, astaxanthin, coenzyme Q10 and folic acid (NComb) on plasma lipid and glucose levels have been reported in some but not all clinical trials. To address this inconsistency, we tried to estimate the size of lipid- and glucose-lowering effects of NComb through a systematic review and meta-analysis of randomized controlled trials. A systematic literature search in PubMed-Medline, SCOPUS and Google Scholar databases was conducted to identify randomized controlled trials investigating the effects of NComb on plasma lipids and glucose levels. Inverse variance-weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated for net changes in lipid and glucose levels using a random-effects model. Random-effects meta-regression was performed to assess the effect of putative confounders on plasma lipid and glucose levels. Fourteen trials (1670 subjects in the NComb arm and 1489 subjects in the control arm) met the eligibility criteria for lipid analysis and 10 trials (1014 subjects in the NComb arm and 962 subjects in the control arm) for glucose analysis. Overall, WMDs were significant for the impact of NComb supplementation on plasma levels of total cholesterol (-26.15mg/dL, p<0.001), LDL-cholesterol (-23.85mg/dL, p<0.001), HDL-cholesterol (2.53mg/dL, p<0.001), triglycerides (-13.83mg/dL, p<0.001) and glucose (-2.59mg/dL, p=0.010). NComb-induced amelioration of lipid profile was not affected by duration of supplementation nor by baseline lipid levels; conversely, a greater glucose-lowering effect of NComb was found with higher baseline glucose levels and longer durations of supplementation. In conclusion, the present results suggest that NComb supplementation is associated with improvement of lipid and glucose profile. Short-term beneficial effects of NComb supplementation appear to be maintained in the long term.

Effect of statin therapy on plasma proprotein convertase subtilisin kexin 9 (PCSK9) concentrations: A systematic review and meta-analysis of clinical trials

To evaluate the magnitude of the effect of statin therapy on plasma proprotein convertase subtilisin kexin 9 (PCSK9) levels through a systematic review and meta‐analysis of clinical trials.

Family History of Hypertension and Cardiovascular Risk Factors in Prepubertal Children

BACKGROUND To determine the relationship between family history of hypertension (FHH) and cardiovascular risk factors (CVRF) in healthy prepubertal children. METHODS DESIGN Cross-sectional, population-based study. SETTING Elementary schools from San Luis Potosi and Durango, cities in middle and northern Mexico. PARTICIPANTS A total of 358 randomly enrolled, healthy boys and girls aged 6-10 years in Tanner stage 1, with and without FHH. OUTCOME MEASURES Odds ratio (OR) that estimates the relationship between FHH and CVRF. RESULTS FHH was identified in 72 (20.1%) children; 212 (59.2%) children had at least one CVRF, where low high-density lipoprotein (HDL)-cholesterol (36.3%), elevated waist circumference (WC) (29.3%), and hypertriglyceridemia (28.8%) were the most frequent; high-blood pressure (HBP) and hyperglycemia were recognized in 10 (3.3%) and 1 (0.3%) children. Metabolic syndrome and hyperinsulinemia were identified in 36 (10.0%) and 48 (13.4%) children. In all subjects, hyperinsulinemia (OR 2.0; 95% confidence interval (CI) 1.2-8.4), but not other CVRF was significantly associated with FHH. Subsequent analysis stratified by WC showed that FHH was not associated with CVRF in children with elevated WC. Among children with nonelevated WC, FHH in the maternal branch, but not in the paternal branch, was associated with hyperinsulinemia (OR 1.5; 95% CI 1.1-5.5), HBP (OR 4.0; 95% CI 1.3-30.1), hypertriglyceridemia (OR 1.6; 95% CI 1.1-7.2), and low HDL-cholesterol (OR 1.3; 95% CI 1.1-3.0). CONCLUSION Results show that FHH in the maternal branch is associated with CVRF in children with nonelevated WC.