Nuevos hipoglucemiantes orales y riesgo cardiovascular. Cruzando la frontera metabólica / New oral hypoglycemic agents and cardiovascular risk. crossing the metabolic border

Los inhibidores del cotransportador de sodio-glucosa tipo 2 son una nueva clase de hipoglucemiantes orales que aumentan de la excreción urinaria de glucosa independientemente de la secreción de insulina. Sin embargo, este mecanismo aparentemente sencillo conduce a efectos metabólicos indirectos más complejos. Los resultados clínicos demuestran su efectividad en el control de la glucemia, pues reducen la glucohemoglobina y, al mismo tiempo, logran una disminución del peso corporal y de la presión arterial sistólica. Esta revisión proporciona una visión general de la evidencia disponible hasta el momento sobre el mecanismo de acción, la eficacia y la seguridad, así como otros factores de riesgo más allá de la glucosa que se podría modular de manera positiva con los fármacos comercializados actualmente. Datos recientes sobre la empagliflozina que muestran un beneficio cardiovascular específico obligan a actualizar el conocimiento de esta nueva clase terapéutica para el tratamiento de la diabetes mellitus tipo 2 (AU)

Sodium-glucose cotransporter 2 inhibitors are a novel pharmacological class of oral hypoglycemic agents that lower glucose levels by increasing renal glucose excretion in an insulin-independent manner. However, this seemingly simple mechanism has more complex indirect metabolic effects. The results of randomized clinical trials have shown that these inhibitors effectively lower blood glucose and glycated hemoglobin levels without increasing the risk of hypoglycemia and, at the same time, also reduce bodyweight and systolic blood pressure. In this review, we describe the mechanism of action, efficacy, and safety of currently marketed drugs, as well as other risk factors besides glucose that can potentially be modulated positively. Recent data on empagliflozin showing a significant cardiovascular benefit have compelled us to update knowledge of this new therapeutic class for the treatment of type 2 diabetes (AU)

New Oral Hypoglycemic Agents and Cardiovascular Risk. Crossing the Metabolic Border.

Sodium-glucose cotransporter 2 inhibitors are a novel pharmacological class of oral hypoglycemic agents that lower glucose levels by increasing renal glucose excretion in an insulin-independent manner. However, this seemingly simple mechanism has more complex indirect metabolic effects. The results of randomized clinical trials have shown that these inhibitors effectively lower blood glucose and glycated hemoglobin levels without increasing the risk of hypoglycemia and, at the same time, also reduce bodyweight and systolic blood pressure. In this review, we describe the mechanism of action, efficacy, and safety of currently marketed drugs, as well as other risk factors besides glucose that can potentially be modulated positively. Recent data on empagliflozin showing a significant cardiovascular benefit have compelled us to update knowledge of this new therapeutic class for the treatment of type 2 diabetes.

Eliminación renal de glucosa como tratamiento de la diabetes: de un antiguo método diagnóstico a una nueva forma de tratamiento / Glucose renal excretion as diabetes treatment: from an old diagnostic method to a new way of treatment

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Prevalencia de tumores benignos y malignos en pacientes acromegálicos / Prevalence of benign and malignant tumors in acromegalic patients

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Parámetros de control glucémico en pacientes con diabetes tipo 2 no insulinizados derivados a consulta de Endocrinología, y grado de implementación del consenso nacional sobre el tratamiento de la hiperglucemia / Glycemic control parameters in insulin-naïve patients with uncontrolled type 2 diabetes referred to endocrinologists, and degree of implementation of the national Spanish consensus for the management of hyperglycemia

OBJETIVO: Evaluar el control glucémico en pacientes con diabetes tipo 2 que son remitidos a Endocrinología desde Atención Primaria (AP) por no estar controlados con antidiabéticos orales sin insulinoterapia; y el grado de implementación del consenso nacional de la Sociedad Española de Diabetes, valorando los sucesivos escalones, primero (Pe), segundo (Se) y tercero (Te), del abordaje terapéutico. MATERIAL Y MÉTODOS: Estudio observacional retrospectivo en el que 81 endocrinólogos evaluaron los pacientes mayores de 40 años remitidos por AP entre julio de 2012 y julio de 2013, tratados con 1-2 antidiabéticos orales, no insulinizados, con una hemoglobina glucosilada (HbA1c) ≥ 6,5%, y en los que se disponía en los 3 meses previos de Hb1Ac, glucosa capilar en ayunas y glucosa capilar posprandial. RESULTADOS: Fueron evaluables 285 pacientes (57,6% varones), con una edad media (DE) de 63,1 (9,7) años, HbA1c media de 8,5 (1,2) %, glucosa capilar en ayunas 171,7 (43) mg/dl y glucosa capilar posprandial 206,8 (50) mg/dl. En AP el 26,0% de los pacientes se situaban en Pe terapéutico y el 74,0% en el Se. En atención especializada solo el 9,8% de la cohorte está en el Pe, el 42,8% en el Se y el 47,4% en el Te. Los fármacos más prescritos en AP fueron metformina (90,2%), inhibidores DPP-4 (34,4%) y sulfonilureas (30,5%), mientras que en Endocrinología fueron metformina (86%), insulina (56,8%) e inhibidores DPP-4 (49,8%). Las guías clínicas más seguidas fueron las de la American Diabetes Association y el consenso de la Sociedad Española de Diabetes, en un 77 y 45% respectivamente. CONCLUSIONES: Aproximadamente la mitad de los pacientes con diabetes mellitus 2 no insulinizados y tratados con antidiabéticos orales en AP, son tratados con insulina en Endocrinología. La guía clínica más seguida por el especialista es la de la American Diabetes Association

OBJECTIVE: To assess blood glucose in patients with uncontrolled type 2 diabetes mellitus treated with oral antidiabetic drugs in primary care at the time of referral to specialized endocrinologists, and the degree of implementation of the national consensus guidelines of the Spanish Society of Diabetes by evaluating steps one (S1), two (S2), and three (S3) of the escalating therapy. MATERIAL AND METHODS: Retrospective, observational study where 81 endocrinologists evaluated patients ≥ 40 years of age referred from primary care between July 2012 and July 2013, treated with 1 to 2 oral antidiabetic drugs but no insulin therapy, and with glycosylated hemoglobin (HbA1c) levels ≥ 6.5%. Patients also had to have HbA1c levels and both fasting and postprandial plasma glucose measurements from the previous three months. RESULTS: A total of 285 patients (57.6% males) were assessed. Mean (SD) age was 63.1 (9.7) years, mean HbA1c was 8.5 (1.2) %, mean FPG was 171.7 (43) mg/dL, and mean postprandial plasma glucose was 206.8 (50) mg/dL. In primary care, 26.0% of patients were at S1 and 74.0% were at S2. After referral to the endocrinologist, 9.8% of patients moved onto S1, 42.8% onto S2, and 47.4% onto S3. Oral antidiabetic drugs most commonly prescribed in primary care were metformin (90.2%), DPP-4 inhibitors (34.4%), and sulfonylureas (30.5%), while drugs most commonly used in the specialized endocrinology setting were metformin (86%), insulin (56.8%), and DPP-4 inhibitors (49.8%). The most commonly followed guidelines were those of the American Diabetes Association and the consensus guidelines of the Spanish Society of Diabetes, in 77% and 45% of cases respectively. CONCLUSIONS: Approximately half the patients treated with oral antidiabetic drugs in primary care are prescribed insulin after referral to an endocrinology specialist. The most commonly followed guidelines in specialized care are the American Diabetes Association guidelines

Glycemic control parameters in insulin-naïve patients with uncontrolled type 2 diabetes referred to endocrinologists, and degree of implementation of the national Spanish consensus for the management of hyperglycemia.

OBJECTIVE: To assess blood glucose in patients with uncontrolled type 2 diabetes mellitus treated with oral antidiabetic drugs in primary care at the time of referral to specialized endocrinologists, and the degree of implementation of the national consensus guidelines of the Spanish Society of Diabetes by evaluating steps one (S1), two (S2), and three (S3) of the escalating therapy. MATERIAL AND METHODS: Retrospective, observational study where 81 endocrinologists evaluated patients ≥40 years of age referred from primary care between July 2012 and July 2013, treated with 1 to 2 oral antidiabetic drugs but no insulin therapy, and with glycosylated hemoglobin (HbA(1c)) levels ≥6.5%. Patients also had to have HbA(1c) levels and both fasting and postprandial plasma glucose measurements from the previous three months. RESULTS: A total of 285 patients (57.6% males) were assessed. Mean (SD) age was 63.1 (9.7) years, mean HbA1c was 8.5 (1.2) %, mean FPG was 171.7 (43) mg/dL, and mean postprandial plasma glucose was 206.8 (50) mg/dL. In primary care, 26.0% of patients were at S1 and 74.0% were at S2. After referral to the endocrinologist, 9.8% of patients moved onto S1, 42.8% onto S2, and 47.4% onto S3. Oral antidiabetic drugs most commonly prescribed in primary care were metformin (90.2%), DPP-4 inhibitors (34.4%), and sulfonylureas (30.5%), while drugs most commonly used in the specialized endocrinology setting were metformin (86%), insulin (56.8%), and DPP-4 inhibitors (49.8%). The most commonly followed guidelines were those of the American Diabetes Association and the consensus guidelines of the Spanish Society of Diabetes, in 77% and 45% of cases respectively. CONCLUSIONS: Approximately half the patients treated with oral antidiabetic drugs in primary care are prescribed insulin after referral to an endocrinology specialist. The most commonly followed guidelines in specialized care are the American Diabetes Association guidelines.

Alteraciones del metabolismo hidrocarbonado en la acromegalia / Abnormalities of carbohydrate metabolism in acromegaly

Fundamento y objetivo: Hasta un 50% de los pacientes con acromegalia presentan alteraciones en el metabolismo hidrocarbonado (AMHC). La evolución natural de la enfermedad y las distintas alternativas terapéuticas impactan de forma diferente en esta predisposición. El objetivo de este trabajo fue valorar la prevalencia, las características de los pacientes y el efecto de los distintos tratamientos en la AMHC en los pacientes acromegálicos de nuestro centro. Pacientes y método: Se realizó un estudio transversal que incluyó a 55 pacientes con acromegalia. Se analizaron: edad, sexo, índice de masa corporal (IMC), factor de crecimiento insulínico tipo 1 (IGF-1), tamaño tumoral, tratamientos, y presencia de diabetes mellitus (DM) y grado de control metabólico inicial y tras las distintas alternativas terapéuticas. Resultados: De los 55 pacientes estudiados, el 54% eran varones, con una edad media (DE) de 50 (17) años y un IMC de 27,9 (3,8) kg/m2. Las AMHC estaban presentes en el 50,9% (n = 28) (DM en el 24% y glucosa basal alterada en el 27%). Los pacientes con DM no presentaban diferencias en el IMC, la edad ni el IGF-1 inicial respecto a los que no tenían DM. Sin embargo, presentaban más macroadenomas. En los pacientes diabéticos, la hemoglobina glucosilada (HbA1c) descendió después de la cirugía de 7,6 a 6,7% y después de los análogos de la somatostatina de 7,1 a 6,6%, pero solo con pegvisomant hemos observado una reducción significativa de HbA1c: del 9,8 al 5,6% (p < 0,05). Es más, solo pegvisomant ha permitido disminuir la intensidad del tratamiento hipoglucemiante. Conclusiones. La prevalencia de AMHC supera al 50% de los casos y se correlaciona con el tamaño tumoral. No hemos observado diferencias en el control glucémico en los pacientes tratados con las diferentes alternativas terapéuticas, excepto en el grupo que recibió pegvisomant, que logró una mejoría del mismo, junto con una reducción del tratamiento hipoglucemiante (AU)

Background and objective: Carbohydrate metabolism (CHM) is impaired in over 50% of acromegalic patients. Natural history of acromegaly and treatment modalities may impact in a different way on CHM. We assessed CHM alterations in acromegaly and their relationship with clinical features and treatment options. Patients and method: Retrospective study with 55 patients with acromegaly. Age, sex, body mass index (BMI), tumor size, insulin growth factor type 1 (IGF-1) levels and the presence of impaired fasting glucose (IFG) or diabetes mellitus (DM) were analyzed before and after surgery or medical treatment. Results: There were 30 men and 25 women. Mean age was 50 17 years and mean BMI was 27.9 3.8 Kg/ m2. Impaired CHM was found in 50.9% (n = 28) (DM in 27% and IFG in 24%). In diabetic patients, we found no differences in age, sex, BMI and IGF-1 levels between IFG/DM and patients without CHM impairment. However, IFG/DM patients had macroadenomas more commonly. In diabetic patients, glycosylated hemoglobin (HbA1c) decreased after surgery from 7.6 to 6.7% and after somatostatin analogues from 7.1 to 6.6%; in patients on pegvisomant we observed a significant reduction of HbA1c: from 9.8 to 5.6% (P < .005). Furthermore, only in the pegvisomant group, insulin and/or oral agents had to be lowered. Conclusions: Up to 50% of patients with active acromegaly have CHM impairment which correlates with tumor size. Only pegvisomant is associated with significant improvement in glycemic control and a reduction in hypoglycemic treatment (AU)

[Abnormalities of carbohydrate metabolism in acromegaly]. / Alteraciones del metabolismo hidrocarbonado en la acromegalia.

BACKGROUND AND OBJECTIVE: Carbohydrate metabolism (CHM) is impaired in over 50% of acromegalic patients. Natural history of acromegaly and treatment modalities may impact in a different way on CHM. We assessed CHM alterations in acromegaly and their relationship with clinical features and treatment options. PATIENTS AND METHOD: Retrospective study with 55 patients with acromegaly. Age, sex, body mass index (BMI), tumor size, insulin growth factor type 1 (IGF-1) levels and the presence of impaired fasting glucose (IFG) or diabetes mellitus (DM) were analyzed before and after surgery or medical treatment. RESULTS: There were 30 men and 25 women. Mean age was 50 ± 17 years and mean BMI was 27.9 ± 3.8 Kg/m(2). Impaired CHM was found in 50.9% (n = 28) (DM in 27% and IFG in 24%). In diabetic patients, we found no differences in age, sex, BMI and IGF-1 levels between IFG/DM and patients without CHM impairment. However, IFG/DM patients had macroadenomas more commonly. In diabetic patients, glycosylated hemoglobin (HbA1c) decreased after surgery from 7.6 to 6.7% and after somatostatin analogues from 7.1 to 6.6%; in patients on pegvisomant we observed a significant reduction of HbA1c: from 9.8 to 5.6% (P < .005). Furthermore, only in the pegvisomant group, insulin and/or oral agents had to be lowered. CONCLUSIONS: Up to 50% of patients with active acromegaly have CHM impairment which correlates with tumor size. Only pegvisomant is associated with significant improvement in glycemic control and a reduction in hypoglycemic treatment.

Tratamiento de la hiperglucemia en el hospital. Impresiones y conocimientos del médico residente / Interns’ viewpoints and knowledge about management of hyperglycemia in the hospital setting

Antecedentes y objetivo En muchos hospitales se han instaurado nuevos protocolos de insulinoterapia, a pesar de lo cual, no se logra un adecuado control. Evaluamos mediante una encuesta, la percepción de los médicos residentes ante la hiperglucemia, determinamos las barreras para obtener un óptimo control, y el impacto en las mismas de un programa de insulinización. Material y métodos Se aplicó un cuestionario, que valoraba el grado de conocimiento y la práctica habitual ante la hiperglucemia, antes y a los 6 meses de la implantación de un protocolo de insulinoterapia intrahospitalario. Resultados Completaron el cuestionario 25 residentes. El control glucémico se consideró «muy importante» en todas las situaciones de ingreso; sin embargo, en la hospitalización convencional solo lo consideró el 36%. La mayor parte se sentían «cómodos» utilizando la pauta de «solo insulina rápida», que fue la más empleada, pero no con la pauta basal/bolo que era «poco/nada» utilizada. A los 6 meses, aumentó la percepción del número de pacientes bien controlados, el bienestar y utilización de las pautas basal/bolo, aunque el empleo de «solo insulina rápida» se mantuvo. La mayor dificultad referida para un adecuado manejo de la hiperglucemia fue la falta de conocimientos. Conclusiones Los facultativos residentes conocen la importancia de un adecuado control, pero la falta de conocimientos impide obtenerlo. El programa formativo y la protocolización conllevaron una mejoría en la percepción y aplicabilidad de las pautas intensificadas. Sin embargo, a pesar del esfuerzo, sigue siendo elevado el empleo de pautas basadas exclusivamente de insulina rápida. En el programa formativo de los residentes debería destacarse el majo de la hiperglucemia (AU)

Background and objective: In many hospitals, adequate glycemic control is not achieved despite implementation of new insulin therapy protocols. Our aim was to assess resident physician’ attitudes toward inpatient hyperglycemia, barriers to achieve optimum control, and impact on them of an insulin training program Material and methods: A questionnaire was used to assess understanding and standard management of hyperglycemia before and six months after implementation of an inpatient insulin treatment program. Results: Twenty-five interns completed the questionnaire. Glycemic control was considered ‘‘very important’’ in all admission situations, but was only considered ‘‘very important’’ inconventional hospitalization by 36% of interns. Most of these felt ‘‘comfortable’’ using sliding scales, but not with the basal/bolus regimen, which was the least commonly used. Perception of number of well-controlled patients and comfort and use of basal/bolus therapy increased at six months, but use of ‘‘sliding scales’’ remained high. The greatest difficulty reported for adequate management of hyperglycemia was the lack of knowledge. Conclusions: Most residents are aware of the importance of adequate glycemic control, but cannot achieve it because of inadequate knowledge. The insulin training program led to an improved perception and applicability of basal-bolus insulin regimens. However, despite all efforts, use of sliding scales remains high. Training programs should emphasize management of hyperglycemia (AU)

[Interns' viewpoints and knowledge about management of hyperglycemia in the hospital setting]. / Tratamiento de la hiperglucemia en el hospital. Impresiones y conocimientos del médico residente.

BACKGROUND AND OBJECTIVE: In many hospitals, adequate glycemic control is not achieved despite implementation of new insulin therapy protocols. Our aim was to assess resident physician' attitudes toward inpatient hyperglycemia, barriers to achieve optimum control, and impact on them of an insulin training program MATERIAL AND METHODS: A questionnaire was used to assess understanding and standard management of hyperglycemia before and six months after implementation of an inpatient insulin treatment program. RESULTS: Twenty-five interns completed the questionnaire. Glycemic control was considered "very important" in all admission situations, but was only considered "very important" in conventional hospitalization by 36% of interns. Most of these felt "comfortable" using sliding scales, but not with the basal/bolus regimen, which was the least commonly used. Perception of number of well-controlled patients and comfort and use of basal/bolus therapy increased at six months, but use of "sliding scales" remained high. The greatest difficulty reported for adequate management of hyperglycemia was the lack of knowledge. CONCLUSIONS: Most residents are aware of the importance of adequate glycemic control, but cannot achieve it because of inadequate knowledge. The insulin training program led to an improved perception and applicability of basal-bolus insulin regimens. However, despite all efforts, use of sliding scales remains high. Training programs should emphasize management of hyperglycemia.

Preoperative thyrotropin serum concentrations gradually increase from benign thyroid nodules to papillary thyroid microcarcinomas then to papillary thyroid cancers of larger size.

We evaluated the preoperative serum thyrotropin (TSH) levels in 386 patients operated on for nodular thyroid disease (NTD). TSH levels for cases with final benign disease and differentiated thyroid carcinoma (DTC) were compared. No evidence of cancer was detected in 310 patients (80.3%), whereas malignancy was present in 76 cases (19.7%). Mean TSH concentration was 1.36 ± 1.62 mU/L in benign patients and 2.08 ± 2.1 in cases with malignant lesions (P = 0.0013). The group of malignancy was subdivided in papillary thyroid carcinoma (PTMC) versus thyroid cancer of larger size (TCLS). Mean TSH was 1.71 ± 1.52 in PTMC and 2.42 ± 2.5 in TCLS. Significant differences were found when all groups (benign, PTMC and TCLS) were compared (P < 0.001). However, pairwise comparisons between them showed that differences were only significant between benign and TCLS groups (P < 0.01). In conclusion, TSH levels were higher in patients with a final diagnosis of DTC. Moreover, it appears that there exists an increment in tumor size as a function of increment in the TSH level.