Health impact assessment after Danio rerio long-term exposure to environmentally relevant concentrations of metformin and guanylurea.

The antidiabetic drug metformin (MET) and its metabolite guanylurea (GUA) have been frequently and ubiquitously detected in surface water. Consequently, there has been a consistent rise in studying the toxicity of MET and GUA in fish over the past decade. Nonetheless, it is noteworthy that no study has assessed the harmful effects both compounds might trigger on fish blood and organs after chronic exposure. Taking into consideration the data above, our research strived to accomplish two primary objectives: Firstly, to assess the effect of comparable concentrations of MET and GUA (1, 40, 100 µg/L) on the liver, gills, gut, and brain of Danio rerio after six months of flow-through exposure. Secondly, to compare the outcomes to identify which compound prompts more significant oxidative stress and apoptosis in organs and blood parameter alterations. Herein, findings indicate that both compounds induced oxidative damage and increased the expression of genes associated with apoptosis (bax, bcl2, p53, and casp3). Chronic exposure to MET and GUA also generated fluctuations in glucose, creatinine, phosphorus, liver enzymes, red and white blood count, hemoglobin, and hematocrit levels. The observed biochemical changes indicate that MET and GUA are responsible for inducing hepatic damage in fish, whereas hematological alterations suggest that both compounds cause anemia. Considering GUA altered to a more considerable extent the values of all endpoints compared to the control group, it is suggested transformation product GUA is more toxic than MET. Moreover, based on the above evidence, it can be inferred that a six-month exposure to MET and GUA can impair REDOX status and generate apoptosis in fish, adversely affecting their essential organs' functioning.

The Health System in Costa Rica: Focus on the Management of Diabetes Mellitus.

Costa Rica's health system was established in 1941 by the president at the time, Rafael Angel Calderon Guardia. Since then, the public health system has expanded, and a private system was also introduced. Diabetes management differs greatly between both systems, as well as the medications available. Publicly, the system faces many challenges when treating diabetes; including a limited range and selection of medications, as well as a blatant lack of support (nutritional, physical, and psychological). Privately, the costs adjacent to a diabetes diagnosis represent an unbearable burden to some patients, with medications such as a weekly dose of 1.0 mg of semaglutide representing approximately 47.5% of Costa Rica's minimum wage. Despite its flaws, both systems provide the Costa Rican population with options for treatment. The Caja Costarricense de Seguro Social covers around 90% of the population, which puts Costa Rica on par with developed countries.

Antihyperglycemic Effects of Annona cherimola Miller and the Flavonoid Rutin in Combination with Oral Antidiabetic Drugs on Streptozocin-Induced Diabetic Mice.

Ethanolic extract obtained from Annona cherimola Miller (EEAc) and the flavonoid rutin (Rut) were evaluated in this study to determine their antihyperglycemic content, % HbA1c reduction, and antihyperlipidemic activities. Both treatments were evaluated separately and in combination with the oral antidiabetic drugs (OADs) acarbose (Aca), metformin (Met), glibenclamide (Gli), and canagliflozin (Cana) in acute and subchronic assays. The evaluation of the acute assay showed that EEAc and Rut administered separately significantly reduce hyperglycemia in a manner similar to OADs and help to reduce % HbA1c and hyperlipidemia in the subchronic assay. The combination of EEAc + Met showed the best activity by reducing the hyperglycemia content, % HbA1c, Chol, HDL-c, and LDL-c. Rutin in combination with OADs used in all treatments significantly reduced the hyperglycemia content that is reflected in the reduction in % HbA1c. In relation to the lipid profiles, all combinate treatments helped to avoid an increase in the measured parameters. The results show the importance of evaluating the activity of herbal remedies in combination with drugs to determine their activities and possible side effects. Moreover, the combination of rutin with antidiabetic drugs presented considerable activity, and this is the first step for the development of novel DM treatments.

Effects of antidiabetics and exercise therapy on suppressors of cytokine signaling-1, suppressors of cytokine signaling-3, and insulin receptor substrate-1 molecules in diabetes and obesity

SUMMARY OBJECTIVE: Pathological destruction of insulin signaling molecules such as insulin receptor substrate, especially due to the increase in suppressors of cytokine signaling molecules, has been demonstrated in experimental diabetes. The contribution of suppressors of cytokine signaling proteins to the development of insulin resistance and the effects of antidiabetic drugs and exercise on suppressors of cytokine signaling proteins are not clearly known. METHODS: A total of 48 Wistar albino adult male rats were divided into six groups: control group, obese group with diabetes, obese diabetic rats treated with metformin, obese diabetic rats treated with pioglitazone, obese diabetic rats treated with exenatide, and obese diabetic rats with applied exercise program. Immunohistochemical staining was performed in both the liver and adipose tissue. RESULTS: There was a statistically significant decrease in suppressors of cytokine signaling-1, a decrease in suppressors of cytokine signaling-3, an increase in insulin receptor substrate-1, and a decrease in immunohistochemical staining in the obese group treated with metformin and exenatide compared to the obese group without treatment in the liver tissue (p<0.05). A statistically significant decrease in immunohistochemical staining of suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 was found in the obese group receiving exercise therapy compared to the obese group without treatment in visceral adipose tissue (p<0.05). Likewise, no significant immunohistochemistry staining was seen in diabetic obese groups. CONCLUSION: Metformin or exenatide treatment could prevent the degradation of insulin receptor substrate-1 protein by reducing the effect of suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 proteins, especially in the liver tissue. In addition, exercise can play a role as a complementary therapy by reducing suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 proteins in visceral adipose tissue.

[Interactions in antithrombotic and hypoglycemic therapy]. / Interacciones en el tratamiento antitrombótico e hipoglucemiante.

This review is an update on antiplatelet therapy and its interaction with oral hypoglycemic agents in diabetic patients with ischemic heart disease. We summarize the main pathophysiological mechanisms that intervene in diabetic patients and that increase the ischemic risk, the effects of the combination of oral hypoglycemic agents, their antithrombotic effects and their interaction with antiplatelet, and finally the studies that demonstrated the benefits of antiplatelet in diabetic patients in different scenarios of ischemic heart disease. The different mechanisms of action involve improved glycemic control, increased bioavailability of nitric oxide, reduced oxidative stress and, for certain molecules, direct inhibition of platelet activation and aggregation.

Esta revisión consiste en una puesta al día del tratamiento antiplaquetario y la interacción que presenta con los hipoglucemiantes orales en pacientes diabéticos con cardiopatía isquémica. Resumimos los principales mecanismos fisiopatológicos que intervienen en el aumento del riesgo cardiovascular en este grupo, los efectos de la combinación entre los hipoglucemiantes orales, sus efectos antitrombóticos y su interacción con los antiplaquetarios y, por último, los trabajos que estudiaron los beneficios de los antiplaquetarios en pacientes diabéticos en diferentes escenarios de la cardiopatía isquémica. Los variados mecanismos de acción implican una mejora del control de la glucemia, del aumento de la biodisponibilidad del óxido nítrico, reducción del estrés oxidativo y, para ciertas moléculas, una inhibición directa de la activación y de la agregación plaquetaria.

Interacciones en el tratamiento antitrombótico e hipoglucemiante / Interactions in antithrombotic and hypoglycemic therapy

Resumen Esta revisión consiste en una puesta al día del tratamiento antiplaquetario y la interacción que presenta con los hipoglucemiantes orales en pacientes diabéticos con cardiopatía isquémica. Re sumimos los principales mecanismos fisiopatológicos que intervienen en el aumento del riesgo cardiovascular en este grupo, los efectos de la combinación entre los hipoglucemiantes orales, sus efectos antitrombóticos y su interacción con los antiplaquetarios y, por último, los trabajos que estudiaron los beneficios de los antiplaque tarios en pacientes diabéticos en diferentes escenarios de la cardiopatía isquémica. Los variados mecanismos de acción implican una mejora del control de la glucemia, del aumento de la biodisponibilidad del óxido nítrico, reducción del estrés oxidativo y, para ciertas moléculas, una inhibición directa de la activación y de la agregación plaquetaria.

Abstract This review is an update on antiplatelet therapy and its interaction with oral hypoglycemic agents in diabetic patients with ischemic heart disease. We summarize the main pathophysiological mechanisms that intervene in diabetic patients and that increase the ischemic risk, the effects of the combination of oral hypoglycemic agents, their antithrombotic ef fects and their interaction with antiplatelet, and finally the studies that demonstrated the benefits of antiplatelet in diabetic patients in different scenarios of ischemic heart disease. The different mechanisms of action involve improved glycemic control, increased bioavailability of nitric oxide, reduced oxidative stress and, for certain mol ecules, direct inhibition of platelet activation and aggregation.

Glucose-Lowering and the Risk of Cardiovascular Events With Antidiabetic Therapies: A Systematic Review and Additive-Effects Network Meta-Analysis.

Aim: To assess the impact of the HbA1c levels achieved with antidiabetic therapies (ADTs) on the risk of MACE. Methods: A systematic search was performed in PubMed, Cochrane, and ClinicalTrials. gov for RCTs published up to March 2022 reporting the occurrence of MACE and all-cause mortality in individuals with T2DM treated with all marketed ADTs, including a sample size ≥100 individuals in each study arm and follow-up ≥24 weeks. A systematic review and additive-effects network meta-analysis with random effects and a multivariate meta-regression were utilized to assess the impact of achieved HbA1c on incident MACE. Results: We included 126 RCTs with 143 treatment arms, 270,874 individuals, and 740,295 individuals-years who were randomized to an active treatment vs. control group. Among all ADTs, only therapy with SGLT2i, GLP1-RA, or pioglitazone similarly reduced the risk of MACE compared to placebo. The achievement of HbA1c ≤ 7.0% in RCTs with the 3 drug classes in the active arm was associated with an adjusted HR of 0.91 (95% CI 0.80, 0.97; p = 0.017) compared with HbA1c>7.0%, without affecting all-cause mortality. These results, however, were not maintained among all ADTs. Conclusions: Achieving lower glucose levels with SGLT2i, GLP1-RA, or pioglitazone is linearly associated with a reduced risk of MACEs, without affecting all-cause mortality. Systematic Review Registration: www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020213127, identifier: CRD42020213127.

Latin American Expert Consensus for Comprehensive Management of Type 2 Diabetes from a Metabolic-Cardio-Renal Perspective for the Primary Care Physician.

Growing scientific evidence from studies on type 2 diabetes (T2D) has recently led to a better understanding of the associated metabolic-cardio-renal risks. The large amount of available information makes it essential to have a practical guide that summarizes the recommendations for the initial management of patients with T2D, integrating different aspects of endocrinology, cardiology, and nephrology. The expert consensus presented here does not attempt to summarize all the evidence in this regard but rather attempts to define practical summary recommendations for the primary care physician to improve the clinical prognosis and management of patients with T2D, while ensuring economic sustainability of health systems, beyond glycemic control.

Antidiabéticos en Insuficiencia Cardíaca

Resumen: Introducción: La insuficiencia cardíaca se reconoce como una enfermedad sistémica, por lo que se debe hacer un abordaje holístico y no enfocado exclusivamente a la falla cardíaca. La insuficiencia cardíaca se asocia con múltiples comorbilidades, siendo la diabetes mellitus una de las más frecuentes, estas comparten procesos fisiopatológicos con un comportamiento bidireccional, donde la mala evolución de una puede afectar a la otra. Por tanto, al considerar el tratamiento farmacológico de una de ellas, hay que tener en cuenta que el mismo no sea deletéreo para la otra. En los últimos años se requiere que cualquier tratamiento antidiabético tenga un efecto beneficioso o neutro a nivel cardiovascular. Este hecho es el constante desafío clínico al que el médico se enfrenta en estos pacientes. El objetivo de esta revisión es hacer una puesta a punto de la mejor evidencia disponible en el uso de los antidiabéticos en pacientes con insuficiencia cardíaca. Métodos: Se realizó una revisión sistemática de los principales estudios observacionales, ensayos clínicos, revisiones y metaanálisis publicados del uso de antidiabéticos y efecto cardiovascular, hasta diciembre del 2020, utilizando la base de datos de Pubmed y ScienceDirect. Conclusiones: De la revisión realizada se puede concluir que el fármaco de primera línea en pacientes con diabetes e insuficiencia cardíaca es la metformina, compartiendo este primer eslabón con los iSGLT2 (Empagliflozina, Canagliflozina y Dapagliflozina), según la última evidencia disponible, los que han demostrado ser eficaces en la reducción de las hospitalizaciones por insuficiencia cardíaca entre los pacientes con o sin diabetes y muerte cardiovascular, recientes estudios extienden además beneficio a los pacientes que también asocian enfermedad renal crónica.

Abstract: Introduction: Heart failure is recognized as a systemic disease, thus a holistic approach that is not exclusively focused on heart failure should be used. Heart failure is associated with multiple comorbidities, being diabetes mellitus one of the most frequent. These share pathophysiological processes with a bidirectional behavior, where the poor evolution of one can affect the other. Therefore, when considering the pharmacological treatment of one of them, it must be taken into account that it should not be detrimental to the other. In recent years, any antidiabetic treatment is required to have either a beneficial or a neutral effect at the cardiovascular level. This fact is the constant clinical challenge that physicians have to deal with when treating these patients. The objective of this review is to refine the best available evidence on the use of antidiabetic agents in patients with heart failure. Methods: A systematic review of the main observational studies, clinical trials, reviews and meta-analysis published on the use of antidiabetics agents and cardiovascular effect was carried out until December 2020, using Pubmed and ScienceDirect databases. Conclusions: From the review carried out, it can be concluded that the first-line drug for patients with diabetes and heart failure is metformin. This first link is shared with iSGLT2 (Empagliflozin, Canagliflozin and Dapagliflozin), according to the latest available evidence, which have been proven to be effective in reducing hospitalizations for heart failure among patients with or without diabetes and cardiovascular death. Recent studies also extend benefits to patients who are also associated with chronic kidney disease.

Resumo: Introdução: A insuficiência cardíaca é reconhecida como uma doença sistêmica, portanto, uma abordagem holística deve ser feita e não focada exclusivamente na insuficiência cardíaca. A insuficiência cardíaca está associada a múltiplas comorbidades, o diabetes mellitus uma das mais frequentes, pois compartilham processos fisiopatológicos com comportamento bidirecional, onde a má evolução de um pode afetar o outro. Portanto, ao se considerar o tratamento farmacológico de um deles, deve-se levar em consideração que não é prejudicial ao outro. Nos últimos anos, qualquer tratamento antidiabético é necessário para ter um efeito benéfico ou neutro no nível cardiovascular. Esse fato é o constante desafio clínico que o médico enfrenta nesses pacientes. O objetivo desta revisão é fazer uma pesquisa das melhores evidências disponíveis sobre o uso de anti-diabeticos em pacientes com insuficiência cardíaca. Métodos: Foi realizada uma revisão sistemática dos principais estudos observacionais, ensaios clínicos, revisões e metanálises sobre o uso de antidiabéticos e efeito cardiovascular, até dezembro de 2020, nas bases de dados Pubmed e ScienceDirect. Conclusões: A partir da revisão realizada, pode-se concluir que o medicamento de primeira linha em pacientes com diabetes e insuficiência cardíaca é a metformina, compartilhando esta primeira linha com o iSGLT2 (Empagliflozin, Canagliflozin e Dapagliflozin), de acordo com as últimas evidências disponíveis, para aqueles que se mostraram eficazes na redução de hospitalizações por insuficiência cardíaca entre pacientes com ou sem diabetes e morte cardiovascular, estudos recentes também estendem o benefício a pacientes que também associam doença renal crônica.

Activation of AMPK by Medicinal Plants and Natural Products: Its Role in Type 2 Diabetes Mellitus.

Type-2 Diabetes (T2D) is a metabolic disease characterized by permanent hyperglycemia, whose development can be prevented or delayed by using therapeutic agents and implementing lifestyle changes. Some therapeutic alternatives include regulation of glycemia through modulation of different mediators and enzymes, such as AMP-activated protein kinase (AMPK), a highly relevant cellular energy sensor for metabolic homeostasis regulation, with particular relevance in the modulation of liver and muscle insulin sensitivity. This makes it a potential therapeutic target for antidiabetic drugs. In fact, some of them are standard drugs used for treatment of T2D, such as biguanides and thiazolidindiones. In this review, we compile the principal natural products that are activators of AMPK and their effect on glucose metabolism, which could make them candidates as future antidiabetic agents. Phenolics such as flavonoids and resveratrol, alkaloids such as berberine, and some saponins are potential natural activators of AMPK with a potential future as antidiabetic drugs.

Hipoglucemia grave en pacientes con diabetes mellitus 2 y azoados normales / Severe hypoglycemia in patients with diabetes mellitus type 2 and normal creatinine serum values

Resumen: ANTECEDENTES: la hipoglucemia grave es causa frecuente de hospitalización en México. OBJETIVO: identificar las características clínicas y de laboratorio asociadas con hipoglucemia grave en pacientes consecutivos con hipoglucemia grave y azoados normales. PACIENTES Y MÉTODO: estudio prospectivo en el que del 11 agosto de 2011 al 31 mayo de 2013 se incluyeron pacientes con hipoglucemia grave y creatinina normal. Se registró edad, sexo, tiempo de evolución de la diabetes mellitus, tratamiento antidiabético, comorbilidades y depuración de creatinina en orina de 24 horas. RESULTADOS: ingresaron 234 pacientes con hipoglucemia grave, 21 9% tenían creatinina normal: 13 mujeres 62% y 8 38% hombres, con edad promedio de 64.76 años límites: 42-84; 13 62% eran mayores de 60 años; 15 71% tenían más de 5 años con diabetes mellitus 2 promedio de evolución de 9.2 años; 15 recibían glibenclamida 71%, 4 en combinación con insulina 19% y 8 con metformina 38%; 2 recibían rosiglitazona más insulina. Cuatro no tenían comorbilidades 19%; 14 tenían hipertensión arterial 71% y 3 neoplasia adenocarcinoma, carcinoma gástrico y carcinoma esofágico; 11 52% ingresaron con pérdida del estado de alerta; 5 con desorientación 24%, 4 con trastornos de conducta 19%, uno con dislalia 5%; 15 de 21 71% tenían grado avanzado de deterioro renal, a pesar de tener azoados normales. CONCLUSIONES: es importante determinar la depuración de creatinina en todos los niveles de atención, única guía para prescribir tratamientos seguros de acuerdo con la función renal. La glibenclamida debe prescribirse con cautela en adultos mayores, con más de 10 años de evolución de la diabetes mellitus 2 y evitarse en los sujetos con insuficiencia renal crónica documentada.

Abstract: BACKGROUND: Severe hypoglycemia is a frequent cause of hospitalization in Mexico. OBJECTIVE: To identify the clinical and laboratory characteristics associated to severe hypoglycemia in consecutive patients with severe hypoglycemia and normal creatinine serum values. PATIENTS AND METHOD: A prospective study was done from August 11, 2011 to May 31, 2013, including patients with severe hypoglycemia and normal creatinine serum values. Age, sex, time of evolution of diabetes mellitus 2, antidiabetic treatment, comorbidities and 24-hour urine creatinine clearance were recorded. RESULTS: From 234 patients with severe hypoglycemia admitted, 21 9% had normal creatinine: 13 women 62% and 8 38% men, with a mean age of 64.76 years range: 42-84; 13 62% were older than 60 years; 15 71% had more than 5 years with DM2 mean evolution of 9.2 years; 15 received glibenclamide 71%, 4 in combination with insulin 19% and 8 with metformin 38%. Two received rosiglitazone plus insulin. Four patients had not comorbidities 19%; 16 had arterial hypertension 71% and 3, neoplasms adenocarcinoma, gastric carcinoma and esophageal carcinoma. Eleven patients 52% were admitted with syncope, 5 with disorientation 24%, 4 with conduct disorders 19% and one with dyslalia 5%; 15 of 21 patients 71% had advanced degrees of renal impairment, despite normal creatinine serum values. CONCLUSIONS: It is important to perform creatinine clearance at all levels of care, the only guide for safe treatments according to kidney function. Glibenclamide should be cautiously prescribed in older adults with a history of more than 10 years of diabetes mellitus 2 and should be avoided in those with documented chronic renal failure.

Moieties in antidiabetic drugs as a target of insulin receptors in association with common neurological disorders.

Insulin is a peptide that can be harmful with regards to neuroplasticity, neuroprotection and neuromodulation. Furthermore, the role of insulin highlights its relevance in the progress of diverse clinical disorders as well as in the mechanisms associated with certain pathogenesis and their evolution towards diabetes, obesity and neurodegenerative diseases. The precise molecular mechanisms by which these diseases are induced remain to be elucidated. The benefits in knowing/discovering these mechanisms in animal models and humans cannot be undermined. An in depth understanding of the principal risk factors leading to obesity and their management is vital in the implementation of early-life strategies of intervention and prevention, with a view to avoid adverse late-life outcomes. Therefore, the aim of the present study was to review their possible association with antidiabetic drugs.

Management of diabetes mellitus in individuals with chronic kidney disease: therapeutic perspectives and glycemic control

The purpose of this study was to evaluate the therapeutic options for diabetes treatment and their potential side effects, in addition to analyzing the risks and benefits of tight glycemic control in patients with diabetic kidney disease. For this review, a search was performed using several pre-defined keyword combinations and their equivalents: “diabetes kidney disease” and “renal failure” in combination with “diabetes treatment” and “oral antidiabetic drugs” or “oral hypoglycemic agents.” The search was performed in PubMed, Endocrine Abstracts and the Cochrane Library from January 1980 up to January 2015. Diabetes treatment in patients with diabetic kidney disease is challenging, in part because of progression of renal failure-related changes in insulin signaling, glucose transport and metabolism, favoring both hyperglycemic peaks and hypoglycemia. Additionally, the decline in renal function impairs the clearance and metabolism of antidiabetic agents and insulin, frequently requiring reassessment of prescriptions. The management of hyperglycemia in patients with diabetic kidney disease is even more difficult, requiring adjustment of antidiabetic agents and insulin doses. The health team responsible for the follow-up of these patients should be vigilant and prepared to make such changes; however, unfortunately, there are few guidelines addressing the nuances of the management of this specific population.

Simultaneous determination of oral antidiabetic drugs in human plasma using microextraction by packed sorbent and high-performance liquid chromatography.

In this study, a simple method using microextraction by packed sorbent and high-performance liquid chromatography with ultraviolet detection for simultaneous determination of chlorpropamide, gliclazide and glimepiride in human plasma was developed and validated. A fractional factorial design and a complete factorial design were applied to evaluate the parameters which could affect the extraction and desorption steps, respectively. All parameters in the extraction step (pH, sample volume, sample dilution and number of aspiration/ejection cycles) and in the desorption step (percentage of acetonitrile in the elution solvent and number of aspirations of elution solvent through the device) were statistically significant (p>0.05) when recovery was used as response. The developed method allowed the use of small volumes of sample and solvents and rapid separation by using a fused core column (only 2.2min were needed). This method was fully validated showing selectivity, precision, accuracy and linearity over the range 1.0-50.0µgmL(-1) for chlorpropamide, 1.0-10.0µgmL(-1) for gliclazide and 0.1-1.0µgmL(-1) for glimepiride. Finally, the validated method was applied in the analysis of samples from volunteers containing the three tested analytes.

Adesão aos antidiabéticos orais: prevalência e fatores associados

Objetivo: Avaliar a prevalência de adesãomedicamentosa aos antidiabéticos orais (ADO) emindivíduos com diabetes mellitus tipo 2 (DM2), suarelação com variáveis sociodemográficas, clínicas,laboratoriais e com outros métodos indiretos utilizadospara inferir adesão.Método: Estudo observacional, descritivo,apresentando dois cortes transversais com 25 a 50 diasde intervalo, em 36 pacientes em tratamento com ADOhá mais de 2 meses nos ambulatórios do HU-UFSC.Entre as entrevistas, realizou-se a contagem doscomprimidos ADO utilizados. Os pacientes foramconsiderados aderentes quando houve o uso de 80% a110% dos comprimidos prescritos. Foram avaliados dadossociodemográficos, clínicos e antropométricos, exameslaboratoriais, relato de adesão (auto-afirmação e testede Morisky), controle glicêmico e conhecimento sobreADO em uso.Resultados: Metade dos pacientes aderiu aotratamento. A adesão não apresentou relação com fatoressociodemográficos ou com relato dos pacientes. A máadesão foi associada com história de uso de álcool(p=0,045), tratamento há menos de 2 anos (p=0,0029) edesconhecimento dos ADO em uso (p=0,04). Adequadaadesão medicamentosa foi associada com média depressão arterial (PA) até 130/80 mmHg (p=0,044),glicemia capilar casual com valor máximo até 140 mg/dL (p=0,018), valor de hemoglobina glicada (HbA1c) até7% (p=0,044) e até 8% (p=0,0008).Conclusão: O tratamento medicamentoso apresentaalta taxa de má-adesão. Tempo de tratamento, históriade etilismo e controle da PA influenciam a adesãomedicamentosa. Ao contrário do relato de adesão,conhecimento sobre medicação em uso, valores deHbA1c e glicemias capilares são métodos indiretos quese associam com adesão medicamentosa.

Objective: To identify, in patients with diabetesmellitus type 2, the prevalence of adherence to oralantidiabetic drugs (OAD) therapy and relate it with socialdemographic,clinical and laboratorial aspects, as wellas with other indirect methods of adherence measure.Method: Observational, descriptive and crosssectionalstudy with 36 patients who were undergoingtreatment for at least 2 months, at clinics from HU-UFSC.The method used was pill counts between two interviewsdistanced 25 to 50 days. Patients with use of 80% to110% of prescribed pills were classified as adherents.The study analyzed social-demographic, clinical,anthropometric and laboratorial variables, adherencereport (self-report and Morisky et al. test), glicemiccontrol and OAD knowledge.Results: Half of the patients were adherent totreatment. There were no significant differences betweenadherence and social-demographic variables. History ofalcohol consumption was related with poor adherence(p=0,045), as well as use of OAD for less than 2 years(p=0,0029) and ignoring OAD names (p=0,04). Greateradherence was identified in patients with mean of bloodpressure (BP) until 130/80 mmHg (p=0,044), maximumcasual capillary glucose until 140 mg/dL and glycatedhemoglobin values less than 7% (p=0,044) and less than8% (p=0,0008).Conclusions: There is a high rate of non-adherenceto OAD therapy. Years of treatment, history of alcoholconsumption and BP control interfere in adherence.Knowledge of OAD?s names, values of glycatedhemoglobin and casual capillary glucose are indirectmethods associated with adherence.

Aspectos clínicos e farmacológicos do emprego do exenatide na terapêutica do diabetes mellitus tipo 2 / Clinical and pharmacological aspects of the use of exenatide for the treatment of type II diabetes mellitus

O papel do exenatide no tratamento do diabetes mellitus tipo 2 tem sido foco de intensa pesquisa. Este fármaco age como um agonista do glucagon-like peptide 1 (GLP-1), interagindo com o receptor GLP-1, estimulando a secreção de insulina pelas células ß. O exenatide também tem se mostrado altamente eficaz na redução da secreção do glucagon, esvaziamento gástrico e ingestão alimentar. Esta revisão apresenta os principais aspectos clínicos e farmacológicos do uso do exenatide em pacientes diabéticos tipo 2. Assim, concluiu-se que o exenatide representa um novo fármaco antidiabético, uma vez que estimula a secreção de insulina por um mecanismo diferente do apresentado pelas sulfoniluréias e metiglinidas (bloqueadores de canais de potássio). Além disso, enquanto todos secretagogos de insulina (incluindo os inibidores da dipepdil peptidase-4) promovem ganho de peso, o exenatide, ao contrário, favorece a perda de peso, por sua ação inibidora do apetite.

The role of exenatide in the treatment of type II Diabetes Mellitus has become the focus of intense research. This drug works as a glucagon-like peptide 1 (GLP-1) agonist as it interacts with GLP-1 receptor through the stimulation of the insulin secretion in ß cells. The exenatide also has presented to be highly effective to reduce glucagon secretion, gastric emptiness, and food intake. This review shows the major clinical and pharmacological aspects of using exenatide in type II Diabetes Mellitus patients. Thus, it was concluded that exenatide is a new antidiabetic drug; since exenatide stimulates insulin secretion by a different mechanism of sulfonylureas and metiglinides (potassium channels blockers). Moreover, in spite of the fact that all insulin secretagogues (including the dipeptidyl peptidase-4 inhibitors) in contrast exenatide promotes weight gain mediated by its inhibitory appetite action.

Influência do tratamento com metformina sobre a tolerância à glicose induzida por corticosteróides em ratos Wistar / Influence of metformin treatment on glucose tolerance induced by corticosteroid administration in rats Wistar

Corticóides induzem um estado de intolerância à glicose, resistência à insulina e hiperglicemia. Este trabalho teve por objetivo avaliar a participação de corticosteróides endógenos sobre a hiperglicemia aguda em modelo experimental de intolerância à glicose induzida por dexametasona (0,1 mg kg-1, s.c., 4 dias). O modelo experimental foi caracterizado pela determinação da concentração de glicose sanguínea, volume urinário de 24 horas, consumo de ração e água. Os ratos foram tratados com clorpropamida (100 mg kg-1), metformina (300 mg kg-1) ou pioglitazona (10 mg kg-1) durante 4 dias e o efeito do tratamento foi avaliado pelo teste de tolerância à glicose endovenoso (GTT). A adrenalectomia corrigiu o quadro de intolerância à glicose destes animais, demonstrando que a dexametasona promove hiperglicemia por meio de um provável efeito sinérgico sobre os corticosteróides endógenos. O tratamento com metformina reduziu a alteração glicêmica. Nossos resultados sugerem um efeito benéfico na utilização da metformina como profilático no uso de corticóides em pacientes hiperglicêmicos.

This work evaluated the effect of the corticosteroid administration on glucose intolerance state induced by dexamethasone (0.1 mg kg-1, s.c., 4 days). The experimental model was characterized through blood and urine glucose levels determination, 24 hour urinary volume, food and water intake. The rats were treated with chlorpropamide (100 mg kg-1), metformin (300 mg kg-1) or pioglitazone (10 mg kg-1) during 4 days. The effect of adrenalectomy or the drugs treatment effectiveness on hyperglycemia state were evaluated during intravenous GTT. Metformin treatment restored the altered hyperglycemia observed in this experimental model. Results suggest that dexamethasone promotes a hyperglycemia state through a synergic effect on endogenous corticosteroids, and that metformin treatment restores these altered responses. Indeed, the dexamethasone induced insulin resistance in humans, promoting hyperglycemia, which should be avoid by the prophylactic administration of metformin.