Pharmacogenetics of Metformin in Type 2 Diabetes: Perspectives for Latin America

Metformin, in the anti-hyperglycemic pharmacological therapy, is consumed by more than 150 million people annually in the world due to its affordable price, safety, and because of considerable pleiotropic effect that has a positive impact on the control of glycemia, insulin resistance, cardiovascular health, and cancer in patients with type 2 diabetes (T2D). Differences in metformin’s effect on glycemic control have been associated with diet, abdominal obesity, years of T2D evolutions, and genetic factors. The Population of Latin America presents an important genetic component of Amerindians that could be explained to some extent in the response to metformin in glycemic control. The most recognized effect of metformin is to inhibit gluconeogenesis hepatica. In recent years, it has been observed to reduce the effect on body mass, positive effects on inflammation, and recently on the intestine with changes in the microbiome that favor suppression of postprandial hyperglycemia. Association studies between genetic variants coding for proteins related to metformin pharmacodynamics have shown different effects on glycemic control in several ethnic groups with European and Asian ancestry, but in Latin America they are scarce or none. Nutrients can interact with metformin favoring or decreasing its anti-hyperglycemic effect, so the diet should be considered

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Epidemiología de las hepatitis virales en México Epidemiology of viral hepatitis in Mexico

Las hepatitis virales son una de las causas principales de daño hepático en México. En este estudio se analiza el estado actual de las hepatitis virales en México. La Secretaría de Salud informa un total de 192 588 casos de hepatitis virales entre 2000 y 2007. De éstos, 79% corresponden aVHA, 3.3% aVHB, 6% a VHC y 11.7% a casos sin agente etiológico descrito. No obstante, el VHB se podría estar subdiagnosticando, ya que hay zonas de alta endemia en poblaciones indígenas, existen limitaciones en la sensibilidad y especificidad de las pruebas inmunológicas y podría ser común la hepatitis B oculta. ElVHE podría ser uno de los agentes etiológicos de aquellos casos que carecen de un agente etiológico conocido. Se proponen estrategias específicas para el control de las hepatitis virales tendientes a disminuir el número de casos.<br>The main etiology of liver disease in Mexico is alcohol and viral hepatitis. The aim of the present study was to analyze the current epidemiology of viral hepatitis in Mexico. From 2000 to 2007 the Ministry of Health reported 192 588 cases of hepatitis, 79% HAV, 3.3% HBV, 6% HCV, and 12% without a specific etiologic factor. Due to high endemic areas for HBV infection in native Mexican population, limitations in the diagnostic sensitivity and specificity of the serological immunoassays used to date and presence of occult hepatitis B in the country, the real prevalence of HBV infection could be even higher than HCV in Mexico. Hepatitis E virus in cirrhotic patients and in porcine farms could at least partially explain the cases of hepatitis that are diagnosed without a specific etiologic agent. Specific strategies to establish control regulations against viral hepatitis infections in Mexico are proposed

Prevalence of hepatitis A, B and C serological markers in children from western Mexico(◆)(◆)This work was partially funded by a grant to AP from the Consejo Estatal de Ciencia y Tecnologia de Jalisco, México (COECYTJAL-UdeG).

Introduction. Viral hepatitis in children is a major public health problem worldwide.Aim. To evaluate the prevalence of serological markers for hepatitis A, B and C infections in Mexican children diagnosed with hepatitis during a five-year period.Material and methods. A total of 31,818 children admitted to a tertiary level hospital in Mexico from 2005 to 2009 were evaluated for hepatitis.Results. Hepatitis was found in 215 (0.7%) of the children. Serum samples from hepatitis-positive children were screened for anti-HAV IgM, HBsAg, total anti-HBc and anti-HCV. HAV was the leading cause of viral hepatitis (81%), followed by HBV and HCV (3.1 and 2%, respectively), whereas no serological marker was observed in 13.9% of the analyzed samples. Furthermore, when children were categorized by age, a significant increase in anti-HAV detection was observed in school-aged children (7-11 years old) (p < 0.001) and a reduction in adolescents (12-15 years old).Conclusion. In conclusion, hepatitis A is the most prevalent viral hepatitis infection detected in children, followed by HBV and HCV. In addition, the high percentage of hepatitis infections without a known etiological agent and the serological test limitations require the detection of occult HBV, HCV and hepatitis E infections. The age-dependent vulnerability of groups with HAV infections emphasizes the importance of HAV vaccination in young children in Mexico

SARS-CoV-2 and Dengue Virus Coinfection in a Mexican Pediatric Patient: A Case Report from Early Molecular Diagnosis

Mexico is an endemic region for dengue virus (DENV). The increase in this disease coincides with outbreaks of COVID-19, both of which are single-stranded positive RNA viruses. These characteristics make it difficult to distinguish each disease because they share clinical and laboratory features, which can consequently result in misdiagnoses. This is why the use of precision confirmatory tests (qRT-PCR) are crucial for early diagnosis. We herein report a pediatric patient who presented a coinfection for DENV and COVID-19, &ldquo;SARS-CoV-2/Dengue&rdquo;. This patient initially presented a fever, cough, and headache and, three days later, developed generalized pain and epistaxis. Blood studies revealed thrombocytopenia and leukopenia, and the patient was admitted to the hospital for a probable DENV infection. Within 48 h, qRT-PCR tests specific for SARS-CoV-2 and DENV were performed and resulted as positive. The patient immediately received pharmacological treatment with azithromycin, oseltamivir, and metamizole. During hospitalization (9 days), the patient had no signs of respiratory distress and maintained normal body temperature and normal blood oxygen saturation. This case warns of the need for early diagnosis and adequate clinical and pharmacological management in the face of a &ldquo;SARS-CoV-2/Dengue&rdquo; coinfection. Early molecular detection of both viruses and timely treatment helped the patient to achieve a favorable recovery

Multiple cytokine expression profiles reveal immune-based differences in occult hepatitis B genotype H-infected Mexican Nahua patients

A high prevalence of occult hepatitis B (OHB) genotype H infections has been observed in the native Mexican Nahua population. In addition, a low incidence of hepatitis B virus (HBV)-associated hepatocellular carcinoma has been described in Mexico. The immune response to infection among OHB-infected patients has been poorly evaluated in vivo. Therefore, we assessed the expression profiles of 23 cytokines in OHB genotype H-infected Nahua patients. A total of 41 sera samples from natives of the Nahua community were retrospectively analysed. Based on their HBV antibody profiles, patients were stratified into two groups: OHB patients (n = 21) and patients that had recovered from HBV infection (n = 20). Herein, we report distinctive cytokines profiles in OHB-infected individuals. Compared to healthy controls (n = 20) and patients who resolved HBV infection, OHB-infected patients displayed an increase in interleukin (IL)-2 secretion in addition to a characteristic inflammation profile (decrease in IL-8 and tumour necrosis factor-alpha levels and increased levels of tumour growth factor-beta). IL-15 and interferon-gamma levels were reduced in OHB-infected individuals when compared to those patients who resolved HBV infection. In contrast, OHB patients showed an increase in monocyte chemoattractant protein (MCP)-1 and MCP-2 compared to healthy controls and patients who resolved HBV infection. These findings suggest that cytokine expression can influence the severity of OHB disease and could lead to new investigation into the treatment of liver and other infectious diseases