Canagliflozin for the treatment of adults with Type 2 diabetes

AdultosCanagliflozin is a competitive, reversible and potent inhibitor of SGLT2 that lowers the renal threshold for glucose and consequently increases urinary glucose excretion in people with Type 2 diabetes with a blood glucose level above 70–90 mg/dl. Its oral administration in daily doses of 100 and 300 mg in onotherapy, dual therapy or triple therapy including insulin produces a mean HbA1c reduction of 0.7 and 0.85%, respectively, when compared with placebo, a similar reduction to sitagliptin and glimepiride. There is also a modest reduction in weight with both doses. The main adverse effects are genital fungal infections, particularly in women, and, less frequently, urinary tract infections.https://orcid.org/0000-0002-6860-3620N/

La dieta en el manejo de diabetes

Actualmente, la palabra “dieta” ha adquirido una connotación negativa y se ha querido cambiar por otras como “régimen alimenticio”, pero su interpretación clínica como restricción calórica sigue siendo la clave para el manejo inicial de la diabetes tipo 2 (DT2), como lo demostró el estudio Direct (1), el cual logró la remisión en 46?% de los casos de DT2 al cabo del primer año y de 36?% al final de dos años, mediante la prescripción inicial de una dieta de muy bajas calorías (~ 800 kcal/día). La remisión, entonces, estuvo entre el 86?% y el 70?% en aquellos pacientes que perdieron ? 15 kg. Probablemente la falla en lograr que las personas con DT2 pierdan peso es una de las mayores formas de inercia terapéutica, conduciendo a un escalamiento innecesario de antidiabéticos hasta el punto de ver personas todavía obesas aplicándose insulina. Se calcula que más del 80?% de las personas con DT2 debutan con algún grado de exceso de peso. En ese momento, su identificación mediante un índice de masa muscular (IMC) ? 27 kg/m² obliga a una intervención estructurada que debería incluir fármacos antiobesidad o preferiblemente de acción dual (también antidiabéticos). El exceso de grasa visceral (circunferencia de cintura ? 94cm o ? 90cm en hombres y mujeres, respectivamente) indica un alto grado de resistencia a la insulina y le da un sentido de urgencia a la intervención (por el riesgo cardiovascular que conlleva). Aunque el IMC no refleja con precisión la masa grasa, como lo sugieren los autores en el artículo incluido en este número (2), es suficiente para tomar decisiones clínicas. Un método como la bioimpedancia, con instrumentos debidamente calibrados, puede ser útil para evaluar cambios en la grasa corporal con diferentes intervenciones y para comprender mejor sus mecanismos de acción

Aislamiento y purificación de prolactina humana. ii. purificación y caracterización parcial

En este trabajo se describe un sistema cromatográfico en dos etapas que permite la purificación de prolactina humana (hPRL), a partir del residuo obtenido después de la extracción con solución salina de hipófisis conservadas congeladas. La PRL se solubilizó en acetato de amonio 50 mM, pH 10 y se purificó por medio de cromatografía de interacción hidrofóbica, sobre el soporte Fenil-Sepharosa en presencia de un gradiente lineal de acetonltrílo (0-40%). La fracción con actividad de PRL se aplicó a una columna de DEAE-Celulosa en presencia de acetonítrilo (20%) y se eluyó con un gradiente salino. El rendimiento del proceso fue de 7.75 mg PRL por 100 glándulEis, lo que corresponde a una recuperación global de 33%. Por radioinmunoanálisis especifico (RÍA) se encontró una potencia de 10.6 Ul/mg de proteina en la preparación final. El análisis electroforético mostró dos componentes principales de pesos 27.000 Dattons, que corresponde al monómero principal y 64.000 Daltons, que sugiere una forma agregada o glicosilada, cuya existencia ha sido reportada en el suero. La presencia de isohormonas también fue detectada por el análisis de electroenfoque, encontrándose un valor de punto isoeléctrico (PI) de 5.7 para la especie principal. Este comportamiento también se observó con la preparación internacional de referencia usada en este trabajo

Insulin glargine compared with premixed insulin for management of insulin-naïve type 2 diabetes patients uncontrolled on oral antidiabetic drugs : the open-label, randomized GALAPAGOS study

Q3Q1Aims: Demonstrate superiority of insulin glargine (±glulisine) strategy versus premixed insulin strategy for percentage of patients reaching HbA1c b7% (b53 mmol/mol) at study end without any documented symptomatic hypoglycemia (bloof glucose [BG] ≤3.1 mmol/L) in type 2 diabetes (T2DM) patients failing oral agents. Methods: This 24-week, open-label, multinational trial randomized patients to glargine OD or premix OD or BID, continuing metformin ± insulin secretagogue (IS). Second premix injection could be added any time; glulisine could be added with main meal in glargine OD patients with HbA1c ≥7% and fasting blood glucose (FBG) b7 mmol/L at week 12. IS was stopped with any second injection. Insulin titration targeted FBG ≤5.6 mmol/L. Results: Modifiedintent-to-treat population comprised 923 patients (glargine, 462; premix, 461). Baseline characteristics were similar (mean T2DM duration: 9 years; HbA1c: 8.7% (72 mmol/mol); FBG: 10.4 mmol/L). Primary endpoint was achieved by 33.2% of glargine (±glulisine) and 31.4% of premix patients. Superiority was not demonstrated, but non-inferiority was (pre-specifiedmargin: 25% of premix rate). More patients using premix achieved target (52.6% vs. 43.2%, p = 0.005); symptomatic hypoglycemia was less with glargine (1.17 vs. 2.93 events/patient–year). Conclusions: Glargine (±glulisine) and premix strategies resulted in similar percentages of well-controlled patients without hypoglycemia, with more patients achieving target HbA1c with premix whereas overall symptomatic hypoglycemia was less with glargine.N/

Triple combination of insulin glargine, sitagliptin and metformin in type 2 diabetes : the EASIE post-hoc analysis and extension trial

Q3Q1Aim We examined the effects of adding glargine to metformin–sitagliptin (MS + G) or sitagliptin to metformin–glargine (MG + S) therapy in type 2 diabetic persons uncontrolled after 24-week MS or MG dual therapy. Methods Subjects with A1c ≥ 7% on MS or MG treatment were respectively given glargine (0.2 U/kg starting dose) or sitagliptin (100 mg daily) for 12 weeks. The primary endpoint was number of subjects attaining A1c goal defined as < 7%. Results After receiving 24-week MS or MG dual therapy in the original EASIE Study, 42% (104/248) on MS and 68% (152/224) on MG attained A1c < 7% (p < 0.0001). The reduction in A1c was negatively associated with baseline fasting blood glucose (FBG) only in the MG group. Reduction in A1c was not related to baseline postprandial blood glucose (PPBG) in either the MG or MS group. Amongst 194 eligible patients, 57.7% (n = 111) entered the 12-week extension trial [MS + G:74/131, 57.3%; MG + S:37/63, 58.7%) with 55 (51.9%) subjects attaining goal [MS + G:59.2%; MG + S:37.1%] at week 12. The final insulin dosage was similar in both groups [MS + G: 0.46 U/kg; MG + S: 0.45 U/kg] with a higher rate of hypoglycemia in the MG + S (6.5 events/patient-year) than the MS + G group (3.2 events/patient-year), although neither group had severe hypoglycemia. Conclusion In metformin-treated type 2 diabetes patients, high fasting BG predicted greater A1c reductions with the addition of glargine, but not with sitagliptin. In subjects uncontrolled with 6-month dual therapy of MS or MG, 50% attained A1c < 7% with triple therapy of MS + G or MG + S in 12 weeks. The increased rate of hypoglycemia with MG + S (but not with MS + G) underlines the need to take measures to avoid the hypoglycemia

Effects of performing morning versus afternoon exercise on glycemic control and hypoglycemia frequency in type 1 diabetes patients on sensor-augmented insulin pump therapy

Q1Artículo original619-624Background: Although physical exercise (PE) is recommended for individuals with type 1 diabetes (DM1), participation in exercise is challenging because it increases the risk of severe hypoglycemia and the available therapeutic options to prevent it frequently result in hyperglycemia. There is no clear recommendation about the best timing for exercise. The aim of this study was to compare the risk of hypoglycemia after morning or afternoon exercise sessions up to 36 hours postworkout. Methods: This randomized crossover study enrolled subjects with DM1, older than 18 years of age, on sensor-augmented insulin pump (SAP) therapy. Participants underwent 2 moderate-intensity exercise sessions; 1 in the morning and 1 in the afternoon, separated by a 7 to 14 day wash-out period. Continuous glucose monitoring (CGM) data were collected 24 hours before, during and 36 hours after each session. Results: Thirty-five subjects (mean age 30.31 ± 12.66 years) participated in the study. The rate of hypoglycemia was significantly lower following morning versus afternoon exercise sessions (5.6 vs 10.7 events per patient, incidence rate ratio, 0.52; 95% CI, 0.43-0.63; P < .0001). Most hypoglycemic events occurred 15-24 hours after the session. On days following morning exercise sessions, there were 20% more CGM readings in near-euglycemic range (70-200 mg/dL) than on days prior to morning exercise (P = .003). Conclusions: Morning exercise confers a lower risk of late-onset hypoglycemia than afternoon exercise and improves metabolic control on the subsequent day

Economic evaluation of second line oral antidiabetics for Type 2 diabetes in Colombia

Q1Q1A608-A609Objectives: Establish incremental cost-effectiveness ratio (ICER) in cost per additional patient with glycemic control for all the oral antidiabetic medications available in Colombia, as a second-line treatment for adult patients with type 2 diabetes (DM2), who do not reach therapeutic targets with metformin and are not yet considered candidates for insulin therapy. Methods: Oral antidiabetic medications were divided into drug classes: sulfonylureas (divided between glibenclamide, other sulphonylureas), thiazolidinediones, GLP-1 receptor agonists, and DPP4 inhibitors. A systematic review of the literature was done to obtain transition probabilities in a Markov model (monthly cycles, time horizon one year) designed to represent the Colombian health system perspective. The main outcome considered was glycemic control, but data on adherence and adverse events were also collected. Costs (in 2014 Colombian pesos; 1 euro = COP 2,660) were estimated from base cases obtained from multidisciplinary expert panel meetings, with local costs applied from national tariff manuals and official drug price registries. Sensitivity analyses were performed. Results: Annual treatment costs ranged from € 116 for glibenclamide, and € 98 for other sulphonylureas, to € 12,205 for GLP-1 receptor agonists. Number of patients with glycemic control (per 1000) were glibenclamide 145, sulphonylureas 265, thiazolidinediones 472, GLP-1 receptor agonists 326, and DPP4 inhibitors 417: Compared against other sulfonylureas, glibenclamide was dominated, while ICERs per additional patient with glycemic control per year would be € 516 for DPP-4 inhibitors, € 712 for thiazolidinediones and € 66,790 for GLP-1 receptor agonists. Critical variables in the sensitivity analyses were drug costs (particularly for GLP-1 receptor agonists), but also patient adherence to medication (with insuficient local information). Conclusions: Sulfonylureas, other than glibenclamide, DPP-4 inhibitors and thiazolidinediones are cost-effective alternatives as second-line treatment for DM2 patients that require oral antidiabetics in Colombia. Patient adherence requires further local research

Visceral, subcutaneous abdominal adiposity and liver fat content distribution in normal glucose tolerance, impaired fasting glucose and/or impaired glucose tolerance

Q1Q1Objectives: To examine the specific distribution of liver fat content, visceral and subcutaneous adiposity in normal glucose tolerance (NGT/NGT), isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT) and combined conditions (IFG+IGT), as well as with newly diagnosed type 2 diabetes (nT2D). Design: Multicenter, international observational study: cross-sectional analysis. Subjects: Two thousand five hundred and fifteen patients (50.0% women, 54.5% non-Caucasian) without previously known diabetes were recruited from 29 countries. Abdominal fat distribution was measured by computed tomography (CT). Liver fat was estimated using the CT-liver mean attenuation. Results: Compared with NGT/NGT patients, increased visceral adiposity was found in iIFG, iIGT, IFG+IGT and nT2D; estimated liver fat progressively increased across these conditions. A one-s.d. increase in visceral adiposity was associated with an increased risk of having iIFG (men: odds ratio (OR) 1.41 (95% confidence interval (CI) 1.15–1.74), women: OR 1.62 (1.29–2.04)), iIGT (men: OR 1.59 (1.15–2.01), women: OR 1.30 (0.96–1.76)), IFG+IGT (men: OR 1.64 (1.27–2.13), women: OR 1.83 (1.36–2.48)) and nT2D (men: OR 1.80 (1.35–2.42), women: OR 1.73 (1.25–2.41)). A one-s.d. increase in estimated liver fat was associated with iIGT (men: OR 1.46 (1.12–1.90), women: OR 1.81 (1.41–2.35)), IFG+IGT (men: OR 1.42 (1.14–1.77), women: OR 1.74 (1.35–2.26)) and nT2D (men: OR 1.77 (1.40–2.27), women: OR 2.38 (1.81–3.18)). Subcutaneous abdominal adipose tissue showed an inverse relationship with nT2D in women (OR 0.63 (0.45–0.88)). Conclusions: Liver fat was associated with iIGT but not with iIFG, whereas visceral adiposity was associated with both. Liver fat and visceral adiposity were associated with nT2D, whereas subcutaneous adiposity showed an inverse relationship with nT2D in women

Clinical practice guidelines for the prevention, early detection, diagnosis, treatment and monitoring of dyslipidemia : non-pharmacological treatment with exercise

Objetivo: Evaluar el impacto del ejerciciocomo una intervención no farmacológica parala prevención primaria y secundaria de eventoscardio y cerebrovasculares asociados a dislipidemiaen personas con hipercolesterolemia.Métodos: Se elaboró una guía de práctica clínicasiguiendo los lineamientos de la guía metodológicadel Ministerio de Salud y ProtecciónSocial para recolectar de forma sistemática laevidencia científica y formular las recomendacionesutilizando la metodología GRADE. Setomó la información específica acerca de ejerciciocomo medida terapéutica en el tratamientode dislipidemia. Resultados: Tanto el ejercicioaeróbico como el de resistencia se asocian adisminución en el colesterol con lipoproteínasde baja densidad y los triglicéridos, cambiosque fueron estadísticamente significativos; peroestos no son clínicamente relevantes, dado quese trata de una reducción mínima. No se encontróun cambio estadísticamente significativo enlos valores de colesterol de alta densidad. Conclusiones:Se presenta evidencia a favor del usode ejercicio como parte fundamental del tratamientode hipercolesterolemia. Aunque no seencontraron diferencias clínicamente significativasen los valores de colesterol o triglicéridos,el ejercicio físico es una actividad con ampliosbeneficios para el paciente en otros dominiosclínicos de interés, por lo que al considerar elriesgo y el beneficio de esta práctica, los beneficiosson claros y superan ampliamente el bajoriesgo al que se expone una persona al realizaruna rutina de ejercicio, como parte de su vidacotidiana.Artículo original34-43Objective: To evaluate the impact of exercise as a non-pharmacological intervention for primary and secondary prevention of cardiovascular events in people with hypercholesterolemia. Methods: A clinical practice guideline was developed following the guidelines of the methodological guidance of the Ministry of Health and Social Protection to collect systematically the evidence and make recommendations using the GRADE methodology. Results: Both aerobic and resistance exercise are associated with decreased LDL cholesterol and triglycerides, changes were statistically significant, but these changes are not clinically relevant since it is a minimal reduction in these values. No statistically significant change was found in HDL cholesterol values. Conclusions: Recommendations for the use of exercise as a fundamental part of the treatment of hypercholesterolemia are formulated. Although no clinically significant differences in the values of cholesterol or triglycerides, exercise is an activity with great benefits for the patient in other clinical domains of interest, being part of healthy lifestyles and exposure to low risk, so when you consider the risks and benefits of this practice, the benefits are clear and far outweigh the low risk to which a person is exposed when performing an exercise routine as part of their daily lives

Guía de práctica clínica para la prevención, detección temprana, diagnóstico, tratamiento y seguimiento de las dislipidemias en la población mayor de 18 años

La Guía de práctica clínica para la prevención, detección temprana, diagnóstico, tratamiento y seguimiento de las dislipidemias en la población mayor de 18 años está dirigida a los adultos en riesgo para el desarrollo de dislipidemia o con diagnóstico establecido de dislipidemia, como también, para todo el personal de salud encargado de su atención en los diferentes niveles de complejidad del sistema de salud colombiano. Permitirá brindar parámetros de práctica clínica, basados en la mejor evidencia disponible para la atención en salud y el uso racional de recursos en esta patología. Se introducen cambios en el proceso de atención, que buscan disminuir la variabilidad injustificada en el abordaje de este grupo de pacientes generando procesos eficientes, sencillos y ajustados a la población colombiana; la guía es el resultado de un arduo proceso en el que se contó con la participación de expertos temáticos y expertos metodológicos, así como representantes de los pacientes y de las sociedades científicas y las universidades involucradas, y del Ministerio de Salud y Protección Social. En la siguiente sección se presentarán de forma resumida las recomendaciones y los puntos de buena práctica clínica para cada una de las preguntas formuladas, información que se amplía posteriormente en el capítulo respectivo.Guía de práctica clínica1-6