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Background: Type 2 diabetes (T2D) is one of the leading causes of mortality and is a public health challenge worldwide. Metformin is the first-choice treatment for T2D; its pharmacokinetics (PK) is facilitated by members of the solute carrier (SLC) superfamily of transporters, it is not metabolized, and it is excreted by the kidney. Although interindividual variability in metformin pharmacokinetics is documented in the Mexican population, its pharmacogenomics is still underexplored. We aimed to identify variants in metformin SLC transporter genes associated with metformin PK and response in Mexican patients. Methods: Using exome data from 2217 Mexican adults, we identified 86 biallelic SNVs in the eight known genes encoding SLC transporters, with a minor allele frequency ≥ 1%, which were analyzed in an inadequate glycemic control (IGC) association study in T2D metformin treated patients. Metformin PK was evaluated in a pediatric cohort and the effect of associated SNVs was correlated. Results: Functional annotation classified two SNVs as pathogenic. The association study revealed two blocks associated with IGC. These haplotypes comprise rs622591, rs4646272, rs4646273, and rs4646276 in SLC22A1; and rs1810126 and rs668871 in SLC22A3. PK profiles revealed that homozygotes of the SLC22A1 haplotype reached lower plasma metformin concentrations 2 h post administration than the other groups. Conclusions: Our findings highlight the potential of pharmacogenomics studies to enhance precision medicine, which may involve dosage adjustments or the exploration of alternative therapeutic options. These hold significant implications for public health, particularly in populations with a high susceptibility to develop metabolic diseases, such as Latin Americans. [ABSTRACT FROM AUTHOR]

Overweight children and childhood obesity are a public health problem in Mexico. Obesity is traditionally assessed using body mass index (BMI), but an excess of adiposity does not necessarily reflect a high BMI. Thus, body composition indexes are a better alternative. Our objective was to generate body composition percentile curves in children from Mexico City. A total of 2026 boys and 1488 girls aged 6 to 12 years old were studied in Mexico City. Body weight, height, and BMI calculation were measured. Total body fat percentage (TBFP) was derived from the skinfold thicknesses, and fat mass (FMI) and free fat mass indexes (FFMI) were calculated. Finally, age- and gender-specifıc smoothed percentile curves were generated with Cole's Lambda, Mu, and Sigma (LMS) method. In general, height, weight, waist circumference (WC), and TBFP were higher in boys, but FFM was higher in girls. TBFP appeared to increase significantly between ages 8 and 9 in boys (+2.9%) and between ages 10 and 11 in girls (+1.2%). In contrast, FFM% decreased noticeably between ages 8 and 9 until 12 years old in boys and girls. FMI values peaked in boys at age 12 (P97 = 14.1 kg/m²) and in girls at age 11 (P97 = 8.8 kg/m²). FFMI percentiles increase at a steady state reaching a peak at age 12 in boys and girls. Smoothed body composition percentiles showed a different pattern in boys and girls. The use of TBFP, FMI, and FFMI along with BMI provides valuable information in epidemiological, nutritional, and clinical research.

Copyright of Acta Pediatrica de Mexico is the property of Instituto Nacional de Pediatria (INP) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This is a descriptive review of the elaboration routes, the physical and chemical characteristics, metabolism and clearance, sweetener level, residual flavor, maximal recommended ingestion, security levels and the assessment of growth and development problems in children (from newborns, including prematures, to the end of puberty), of the main no caloric edulcorants used in Mexico. The no caloric edulcorants included in this review are: aspartame, acesulfame-K, sucralose, sacarin, ciclamates, thaumatin, D- tagatose, estevia and alitame.

We analyze the health normativity for the denomination of non caloric edulcorants in Mexico, and the authorization for the use of natural and synthetic non caloric edulcorants in newborn and until puberty. Special emphasis was given to the consecutive points of safety required in order to assure that they are free of secondary effects. For each non caloric edulcorant available in Mexico, we looked into the studies which mention their side effects in terms of growth and overall.

Copyright of Revista Mexicana de Endocrinología, Metabolismo y Nutrición is the property of Publicidad Permanyer SLU and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Human islet amyloid peptide (hIAPP1–37) aggregation is an early step in Diabetes Mellitus. We aimed to evaluate a family of pharmaco-chaperones to act as modulators that provide dynamic interventions and the multi-target capacity (native state, cytotoxic oligomers, protofilaments and fibrils of hIAPP1–37) required to meet the treatment challenges of diabetes. We used a cross-functional approach that combines in silico and in vitro biochemical and biophysical methods to study the hIAPP1–37 aggregation-oligomerization process as to reveal novel potential anti-diabetic drugs. The family of pharmaco-chaperones are modulators of the oligomerization and fibre formation of hIAPP1–37. When they interact with the amino acid in the amyloid-like steric zipper zone, they inhibit and/or delay the aggregation-oligomerization pathway by binding and stabilizing several amyloid structures of hIAPP1–37. Moreover, they can protect cerebellar granule cells (CGC) from the cytotoxicity produced by the hIAPP1–37 oligomers. The modulation of proteostasis by the family of pharmaco-chaperones A–F is a promising potential approach to limit the onset and progression of diabetes and its comorbidities. [ABSTRACT FROM AUTHOR]

Conformational diseases represent a new aspect of proteomic medicine where diagnostic and therapeutic paradigms are evolving. In this context, the early biomarkers for target cell failure (neurons, β-cells, etc.) represent a challenge to translational medicine and play a multidimensional role as biomarkers and potential therapeutic targets. This systematic review, which follows the PICO and Prisma methods, analyses this new-fangled multidimensionality, its strengths and limitations, and presents the future possibilities it opens up. The nuclear diagnosis methods are immunoassays: ELISA, immunodot, western blot, etc., while the therapeutic approach is focused on pharmaco- and molecular chaperones. [ABSTRACT FROM AUTHOR]

Copyright of Acta Pediatrica de Mexico is the property of Instituto Nacional de Pediatria (INP) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Pediatrica de Mexico is the property of Instituto Nacional de Pediatria (INP) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Pediatrica de Mexico is the property of Instituto Nacional de Pediatria (INP) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The modulators that diminish appetite and increase metabolic calorie needs at hypothalamus level are synthesized in different tissues: gastrointestinal system (glucagons-like peptide-1, pancreatic polypeptide, peptide YY, cholecystokinin and oxyntomodulin), the endocrine system (insulin, beta effects of adrenalin, and estrogens), adipose tissue (leptin, visfatin and omentin-1), peripheral nervous system (noradrenaline beta effects) and central nervous system (corticotropin released hormone, melanocortin, agouti protein, cocacine-amphetamine-regulated transcript and MCH). Those factors increasing appetite and lower basal metabolism comes from gastrointestinal system (ghrelin and growth hormone re lease hormone from pancreas), and central nervous system (neuropeptide Y, orexins and cannabinoids). In the hypothalamus, the neural and neuroendocrine afferents are integrated with the purpose of regulate appetite (hunger or satiety signals), and metabolic needs (increasing or decreasing basal metabolism and brown adipose tissue thermoregulation efficacy) according to body energy balance. The arcuate nucleus contains 2 main cellular systems: one rich in proopiomelanocortin (precursor of alpha melanocytes stimulating hormone and agonist of melanocortin 3 and 4 receptors), which decreases appetite, and other rich in neuropeptide Y and agouti-related peptide which increase appetite. [ABSTRACT FROM AUTHOR]

Human islet amyloid peptide (hIAPP 1-37 ) aggregation is an early step in Diabetes Mellitus. We aimed to evaluate a family of pharmaco-chaperones to act as modulators that provide dynamic interventions and the multi-target capacity (native state, cytotoxic oligomers, protofilaments and fibrils of hIAPP 1-37 ) required to meet the treatment challenges of diabetes. We used a cross-functional approach that combines in silico and in vitro biochemical and biophysical methods to study the hIAPP 1-37 aggregation-oligomerization process as to reveal novel potential anti-diabetic drugs. The family of pharmaco-chaperones are modulators of the oligomerization and fibre formation of hIAPP 1-37 . When they interact with the amino acid in the amyloid-like steric zipper zone, they inhibit and/or delay the aggregation-oligomerization pathway by binding and stabilizing several amyloid structures of hIAPP 1-37 . Moreover, they can protect cerebellar granule cells (CGC) from the cytotoxicity produced by the hIAPP 1-37 oligomers. The modulation of proteostasis by the family of pharmaco-chaperones A - F is a promising potential approach to limit the onset and progression of diabetes and its comorbidities., Competing Interests: The author declares having filled two patent applications WO2010118706 A2 and WO2014131374 A1.

The bone mass peak is the maximum bone quantity to be achieved through bone modeling. About 40% of the total bone mass is achieved at puberty; therefore, adolescence is critical on the skeletal development. This paper is about the transfunctional analysis of nutrition, mineral metabolism, endocrinology and life style in adolescence. Core factors to achieve the maximum potential of bone modeling through puberty and prevent osteoporosis from a pediatric stage are addressed.

Context: Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset and a primary insulin secretion defect. Certain MODY gene sequence variants may be involved in polygenic forms of type 2 diabetes., Objective: We assessed the contribution of MODY genes to the etiology of type 2 early-onset diabetes in 23 Mexican families, including five with apparently autosomal dominant inheritance., Patients: Twenty-three unrelated Mexican families with early-onset type 2 diabetes previously screened for the presence of glucokinase mutations, were studied., Design: We screened MODY genes for sequence variants by PCR-SSCP analysis and automated sequencing. We performed a functional analysis of the HNF-1alpha P379H recombinant protein in vitro in both HeLa and RINm5f beta-cell lines., Main Outcome Measures: MODY gene mutation screening and P379H mutant protein transactivation assay., Results: No mutations were detected in the HNF-4alpha, IPF-1, NEUROD1 or HNF-1beta genes in any of the families studied. A new mutation (P379H) of the HNF-1alpha gene was identified in one MODY family. RINm5f and HeLa cell transfection assays revealed decreased transactivation activity of the mutant protein on the human insulin promoter., Conclusions: All known MODY genes were screened for abnormalities in this cohort of early-onset diabetes families which included 5 MODY pedigrees. We identified a new HNF-1alpha MODY mutation (P379H) and demonstrated that it reduces the transactivation potential of the mutant protein on the human insulin promoter. No other mutation was identified in this cohort indicating that abnormalities in MODY genes are generally not a common cause of early-onset diabetes and this includes MODY families in Mexico.