Ricardo Pérez-Fuentes

Prediabetes and its relationship with obesity in Mexican adults: The Mexican Diabetes Prevention (MexDiab) Study.

BACKGROUND Epidemiological data on impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) based on a representative Mexican sample are not available; thus, the objectives of this study were to determine the prevalence and distribution of IFG and IGT, and to establish its relationship with obesity in Mexican adults. METHODS We performed a cross-sectional population-based study on a representative sample of Mexican adults aged 30 to 65 years. Anthropometric measurements of obesity that included waist circumference (WC) and total body fat percentage were collected and the body mass index calculated. All subjects also underwent an oral glucose tolerance test. Diagnosis of glucose metabolism disorders was based on criteria of the American Diabetes Association. RESULTS Prevalence of IFG, IGT, and IFG+IGT was 24.6%, 8.3%, and 10.3%, respectively. The age-adjusted prevalence of IFG (49.5% and 50.5%), IGT (49.1% and 50.9%), and IFG+IGT (57.3% and 42.7%) was similar in men and women. Prevalence of obesity was 45.9% with predominance in women (48.8% versus 42.1%, P = 0.01). A total of 394 (31.0%) individuals were overweight. Among the 550 prediabetic normal weight subjects, 70 (22.4%), 15 (14.2%), and 7 (5.3%) had IFG, IGT, or IFG+IGT. The odds ratio (OR) between WC and IFG (OR 3.1, CI(95%) 1.4-9.7), IGT (OR 3.2, CI(95%) 1.2-9.1), and IFG+IGT (OR 2.8, CI(95%) 1.3-8.2) was higher than the OR of other measurements of obesity. CONCLUSIONS Prevalence of prediabetes in the Mexican adult population is high. WC is the measure of obesity more strongly associated with metabolic glucose disorders. A high proportion of subjects with normal weight exhibit prediabetes.

Clinical forms of Trypanosoma cruzi infected individuals in the chronic phase of Chagas disease in Puebla, Mexico

In Mexico, despite the relatively high seroprevalence of Trypanosoma cruzi infection in humans in some areas, reported morbidity of Chagas disease is not clear. We determined clinical stage in 71 individuals seropositive to T. cruzi in the state of Puebla, Mexico, an area endemic for Chagas disease with a reported seroprevalence of 7.7%. Diagnosis of Chagas disease was made by two standardized serological tests (ELISA, IHA). Individuals were stratified according to clinical studies. All patients were submitted to EKG, barium swallow, and barium enema. Groups were identified as indeterminate form (IF) asymptomatic individuals without evidence of abnormalities (n = 34 cases); those with gastrointestinal alterations (12 patients) including symptoms of abnormal relaxation of the lower esophageal sphincter and absent peristalsis in the esophageal body, grade I megaesophagus, and/or megacolon; patients with clinical manifestations and documented changes of chronic Chagas heart disease who were subdivided as follows: mild (8 patients)--mild electrocardiographic changes of ventricular repolarization, sinus bradychardia); moderate (6 patients)--left bundle branch block, right bundle branch block associated with left anterior fascicular block); severe (8 patients)--signs of cardiomegaly, dilated cardiomyopathy); and the associated form (3 cases) that included presence of both cardiomyopathy and megaesophagus. These data highlight the importance of accurate evaluation of the prevalence and clinical course of Chagas disease in endemic and non-endemic areas of Mexico.

Trypanosoma cruzi strains isolated from human, vector, and animal reservoir in the same endemic region in Mexico and typed as T. cruzi I, discrete typing unit 1 exhibit considerable biological diversity

In this study, three strains of Trypanosoma cruzi were isolated at the same time and in the same endemic region in Mexico from a human patient with chronic chagasic cardiomyopathy (RyC-H); vector (Triatoma barberi) (RyC-V); and rodent reservoir (Peromyscus peromyscus) (RyC-R). The three strains were characterized by multilocus enzyme electrophoresis, random amplified polymorphic DNA, and by pathological profiles in experimental animals (biodemes). Based on the analysis of genetic markers the three parasite strains were typed as belonging to T. cruzi I major group, discrete typing unit 1. The pathological profile of RyC-H and RyC-V strains indicated medium virulence and low mortality and, accordingly, the strains should be considered as belonging to biodeme Type III. On the other hand, the parasites from RyC-R strain induced more severe inflammatory processes and high mortality (> 40%) and were considered as belonging to biodeme Type II. The relationship between genotypes and biological characteristics in T. cruzi strains is still debated and not clearly understood. An expert committee recommended in 1999 that Biodeme Type III would correspond to T. cruzi I group, whereas Biodeme Type II, to T. cruzi II group. Our findings suggest that, at least for Mexican isolates, this correlation does not stand and that biological characteristics such as pathogenicity and virulence could be determined by factors different from those identified in the genotypic characterization.

Cardiovascular Risk Factors and Acculturation in Yaquis and Tepehuanos Indians from Mexico

BACKGROUND Cardiovascular (CV) risk factors are influenced by behavioral, cultural, and social factors, suggesting that acculturation plays a significant role in the emergency and growth of chronic disease. The objective of this study was to determine the relation between CV risk factors and the main components of acculturation, in Yaquis and Tepehuanos Indians from Mexico. METHODS This was a cross-sectional population-based study in Yaquis and Tepehuanos communities from the Yaqui Valley in Sonora and the Sierra Madre Occidental Mountains in Durango, in northwest Mexico. Acculturation status is different in both ethnic groups, with Tepehuanos living in small and remote communities retaining their traditional lifestyle and Yaquis living in well-communicated communities that have assumed Westernized lifestyles. RESULTS A total of 278 indigenous (120 Tepehuanos and 158 Yaquis) were randomly enrolled. Prevalence of obesity (48.1 and 6.7%, p <0.001), diabetes (18.3 and 0.83%, p <0.001), hypertriglyceridemia (43.0 and 15.0%, p <0.001), alcohol consumption (46.8 and 26.6%, p >0.001), and smoking (29.7 and 15.0%, p = 0.006) were significantly higher in Yaquis Indians. High blood pressure (6.3 and 3.3%, p = 0.40) and low HDL-cholesterol (42.4 and 34.2%, p = 0.22) were similar between Yaquis and Tepehuanos. Multivariate regression analysis adjusted by sex and age showed a significant association between calorie intake from saturated fat, but not other nutrients of customary diet, with hyperglycemia (OR 7.4, 95% CI 2.6-20.1), hypertriglyceridemia (OR 3.1, 95% CI 1.5-6.3), and obesity (OR 3.4, 95% CI 1.6-10.1). CONCLUSIONS Among the components of acculturation, intake of saturated fat is the most strongly associated with the development of CV risk factors.

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.

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.

Obese First-Degree Relatives of Patients with Type 2 Diabetes with Elevated Triglyceride Levels Exhibit Increased β-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 β-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). β-cell function, IR, and IS were determined by the homeostasis model assessment of β-cell function (HOMA2-β), 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 β-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 β-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 β-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.

c.+62G>A and g.-420C>G RETN Polymorphisms and the Risk of Developing Type 2 Diabetes and Obesity: Original Research on a Mexican Population and Meta-analysis

Objective: To determine the association between the c.+62G>A and g.-420C>G polymorphisms and Type 2 Diabetes (T2D) or obesity susceptibility for Mexicans. Additionally, we examined their overall effect across different populations by a systematic review. Methods: 164 Mexicans were classified as Healthy, Obese, or T2D. Genotypes were determined and associated risk for the heterozygous, homozygous, dominant, recessive, and allelic genetic models were determined by calculating the Odds Ratios (OR). For the meta-analysis, original publications that had determined RETN polymorphisms in T2D or obese subjects were searched for in PubMed, Scopus, EBSCO, Ovid, and Wiley databases until November 2015, using the search terms: T2D, obesity, RETN, and polymorphism. Pooled ORs were computed using a random-effects or fixed-effects models. Results: For our cohort, no associations were observed between the polymorphisms and obesity or T2D. The metaanalysis indicates an increased risk of obesity among carriers of the g.-420G allele for the heterozygous and dominant models (OR=1.33 and OR=1.30, p<0.05, respectively). By regional assessment, Africans were associated with an elevated risk of developing T2D (OR=2.35-7.17, p<0.05) and obesity (OR=1.54-2.13, p<0.05). North Americans had an increased risk of developing obesity for the heterozygous and dominant models (OR=1.49and OR=1.42, p<0.05, respectively). No associations were determined between the c.+62 polymorphism and obesity or T2D. Conclusion: For Mexicans, none of the polymorphisms were associated with a risk of developing obesity or T2D. However, there is an increased risk of developing obesity for the whole population for subjects who carry the g.-420G allele.

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.