Silvia Esperanza Flores-Martínez

Acute and recurrent pancreatitis in children: etiological factors

Objectives: To describe the clinical picture and outcome, and to assess the etiological factors of acute and recurrent pancreatitis in children.

Urinary Glycosaminoglycan Excretion in Healthy Subjects and in Patients with Mucopolysaccharidoses

BACKGROUND The mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by deficiency of enzymes catalyzing the stepwise degradation of glycosaminoglycans (GAGs), and are transmitted in an autosomal recessive manner, except for Hunter syndrome. METHODS The levels of GAGs in 150 healthy subjects and 33 patients with MPS were determined, and results were expressed as milligrams of GAGs per grams of creatinine. RESULTS We found that this ratio decreased with age during the first 15 years of life, but had a constant low rate between the ages of 17-40 years in healthy individuals. A different tendency was present in patients with MPS, because levels of GAG excretion in this group were higher (by four standard deviations up) compared with healthy individuals. The electrophoretic patterns of urinary GAGs in healthy subjects showed that the higher levels detected in urine were chondroitin sulfate (4 and 6) and a smaller quantity of dermatan sulfate, but in each MPS type its characteristic pattern was identified. CONCLUSIONS This is a simple, reproducible method suitable for routine laboratory separation, identification, and quantity of urinary GAGs and for diagnosing MPS syndromes.

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.

Influence of CRP, IL6, and TNFA gene polymorphisms on circulating levels of C-reactive protein in Mexican adolescents.

BACKGROUND AND AIMS Obesity correlates with a chronic and low-grade inflammation status. C-reactive protein (CRP) measurement has been used as an independent risk marker for future cardiovascular events. CRP level shows interindividual variability due to environmental and genetic factors. The aim of this study was to assess the association of functional polymorphisms on CRP, IL6, and TNFA genes with serum CRP levels in Mexican mestizo adolescents. METHODS Body mass index (BMI), serum high-sensitivity C-reactive protein (hsCRP) levels, and genotypes for CRP+1444C>T, IL6-174G>C, and TNFA-308G>A polymorphisms were obtained from 418 unrelated Mexican adolescents. Genetic association with hsCRP levels was evaluated by means of a dominant genetic model with uni- and multivariate analysis. RESULTS Genotype frequencies for all three polymorphisms were according to Hardy-Weinberg equilibrium (HWE). CRP+1444T, TNFA-308A, and IL6-174C allele frequencies were 37, 7, and 10%, respectively. CRP+1444T was associated with higher mean CRP levels independent of age, gender and BMI (β = 0.21; 95% confidence interval [95% CI] = 0.02-0.39); p = 0.030). IL6-174C was associated with low CRP levels in the overweight group (p = 0.005). IL6-174G>C and TNFA-308G>A allele frequencies observed from this Mexican sample were similar to data for other Mexican populations. CONCLUSIONS The CRP+1444C>T polymorphism was associated with CRP levels in Mexican adolescents and could be used as a genetic marker for the early detection of individuals at risk for developing obesity-related conditions such as cardiovascular disease or type 2 diabetes mellitus in early adulthood.

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.

Tumor Necrosis Factor-Alpha Gene Promoter −308G/A and −238G/A Polymorphisms in Mexican Patients with Type 2 Diabetes Mellitus

The association between some Tumor necrosis factor-alpha (TNF-α) promoter polymorphisms and Type 2 diabetes mellitus (T2DM) remains controversial. Ethnic differences may play a role in these conflicting results. The aim of this study was to investigate the association between −308G/A and −238G/A polymorphisms located in the promoter region of the TNF-α gene and T2DM in Mexican mestizo patients. Nine hundred four individuals (259 patients with T2DM and 645 controls) were genotyped for the −308G/A and −238G/A polymorphisms by PCR—RFLP. We found that the −238A allele increased the risk of developing T2DM in Mexican patients (OR = 1.57, 95% CI: 1.07–2.29; p = 0.018). Moreover, we found that the frequency of the GA haplotype (created by the −308G and −238A alleles) was significantly increased in patients with T2DM when compared with controls (OR = 1.56, 95% CI: 1.05–2.31; p = 0.026). Our results suggest that the −238G/A polymorphism and a specific haplotype (GA) are genetic risk factors for the development of T2DM in Mexican population.

Association Analysis Between –308G/A and –238G/A TNF-Alpha Gene Promoter Polymorphisms and Insulin Resistance in Mexican Women With Gestational Diabetes Mellitus

Background Gestational diabetes mellitus (GDM) is characterized by insulin resistance. It has been described that tumor necrosis factor α (TNF-α) plays a key role in the pathogenesis of insulin resistance; moreover, increased levels of this proinflammatory cytokine have been reported in women with GDM. Therefore, this study was aimed to assess the presence of associations between the –308G/A and –238G/A polymorphisms and specific haplotypes of the TNF-α gene promoter region and insulin resistance in Mexican women with GDM. Methods This study included 51 women with GDM and 44 pregnant women with normal glucose tolerance. Measurements of anthropometric parameters and biochemical estimations were performed. We genotyped the TNF-α –308G/A and –238G/A polymorphisms using polymerase chain reaction–restriction fragment length polymorphism analysis. Results The genotype and allele frequencies of both polymorphisms did not differ significantly between the women with GDM and the controls. However, we found that the frequency of the AG haplotype was significantly increased in the patients with GDM compared with controls (P = 0.019; odds ratio, 4.11; 95% confidence interval, 1.31–12.85). In patients with GDM, we observed that insulin levels and homeostasis model assessment of insulin resistance were significantly higher in women bearing the G/G genotype than in carriers of the G/A and A/A genotypes of the –308G/A polymorphism (P = 0.022 and P = 0.043, respectively). Conclusions Our results suggest that the G/G genotype of the TNF-α –308G/A polymorphism increases insulin levels and insulin resistance in women with GDM and that the AG haplotype is a genetic risk factor for GDM in our study population.

Screening of R122H and N29I mutations in the PRSS1 gene and N34S mutation in the SPINK1 gene in Mexican pediatric patients with acute and recurrent pancreatitis.

Objectives The study’s objective was to assess the association between the PRSS1 R122H and N29I and the SPINK1 N34S mutations and acute pancreatitis (AP) and recurrent pancreatitis in Mexican pediatric patients. Methods The N34S and R122H mutations were detected using polymerase chain reaction–restriction fragment length polymorphism, and the N29I mutation was detected using allele-specific polymerase chain reaction in 92 pancreatitis patients (58 AP and 34 recurrent pancreatitis patients) and 144 controls. Results We found 1 mutated allele in 4 (4.3%) of 92 pancreatitis patients and none in the controls. All 4 patients bearing mutations had AP, with a frequency of 6.8% (4/58). Three (5.2%) of 58 patients were heterozygous for the N34S mutation, and 1 (1.7%) of 58 patients was heterozygous for the N29I mutation. The comparison between the AP and control groups revealed both a significant number of patients carrying any mutations in the screened genes (P = 0.008) and bearing the N34S mutation (P = 0.023). Moreover, we found that the N34S G allele increased the risk of developing AP (odds ratio, 10.3; confidence interval, 1.1–248.8). Conclusions Patients bearing the N34S G allele exhibited a 10-fold increased risk of developing AP compared with controls, suggesting that the SPINK1 N34S mutation represents an etiologic risk factor for AP in our Mexican pediatric patients.

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.

Body adiposity but not insulin resistance is associated with -675 4G/5G polymorphism in the PAI-1 gene in a sample of Mexican children

OBJECTIVE To assess whether the -675 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene is associated with obesity and insulin resistance in Mexican children. METHODS A cross-sectional study was performed in 174 children, 89 with normal-weight and 85 with obesity, aged from 6 to 13 years. All children were from state of Guerrero, and recruited from three primary schools in the city of Chilpancingo, state of Guerrero, Mexico. Insulin levels were determined by immunoenzymatic assay. The homeostasis model assessment was used to determine insulin resistance. The -675 4G/5G polymorphism in PAI-1 gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS The prevalence of insulin resistance in the obese group was higher (49.41%) than in the normal-weight group (16.85%). The 4G/5G PAI-1 polymorphism was found in Hardy Weinberg equilibrium. The 4G/5G genotype contributed to a significant increase in waist-hip ratio (β=0.02, p=0.006), waist circumference (β=4.42, p=0.009), and subscapular skinfold thickness (β=1.79, p=0.04); however, it was not related with insulin resistance. CONCLUSION The -675 4G/5G genotype of PAI-1 gene was associated with increase of body adiposity in Mexican children.