Terapia basada en incretinas para control glucémico de los pacientes hospitalizados con diabetes tipo 2: una revisión sistemática / Incretin-based therapy for glycemic control of hospitalized patients with type 2 diabetes: a systematic review

La terapia basada en incretinas lleva al control glucémico de una manera dependiente de glucosa con un bajo riesgo de hipoglucemia, por lo que resulta atractiva para su uso hospitalario. El objetivo de esta revisión sistemática fue evaluar los beneficios de la terapia basada en incretinas en pacientes con diabetes tipo 2 hospitalizados fuera de la unidad de cuidados intensivos. Se buscaron estudios publicados hasta agosto de 2021 en las bases de datos PubMed y Scopus. Se seleccionaron los ensayos clínicos que comparaban la terapia basada en incretinas (sola o en combinación con insulina) versus el régimen con insulina. Los resultados de los estudios incluidos mostraron que la terapia basada en incretinas registró un promedio de glucosa sanguínea, un porcentaje de registros dentro de meta terapéutica y un porcentaje de falla al tratamiento similar al manejo con insulina, particularmente en pacientes con hiperglucemia leve a moderada. Además, el tratamiento basado en incretinas se asoció con una menor dosis total de insulina y una menor incidencia de hipoglucemia. En conclusión, la terapia basada en incretinas logró un control glucémico similar al tratamiento con insulina en los pacientes con diabetes tipo 2 hospitalizados fuera de la unidad de cuidados intensivos, con la ventaja de disminuir el requerimiento insulínico y con menor riesgo de hipoglucemia (AU)

Incretin-based therapy leads to glycemic control in a glucose-dependent manner with a low risk of hypoglycemia, making it appealing for use in the hospital. The aim of this systematic review was to assess the benefits of incretin-based therapy in patients with type 2 diabetes hospitalized outside of the intensive care unit. We searched for studies published up to August 2021 in the PubMed and Scopus databases. Clinical trials comparing incretin-based therapy (alone or in combination with insulin) versus an insulin regimen were selected. The results of the included studies showed that incretin-based therapy showed mean blood glucose values, a percentage of records within the therapeutic target, and a percentage of treatment failure similar to insulin management, particularly in patients with mild to moderate hyperglycemia. Furthermore, incretin-based treatment was associated with a lower total insulin dose and a lower incidence of hypoglycemia. In conclusion, incretin-based therapy achieved glycemic control similar to insulin treatment in patients with type 2 diabetes hospitalized outside the intensive care unit and has the advantages of reducing the insulin requirement and a lower risk of hypoglycemia (AU)

Incretin-based therapy for glycemic control of hospitalized patients with type 2 diabetes: a systematic review.

Incretin-based therapy leads to glycemic control in a glucose-dependent manner with a low risk of hypoglycemia, making it appealing for use in the hospital. The aim of this systematic review was to assess the benefits of incretin-based therapy in patients with type 2 diabetes hospitalized outside of the intensive care unit. We searched for studies published up to August 2021 in the PubMed and Scopus databases. Clinical trials comparing incretin-based therapy (alone or in combination with insulin) versus an insulin regimen were selected. The results of the included studies showed that incretin-based therapy showed mean blood glucose values, a percentage of records within the therapeutic target, and a percentage of treatment failure similar to insulin management, particularly in patients with mild to moderate hyperglycemia. Furthermore, incretin-based treatment was associated with a lower total insulin dose and a lower incidence of hypoglycemia. In conclusion, incretin-based therapy achieved glycemic control similar to insulin treatment in patients with type 2 diabetes hospitalized outside the intensive care unit and has the advantages of reducing the insulin requirement and a lower risk of hypoglycemia.

Immunohistochemical detection of l cells in gastrointestinal tract mucosa of patients after surgical treatment for control of type 2 diabetes mellitus / Detecção imunohistoquímica de células l na mucosa do trato gastrointestinal de pacientes após tratamento cirúrgico para controle de diabetes mellitus tipo 2

ABSTRACT - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a disease of global impact that has led to an increase in comorbidities and mortality in several countries. Immunoexpression of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and peptide YY (3-36) (PYY3-36) can be used as a scorer in the gastrointestinal tract to analyze L-cell activity in response to T2DM treatment. OBJECTIVE: This study aimed to investigate the presence, location, and secretion of L cells in the small intestine of patients undergoing the form of bariatric surgery denominated adaptive gastroenteromentectomy with partial bipartition. METHODS: Immunohistochemical assays, quantitative real-time polymerase chain reaction (qPCR), and Western blot analysis were performed on samples of intestinal mucosa from patients with T2DM in both the preoperative and postoperative periods. RESULTS: All results were consistent and indicated basal expression and secretion of GLP-1 and PYY3-36 incretins by L cells. A greater density of cells was demonstrated in the most distal portions of the small intestine. No significant difference was found between GLP-1 and PYY3-36 expression levels in the preoperative and postoperative periods because of prolonged fasting during which the samples were collected. CONCLUSION: The greater number of L cells in activity implies better peptide signaling, response, and functioning of the neuroendocrine system.

RESUMO - RACIONAL: O diabetes tipo 2 (DM2) é uma doença de impacto mundial que tem levado ao aumento de comorbidades e mortalidade em vários países. A imunoexpressão dos hormônios incretínicos glp-1 e pyy3-36, pode ser usada como marcador no trato gastrointestinal para analisar a atividade da célula L em resposta ao tratamento do DM2. OBJETIVO: O presente estudo teve como objetivo investigar a presença, localização e secreção de células L no intestino delgado de pacientes submetidos à forma de cirurgia bariátrica denominada gastroenteromentectomia adaptativa com bipartição parcial. MÉTODOS: Ensaios imunohistoquímicos, reação quantitativa em cadeia de polimerase em tempo real (qPCR) e análise de manchas ocidentais foram realizados em amostras de mucosa intestinal de pacientes com diabetes tipo 2 nos períodos pré- e pós-operatório. RESULTADOS: Todos os resultados foram consistentes e indicaram expressão basal e secreção de peptídeos glucagon-1 (GLP-1) e peptídeos YY (PYY3-36) incretinas por células L. Uma maior densidade de células foi demonstrada nas porções mais distais do intestino delgado. Não foi encontrada diferença significativa entre os níveis de expressão GLP-1 e PYY3-36 nos períodos pré-operatório e pós-operatório, provavelmente devido ao estado de jejum prolongado durante o qual as amostras foram coletadas CONCLUSÃO: O maior número de células L em atividade implica melhor sinalização de peptídeo, resposta e funcionamento do sistema neuroendócrino.

A novel surgical technique focused on the study of the ileum: The preduodenal ileal transposition.

AIMS: Our main goal is to study the effects on the carbohydrate metabolism. Thus, we designed various experimental surgical models on healthy non-obese Wistar rats to reproduce several conditions. In this sense, we report a new experimental model. It is well known that bariatric surgery has important effects on the control of Type 2 Diabetes Mellitus. The underlying reasons are yet unknown, although the different theories focused in the release of different hormones after the pass of the nutrients through the tract. These released hormones have opposite effects that come together in a balanced glycemic metabolism. MATERIALS AND METHODS: After bariatric surgical techniques, the modified anatomy resulted in an imbalance of the secreted hormones. Wistar rats were randomized in two groups Sham and surgical group. Our model consisted on the transposition of the terminal ileum right after the pylorus. Weight gain, food intake, and basal glycemia were measured weekly. RESULTS: We did not obtain significant differences between both groups for these functional variables. CONCLUSIONS: This technique involved an early pass of the bolus through the ileum. The change on the luminal pH, along with the lack of enzymes to absorb the content, or the changes in the release of several hormones must be variables to the study. The mortality rate was assumable considering it was an experimental model on animals.

OBJETIVO: Crear un nuevo modelo quirúrgico experimental en ratas Wistar sanas no obesas para estudiar los efectos del metabolismo glucídico. Es bien sabido que las técnicas de cirugía bariátrica tienen un efecto importante sobre la resolución de la diabetes mellitus tipo 2. Se han invocado diferentes hipótesis, algunas centradas en el papel que tienen distintas hormonas secretadas por el propio tubo digestivo tras el paso de los nutrientes a su través, pero las razones últimas subyacentes permanecen desconocidas. El efecto contrapuesto de dichas hormonas consigue un efecto de control glucémico. El desequilibrio hormonal tras las alteraciones anatómicas de las cirugías bariátricas podría estar en la base de dicha mejora del metabolismo glucídico final. MATERIAL Y MÉTODOS: Las ratas fueron operadas en dos grupos (control quirúrgico y experimental) y se procedió a disponerles el íleon anastomosado al antro pilórico, previo al esfínter pilórico. Medimos distintos parámetros funcionales (ganancia de peso, ingesta y glucemias semanales). RESULTADOS: No obtuvimos diferencias significativas en la evolución de estos parámetros. CONCLUSIONES: Este modelo será útil para nuestro propósito de estudiar el íleon, en su componente secretor de enterohormonas, cuando el paso de los nutrientes se produzca tempranamente. La mortalidad fue asumible, dada la innovación técnica realizada.

When does diabetes start? Early detection and intervention in type2 diabetes mellitus. / ¿Cuándo empieza la diabetes? Detección e intervención tempranas en diabetes mellitus tipo 2.

Type 2 diabetes mellitus (DM2) is a progressive disease whose pathophysiological changes occur several years before its detection. An approach based on the pathophysiological development of DM2 and its complications emphasises the importance of early and intensive intervention, not only to prevent beta-cell dysfunction but also to act on the potential associated cardiovascular risk factors before reaching the blood glucose thresholds currently set for diagnosing DM2. In the field of recently diagnosed DM2, the VERIFY study has shown that early treatment combined with metformin-vildagliptin provides relevant improvements in long-term glycaemic control and can positively affect the disease's progression.

Importance of the gastrointestinal tract in type 2 diabetes. Metabolic surgery is more than just incretin effect. / Importancia del tracto gastrointestinal en la diabetes de tipo 2. La cirugía metabólica es más que incretinas.

Bariatric and metabolic surgery is creating new concepts about how the intestine assimilates food. Recent studies highlight the role of the gastrointestinal tract in the genesis and evolution of type 2 diabetes. This article has been written to answer frequent questions about metabolic surgery results and the mechanisms of action. For this purpose, a non-systematic search of different databases was carried out, identifying articles published in the last decade referring to the mechanisms of action of metabolic techniques. Understanding these mechanisms will help grasp why some surgeries are more effective than others and why the results can be so disparate among patients undergoing the same surgical approach.

[Use of dipeptidyl peptidase-4 inhibitors in diabetic patients in special situations]. / Uso de inhibidores de la dipeptidil peptidasa 4 en pacientes con diabetes en situaciones especiales.

Dipeptidyl peptidase-4 inhibitors form part of the group of incretin derivatives and conse-quently have a specific mechanism of action. The incretin effect avoids the adverse ef-fects of classic drugs (sulphonylureas) and provides specific benefits for their use in as-sociation with other drugs and in special situations. Because they have a low risk of pro-ducing hypoglycaemia or weight gain, these inhibitors are useful in combination with other oral antidiabetic drugs and even with insulin, although this latter combination may increase the risk of hypoglycaemia. Large studies of cardiovascular non-inferiority have reported that dipeptidyl peptidase-4 inhibitors are non-inferior to placebo, although one drug (saxagliptin) may increase the risk of hospital admission for heart failure. Because of these cardiovascular advantages, even in peripheral arterial disease, their usefulness in diabetic retinopathy, and their low risk of hypoglycaemia in renal insufficiency, dipeptidyl peptidase-4 inhibitors are the drugs of choice in elderly patients. Given the risk, although still not well defined, these drugs are not recommended in pa-tients with a history or risk of pancreatic disease, in children, in patients with type 1 diabetes, in adolescents, or in pregnant or breastfeeding women. Each of these special situ-ations is discussed in the present article.

Manejo de pacientes diabéticos hospitalizados / Management of diabetes in hospitals

Resumen La diabetes es una enfermedad con importante prevalencia en todo el mundo. Se calcula que cerca de 415 millones de personas la padecen en la actualidad y que para el año 2040 esta cifra aumentará poco más del 50%. Debido a esto, se estima que gran parte de los ingresos por urgencias serán de pacientes diabéticos o sujetos a los cuales esta patología se les diagnosticará en dicha hospitalización; esta situación hace necesario conocer los lineamientos y las recomendaciones de las guías para el manejo intrahospitalario de los pacientes con hiperglucemia. El pilar fundamental del manejo hospitalario de diabetes es la monitorización intensiva, junto con la educación al paciente y la administración de insulina. El control glicémico es clave debido a que disminuye complicaciones intrahospitalarias. Cabe resaltar que el control estricto puede llevar a hipoglucemias, por lo que los episodios deben ser debidamente documentados y su causa corregida de inmediato.

Abstract Diabetes is a disease with significant prevalence worldwide. According to the latest estimates, about 415 million people suffer from this condition and this figure will almost double by 2040. For this reason, a large part of emergency admissions will be related to diabetic patients or subjects who will be diagnosed with this pathology while hospitalized. Hospital-related hyperglycemia due to stress, medications and parenteral nutrition are also a common finding. In consequence, it is imperative for health care providers to become familiar with inpatient hyperglycemia management. Intensive glucose monitoring, patient education and insulin administration are essential for treating this condition. Glycemic control is fundamental as it decreases nosocomial complications. It should be noted that strict control may lead to hypoglycemia, so episodes should be properly documented and their cause corrected immediately.

Comparação dos níveis de proteína C reativa, GLP-1 e GLP-2 entre indivíduos diabéticos, obesos mórbidos e controles saudáveis: um estudo exploratório / Comparison of the levels of c-reactive protein, glp-1 and glp-2 among individuals with diabetes, morbid obesity and healthy controls: an exploratory study

ABSTRACT BACKGROUND: The glucagon-like peptides 1 and 2 (GLP-1/GLP-2) are gut hormones that may directly affect the glucose homeostasis and their activity seems to be significantly affected by chronic inflammation. OBJECTIVE: To evaluate the postprandial levels of glucagon-like peptides 1 and 2 (GLP-1/GLP-2), C-reactive protein (CRP), and the postprandial glucose and insulin levels among individuals with obesity, type 2 diabetes, and healthy controls. METHODS: An exploratory cross-sectional study, which involved individuals awaiting for bariatric/metabolic surgery and healthy controls. Postprandial levels of GLP-1, GLP-2, glucose, and insulin were obtained after a standard meal tolerance test. Inflammation was assessed by means of CRP. RESULTS: There were 30 individuals enrolled in the study, divided into three groups: non-diabetic with morbid obesity (NDO; n=11 individuals), diabetic with mild obesity (T2D; n=12 individuals), and healthy controls (C; n=7 individuals). The mean CRP levels were significantly higher in the NDO group (6.6±4.7 mg/dL) than in the T2D (3.3±2.2 mg/dL) and C groups (2.5±3.2 mg/dL) (P=0.038). The GLP-1 levels following standard meal tolerance test and the area under the curve of GLP-1 did not differ among the three groups. The GLP-2 levels were significantly lower in the NDO and T2D than in the C group following standard meal tolerance test at all the times evaluated. The area under the curve of the GLP-2 was significantly lower in the NDO and T2D groups than in the C group (P=0.05 and P=0.01, respectively). CONCLUSION: GLP-2 levels were impaired in the individuals with obesity and diabetes. This mechanism seems to be enrolled in preventing the worsening of the glucose homeostasis in these individuals.

RESUMO CONTEXTO: Os peptídeos semelhantes ao glucagon 1 e 2 (GLP-1/GLP-2) são hormônios gastrointestinais que podem afetar diretamente a homeostase glicêmica; a atividade de ambos parece ser significativamente afetada pela inflamação crônica. OBJETIVO: Avaliar os níveis pós-prandiais dos peptídeos semelhantes ao glucagon 1 e 2 (GLP-1/GLP-2), proteína C reativa (PCR) e as curvas pós-prandiais de glucose e insulina entre indivíduos com obesidade, diabetes tipo 2 e controles saudáveis. MÉTODOS: Estudo piloto transversal, que envolveu indivíduos aguardando a realização de cirurgia bariátrica/metabólica e controles saudáveis. Os níveis de GLP-1, GLP-2, glucose e insulina foram obtidos após um teste de refeição padrão. A inflamação foi avaliada através dos níveis de PCR. RESULTADOS: Houve 30 indivíduos avaliados no estudo, divididos em três grupos: obesos mórbidos sem diabetes (NDO; n=11 pacientes), diabéticos com obesidade leve (T2D; n=12 pacientes) e controles (C; n=7 pacientes). Os níveis médios de PCR foram significativamente maiores no grupo NDO (6,6±4,7 mg/dL) do que nos grupos T2D (3,3±2,2 mg/dL) e C (2,5±3,2 mg/ dL) (P=0,038). Os níveis de GLP-1 após o teste de refeição padrão e a área sob a curva do GLP-1 não diferiram significativamente entre os grupos. Os níveis de GLP-2 foram significativamente mais baixos nos grupos NDO e T2D do que no grupo C em todos os tempos avaliados. A área sob a curva do GLP-2 foi significativamente menor nos grupos NDO e T2D do que no grupo C (P=0,05 and P=0,01, respectivamente). CONCLUSÃO: Os níveis de GLP-2 encontram-se alterados em indivíduos com obesidade e diabetes. Este mecanismo parece estar envolvido na prevenção da piora da homeostase glicêmica nestes indivíduos.

Bipartición de tránsito intestinal, la nueva era de la cirugía metabólica para la diabetes mellitus de tipo 2 / Intestinal transit bipartition, the new era in metabolic surgery for type 2 diabetes

Antecedentes. La diabetes mellitus de tipo 2 es el principal reto de salud pública que enfrentamos actualmente, constituye la primera causa de discapacidad y es o está asociada a las principales causas de muerte en nuestro país. En Ciudad de México, se reportó que más del 79 % de los pacientes diabéticos no tienen cifras óptimas de HbA1c (<6,5 %), mientras que el 47 % presentan descontrol importante (HbA1c >9 %). La cirugía metabólica es el mejor tratamiento en términos de remisión, sin embargo, los mecanismos involucrados no son los tradicionalmente considerados. Objetivo. Ofrecer actualización acerca de los mecanismos involucrados en la remisión de la diabetes mellitus de tipo 2 después de la cirugía metabólica. Metodos. Se hizo una revisión bibliográfica utilizando las palabras clave en términos MeSH; hasta el 1° de junio del 2018, se encontraron 83 artículos de referencia considerados como pertinentes. Resultados. La remisión de la diabetes mellitus de tipo 2 lograda por procedimientos quirúrgicos, depende de complejas interacciones entre la microbiota, los ácidos biliares y el epitelio intestinal, más que de procesos malabsortivos o restrictivos. La bipartición de tránsito intestinal es una opción quirúrgica basada en los principios fisiológicos responsables en la remisión de la diabetes, y es la más sencilla y segura para el manejo de la diabetes mellitus. Conclusiones. La cirugía metabólica ofrece mejores tasas de remisión y control de complicaciones de la diabetes tipo 2 al modificar la secreción de enterohormonas, la concentración e interacciones de los ácidos biliares y al modificar la microbiota

Background: Diabetes mellitus type 2 (DM2) is a major public health challenge that we face today; it is the first cause of disability and is associated with the main causes of death in our country. In Mexico City, it was reported that more than 79% of diabetic patients did not have optimal levels of HbA1c (<6.5%), while 47% are not properly controlled (HbA1c> 9%). Metabolic surgery is the best treatment option for DM2, yet the presumed involved mechanisms are not traditionally considered. Objective: To provide an update on the mechanisms involved in the remission of DM2 following metabolic surgery. Methods: Narrative review of the literature, using MeSH terms, until June 1, 2018, encountering 83 articles considered pertinent. Methods: Narrative review of the literature, using MeSH terms, until June 1, 2018, encountering 83 articles considered pertinent. Results: DM2 remission after surgery depends on complex interactions between the microbiota, biliary acids and the intestinal epithelium, more so than of malabsortion or restrictive processes. Bipartition of the intestinal transit constitutes a surgical option based on the physiologic principles responsible of the remission of diabetes, and it is a simple and most secure procedure for the management of diabetes. Mechanisms include restoration/ enhancement of incretin secretion; as well as an improvement of bile acid concentration and microbiome manipulation, rather than the commonly accepted restriction and malabsorption. Intestinal transit bipartition is a novel and simple procedure that complies with the actual involved mechanisms, with comparable results in terms of safety and efficacy with the more complex and demanding techniques, such as the gastric bypass. Conclusions: Metabolic surgery is the best treatment for DM2 in terms of remission and prevention of complications, modifying the secretion of enterohormones, the concentration of biliary acids, and the modification of the microbiota

Inhibidores de la dipeptidil peptidasa 4 y una nueva estrategia farmacológica en la diabetes mellitus tipo 2 / Inhibitors of dipeptidil peptidase 4 new pharmacologic strategic in the diabetes mellitus type 2

La diabetes mellitus sigue siendo una enfermedad temible. El uso adecuado de la farmacoterapia para el control metabólico, ayudaría a disminuir la incidencia de complicaciones. Actualmente se dispone de variados grupos farmacológicos para el control temporal de las cifras de glucemias de pacientes con diabetes mellitus tipo 2, entre ellos están los inhibidores de la dipeptidil peptidasa 4 caracterizados por estimular el aumento de la concentración del péptido similar a glucagón tipo 1 GLP-1 y la secreción de insulina en la célula beta del islote pancreático. La eficacia, en términos de hemoglobina glucosilada, ha mostrado ser inferior a la de la insulina, pero sin el potencial del peligro de hipoglucemia, así como el efecto neutro o la disminución del peso corporal. Se realizó esta revisión bibliográfica con el objetivo de actualizar los conocimientos sobre el papel de las sustancias con acción incretinas en el control metabólico de los pacientes con diabetes mellitus tipo 2 y específicamente la acción de los IDPP4, ya que es creciente el problema de dicha enfermedad y se requiere, cada vez más, una mejor información de los fármacos a utilizar, aunque en el futuro los datos obtenidos concluirán su efectividad(AU)

Diabetes mellitus remains a fearsome disease. Proper use of pharmacotherapy for metabolic control, would help reduce the incidence of complications. Currently there are various pharmacological groups for temporary control of blood glycemia of patients with diabetes mellitus type 2. One of them is dipeptidyl peptidase-4 inhibitor characterized by stimulating increased concentration like peptide glucagon type 1 GLP -1 and insulin secretion in pancreatic islet beta cell. The effectiveness in terms of glycosylated hemoglobin has shown to be less than that of insulin, but without the potential danger of hypoglycaemia and the neutral effect or decrease in body weight. These facts prompt this literature review which was conducted to update the knowledge on the role of substances with incretin action in the metabolic control of patients with diabetes mellitus type 2, specifically the action of IDPP4, as this disease is an growing problem requiring better information on drug use(AU)

Inhibidores de dipeptidil dipeptidasa-IV: de la teoría a la práctica / Dipeptidil dipeptidase-IV inhibidors: from the theory to the practice

Esta revisión de los inhibidores de dipeptidil peptidasa-IV busca motivar el uso racional de tal grupo farmacológico en la práctica diaria. Este grupo es una nueva opción terapéutica en monoterapia o terapia combinada para el tratamiento de los pacientes con diabetes mellitus tipo 2. En Colombia, se encuentran disponibles: sitagliptina, vildagliptina, saxagliptina y linagliptina. Si bien todas las gliptinas tienen el mismo mecanismo de acción-aumentan la vida media del péptido similar al glucagón-, esta revisión presenta las diferencias entre sus propiedades farmacológicas, eventos adversos y perfil de seguridad. Estos medicamentos son de segunda o tercera línea para el tratamiento oral de los pacientes con diabetes mellitus tipo 2, o primera línea en los pacientes intolerantes a la metformina. Además, algunas de las ventajas que tienen son que: generan menor riesgo de hipoglucemia, tienen efecto neutro sobre el peso, son seguros en adultos mayores, disminuyen la variabilidad de la glucemia y, adicionalmente, se pueden utilizar en la enfermedad renal crónica avanzada, con o sin terapia de reemplazo renal, y en la insuficiencia hepática.

This review of dipeptidyl peptidase-IV inhibitors seeks to encourage the rational use of these drugs in daily practice; this group is a new therapeutic option in monotherapy or combination therapy for the treatment of patients with diabetes mellitus type 2. Sitagliptin, vildagliptin, saxagliptin and linagliptin are available in Colombia. While all gliptins have the same mechanism of action-they increase the average life of glucagon-like peptide-, this review presents the differences among their pharmacological properties, adverse events and safety profile. These drugs are second or third-line for the oral treatment of patients with diabetes mellitus type 2, or first-line in patients intolerant to metformin. They also have some advantages like lower risk of hypoglycemia, neutral effect on weight, safety for the elderly, reduction of glycaemia variability; additionally, they can be used in advanced chronic kidney disease, with or without renal replacement therapy, and in liver failure.

Vaciamiento gástrico y diabetes mellitus tipo 2 / Gastric emptying and Type 2 diabetes mellitus

El adecuado control de la diabetes mellitus tiene una gran importancia desde muchos puntos de vista. En los últimos años, se ha destacado el impacto que tienen los niveles de la glucemia postprandial sobre el manejo y las complicaciones de esta enfermedad. Controlar la hiperglucemia postprandial y, por lo tanto, su participación en el deterioro clínico de los pacientes con diabetes puede conseguirse retardando el vaciamiento gástrico y estimulando el efecto incretina, los cuales se pueden promover utilizando los análogos del péptido similar al glucagón tipo 1 (GLP-1). En este artículo se revisa el concepto del efecto incretina y la utilidad de los análogos GLP-1 en el control de la glicemia en los pacientes con diabetes mellitus tipo 2.

Proper control of diabetes mellitus is very important from many points of view. In recent years, the impact of postprandial blood glucose levels on the treatment and complications of this disease has been highlighted. Controlling postprandial hyperglycemia-and, therefore, its participation in the clinical deterioration of patients with diabetes-can be achieved by delaying gastric emptying and stimulating the incretin effect, which can be promoted using the analogues of glucagon-like peptide-1 (GLP-1). In this article, the concept of the incretin effect and usefulness of GLP-1 analogues for glycemic control in patients with type 2 diabetes mellitus is reviewed.

[Extrapancreatic effects of GLP-1 receptor agonists: an open window towards new treatment goals in type 2 diabetes]. / Efectos extrapancreáticos de los agonistas del receptor de GLP-1: una ventana hacia nuevos objetivos del tratamiento farmacológico de la diabetes mellitus tipo 2.

The wide ubiquity of GLP-1 receptors in the body has stimulated the search for different extrapancreatic actions of GLP-1 and its receptor agonists. Thus, severe cardioprotective effects directed on myocardial ischaemia and dysfunction as well as diverse antiaterogenic actions have been reported. Also, native and GLP-1 receptor agonists have demonstrated significant beneficial effects on liver steatosis and fibrosis and on neuronal protection in experimental models of Alzheimer, and Parkinson's disease as well as on cerebral ischaemia. Recent evidences suggest that these drugs may also be useful for prevention and treatment of diabetic retinopathy, nephropathy and peripheral neuropathy. Good results have also been reported in psoriasis. Despite we still need confirmation that these promising effects can be applied to clinical practice, they offer new interesting perspectives for treatment of type 2 diabetes associated complications and give to GLP-1 receptor agonists an even more integral position in diabetes therapy.

[Twice-daily and weekly exenatide: clinical profile of two pioneer formulations in incretin therapy]. / Exenatida diaria y semanal: perfil clínico de dos formulaciones pioneras en la modulación incretínica.

GLP-1 receptors agonists have been a substantial change in treatment of type 2 diabetes mellitus, and its weekly administration has broken pre-established schemes. Daily exenatide is administered every 12 hours (BID) subcutaneously, while weekly exenatide is administered once a week. Both molecules share a common mechanism of action but have differential effects on basal and postprandial glucose. We review the major clinical trials with both exenatide BID and weekly exenatide. It can be concluded that exenatide BID shows a hypoglycemic effect similar to other treatments for type 2 DM but adding significant weight loss with low incidence of hypoglycemia. Weekly exenatide decreases HbA1c similar to liraglutide but larger than exenatide BID, both glargine and biphasic insulin, sitagliptin, and pioglitazone, maintaining weight loss and adding to gastrointestinal intolerance the induration at the injection site as a side effect.

[Incretin mimetic drugs: therapeutic positioning]. / Fármacos incretín miméticos: posicionamiento terapéutico.

Type 2 diabetes is a chronic and complex disease, due to the differences among affected individuals, which affect choice of treatment. The number of drug families has increased in the last few years, and these families have widely differing mechanisms of action, which contributes greatly to the individualization of treatment according to the patient's characteristics and comorbidities. The present article discusses incretin mimetic drugs. Their development has been based on knowledge of the effects of natural incretin hormones: GLP-1 (glucagon-like peptide 1), GIP (glucose-dependent insulinotropic peptide) and dipeptidyl peptidase enzyme 4 (DPP4), which rapidly degrade them in the systemic circulation. This group is composed of 2 different types of molecules: GLP-1 analogs and DPP4 enzyme inhibitors. The benefits of these molecules include a reduction in plasma glucose without the risk of hypoglycemias or weight gain. There are a series of questions that require new studies to establish a possible association between the use of these drugs and notification of cases of pancreatitis, as well as their relationship with pancreatic and thyroid cancer. Also awaited is the publication of several studies that will provide information on the relationship between these drugs and cardiovascular risk in people with diabetes. All these questions will probably be progressively elucidated with greater experience in the use of these drugs.

[Twice-daily and weekly exenatide: Clinical profile of two pioneer formulations in incretin therapy]. / Exenatida diaria y semanal: perfil clínico de dos formulaciones pioneras en la modulación incretínica.

GLP-1 receptors agonists have been a substantial change in treatment of type 2 diabetes mellitus, and its weekly administration has broken pre-established schemes. Daily exenatide is administered every 12 hours (BID) subcutaneously, while weekly exenatide is administered once a week. Both molecules share a common mechanism of action but have differential effects on basal and postprandial glucose. We review the major clinical trials with both exenatide BID and weekly exenatide. It can be concluded that exenatide BID shows a hypoglycemic effect similar to other treatments for type 2 DM but adding significant weight loss with low incidence of hypoglycemia. Weekly exenatide decreases HbA1c similar to liraglutide but larger than exenatide BID, both glargine and biphasic insulin, sitagliptin, and pioglitazone, maintaining weight loss and adding to gastrointestinal intolerance the induration at the injection site as a side effect.

[Extrapancreatic effects of GLP-1 receptor agonists: an open window towards new treatment goals in type 2 diabetes]. / Efectos extrapancreáticos de los agonistas del receptor de GLP-1: una ventana hacia nuevos objetivos del tratamiento farmacológico de la diabetes mellitus tipo 2.

The wide ubiquity of GLP-1 receptors in the body has stimulated the search for different extrapancreatic actions of GLP-1 and its receptor agonists. Thus, severe cardioprotective effects directed on myocardial ischaemia and dysfunction as well as diverse antiaterogenic actions have been reported. Also, native and GLP-1 receptor agonists have demonstrated significant beneficial effects on liver steatosis and fibrosis and on neuronal protection in experimental models of Alzheimer, and Parkinson's disease as well as on cerebral ischaemia. Recent evidences suggest that these drugs may also be useful for prevention and treatment of diabetic retinopathy, nephropathy and peripheral neuropathy. Good results have also been reported in psoriasis. Despite we still need confirmation that these promising effects can be applied to clinical practice, they offer new interesting perspectives for treatment of type 2 diabetes associated complications and give to GLP-1 receptor agonists an even more integral position in diabetes therapy.

Effect of treatment with sitagliptin on somatosensory-evoked potentials and metabolic control in patients with type 2 diabetes mellitus / Efeito do tratamento com sitagliptina sobre os potenciais evocados somatossensoriais e controle metabólico de pacientes com diabetes melito tipo 2

Objective: To evaluate the effect of sitagliptin on somatosensory-evoked potentials (SEPs) and metabolic control in patients with type 2 diabetes mellitus without clinical diabetic neuropathy. Materials and methods: Interventional, prospective, and open study. Patients with less than six months from the diagnosis were included. Examinations of SEPs and laboratory tests at fasting and after food stimulation were performed before and after three months of treatment with sitagliptin (100 mg/day). Results: There was a reduction in the mean levels of HbA1c (P < 0.0001), fasting glucose (P = 0.001), total cholesterol (P = 0.019), and ALT (P = 0.022). An increase in active GLP-1 was found at the end of the study (P = 0.0025). Several SEPs showed statistically significant differences when analyzed before and after treatment with sitagliptin. Conclusion: The results give a glimpse of the possible use of sitagliptin in the treatment of some neurodegenerative conditions of the peripheral nervous system, in addition to its already established role in glycemic control. .

Objetivo: Avaliar o efeito da sitagliptina nos potenciais evocados somatossensoriais (PESS) e controle metabólico de pacientes com diabetes melito tipo 2, sem neuropatia diabética. Materiais e métodos: Estudo de intervenção, prospectivo e aberto. Os pacientes com menos de seis meses de diagnóstico foram incluídos. Exames dos PESS e testes laboratoriais em jejum e após a estimulação com alimentos foram realizados antes e depois de três meses de tratamento com sitagliptina (100 mg/dia). Resultados: Houve redução nos níveis médios de HbA1c (P < 0,0001), glicemia de jejum (P = 0,001), colesterol total (P = 0,019) e ALT (P = 0,022). Verificou-se aumento de GLP-1 ativo (P = 0,0025). Vários PESS mostraram diferenças estatisticamente significativas quando os valores foram analisados antes e após o tratamento com sitagliptina. Conclusão: Os resultados vislumbram a possível utilização de sitagliptina no tratamento de algumas condições neurodegenerativas do sistema nervoso periférico, em adição ao seu papel no controle glicêmico. .

Efeitos da Exenatida e da Sitagliptina durante a indução da periodontite em ratos / Effects of exenatide and sitagliptin during periodontitis induction in rats

A diabetes mellitus e a periodontite são patologias inflamatórias prevalentes e que se agravam mutuamente. Os novos medicamentos para o tratamento da diabetes, os agonistas do receptor do peptídeo semelhante ao glucagon-1 (GLP-1) e os inibidores da enzima dipeptidil peptidase-4 (DPP-4), têm apresentado efeitos pleiotrópicos como estimulação da formação e inibição da reabsorção óssea e características anti-inflamatórias. O objetivo deste trabalho foi avaliar os efeitos do uso da exenatida (agonista do GLP-1) e da sitagliptina (inibidor da DPP-4) na periodontite induzida em ratos. Foram utilizados 40 ratos divididos em quatro grupos: 1) exenatida (GE):animais com periodontite induzida e que receberam 3 μg/Kg/dia de exenatida por via subcutânea; 2) sitagliptina (GS) animais com periodontite induzida e que receberam 10 mg/Kg/dia de sitagliptina por via oral; 3) com doença periodontal (DP) e 4) controle (GC), ambos receberam os veículos de dissolução dos medicamentos. A periodontite foi induzida pela inserção de ligadura ao redor dos primeiros molares inferiores e os medicamentos foram administrados por 28 dias. No dia do sacrifício, os animais foram pesados e foi coletado sangue para análise sorológica de polipeptídeo insulinotrópico dependente de glicose (GIP), GLP-1, DPP-4 e glicose. As hemimandíbulas foram submetidas à análise radiográfica para avaliação do suporte ósseo alveolar, e a processamento histológico para análise histomorfométrica (área de perda óssea alveolar na região de furca, perda óssea linear interproximal e porcentagem de colágeno). O uso dos medicamentos levou a menor porcentagem de ganho de peso e mas não influenciou a glicemia dos animais. A sitagliptina reduziu a concentração de DPP-4, enquanto a exenatida não aumentou os valores de GLP-1. Nas análises radiográfica e histomorfométrica, comprovou-se a eficácia da indução da periodontite, com diferença significante de suporte ósseo, perda óssea alveolar e porcentagem de colágeno entre os ...

Diabetes Mellitus is a high prevalent disease as well as periodontitis. The literature supports a two way relationship between them. A new class of drugs for diabetes treatment, peptide-like glucagon-1 (GLP-1) agonists and dypeptidyl peptidase-4 (DPP-4) inhibitors, has shown pleiotropic effects, like bone anabolic, antiresoptive and antiinflammatory actions. The aim of this study was to evaluate the effect of exenatide (GLP-1 agonist) and sitagliptin (DPP-4 inhibitor) during periodontitis induction in rats. Forty male rats were divided into four groups:1) exenatide group (GE): animals with induced periodontitis that received 3 μg/Kg/day of exenatide subcutaneously; 2) sitagliptin group (GS): animals with induced periodontitis that received 10 mg/Kg/day with sitagliptin orally; 3) periodontal disease group (PD) and 4) control group (CG); both treated with the drug vehicles. Periodontitis was induced by the insertion of ligature around the first molars and the drugs were administered for 28 days. On the day of sacrifice, animals were weigthed and blood were colleccted for serum analysis of GIP, GLP-1 and DPP-4. The mandibles underwent radiographic analysis for assessment of alveolar bone support, and the histological processing for histomorphometric analysis (area of bone loss in the furcation area, linear interproximal bone loss and percentage of collagen). The use of the drugs led to a lower percentage of weight gain and had no influence on glucose levels. Sitagliptin reduced the concentration of DPP-4, while exenatide had no influence on GLP-1 levels. In radiographic and histomorphometric analysis, it was proved the effectiveness of induction of periodontitis, with a significant difference of bone support, alveolar bone loss and percentage of collagen between the PD and CG. On the other hand there was no statistical difference between the test groups and PD group. In conclusion, within the parameters of this study, both exenatide and sitagliptin were not ...