TG/HDL index to identify subjects with metabolic syndrome in the Mexican population.

BACKGROUND: The triglyceride/high-density lipoprotein (TG/HDL) index has been proposed as an indicator of cardiovascular risk. In Mexico, there is a study in young adults that relates it to insulin resistance, but no cutoff point that distinguishes subjects with metabolic syndrome has been defined. OBJECTIVE: To determine the cutoff point for the TG/HDL index that identifies subjects with metabolic syndrome in the Mexican population. METHODS: Metabolic syndrome was diagnosed using the criteria established in the Third Report of the Adult Treatment Panel of the National Cholesterol Education Program adapted to the Mexican population. To identify the TG/HDL index cutoff point, ROC curve analysis and the Youden index were used. RESULTS: 1,318 subjects aged 40.9 ± 13.0 years participated in the study; 65.6% were women and 34.4% men; 41.2% had metabolic syndrome. The TG/HDL index obtained an area under the curve of 0.85 and an optimal cutoff point value ≥ 3.46, with a sensitivity of 79.6% and specificity of 76.4%. CONCLUSIONS: TG/HDL index cutoff point ≥ 3.46 is suitable for identifying subjects with metabolic syndrome in the Mexican population.

ANTECEDENTES: El índice triglicéridos/lipoproteína de alta densidad (TG/HDL) ha sido propuesto como un indicador de riesgo cardiovascular. En México, existe un estudio en adultos jóvenes que lo relaciona con resistencia a la insulina, pero no se ha definido un punto de corte que distinga a sujetos con síndrome metabólico. OBJETIVO: Determinar el punto de corte para el índice TG/HDL que identifique a sujetos con síndrome metabólico en población mexicana. MÉTODOS: El síndrome metabólico se diagnosticó mediante los criterios establecidos en el Tercer Reporte del Panel de Tratamiento para Adultos del Programa Nacional de Educación en Colesterol adaptados a la población mexicana. Para identificar el punto de corte del índice TG/HDL se utilizó el análisis de curvas ROC y el índice de Youden. RESULTADOS: En el estudio participaron 1318 sujetos con edad de 40.9 ± 13.0 años; 65.6 % fuerin mujeres y 34.4 % hombres; 41.2% presentó síndrome metabólico. El índice TG/HDL obtuvo un valor del área bajo la curva de 0.85 y un valor óptimo de punto de corte ≥ 3.46, con sensibilidad de 79.6 % y especificidad de 76.4 %. CONCLUSIONES: El punto de corte ≥ 3.46 para el índice TG/HDL es adecuado para identificar a sujetos con síndrome metabólico en población mexicana.

Índice TG/HDL para identificar a sujetos con síndrome metabólico en población mexicana / TG/HDL index to identify subjects with metabolic syndrome in the Mexican population

Resumen Antecedentes: El índice triglicéridos/lipoproteína de alta densidad (TG/HDL) ha sido propuesto como un indicador de riesgo cardiovascular. En México, existe un estudio en adultos jóvenes que lo relaciona con resistencia a la insulina, pero no se ha definido un punto de corte que distinga a sujetos con síndrome metabólico. Objetivo: Determinar el punto de corte para el índice TG/HDL que identifique a sujetos con síndrome metabólico en población mexicana. Métodos: El síndrome metabólico se diagnosticó mediante los criterios establecidos en el Tercer Reporte del Panel de Tratamiento para Adultos del Programa Nacional de Educación en Colesterol adaptados a la población mexicana. Para identificar el punto de corte del índice TG/HDL se utilizó el análisis de curvas ROC y el índice de Youden. Resultados: En el estudio participaron 1318 sujetos con edad de 40.9 ± 13.0 años; 65.6 % fuerin mujeres y 34.4 % hombres; 41.2% presentó síndrome metabólico. El índice TG/HDL obtuvo un valor del área bajo la curva de 0.85 y un valor óptimo de punto de corte ≥ 3.46, con sensibilidad de 79.6 % y especificidad de 76.4 %. Conclusiones: El punto de corte ≥ 3.46 para el índice TG/HDL es adecuado para identificar a sujetos con síndrome metabólico en población mexicana.

Abstract Background: The triglyceride/high-density lipoprotein (TG/HDL) index has been proposed as an indicator of cardiovascular risk. In Mexico, there is a study in young adults that relates it to insulin resistance, but no cutoff point that identifies subjects with metabolic syndrome has been defined. Objective: To determine the cutoff point for the TG/HDL index that identifies subjects with metabolic syndrome in the Mexican population. Methods: Metabolic syndrome was diagnosed using the criteria established by the Third Report of the Adult Treatment Panel of the National Cholesterol Education Program adapted to the Mexican population. To identify the TG/HDL index cutoff point, ROC curve analysis and the Youden index were used. Results: 1,318 subjects aged 40.9 ± 13.0 years participated in the study; 65.6% were women and 34.4% men; 41.2% had metabolic syndrome. The TG/HDL index obtained an area under the curve of 0.85 and an optimal cutoff point value ≥ 3.46, with a sensitivity of 79.6% and specificity of 76.4%. Conclusions: TG/HDL index cutoff point ≥ 3.46 is suitable for identifying subjects with metabolic syndrome in the Mexican population.

Association of the Metabolic Syndrome with Antioxidant Defense and Outstanding Superoxide Dismutase Activity in Mexican Subjects.

BACKGROUND: Metabolic syndrome (MetS) is considered a public health problem worldwide. Recently, oxidative stress (OS) has been proposed as a factor related with the genesis of MetS. Different studies have reported decreased antioxidant defense, such as superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRed) activities, and reduced glutathione (GSH) concentration, and, on the other hand, an increase in nitrotyrosine concentration in MetS patients. However, it is not known whether there is a direct association of antioxidant defense with MetS in a Mexican population. The aim of the study was to determine the relationship between antioxidant defense and MetS in Mexican subjects. MATERIALS AND METHODS: The subjects were Mexican mestizos, who were anthropometrically, biochemically, and clinically characterized. MetS was diagnosed by National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III)-modified criteria. Antioxidant defense was determined by activity of SOD, GPx, GRed, and GSH concentrations; as a marker of OS, nitrotyrosine concentration was determined. RESULTS: The study included 376 subjects, among whom 152 subjects had MetS and 224 were assigned to the non-MetS group. Statistical association was found between MetS and SOD activity (Odds ratio: 167.1; P < 0.01; adjusted by age, gender, and waist circumference). It is noteworthy that a significant correlation between antioxidant defense (SOD and GPx activities, and GSH) and different MetS components was found and between MetS and nitrotyrosine concentration (P < 0.05). CONCLUSION: The results indicate that SOD activity is associated with MetS in Mexican subjects, allowing us to suggest that this enzyme plays an important role in the pathophysiology of MetS.

C-Peptide Is a Sensitive Indicator for the Diagnosis of Metabolic Syndrome in Subjects from Central Mexico.

BACKGROUND: Metabolic Syndrome (MetS) is associated with elevated risk for developing diabetes and cardiovascular disease. A key component of MetS is the development of insulin resistance (IR). The homeostatic model assessment (HOMA) model can determine IR by using insulin or C-peptide concentrations; however, the efficiency of insulin and C-peptide to determine MetS has not been compared. The aim of the study was to compare the efficiency of C-peptide and insulin to determine MetS in Mexicans. METHODS: Anthropometrics, glucose, insulin, C-peptide, triglycerides, and high-density lipoproteins were determined in 156 nonpregnant females and 114 males. Subjects were separated into normal or positive for MetS. IR was determined by the HOMA2 calculator using insulin or C-peptide. Correlations were calculated using the Spearman correlation coefficient (ρ). Differences between correlations were determined by calculating Steiger's Z. The sensitivity was determined by the area under receiver operating characteristics curve (AUC) analysis. RESULTS: Independent of the MetS definition [Adult Treatment Panel III (ATP III), International Diabetes Federation (IDF), or World Health Organization (WHO)], C-peptide and insulin were significantly higher in MetS subjects (P < 0.05). C-peptide and insulin correlated with all components of MetS; however, for waist circumference, waist-to-hip ratio, and fasting plasma glucose, C-peptide correlated better than insulin (P < 0.05). Moreover, C-peptide (AUC = 0.72-0.78) was a better marker than insulin (AUC = 0.62-0.72) for MetS (P < 0.05). Finally, HOMA2-IR calculated with C-peptide (AUC = 0.80-0.84) was more accurate than HOMA2-IR calculated with insulin (AUC = 0.68-0.75, P < 0.05) at determining MetS. CONCLUSION: C-peptide is a strong indicator of MetS. Since C-peptide has recently emerged as a biomolecule with significant importance for inflammatory diseases, monitoring C-peptide levels will aid clinicians in preventing MetS.

Obese first-degree relatives of patients with type 2 diabetes with elevated triglyceride levels exhibit increased ß-cell function.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized as a disease continuum that is marked by metabolic changes that are present for several years, sometimes well before frank diagnosis of T2DM. Genetic predisposition, ethnicity, geography, alterations in BMI, and lipid profile are considered important markers for the pathogenesis of T2DM through mechanisms that remain unresolved and controversial. The aim of this study was to investigate the relationship between triglycerides (TGs) and ß-cell function, insulin resistance (IR), and insulin sensitivity (IS) in obese first-degree relatives of patients with T2DM (FDR-T2DM) among subjects from central Mexico with normal glucose tolerance (NGT). METHODS: We studied 372 FDR-T2DM subjects (ages,18-65) and determined body mass index (BMI), fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), insulin, and TGs levels. Subjects were categorized based on glycemic control [NGT, prediabetes (PT2DM), or T2DM]. NGT subjects were further categorized by BMI [normal weight (Ob-) or obese (Ob+)] and TGs levels (TG-, <150 mg/dL, or TG+, ≥150 mg/dL). ß-cell function, IR, and IS were determined by the homeostasis model assessment of ß-cell function (HOMA2-ß), homeostasis model assessment of insulin resistance (HOMA2-IR), and Quantitative Insulin Sensitivity Check Index (QUICKI) indices, respectively. RESULTS: The obese subjects with elevated TGs levels had 21%-60% increased ß-cell function when compared to all groups (P<0.05). In addition, this group had insulin levels, IS, and IR similar to PT2DM. Furthermore, only in obese subjects did TGs correlate with ß-cell function (ρ=0.502, P<0.001). CONCLUSION: We characterized FDR-T2DM subjects from central Mexico with NGT and revealed a class of obese subjects with elevated TGs and ß-cell function, which may precede PT2DM.

Glutathione peroxidase 3 serum levels and GPX3 gene polymorphisms in subjects with metabolic syndrome.

BACKGROUND AND AIMS: Glutathione peroxidase 3 (GPx3) plays a main role in removing hydro- and lipoperoxides from the body. Changes in concentration and several single-nucleotide polymorphisms (SNP) at the GPX3 gene have been associated with vascular diseases, but the relationship of GPx3 with metabolic syndrome (MetS) remains unexplored. We undertook this study to determine the association of GPx3 serum levels and several GPX3 SNPs with the presence of MetS in Mexican subjects. METHODS: Clinical, biochemical, and anthropometric evaluation were conducted in 426 subjects assigned to three groups: control (n = 42); risk group (RG, n = 200), and MetS group (n = 184). Insulin sensitivity (IS) and cardiovascular risk were determined by the QUICKI and TG/HDL-C index, respectively. Serum GPx3 was determined by enzyme immunoassay and polymorphisms within GPX3 gene were identified by nucleotide sequencing. RESULTS: MetS group showed low IS and increased cardiovascular risk with respect to controls as well as higher GPx3 serum levels (172.9 ± 32.2 vs. 145.6 ± 24.8 ng/dL; p <0.05). Only three of the ten GPX3 SNPs screened were polymorphic with two haplotypes observed (CCT and TTA-rs8177404, rs8177406, and rs8177409), indicating tight linkage disequilibrium in this genetic region. No differences for either genotype or allele frequencies among groups were observed, but rs8177409 (allele T) was associated with cardiovascular risk (odds ratio [OR], 4.5; p = 0.0125). CONCLUSION: This study shows that serum levels of GPx3 are increased in subjects with MetS and that rs8177409 SNP was associated with cardiovascular risk in a Mexican population.

Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease

Chagas disease, caused by Trypanosoma cruzi, represents an endemic among Latin America countries. The participation of free radicals, especially nitric oxide (NO), has been demonstrated in the pathophysiology of seropositive individuals with T. cruzi. In Chagas disease, increased NO contributes to the development of cardiomyopathy and megacolon. Metallothioneins (MTs) are efficient free radicals scavengers of NO in vitro and in vivo. Here, we developed a murine model of the chronic phase of Chagas disease using endemic T. cruzi RyCH1 in BALB/c mice, which were divided into four groups: infected non-treated (Inf), infected N-monomethyl-L-arginine treated (Inf L-NAME), non-infected L-NAME treated and non-infected vehicle-treated. We determined blood parasitaemia and NO levels, the extent of parasite nests in tissues and liver MT-I expression levels. It was observed that NO levels were increasing in Inf mice in a time-dependent manner. Inf L-NAME mice had fewer T. cruzi nests in cardiac and skeletal muscle with decreased blood NO levels at day 135 post infection. This affect was negatively correlated with an increase of MT-I expression (r = -0.8462, p < 0.0001). In conclusion, we determined that in Chagas disease, an unknown inhibitory mechanism reduces MT-I expression, allowing augmented NO levels.

Early decrease of insulin sensitivity in offspring of individuals with type 2 diabetes. The Mexican Diabetes Prevention Study.

BACKGROUND AND AIMS: Defects in insulin sensitivity (IS) and insulin secretion have been recognized as risk factors for type 2 diabetes (T2D) and its complications. We undertook this study to establish the relationship between healthy type 2 diabetic offspring (OFD) from a Mexican population with IS. METHODS: A total of 602 Mexican subjects, 359 first-degree offspring of T2D (OFD+) and 243 first-degree non-offspring of T2D (OFD-) were classified as young adults (age range, 18-44 years) and middle-aged adults (age range, 45-65 years). Groups were clinically and biochemically characterized. Quantitative insulin sensitivity check index (QUICKI) was used to estimate IS and the homeostasis model assessment B (HOMA-B) was used to estimate B cell function. RESULTS: IS decreased significantly (p <0.05) in OFD+ middle-aged (QUICKI 0.330 ± 0.03) compared with OFD- (0. 370 ± 0.03). Middle-aged adults (OFD+) had the highest prevalence of increased fasting insulin levels (FIL) (13.6%) and decreased IS (22.9%) compared with OFD- groups (3.2%). A binary regression analysis showed the association of OFD+ with increased FIL (odds ratio [OR], 3.71; 95% confidence interval [95% CI], 1.68-8.2; p = 0.001), and QUICKI (OR, 10.87; 95% CI, 2.36-44.69; p <0.01) adjusted by gender, age, and obesity. CONCLUSIONS: Our results suggest that decreased IS itself could be recognized as one of the earliest detectable abnormalities in middle-aged adults. Moreover, prevalence increases with age and is associated with type 2 diabetic offspring, regardless of obesity.

Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease.

Chagas disease, caused by Trypanosoma cruzi, represents an endemic among Latin America countries. The participation of free radicals, especially nitric oxide (NO), has been demonstrated in the pathophysiology of seropositive individuals with T. cruzi. In Chagas disease, increased NO contributes to the development of cardiomyopathy and megacolon. Metallothioneins (MTs) are efficient free radicals scavengers of NO in vitro and in vivo. Here, we developed a murine model of the chronic phase of Chagas disease using endemic T. cruzi RyCH1 in BALB/c mice, which were divided into four groups: infected non-treated (Inf), infected N-monomethyl-L-arginine treated (Inf L-NAME), non-infected L-NAME treated and non-infected vehicle-treated. We determined blood parasitaemia and NO levels, the extent of parasite nests in tissues and liver MT-I expression levels. It was observed that NO levels were increasing in Inf mice in a time-dependent manner. Inf L-NAME mice had fewer T. cruzi nests in cardiac and skeletal muscle with decreased blood NO levels at day 135 post infection. This affect was negatively correlated with an increase of MT-I expression (r = -0.8462, p < 0.0001). In conclusion, we determined that in Chagas disease, an unknown inhibitory mechanism reduces MT-I expression, allowing augmented NO levels.

Low prevalence of interleukin-6 haplotypes associated with a decreased risk of type 2 diabetes in Mexican subjects with a family history of type 2 diabetes.

BACKGROUND AND AIMS: There is evidence that family history of type 2 diabetes (FHT2D) and single nucleotide polymorphisms (SNP) on the IL-6 gene promoter region are separately associated with the risk of developing type 2 diabetes. However the relationship between adult Mexican subjects with FHT2D and genotypes/haplotypes for IL-6 gene has not been explored. The aim of the present work was to study the prevalence of IL-6 -598G>A-572G>C-174G>C haplotypes among subjects with FHT2D and to determine whether their presence influences the relationship between FHT2D and risk factors for diabetes. METHODS: Two hundred fifty eight nondiabetic subjects participated in this study; 153 with and 105 without FHT2D. Polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) was used for genotyping. Logistic regression analysis was employed to assess the impact of IL-6 haplotypes on FHT2D per se and hyperinsulinemia and insulin resistance as risk factors for diabetes. RESULTS: Subjects with FHT2D showed a higher prevalence of hyperinsulinemia and insulin resistance (IR) than those without FHT2D (14.4 vs. 5.7%, p = 0.029, and 14.2 vs. 7.0% p = 0.050, respectively). Lower prevalence of -598 -572-174 (AGC)-haplotype (19%) in subjects with FHT2D was observed as well as a lower prevalence of hyperinsulinemia and IR among AGC haplotype carriers (12 and 14%, respectively). The relationship between FHT2D and IR was modified by the presence of AGC haplotype (from OR, 2.70; 95% CI, 0.99-7.36; p = 0.050 OR, 30.08; 95% CI, 0.58-1,568.06; p = 0.092). CONCLUSIONS: IL-6 -598/-572/-174 (AGC) haplotype has a low prevalence among first-degree relatives of subjects with type 2 diabetes. Our results suggest that this haplotype is associated with decreased risk of type 2 diabetes in Mexican subjects with FHT2D.

Serum levels of glutathione peroxidase 3 in overweight and obese subjects from central Mexico.

BACKGROUND AND AIMS: Overweight and obesity are considered complex entities in which there are alterations in the concentration of antioxidant enzymes. It has been reported that glutathione peroxidase 3 (GPx3), an extracellular enzyme involved in the reduction of both hydro- and lipoperoxides, shows changes both in gene expression and protein concentration in animal models for type 2 diabetes (T2D) and obesity, but the variability of GPx3 levels in different human populations and under different health conditions are currently unclear. We undertook this study to determine the GPx3 levels in overweight and obese subjects from central Mexico. METHODS: Biochemical profile (serum glucose, insulin and lipid profile) and GPx3 concentrations were determined in 28 healthy subjects (control) and 133 subjects who were overweight or obese (OW-OB). RESULTS: The OW-OB group had a higher concentration of triacylglycerides (TAG) compared with the control group (201.2 ± 88.7 vs. 100.3 ± 46.4 mg/dL, p <0.05) and the TAG/high density lipoprotein-cholesterol (HDL-C) index (5.6 ± 2.8 vs. 2.1 ± 1.2, p <0.05), whereas the concentration of HDL-C decreased (38.2 ± 8.7 vs. 50.1 ± 14.5 mg/dL, p <0.05). Serum GPx3 was significantly higher in the OW-OB group than in the control group (175.4 ± 25.4 vs. 143.5 ± 23.1 ng/dL). GPx3 concentration correlated with insulin sensitivity (IS) and the TAG/HDL-C index (Rho = -0.2336 and Rho = 0.2275) (p <0.01). CONCLUSIONS: The TAG/HDL-C index and serum GPx3 concentration increased in the OW-OB group. In addition, GPx3 had a significant correlation with IS, weight, and the TAG/HDL-C index.

Risk factors for diabetes, but not for cardiovascular disease, are associated with family history of Type 2 diabetes in subjects from central Mexico.

BACKGROUND: Independent of obesity, family history of type 2 diabetes mellitus (FHT2DM) is another important risk factor for developing diabetes. AIM: To establish the association among FHT2DM, risk factors for diabetes and cardiovascular disease in subjects from central Mexico. SUBJECTS AND METHODS: Clinical and biochemical studies were performed in 383 first-degree relatives of patients with type 2 diabetes and 270 subjects unrelated to patients with type 2 diabetes-all subjects were from the city of Puebla in central Mexico. Logistic regressions were used to assess the association between FHT2DM and metabolic parameters. Cardiovascular risk was classified by dyslipidemia and the Framingham Risk Score (FRS). RESULTS: FHT2DM was associated with risk factors for diabetes, such as increased fasting insulin levels (OR = 1.731, 95% CI = 1.041-2.877), decreased insulin sensitivity (OR = 1.951, 95% CI = 1.236-3.080) and pre-diabetes (OR = 1.63, 95% CI = 1.14-2.33). FHT2DH was not associated with risk factors for cardiovascular disease, such as dyslipidemia (OR = 1.12, 95% CI = 0.70-1.79) and FRS (OR = 0.74, 95% CI = 0.40-1.36) when adjusted for gender, age, smoking and obesity. CONCLUSION: Diabetic risk factors, but not cardiovascular disease risk factors, are associated with a positive family history of diabetes in subjects from central Mexico, independent of the presence of obesity.

ß-cell function is associated with metabolic syndrome in Mexican subjects.

AIMS: The clinical diagnosis of metabolic syndrome does not find any parameters to evaluate the insulin sensitivity (IS) or ß-cell function. The evaluation of these parameters would detect early risk of developing metabolic syndrome. The aim of this study is to determine the relationship between ß-cell function and presence of metabolic syndrome in Mexican subjects. MATERIAL AND METHODS: This study is part of the Mexican Survey on the Prevention of Diabetes (MexDiab Study) with headquarters in the city of Puebla, Mexico. The study comprised of 444 subjects of both genders, aged between 18 and 60 years and allocated into two study groups: (1) control group of individuals at metabolic balance without metabolic syndrome and (2) group composed of subjects with metabolic syndrome and diagnosed according to the criteria of the Third Report of the National Cholesterol Education Program Expert Panel on Defection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Anthropometric, biochemical, and clinical assessments were carried out. RESULTS: Average age of the subjects in the control group (n = 254) was 35.7 ± 11.5 years and 42.0 ± 10.7 years for subjects in the metabolic syndrome group (n = 190). Subjects at metabolic balance without metabolic syndrome showed decreased IS, increased insulin resistance (IR), and altered ß-cell function. Individuals with metabolic syndrome showed a high prevalence (P ≤ 0.05) of family history of type 2 diabetes (T2D). This group also showed a significant metabolic imbalance with glucose and insulin levels and lipid profile outside the ranges considered safe to prevent the development of cardiovascular disease and T2D. CONCLUSION: The main finding in this study was the detection of altered ß-cell function, decreased IS, an increased IR in subjects at metabolic balance, and the progressive deterioration of ß-cell function and IS in subjects with metabolic syndrome as the number of features of metabolic syndrome increases.