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Diabetic nephropathy is a leading cause of chronic kidney disease (CKD). In diabetes, changes in serum levels of both soluble alpha Klotho (sKL) and fibroblast growth factor 23 (FGF-23) have been associated with CKD progression.To evaluate the associations of circulating levels of sKL and FGF-23 with the presence of early nephropathy (EN) in diabetic patients.A cross-sectional study in 136 Mexicans with type 2 diabetes mellitus (T2DM). Early nephropathy was defined as an estimated glomerular filtration rate (≥60 ml/min) and urinary albumin excretion (≥30 mg/g). Serum concentrations of sKL and FGF-23 were measured using ELISA. Associations were evaluated with multiple logistic regression.Fifty-two subjects had EN. Median values of sKL and FGF-23 for all individuals were 244 pg/mL (interquartile range [IQR]: 201-402) and 92 pg/mL (IQR: 39-507), respectively. A positive correlation was found between levels of sKL and FGF-23 (r = 0.38; p 0.001). FGF-23 levels correlated negatively with angiotensin-II receptor blocker therapy (ARB, r = 0.24; p 0.01). Subjects without EN were younger (59 vs. 63 years old, p = 0.02). Elevated concentrations of FGF-23 were negatively associated with EN (Odds Ratio [ORIn Mexican diabetic patients, serum levels of FGF-23 were positively correlated with sKL but negatively correlated with ARB therapy. In addition, a higher concentration of FGF-23 reduced the odds of early nephropathy in patients with T2DM.

The Interleukin (IL)-1 family of cytokines plays a key role in the inflammatory response. Genes coding for IL-1α, IL-1β, and IL-1Ra are located together as a block gene known as the IL-1 cluster. This genomic region shows wide nucleotide variability, and some polymorphisms have been widely studied and associated with features related to the metabolic syndrome.Eight polymorphisms within three genes of the IL-1 cluster, including IL1A (rs3783553, rs17561, and rs1800587), IL1B (rs1143634, rs1143627, and rs16944) and IL1RN (rs419598 and rs2234663) were genotyped in 460 Mexican adolescents. Genotype and haplotype frequencies are reported, as well as the linkage disequilibrium analysis. Genetic associations with some anthropometric and metabolic traits were evaluated.Allele frequencies were similar to those found in other populations, and genotype proportions were according to the Hardy-Weinberg equilibrium. Seven haplotypes were observed at frequencies ≥5%. Of the entire cluster, only the rs17561-rs1800587 and rs1143627-rs16944 pairs showed highest and significant linkage disequilibrium values. An haplotype of IL1A, rs17561T-rs1800587T, was significantly associated with increase in body mass index in males (p0.008), whereas IL1B and IL1RN variants showed associations with insulin, and hs-CRP (p0.05).Some MetS parameters seem to be influenced by variations in the IL-1 gene cluster in Mexican adolescents. These variations may confer risk for metabolic alterations from early ages, and and these risks may be different when variables such as sex are considered. Strategies leading to generate protective behaviors could be designed to take into account specific variations in the IL-1 gene cluster and biological conditions such as sex.

Background and Aims. Interleukin-6isaninflammatoryresponsemediatorusedasametabolic marker of obesity. Polymorphisms IL6 � 597COA, � 572GOC, and � 174GOC modify the production of this protein. The associations between these haplotypes and obesity or metabolic markers have not been studied in adolescents, so an analysis of these associations was performed. Methods. The cross-sectional study included 745 apparently healthy 14- to 19-year-old adolescents. Obesity, serum glucose, insulin, triglycerides, total cholesterol, low-density lipoproteinecholesterol, high-density lipoproteinecholesterol (HDL-C), and highsensitivity C-reactive protein (hs-CRP) were evaluated, and IL6 � 597GOA, � 572GOC and � 174GOC polymorphisms determined. The associations were analyzed using multivariate logistic regression models. Results. The allele frequencies were 0.15 for � 597A and � 174C and 0.30 for � 572C. Genotypes were in HardyeWeinberg equilibrium. IL-6 � 597/� 572/� 174 haplotypes GGG, GCG, and AGC comprised 99.74% of the total haplotypes. The associations were significant between genotype GCG/GCG and hyperglycemia (OR52.86, 95% CI51.02e7.97); between GCG/GCG and high hs-CRP (OR56.17,95% CI51.13e33.77); betweenAGC/ AGC and obesity (OR 5 4.42, 95% CI 5 1.40e14.01); and between GGG/GCG and low HDL-C (OR 5 1.53, 95% CI 5 1.03e2.28). Conclusions. Genotypes of the IL6 � 597/� 572/� 174 polymorphisms are associated with metabolic risk factors in Mexican adolescents. 2013 IMSS. Published by Elsevier Inc.

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.

Background It is known that insulinemia is the result of the interaction among several factors, such as weight, body fat pattern distribution, and physical activity as well as ethnicity. There is little information regarding this question among Mexican adolescents. The association among fasting insulin levels, weight, fat distribution, physical activity, and cigarette smoking was studied in Mexican adolescents. Methods Cross-sectional data were collected from 352 Mexican adolescents aged 14–19 years (response rate 41.5%). Fasting insulin levels were measured by microparticle enzyme immunoassay; body mass index (BMI), waist-to-hip ratio (WHR), and waist circumference (WC) were determined using standardized techniques, while physical activity was determined by 7-day Stanford physical activity inventory. Cigarette smoking was defined as number of cigarettes/year. Results Increased BMI and waist circumference, low physical activity, younger age, and non-smoking were associated with high insulin levels. Non-smokers had higher fasting insulin levels compared to smokers (57.8 pmol ± 1.84 vs. 49.7 pmol/L ± 2.8; p = 0.034). However, adjusted odds ratio (OR) between insulin and smoking status was not significant. Multivariate analysis showed the following: insulin increased 1.06 pmol/L for each unit of change in BMI; increased 1.02 pmol/L for each unit of change in waist circumference; increased 1.16 pmol/L for non-smoking, and decreased 1.07 pmol/L for each 250 kcal/day of energy expenditure. Conclusions Our results support the concept that Mexican adolescents who are overweight have abdominal fat distribution and physical inactivity, and significant hyperinsulinemia. The relationship between smoking and lower insulinemia found in this research warrants further study.