Electroacupuncture efficacy in diabetic polyneuropathy: Study protocol for a double-blinded randomized controlled multicenter clinical trial.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common complication of type 2 diabetes mellitus (T2DM); its diagnosis and treatment are based on symptomatic improvement. However, as pharmacological therapy causes multiple adverse effects, the implementation of acupunctural techniques, such as electroacupuncture (EA) has been suggested as an alternative treatment. Nonetheless, there is a lack of scientific evidence, and its mechanisms are still unclear. We present the design and methodology of a new clinical randomized trial, that investigates the effectiveness of EA for the treatment of DPN. METHODS: This study is a four-armed, randomized, controlled, multicenter clinical trial (20-week intervention period, plus 12 weeks of follow-up after concluding intervention). A total of 48 T2DM patients with clinical signs and symptoms of DPN; and electrophysiological signs in the Nerve Conduction Study (NCS); will be treated by acupuncture specialists in outpatient units in Mexico City. Patients will be randomized in a 1:1 ratio to one of the following four groups: (a) short fibre DPN with EA, (b) short fibre DPN with sham EA, (c) axonal DPN with EA and (d) axonal DPN with sham EA treatment. The intervention will consist of 32 sessions, 20 min each, per patient over two cycles of intervention of 8 weeks each and a mid-term rest period of 4 weeks. The primary outcome will be NCS parameters, and secondary outcomes will include DPN-related symptoms and pain by Michigan Neuropathy Screening Instrument (MNSI), Michigan Diabetic Neuropathy Score (MDNS), Dolour Neuropatique Score (DN-4), Semmes-Westein monofilament, Numerical Rating Scale (NRS) for pain assessment, and the 36-item Short Form Health Survey (SF-36). To measure quality of life and improve oxidative stress, the inflammatory response; and genetic expression; will be analysed at the beginning and at the end of treatment. DISCUSSION: This study will be conducted to compare the efficacy of EA versus sham EA combined with conventional diabetic and neuropathic treatments if needed. EA may improve NCS, neuropathic pain and symptoms, oxidative stress, inflammatory response, and genetic expression, and it could be considered a potential coadjutant treatment for the management of DPN with a possible remyelinating effect. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05521737 Registered on 30 August 2022. International Clinical Trials Registry Platform (ICTRP) ISRCTN97391213 Registered on 26 September 2022 [2b].

Association of the rs5186 polymorphism of the AGTR1 gene with decreased eGFR in patients with type 2 diabetes from Mexico City.

BACKGROUND: Early biomarkers search for Diabetic Kidney Disease (DKD) in patients with Type 2 Diabetes Mellitus (T2DM), as genetic markers to identify vulnerable carriers of the disease even before Glomerular Filtration Rate (GFR) decline or microalbuminuria development, has been relevant during the last few years. The rs5186 (A116C) polymorphism of the Angiotensin II Receptor Type I gene (AGTR1), has been associated to multiple effects of renal injury risk, commonly detected in patients with Diabetes Mellitus (DM). It has been described that rs5186 could have an effect in stability proteins that assemble Angiotensin II Receptor Type I (AT1), modifying its action, which is why it should be considered as a risk factor for Chronic Kidney Disease (CKD), characterized by a GFR progressive reduction. Even though, the association between rs5186 AGTR1 gene polymorphism and DKD in patients with T2DM has been controversial, inconclusive, and even absent. This disputable issue might be as a result of association studies in which many and varied clinical phenotypes included are contemplated as CKD inductors and enhancers. Although, the sample sizes studied in patients with T2DM are undersized and did not have a strict inclusion criteria, lacking of biochemical markers or KDOQI classification, which have hindered its examination. OBJECTIVE: The aim of our study was to establish an association between rs5186 AGTR1 gene polymorphism and GFR depletion, assessed as a risk factor to DKD development in patients with T2DM. METHODS: We analyzed 297 not related patients with T2DM, divided into 221 controls (KDOQI 1) and 76 cases (KDOQI 2). Arterial pressure, anthropometric and biochemical parameters were measured. rs5186 of AGTR1 genotyping was performed by TaqMan assay real-time PCR method. Allele and genotype frequencies, and Hardy-Weinberg equilibrium were measured. Normality test for data distribution was analyzed by Shapiro-Wilk test, variable comparison by Student's t-test for continuous variables, and Chi-squared test for categorical variables; ANOVA test was used for mean comparison of more than two groups. Effect of rs5186 to DKD was estimated by multiple heritability adjustment models for risk variables of DKD. Statistical significance was indicated by p<0.05. Data was analyzed using Statistical Package STATA v11 software. RESULTS: Dominant and Over-dominant models showed a likelihood ratio to GFR depletion of 1.89 (1.05-3.39, p=0.031) and 2.01 (1.08-3.73, p=0.023) in patients with T2DM. Risk factor increased to 2.54 (1.10-5.89) in women in Over-dominant model. CONCLUSION: In clinical practice, most of nephropathies progress at a slow pace into a total breakdown of renal function, even asymptomatic. This is the first study, reporting that rs5186 polymorphism of AGTR1 gene contribution to GFR depletion, and this could be evaluated as a predisposing factor for DKD in patients with T2DM.

Severe Quantitative Scale of Acanthosis Nigricans in Neck is Associated with Abdominal Obesity, HOMA-IR, and Hyperlipidemia in Obese Children from Mexico City: A Cross-Sectional Study.

Background: Acanthosis nigricans (AN) is a clinical sign that commonly occurs in obesity; however, its specificity and sensitivity have been controversial. It is unknown if AN severity degree can be a useful marker for cardiometabolic disorders screening. We suggest that the stratified analysis of AN severity degree in neck by Burke's scale could be a useful tool in the screening of cardiometabolic alterations in obese children. Objective: The aim of this study was the association of AN severity degree in neck by Burke's scale with anthropometric, biochemical, and inflammatory parameters in obese school-age children from Mexico City. Methods: A cross-sectional study was conducted, including 95 obese school-age children stratified by AN severity degree in neck by Burke's scale. Anthropometric and fasting biochemical measurements were determined. Variables were compared by x 2 test for frequencies and one-way ANOVA with Bonferroni posttest for continuous variables. Linear regression analysis adjusted by gender, BMI, and age was performed to evaluate the association between AN severity degree and cardiometabolic alterations. Statistical significance was set at p < 0.05. Results: As AN severity degree in neck by Burke's scale increased, diastolic blood pressure (p=0.001) and triglycerides (p=0.02) significantly increased and adiponectin significantly decreased (p=0.02). Positive associations between grade 3 AN and waist circumference, HOMA-IR, triglycerides, total cholesterol, and LDL cholesterol were observed. Conclusion: Our findings could be used to identify an easier clinical tool to prevent obesity progression and its complications in pediatrics. There are no similar studies.

AGT rs4762 is associated with diastolic blood pressure in Mexicans with diabetic nephropathy.

AIMS: Since angiotensinogen has a pivotal role in the renin-angiotensin-aldosterone system, the analysis of polymorphisms of the angiotensinogen (AGT) gene could help explain its potential involvement in hypertension and diabetic nephropathy (DN) pathogenesis. For that reason, we investigated 1) the association of AGT rs4762 with blood pressure (BP) and kidney function-related traits and 2) the interaction effect of AGT rs4762 with DN on BP and kidney function-related traits in 546 Mexican adults with type 2 diabetes (T2D). METHODS: We enrolled 546 unrelated Mexican patients with T2D (350 cases with DN and 196 controls without DN). AGT rs4762 was genotyped in all participants using TaqMan technology (effect allele: A). BP and kidney function-related traits, including serum urea and creatinine, urinary albumin, urine albumin to urine creatinine ratio (ACR), and glomerular filtration rate, were studied. DN was defined as having a previous diagnosis of T2D and an ACR ≥ 30 mg/g. The association between these parameters was investigated using logistic regression with adjustment for covariates. RESULTS: AGT rs4762 A allele was significantly associated with diastolic blood pressure (N = 546, ß = 1.243 ± 0.918, p = 0.029). A significant interaction between DN and AGT rs4762 was also observed in relation to diastolic blood pressure (DBP) (N = 546, ß = 0.930 ± 0.433, p=0.032). A follow-up analysis of simple effects particularly revealed a positive association between AGT rs4762 A allele and DBP only in patients with diabetic nephropathy (N = 350, ß = 2.837 ±â€¯1.267, p = 0.026). CONCLUSION: Our results evidence that, although AGT rs4762 is not associated with DN, the AGT rs4762 A allele is positively associated with DBP in the Mexican population with DN.

Association of rs2000999 in the haptoglobin gene with total cholesterol, HDL-C, and LDL-C levels in Mexican type 2 diabetes patients.

Recently, studies have shown significant association between the rs2000999 polymorphism in the haptoglobin-encoding gene (HP) and low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels, which are important risk factors for cardiovascular diseases. However, the association of rs2000999 with serum lipids in Latin American diabetic populations is still uncharacterized. Here, we analyzed the association of rs2000999 with TC, high-density lipoprotein cholesterol (HDL-C), and LDL-C levels in 546 Mexican adults with type 2 diabetes (T2D) and in 654 controls without T2D. In this observational case-control study we included adults from 4 centers of the Mexican Social Security Institute in Mexico City recruited from 2012 to 2015. TC, HDL-C, LDL-C, triglycerides (TG), and glucose levels were measured by an enzymatic colorimetric method. The variant rs2000999 was genotyped using TaqMan real time polymerase chain reaction. The percentage of Native-American ancestry showed a negative association with the rs2000999 A allele. In contrast, the rs2000999 A allele had a strong positive association with European ancestry, and to a lesser extent, with African ancestry. Linear regression was used to estimate the association between the variant rs2000999 and lipid concentrations, using different genetic models. Under codominant and recessive models, rs2000999 was significantly associated with TC and LDL-C levels in the T2D group and in controls without T2D. In addition, the group with T2D showed a significant association between the variant and HDL-C levels. In summary, the rs2000999 A allele in Mexican population is positively associated with the percentage of European and negatively associated with Native American ancestry. Carriers of the A allele have increased levels of TC and LDL-C, independently of T2D diagnosis, and also increased concentrations of HDL-C in the T2D sample.

The rs1256031 of estrogen receptor ß gene is associated with type 2 diabetes.

AIM: To determine the association between the rs1256031 polymorphism and risk of developing type 2 diabetes. MATERIALS AND METHODS: Cases and controls study. 597 individuals with type 2 diabetes and 605 without it participated. Genotyping of the rs1256031 polymorphism of the ERß gene was performed by real-time PCR using TaqMan assay. For the multivariate analysis, a multiple logistic regression was performed that included the main confounding variables. RESULTS AND CONCLUSION: A multiple logistic regression analysis was performed, adjusting for age, WHR, BMI and gender. The dominant model showed a protective effect compared to the TT genotype (OR = 0.596, IC95% [0.458-0.776]). DISCUSSION: The proportions of native American, European and African ancestry were characterized and no difference was found in the study groups. The protective effect obtained in the dominant model could to be due a regulatory function in the transcription or the processing of the primary transcript. Our result are the first to report an association between the polymorphism rs1256031 and the reduction of the risk of T2D in the Mexican population. The rs1256031 polymorphism show reduced risk of developing T2D and is potential markers for predicting T2D.

High Thyroid-stimulating Hormone Levels Increase Proinflammatory and Cardiovascular Markers in Patients with Extreme Obesity.

BACKGROUND AND AIMS: Obesity is an important health problem worldwide and many studies have suggested a relationship between obesity and thyroid function, with controversial results. Interestingly, high TSH levels have been involved with the presence of inflammatory state and risk for developing cardiovascular diseases in hypothyroid and obese patients. The aim in this work was to determine the prevalence of hypothyroidism in patients with extreme obesity and to determine whether their TSH levels were related to increased serum levels of inflammatory and cardiovascular markers. METHODS: A cross-sectional study in 101 patients with extreme obesity (BMI ≥40) was performed. Anthropometric (weight, height and waist circumference) and biochemical (fasting glucose, glycosylated hemoglobin, triglycerides, total cholesterol, LDL-C, HDL-C and insulin) parameters were measured. TSH and FT4 levels as well as clinical exploration for diagnosis of hypothyroidism were carried out. Serum concentration of IL-10, IL-6, adiponectin, resistin, leptin, ICAM-1, VCAM-1 and E-selectin were determined. RESULTS: A high prevalence for diabetes (37.6%), prediabetes (50.5%), dyslipidemia (74.3%), hypertension (61.4%) and hypothyroidism (48.5%) was observed in patients with extreme obesity. The presence of hypothyroidism increased serum concentration of proinflammatory cytokines IL-6 and leptin and decreased the antiinflammatory cytokine adiponectin. In addition, serum TSH levels showed a correlation for waist circumference, weight, BMI, A1c, insulin, IL-6, leptin, ICAM-1 and E-selectin. CONCLUSION: There is a high prevalence for hypothyroidism in patients with extreme obesity. High levels of TSH contribute to elevate proinflammatory and cardiovascular risk markers, increasing the risk for development of cardiovascular diseases.

ADIPOQ and ADIPOR2 gene polymorphisms: association with overweight/obesity in Mexican children.

BACKGROUND: ENSANUT 2012 showed a combined prevalence of overweight and obesity of 34.4% in Mexican children. Single nucleotide polymorphisms (SNPs) of the ADIPOQ and ADIPOR2 genes have been reported in many populations, but their association with obesity has not been confirmed in other studies. Our aim was to determine the association of SNPs from ADIPOQ and ADIPOR2 genes with obesity in Mexican children. METHODS: A total of 2,634 children from 6 to 12 years old were enrolled in the study from four IMSS Units in Mexico City. We selected 1,469 unrelated children (745 normal weight and 724 overweight/obese). Phenotype characterization included anthropometric measurements, blood pressure, biochemical parameters, insulin concentrations and presence of acanthosis nigricans (AN). Analysis of the SNPs rs182052, rs266729, rs2241766, rs822393 of ADIPOQ and rs11061971 of ADIPOR2 was carried out in the DNA samples. RESULTS: The study showed significant differences (p <0.05) between groups in waist circumference, blood pressure, presence of AN, insulin concentrations, HOMA-IR, fasting glucose and lipid parameters, being higher in obese children. No associations in ADIPOQ variants with the presence of overweight/obesity were found. The presence of the variant rs11061971 of ADIPOR2 in children had a significant association with protection of overweight/obesity (OR 0.79, 95% CI 0.68-0.93, p = 0.003). Also, the log-additive model confirmed the association by codominant and dominant models (p <0.05). CONCLUSIONS: The presence of rs11061971 of ADIPOR2 variant confers protection against obesity and could be used as a marker in Mexican children.

[Genetics of pediatric obesity]. / Genética de la obesidad infantil.

Obesity is a major health problem around the globe. The statistics of overweight and obesity at early ages have reached alarming levels and placed our country in the first place in regard to childhood obesity. In the development of obesity two major factors take part, one genetic and the other one environmental. From the perspective of environmental changes both overweight and obesity result from the imbalance in the energy balance: people ingest more energy than they expend. Despite people live in the same obesogenic environment not all of them develop obesity; it requires genetic factors for this to happen. This review focuses on the description of the main methodologies to find genetic markers, as well as the main loci in candidate genes, whose single nucleotide polymorphisms (SNPs) are associated with obesity and its comorbidities in children, highlighting the association of these genes in the Mexican population. Knowledge of the genetic markers associated with obesity will help to understand the molecular and physiological mechanisms, the genetic background and changes in body mass index in the Mexican population. This information is useful for the planning of new hypotheses in the search for new biomarkers that can be used in a predictive and preventive way, as well as for the development of new therapeutic strategies.

La obesidad es uno de los principales problemas de salud a nivel mundial. Las cifras de sobrepeso y obesidad a edades tempranas han alcanzado niveles alarmantes y ubican a nuestro país en el primer lugar de obesidad infantil. En el desarrollo de la obesidad participan dos grandes factores, uno genético y otro ambiental. Desde la perspectiva de las alteraciones ambientales, tanto el sobrepeso como la obesidad resultan del desequilibrio en el balance energético: las personas ingieren mayor cantidad de energía de la que gastan. A pesar de que las personas vivan en el mismo ambiente obesógeno, no todos desarrollan obesidad; para que esto ocurra, se requiere de los factores genéticos. Esta revisión se enfoca en la descripción de las principales metodologías para la búsqueda de marcadores genéticos, así como los principales loci en genes candidatos, cuyos polimorfismos de un solo nucííleótido (SNP, por sus siglas en inglés) se encuentran asociados con la obesidad y sus comorbilidades en la población infantil, de lo cual resalta la asociación de estos genes en la población mexicana. El conocimiento de los marcadores genéticos asociados a la obesidad ayudará a comprender los mecanismos moleculares y fisiológicos, el fondo genético y las modificaciones en el índice de masa corporal en la población mexicana. Esta información es de gran utilidad para el planteamiento de nuevas hipótesis en la búsqueda de nuevos biomarcadores que puedan ser utilizados de una manera predictiva y preventiva, así como para el desarrollo de nuevas estrategias terapéuticas.

ADIPOQ and ADIPOR2 gene polymorphisms: association with overweight/obesity in Mexican children / Polimorfismos de los genes ADIPOQ y ADIPOR2 y su asociación con sobrepeso/obesidad en niños mexicanos

Background: ENSANUT 2012 showed a combined prevalence of overweight and obesity of 34.4% in Mexican children. Single nucleotide polymorphisms (SNPs) of the ADIPOQ and ADIPOR2 genes have been reported in many populations, but their association with obesity has not been confirmed in other studies. Our aim was to determine the association of SNPs from ADIPOQ and ADIPOR2 genes with obesity in Mexican children. Methods: A total of 2,634 children from 6 to 12 years old were enrolled in the study from four IMSS Units in Mexico City. We selected 1,469 unrelated children (745 normal weight and 724 overweight/obese). Phenotype characterization included anthropometric measurements, blood pressure, biochemical parameters, insulin concentrations and presence of acanthosis nigricans (AN). Analysis of the SNPs rs182052, rs266729, rs2241766, rs822393 of ADIPOQ and rs11061971 of ADIPOR2 was carried out in the DNA samples. Results: The study showed significant differences (p <0.05) between groups in waist circumference, blood pressure, presence of AN, insulin concentrations, HOMA-IR, fasting glucose and lipid parameters, being higher in obese children. No associations in ADIPOQ variants with the presence of overweight/obesity were found. The presence of the variant rs11061971 of ADIPOR2 in children had a significant association with protection of overweight/obesity (OR 0.79, 95% CI 0.68-0.93, p = 0.003). Also, the log-additive model confirmed the association by codominant and dominant models (p <0.05). Conclusions: The presence of rs11061971 of ADIPOR2 variant confers protection against obesity and could be used as a marker in Mexican children.

Introducción: ENSANUT 2012 mostró una prevalencia combinada de sobrepeso y obesidad en el 34.4% en niños mexicanos. Se han reportado polimorfismos de un solo nucleótido (SNP) de los genes ADIPOQ y ADIPOR2 en varias poblaciones, pero su asociación con la obesidad ha sido controversial. El objetivo de este trabajo fue determinar la asociación de SNP de ADIPOQ y ADIPOR2 con obesidad en una muestra de niños mexicanos. Métodos: Un total de 2,634 niños de 6-12 años se inscribieron en el estudio en cuatro unidades del Instituto Mexicano del Seguro Social en la Ciudad de México. Se seleccionaron 1,469 niños no emparentados (745 peso normal y 724 sobrepeso/obesidad). Se les tomaron medidas antropométricas, presión arterial, parámetros bioquímicos, insulina y presencia de acantosis nigricans (AN). El análisis de los SNP (rs182052, rs266729, rs2241766, rs822393 de ADIPOQ y rs11061971 de ADIPOR2) se realizó en muestras de ADN. Resultados: Se observaron diferencias significativas (p < 0.05) entre los grupos en la circunferencia de cintura, presión arterial, AN, insulina, HOMA-IR, glucosa en ayunas y parámetros lipídicos siendo elevados en los niños obesos. No se encontró asociación en variantes ADIPOQ con la presencia de sobrepeso/obesidad. La presencia de rs11061971 de ADIPOR2 tuvo una asociación significativa con la protección de sobrepeso/obesidad (OR de 0.79; IC95% 0.68 a 0.93, p = 0.003). El modelo Log-aditivo confirmó la asociación de los modelos codominante y dominante (p < 0.05). Conclusiones: La presencia de la variante rs11061971 de ADIPOR2 confiere protección contra la obesidad, y podría utilizarse como marcador en niños mexicanos.