Cross-sectional association between severe periodontitis and diabetes mellitus: A nation-wide cohort study.

AIM: To evaluate the cross-sectional association between severe periodontitis and diabetes mellitus (DM), in a representative sample of Spanish population. MATERIALS AND METHODS: The di@bet.es epidemiological study is a population-based cohort study aimed to determine the prevalence and incidence of DM in the adult population of Spain. The at-risk sample at the final examination (2016-2017) included 1751 subjects who completed an oral health questionnaire. This questionnaire, together with demographic and risk factors, had been previously validated to build an algorithm to predict severe periodontitis in the Spanish population. Logistic regression models were used to evaluate the association between severe periodontitis and DM with adjustment for confounding factors. RESULTS: In total, 144 subjects developed DM, which yielded 8.2% cumulative incidence. Severe periodontitis was detected in 59.0%, 54.7% or 68.8% of the subjects depending on three different selected criteria at the 2016-2017 exam. All criteria used to define severe periodontitis were associated with DM in unadjusted analysis, but the magnitude of the association decreased after adjusting for significant confounders. The criteria '≥50% of teeth with clinical attachment loss ≥5 mm' presented an odds ratio of 4.9 (95% confidence interval: 2.2-10.7; p ≤ .001) for DM. CONCLUSIONS: Severe periodontitis is associated with DM in the Spanish population.

Metformin and Glucose Concentration as Limiting Factors in Retinal Pigment Epithelial Cell Viability and Proliferation.

Metformin is a well-established drug for the treatment of type 2 diabetes; however, the mechanism of action has not been well described and many aspects of how it truly acts are still unknown. Moreover, regarding in vitro experiments, the glycaemic status when metformin is used is generally not considered, which, added to the suprapharmacological drug concentrations that are commonly employed in research, has resulted in gaps of its mechanism of action. The aim of this study was to determine how glucose and metformin concentrations influence cell culture. Considering that diabetic retinopathy is one of the most common complications of diabetes, a retinal pigment epithelial cell line was selected, and cell viability and proliferation rates were measured at different glucose and metformin concentrations. As expected, glucose concentration by itself positively influenced cell proliferation rates. When the metformin was considered, results were conditioned, as well, by metformin concentration. This conditioning resulted in cell death when high concentrations of metformin were used under physiological concentrations of glucose, while this did not happen when clinically relevant concentrations of metformin were used independently of glucose status. Our study shows the importance of in vitro cell growth conditions when drug effects such as metformin's are being analysed.

100 Years since the Discovery of Insulin, from Its Discovery to the Insulins of the Future.

The term diabetes first emerged in the 3rd century BC, in a reference by Demetrius of Apamea, who described the disease as a dropsy in which any liquid ingested is eliminated in the form of urine. However, the great discovery that revolutionized this field came from the Canadian doctor Frederick Banting, who together with his student and assistant Charles Best, managed to isolate insulin and treat a patient with diabetes on 23 January 1922. This patient was Leonard Thompson, and the results obtained from him were surprising. His glycosuria and ketonuria disappeared and his blood glucose returned to normal. He received daily injections and lived 13 more years. Advances in the treatment of diabetes have been numerous in the 100 years since its discovery. In this review, we recapitulate the most important events that have occurred, and where research is progressing today.

Continuous Glucose Monitoring Alarms in Adults with Type 1 Diabetes: User Characteristics and the Impact of Hypoglycemia and Hyperglycemia Alarm Thresholds on Glycemic Control.

Background: Few studies have evaluated the implications of the alarm thresholds of continuous glucose monitoring (CGM) systems for individuals with diabetes. The present study aimed to investigate the influence of hypoglycemia and hyperglycemia alarm thresholds on glycemic control in adults with type 1 diabetes (T1DM) and the characteristics of patients who use these alarms more frequently. Methods: This observational cross-sectional study included 873 users of the FreeStyle Libre 2 system (501 men, median age 48 years, range 18-90 years) with T1DM from a single center. We investigated the role of demographic and metabolic factors on the use of alarms and the impact of hypoglycemia and hyperglycemia alarms and their thresholds on glycemic control. Results: Alarm users were older than nonusers (median age 49 vs. 43 years, respectively; P < 0.001). The hypoglycemia alarms were set by 76.1% of women and by 69.1% of men (P = 0.022). The hypoglycemia alarms reduced hypoglycemia features and glucose variability, although at the expense of shorter time in range. The higher the hypoglycemia alarm threshold, the greater these effects. The hyperglycemia alarms were effective in reducing hyperglycemia and lowering the glucose management indicator, although at the expense of a greater tendency to hypoglycemia. The lower the hyperglycemia alarm threshold, the greater these effects. Conclusions: CGM alarms contribute to better glycemic control. However, hypoglycemia and hyperglycemia alarms have advantages and disadvantages. Adults with T1DM should explore, under medical supervision, which alarm thresholds will best help them achieve their individual glycemic goals.

Use of Tirzepatide in Adults with Type 2 Diabetes Mellitus: Scientific Evidence and Practical Aspects.

Tirzepatide is a novel antidiabetic medication a single-molecule, agonist to the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors. It is approved in the USA and EU for the treatment of type 2 diabetes mellitus (T2DM) and obesity. Due to the potential novelty represented by incorporating tirzepatide to clinical practice, we aim to review practical aspects of tirzepatide use in T2DM and the supporting scientific evidence. A group of ten endocrinologists involved as investigators in the phase 3 SURPASS clinical trial program followed a nominal group technique, a qualitative research methodology designed as a semi-structured group discussion to reach a consensus on the selection of a set of practical aspects. The scientific evidence for tirzepatide has been reviewed with respect to a number of patients' clinical profiles and care goals. Information of interest related to adverse events, special warnings and precautions, and other considerations for tirzepatide use has been included. Finally, information provided to the patients has been summarized. The practical aspects reported herein may be helpful in guiding physicians in the use of tirzepatide and contribute to optimizing the management of T2DM.

Diferencias de género en la mortalidad de personas con diabetes tipo 2: Estudio Asturias 2018 / Gender differences in the mortality of people with type 2 diabetes: Asturias Study 2018

OBJETIVO: Investigar la influencia del sexo en la mortalidad según la presencia o ausencia de diabetes mellitus tipo 2 (DM2) y otros factores de riesgo cardiovascular en la cohorte del Estudio Asturias. MÉTODO: El Estudio Asturias (iniciado en 1998) es un estudio de cohortes observacional, prospectivo, de una muestra representativa de la población asturiana de entre 30 y 75 años. Se dividió la población en grupos según la presencia o ausencia de DM2 y el sexo para valorar el control de los factores de riesgo cardiovascular. Además, conociendo el estatus vital de la cohorte 18 años después del inicio del estudio, se analizaron las diferencias en causas de mortalidad según las categorías anteriores. RESULTADOS: En 1998 iniciaron el estudio 1034 personas, de las cuales 561 eran mujeres (54,25%) y 473 eran hombres (45,75%). Padecían diabetes 131 (12,66%; 75 varones y 56 mujeres). Las mujeres con DM2 presentaron una hazard ratio (HR) para mortalidad total de 1,64 (intervalo de confianza del 95% [IC95%]: 0,97-2,77), y los hombres de 1,63 (IC95%: 1,07-2,50); para mortalidad cardiovascular, la HR fue de 3,06 (IC95%: 1,44-6,47) en las mujeres y de 1,49 (IC95%: 0,64-3,46) en los hombres. La tasa de mortalidad para las personas con DM2 en ambos sexos fue más alta que para las personas sin DM2. CONCLUSIONES: Las mujeres con DM2 tienen un riesgo de fallecer por causas cardiovasculares tres veces mayor que las mujeres sin DM2. Deberían implementarse estrategias de tratamiento en las mujeres con esta condición

OBJECTIVE: To investigate the influence of gender on mortality according to the presence or absence of type 2 diabetes mellitus (DM2) and other cardiovascular risk factors in the Asturias Study cohort. METHOD: The Asturias Study (started in 1998) is an observational, prospective cohort study of a representative sample of a population of Asturias aged 30-75 years. The population was divided into groups according to the presence or absence of DM2 and according to gender to assess control of cardiovascular risk factors. In addition, aware of the vital status of the cohort 18 years after the beginning of the study, we analyzed differences in causes of mortality according to the previous categories. RESULTS: In 1998, 1034 people started the study, 561 women (54.25%) and 473 men (45.75%). Of these, 131 (12.66%) had diabetes (75 men and 56 women). The women with T2D presented a hazard ratio (HR) for total mortality of 1.64 (95% confidence interval [95%CI]: .97-2.77), which was 1.63 (95%CI: 1.07-2.50) for the men and, for cardiovascular mortality, 3.06 (95%CI: 1.44-6.47) for the females, versus 1.49 (95%CI: 0.64-3.46) for the males. The mortality rate for people with T2D of both sexes was higher than for people without T2D. CONCLUSIONS: Women with T2D have a risk more than three times higher than women without diabetes of dying from cardiovascular causes. We should implement treatment strategies in women with this condition

Evaluación hemodinámica no invasiva a largo plazo de la terapia de resincronización cardíaca endocárdica izquierda / Long-term Non-invasive Hemodynamic Evaluation of Left Endocardial Cardiac Resynchronization Therapy

RESUMEN Introducción: La terapia de resincronización cardíaca presenta una tasa de un 25%-30% de pacientes "no respondedores". La resincronización endocárdica, en la que el catéter del ventrículo izquierdo se implanta en el endocardio, sería una alternativa para estos pacientes, aunque su evolución a largo plazo no ha sido investigada. Objetivos: Evaluación hemodinámica no invasiva a largo plazo de la resincronización endocárdica en respondedores clínicos. Métodos: Se incluyeron pacientes implantados según los criterios para resincronización, usando la técnica Jurdham, con más de 6 meses desde el implante. Todos eran respondedores clínicos. La respuesta hemodinámica se evaluó con un analizador de la función cardíaca, que mide los intervalos sistólicos (períodos preeyectivo y eyectivo) del ventrículo izquierdo y calcula automáticamente un índice de función sistólica y estimar la fracción de eyección (Systocor mod ÍS100). Para determinar la eficacia mecánica de la TRCe se comparó la función cardíaca durante el modo biventricular con el bloqueo completo de la rama izquierda, espontáneo o por estimulación única del ventrículo derecho; los pacientes fueron sus propios controles. Se promediaron al menos 20 latidos en cada modo de estimulación y se consideraron solo los cambios >1% con valor p < 0,01 como clínicamente relevantes y estadísticamente significativos. Resultados: Se incluyeron 17 pacientes, con mediana de seguimiento de 43 meses, rango 9 a 78 meses. La resincronización endocárdica, en comparación con la activación ventricular con BCRI, demostró que todos los pacientes acortaron el período preeyectivo en un promedio de 31 ms (15%), indicativo de disminución de la disincronía interventricular causada por el BCRI. En todos aumentó el índice de función sistólica en 0,3 (23%) y la FE en el 8,3%. En 12/17 (71%) aumentó el período eyectivo en promedio 8,7 mseg (2,9%), lo que sugiere un aumento del volumen sistólico. En todos los cambios el valor de p fue menor de 0,01. Conclusiones: La TRCe ofrece mejoría hemodinámica significativa a largo plazo, detectada por intervalos sistólicos.

ABSTRACT Background: Cardiac resynchronization therapy has 25% to 30% rate of "non-responder" patients. Endocardial cardiac resynchronization therapy (eCRT), in which the left ventricular catheter is implanted in the endocardium, would be an alternative for these patients; however, its long-term outcome has not been investigated. Objectives: The aim of this study was the long-term non-invasive hemodynamic evaluation of eCRT in clinical responders. Methods: Patients implanted according to the criteria for resynchronization, using the Jurdham technique, with more than 6 months after the implant, were included in the study. All were clinical responders. The hemodynamic response was evaluated with a cardiac function analyzer, which measures the left ventricular systolic intervals (preejection and ejection periods) and automatically calculates an index of systolic function and estimates the ejection fraction (Systocor mod ÍS100). To assess the mechanical efficacy of eCRT, the cardiac function during biventricular mode was compared with left bundle branch block (LBBB), either spontaneous or by single stimulation of the right ventricle, with patients as their own controls. At least 20 beats were averaged in each stimulation mode and only changes >1% with p <0.01 were considered as clinically relevant and statistically significant. Results: Seventeen patients were included, with a median follow-up of 43 months, (9 to 78 months). Endocardial resynchronization, compared with LBBB ventricular activation, showed that all patients shortened the preejection period by an average of 31 ms (15%), indicative of decreased interventricular dyssynchrony caused by LBBB. In all patients, systolic function index increased by 0.3 (23%) and the EF by 8.3%. In 12/17 of cases (71%) the ejective period increased on average 8.7 ms (2.9%), suggesting an increase in systolic volume. In all changes p was <0.01. Conclusions: Endocardial resynchronization therapy offers significant long-term hemodynamic improvement, detected by systolic intervals.

Prevalencia, diagnóstico, tratamiento y control de la hipertensión arterial en España. Resultados del estudio Di@bet.es / Prevalence, diagnosis, treatment, and control of hypertension in Spain. Results of the Di@bet.es Study

Introducción y objetivos: El Di@bet.es es un estudio nacional diseñado con el objetivo de estimar la prevalencia de diabetes mellitus y otros factores de riesgo cardiovascular en la población adulta española. Se presenta la prevalencia de hipertensión arterial y en qué grado se reconoce, se trata y se controla. Métodos: Se incluye una muestra de la población española con 5.048 adultos de edad ≥ 18 años. Se realizó un interrogatorio clínico y una exploración que incluyó 3 lecturas de presión arterial en reposo y sedestación para calcular la media de las 3 lecturas. Se definió hipertensión como presión arterial sistólica ≥ 140 mmHg y/o presión arterial diastólica ≥ 90 mmHg y/o en tratamiento farmacológico antihipertensivo. Resultados: El 42,6% de la población adulta española de edad ≥ 18 años es hipertensa, más los varones (49,9%) que las mujeres (37,1%). La prevalencia fue superior entre los prediabéticos (67,9%) y diabéticos (79,4%). El 37,4% de los hipertensos están sin diagnosticar, más los varones (43,3%) que las mujeres (31,5%). Toman tratamiento farmacológico el 88,3% de los hipertensos conocidos y solo el 30% tiene la presión arterial controlada, más las mujeres (24,9%) que los varones (16%). Conclusiones: La prevalencia de hipertensión en España es alta y un importante porcentaje de pacientes hipertensos aún están sin diagnosticar. La hipertensión se asoció con diabetes y prediabetes, y aunque el tratamiento farmacológico es cada vez más frecuente, no logra mejorar el grado de control, que continúa siendo bajo. Es importante desarrollar y promocionar campañas poblacionales de prevención, detección y tratamiento de la hipertensión arterial (AU)

Introduction and objectives: Di@bet.es is a national study designed to estimate the prevalence of diabetes mellitus and other cardiovascular risk factors in the Spanish adult population. The prevalence of hypertension and the degree to which it is recognized, treated, and controlled are described. Methods: The study included a sample of the Spanish population with 5048 adults aged ≥ 18 years. Patients were questioned and examined, with 3 blood pressure readings while seated and at rest to calculate the mean of the 3 readings. Hypertension was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg and/or prescription for antihypertensive drug therapy. Results: Hypertension was found in 42.6% of the Spanish adult population aged ≥ 18 years and was more common among men (49.9%) than women (37.1%). The prevalence was higher among prediabetics (67.9%) and diabetics (79.4%). Undiagnosed hypertension was identified in 37.4% of patients and was more common in men (43.3%) than in women (31.5%). Among patients with known hypertension, 88.3% were receiving drug therapy. Well-controlled blood pressure was found in only 30% and was more common among women (24.9%) than men (16%). Conclusions: The prevalence of hypertension in Spain is high, and a considerable percentage of hypertensive patients have still not been diagnosed. Hypertension is associated with diabetes and prediabetes, and although drug therapy is increasingly common, the degree of control has not improved and remains low. Population campaigns should be developed and promoted for hypertension prevention, detection, and treatment (AU)

Diabetes y cribado de enfermedad coronaria: ¿dónde centramos el esfuerzo? / Diabetes and screening for coronary heart disease: where should we focus our efforts?

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Control de factores de riesgo cardiovascular en pacientes diabéticos revascularizados: un subanálisis del estudio ICP- Bypass / Control of cardiovascular risk factors in revascularized patients with diabetes: A subanalysis of the ICP-bypass study

Introducción y objetivos Los diabéticos tipo 2 con enfermedad coronaria revascularizada son un grupo de muy alto riesgo cardiovascular poco estudiado. Este subanálisis del estudio ICP-Bypass analiza sus características clínicas y el control de factores de riesgo. Métodos Se seleccionó a los diabéticos tipo 2 procedentes de un estudio previo multicéntrico, observacional y transversal (ICP-Bypass) realizado en 2.293 pacientes > 18 años sometidos a cirugía coronaria o intervencionismo coronario percutáneo. Se recogieron y analizaron de manera comparativa variables demográficas y terapéuticas, así como los parámetros clínicos y analíticos. Resultados La edad media ± desviación estándar de los 771 diabéticos fue 67,7 ± 9,6 años (el 71,4% varones; tiempo medio desde la revascularización, 3,5 años). La mayoría (57,8%) recibía tratamiento con antidiabéticos orales solos y el 30,4% recibían insulina sola o combinada. La media de glucohemoglobina fue del 7,1% (en el 70%, < 7,5%). El 74,8% tenía diagnóstico de dislipemia. El colesterol unido a lipoproteínas de baja densidad medio fue 93,5 mg/dl (el 73%, > 70 mg/dl). Se administraban estatinas al 93,6 y el 18,7% recibía una estatina combinada con ezetimiba. Del 78,1% con diagnóstico de hipertensión, el 52% tenía presión arterial sistólica/diastólica < 130/80 mmHg y el 93%, < 140/90 mmHg. Conclusiones En el manejo del riesgo y la prevención cardiovascular de los pacientes diabéticos revascularizados en España se observa margen de mejora en el control de factores de riesgo, fundamentalmente la dislipemia. La existencia de pacientes con glucohemoglobina > 7,5% requeriría la evaluación individual de los objetivos de control glucémico (AU)

Introduction and objectives Patients with type 2 diabetes and revascularized coronary disease are a group with very high cardiovascular risk that has been rarely studied. This ICP-Bypass substudy analyzes the clinical characteristics and risk factor control of these patients. Methods The analysis selected patients with type 2 diabetes who had participated in an earlier multicenter, observational, cross-sectional study (ICP-Bypass) conducted in 2293 patients > 18 years of age who had undergone coronary surgery or percutaneous coronary intervention. Demographic and therapeutic variables, as well as clinical and analytical parameters, were collected and comparatively analyzed. Results The mean age (standard deviation) of the 771 diabetic patients included in the analysis was 67.7 (9.6) years (71.4% men; mean time since revascularization, 3.5 years). Most (57.8%) were receiving treatment with oral hypoglycemics alone, whereas 30.4% were receiving insulin alone or in combination. The mean glycohemoglobin figure was 7.1% (in 70%, < 7.5%); 74.8% had been diagnosed with dyslipidemia. Mean low-density lipoprotein cholesterol was 93.5 mg/dL (in 73%, > 70 mg/dL). Among these patients, 93.6% were receiving statins and 18.7% a statin combined with ezetimib. A total of 78.1% had been diagnosed with hypertension; systolic/diastolic blood pressure was < 130/80 mmHg in 52% and < 140/90 mmHg in 93%.ConclusionsCardiovascular risk and prevention may be improved in revascularized diabetic patients in Spain through further control of risk factors, particularly dyslipidemia. Patients with glycohemoglobin > 7.5% should be individually assessed in terms of glycemic targets (AU)

Tumor neuroendocrino en cérvix uterino: reporte de caso / Neuroendocrine tumor of the uterine cervix: case report

Los tumores neuroendocrinos de cuello uterino son extremadamente raros. Las mujeres con diagnóstico de carcinoma neuroendocrino de células pequeñas del cuello uterino tienen mayor frecuencia de metástasis en los ganglios linfáticos, invasión linfovascular, recurrencia y peor pronóstico en comparación con aquellos con otros tipos de neoplasias cervicales. Se presenta el caso de una mujer de 58 años, con un tiempo de enfermedad de seis años antes del ingreso, caracterizado por sangrado vaginal irregular posmenopáusica, además de sintomatología relacionada a anemia crónica. En el examen ginecológico, se evidenció tumoración de 4 cm que ocupaba tercio superior de vagina y protruía por el cérvix. Fue diagnosticado como mioma abortivo y enviada a estudio anatomopatológico. El resultado fue carcinoma neuroendocrino de células pequeñas grado III en el 90% y carcinoma epidermoide en el 10%. La paciente fue sometida a histerectomía radical más salpingo-ooferectomía bilateral y linfadenectomía pélvica bilateral y para-aortica. El estudio anatomopatológico de la pieza quirúrgica encontró endometrio y miometrio comprometido por neoplasia maligna. Parametrios, anexos y ganglios linfáticos se encontraron libres de neoplasia. A la microscopía el resultado fue carcinoma neuroendocrino grado III (carcinoma de células pequeñas, infiltrante), con extensa embolia linfovascular. El estudio de inmunohistoquímica arrojó sinaptofisina positivo en las áreas con diferenciación neuroendocrina.

Neuroendocrine tumors of the cervix are extremely rare. Women diagnosed with small cell neuroendocrine carcinoma of the cervix have a higher frequency of metastases in the lymph nodes, lymphovascular invasion, recurrence and worse prognosis compared to those with other types of cervical neoplasia. We report the case of a 58-year-old female, with a history of six years of postmenopausal irregular vaginal bleeding, in addition to symptoms related to chronic anemia. Gynecological examination showed a tumor of 4 cm that occupied the upper third of the vagina and protruded through the cervix initially diagnosed as an abortifacient myoma, and sent to histopathology study. 90% of the tumor was small cell neuroendocrine carcinoma grade III, and the remaining 10% was squamous cell carcinoma. The patient underwent into a radical hysterectomy plus bilateral salpingo-oophorectomy, and bilateral pelvic and para-aortic lymphadenectomy. Histopathologic examination of the surgical specimen found endometrium and myometrium compromised by malignancy. Parametrium, annexes and lymph nodes were free of neoplasia. At microscopy, the result was a grade III neuroendocrine carcinoma (small cell carcinoma, infiltrating), with extensive lymphovascular emboli. The immune-histochemical study showed synaptophysin positive in areas with neuroendocrine differentiation.

Efficacy of sodium glucose cotransporter 2 inhibitors as an adjunct treatment for patients with diabetes type 2 / Eficacia de los inhibidores del cotransportador sodio glucosa tipo 2 como tratamiento adyuvante en pacientes con diabetes tipo 2 tratados con insulina

Objective: To analyze the effect of sodium glucose cotransporter 2 (SGLT2) inhibitors in a group of insulin-dependent type 2 diabetes mellitus (T2D) patients. Patients and methods: One hundred and five insulin treated T2D patients were enrolled. Primary endpoints were: fasting plasma glucose, HbA1c, weight, total insulin doses (TDI), total basal insulin (TDB) and total rapid insulin (TDR). Secondary variables were: total cholesterol, LDL cholesterol (cLDL), HDL cholesterol (cHDL), triglycerides and systolic (SBP) and diastolic (DBP) blood pressure. Safety and tolerance were evaluated through the appearance of severe hypoglycemia, ketoacidosis and infections. Results: After 4 months follow-up, a 0.7 (1.0)% HbA1c reduction was found, accompanied by a −2.8 (11.5) UI/day TDI decrease. Weight dropped for 73.7% of patients, with an average −2.0 (2.7) kg reduction. A global cHDL increase was noted after treatment, while no differences were observed for total cholesterol, triglycerides or cLDL. SBP dropped significantly, but no change in DBP was observed. Conclusion: The use of SGLT2 inhibitors in insulin treated T2D patients resulted in reduction of HbA1c, which was associated to weight loss, cHDL increase and SBP decrease

Objetivo: Analizar el efecto de los inhibidores del cotransportador sodio glucosa tipo 2 (iSGLT2) en u grupo de pacientes con diabetes mellitus tipo 2 (DM2) tratados con insulina. Pacientes y métodos: Seleccionamos ciento cinco pacientes con diabetes tipo 2 tratados con insulina. Los objetivos primarios: glucosa plasmática ayunas, HbA1c, peso, dosis total de insulina (DTI), dosis de insulina basal (DTB), dosis de insulina rápida (DTR). Como secundarios: Colesterol total, LDL colesterol (cLDL), HDL colesterol (cHDL), triglicéridos and tensión sistólica (TAS) and diastólica (TAD). La seguridad y tolerancia se valoró como hipoglucemia, cetoacidosis o infecciones. Resultados: Tras 4 meses, la HbA1c se redujo en 0,7 (1,0)% acompañado de una disminución en DTI de −2,8 (11,5) UI/día. El 73,7% de los pacientes perdieron peso, con un descenso medio de −2,0 (2,7) kg. El cHDL aumentó, mientras que no observamos diferencias en el colesterol total, triglicéridos o cLDL. TAS disminuyó significativamente sin observar cambios en TAD. Conclusión: El uso de iSGLT2 en pacientes con DM2 tratados con insulina reduce la HbA1c asociando pérdida de peso, aumento enl cHDL y descenso en TAS

Experiencia tras el cambio de insulina glargina U100 a glargina U300 en pacientes con diabetes tipo 1. Estudio tras un año de tratamiento en vida real / Experience after switching from insulin glargine U100 to glargine U300 in patients with type 1 diabetes mellitus. A study after one year of treatment in real life

Introducción: Los tratamientos insulínicos actuales para diabetes tipo 1 (DM1) no siempre consiguen los objetivos de control metabólico debido, entre otros aspectos, a la aparición de episodios de hipoglucemia asociados al uso de insulina. Material y métodos: Estudio descriptivo en la vida real con 247 pacientes DM1, el 55,5% varones, de 46,53 ± 16,23 años, con un tiempo de evolución de 21,89 ± 11,99 años, a los que se sustituyó su insulina basal, glargina U100, por glargina U300. Los objetivos primarios fueron los cambios en la HbA1c y en el número de hipoglucemias y los secundarios fueron los cambios en el peso y en la dosis de insulina trascurridos 6 y 12 meses. Resultados: Tras un año, no se observaron cambios en la HbA1c en el total de los pacientes, si bien se comprobó un descenso significativo en los pacientes mal controlados. Sin embargo, aumentó el porcentaje de pacientes con HbA1c < 7,5% a los 6 meses (33,5 vs. 40,5%; p < 0,05), que se mantuvo al año. El número de hipoglucemias leves se redujo tras los 12 meses de tratamiento en aquellos pacientes con antecedentes de hipoglucemias leves. En cuanto al peso, no observamos cambios. La dosis total de insulina/kg se incrementó significativamente en un 7,24% a los 6 meses y en un 8,69% al año por el aumento de la insulina basal. Las diferencias en las dosis a los 6 meses y al año no fueron significativas. Este aumento fue similar entre los grupos según el control metabólico, la presencia de hipoglucemias y no se relacionó con la insulina basal inicial, la HbA1c inicial, el número de hipoglucemias leves ni con el peso inicial. Discusión: En la vida real glargina U300 muestra un mejor control glucémico en pacientes mal controlados, al reducir las hipoglucemias en pacientes con antecedentes de hipoglucemias sin incrementar el peso corporal

Introduction: Current treatment of type 1 diabetes mellitus (T1DM) does not always achieve metabolic control because, among other things, the ocurrence of hypoglycemic events associated to insulin use. Material and methods: A descriptive real life study of 247 T1DM patients, 55.5% male, aged 46.53 ± 16.23 years, and with a mean diabetes duration of 21.89 ± 11.99 years, who were switched from basal insulin glargine U100 to glargine U300. The primary endpoints were changes in Hba1c and number of hypoglycemic events, while secondary endpoints included changes in weight and insulin dose after 6 and 12 months. Results: After one year, no changes were seen in HbA1c, but the proportion of patients with HbA1c values <7.5% increased at 6 months (33.5 vs. 40.5%; P<0.05) and remained stable during one year of follow-up. Hypoglycemic events significantly decreased after one year of treatment in patients with previous hypoglycemic events. No changes were seen in body weight. Total insulin dose (U/kg) increased 7.24% at 6 months of treatment and by 8.69% at one year, mainly due to basal insulin. No changes were seen between the doses given at 6 and 12 months. These changes were similar in the different metabolic control groups and in patients with or without hypoglycemia. This increase was not related with prior basal insulin dose, baseline HbA1c level, number of hypoglycemic events or baseline weight. Discussion: Glargine U300 is a good basal insulin alternative to treat T1DM, improving metabolic control in patients with HbA1c levels >7,5 and decreasing hypoglycemic events in patients with history of hypoglycemia without increasing body weight

Necesidades no cubiertas en el tratamiento de la diabetes mellitus tipo 2 / Unmet needs in the treatment of type 2 diabetes

La diabetes mellitus tipo 2 es uno de los problemas de salud más importantes en el mundo debido a su elevada prevalencia y morbimortalidad. Sabemos que un control intensivo de todos los factores de riesgo cardiovascular desde el comienzo de la enfermedad previene la aparición y la progresión de las complicaciones microangiopáticas y macroangiopáticas, pero la realidad es que un escaso porcentaje de pacientes logran alcanzar los estrictos objetivos de control recomendados por las guías. Las causas son múltiples. Unas achacables al propio paciente: incumplimiento terapéutico. Otras al equipo sanitario: inercia terapéutica. Por último, el arsenal terapéutico tiene sus limitaciones, y no disponemos del fármaco ideal, que debería incidir en todas las alteraciones fisiopatológicas de la enfermedad, ser bien tolerado, tener un efecto duradero, no provocar hipoglucemias, facilitar que el paciente pierda peso, mejorar el resto de los factores de riesgo cardiovascular y demostrar una disminución de la morbimortalidad cardiovascular a largo plazo, todo ello con un coste razonable. La aparición de nuevos fármacos con mecanismos de acción atractivos desde el punto de vista fisiológico y con menos efectos secundarios puede ayudar a lograr estos objetivos. Los clínicos estamos esperando los resultados de los estudios que analizan su efecto sobre los eventos cardiovasculares a largo plazo (AU)

Type 2 diabetes represents one of the most important health problems, provided due to its high prevalence and significant morbi-mortality. At present time, we know that an intensive control of all cardiovascular risk factors from the beginning prevents the appearance and progression of micro and macrovascular complications. Nevertheless, only few patients achieve the degree of metabolic control recommended by diabetes therapeutic guidelines. This is due to different reasons such as lack of patients compliance and therapeutic inertia by doctors. Also, the available therapeutic approaches are limited. We still do not have the ideal antidiabetic drug, which should be able to be used in all phases of the disease, have sustained durability, be well tolerated not inducing hypoglycaemia, and promote weight loss, cardiovascular protection and reducing morbi-mortality at a low cost. The launching of new drugs with attractive mechanisms of action and few side effects may help to achieve these goals, though we still should wait for the results of studies demonstrating their effect on cardiovascular endpoints (AU)

Prevalence of plasma lipid abnormalities and its association with glucose metabolism in Spain: The di@bet. es study

Introduction: Dyslipidemia is a significant contributor to the elevated CVD risk observed in type 2 diabetes mellitus. We assessed the prevalence of dyslipidemia and its association with glucose metabolism status in a representative sample of the adult population in Spain and the percentage of subjects at guideline-recommended LDL-C goals. Material and methods: The di@bet.es study is a national, cross-sectional population-based survey of 5728 adults. Results: A total of 4776 subjects were studied. Dyslipidemia was diagnosed in 56.8% of subjects; only 13.2% of subjects were treated with lipid lowering drugs. Lipid abnormalities were found in 56.8% of Spanish adults: 23.3% with high LDL-C, 21.5% high TG, 35.8% high non-HDL-C, and 17.2% low HDL-C. Most normal subjects showed an LDL-C ≤ 3.36 mmol/l. Pre-diabetics presented similar proportion when considering a goal of 3.36 mmol/l, but only 35% of them reached an LDL-C goal ≤ 2.6 mmol/l. Finally, 45.3% of diabetics had an LDL-C ≤ 2.6 mmol/l, and only 11.3% achieved an LDL-C ≤ 1.8 mmol/l. Conclusions: Our study demonstrates a high prevalence of dyslipidemia in the adult Spanish population, and a low use of lipid-lowering drugs. Moreover, the number of subjects achieving their corresponding LDL-C goal is small, particularly in subjects at high cardiovascular risk, such as diabetics

Introducción: La dislipidemia es uno de los factores más importantes implicados en el riesgo de desarrollar enfermedad cardiovascular en la diabetes tipo 2. En el presente estudio evaluamos la prevalencia de dislipidemia y su asociación con el metabolismo hidrocarbonado en una muestra representativa de población adulta española y el porcentaje de sujetos que alcanzaron el objetivo de cLDL. Material y métodos: El estudio Di@bet.es está basado en los datos obtenidos de una encuesta nacional transversal en 5.728 adultos. Resultados: Se estudiaron 4.776 sujetos. La dislipidemia fue diagnosticada en el 56,8% de los sujetos; solo el 13,2% de los individuos estaban en tratamiento con fármacos hipolipemiantes. Las alteraciones lipídicas se distribuyeron del siguiente modo: 23,3% tenían cLDL elevado, el 21,5% TG elevados, el 35,8% elevación de colesterol no HDL, y el 17,2% cHDL bajo. La mayor parte de los sujetos sanos tenían cLDL ≤ 3,36 mmol/l. Los individuos prediabéticos presentaron una proporción similar si consideramos como objetivo cLDL ≤ 3,36 mmol/l, pero solo el 35% de ellos alcanzaron un objetivo de cLDL≤ 2,6 mmol/l. Finalmente, el 45,3% de los diabéticos tenían cLDL≤ 2,6 mmol/l, y solo el 11,3% alcanzaron cLDL-C ≤ 1,8 mmol/l. Conclusiones: Nuestro estudio demuestra una elevada prevalencia de dislipidemia en población adulta española, y un escaso uso de fármacos hipolipemiantes. Además, el número de sujetos que alcanzaron el objetivo de cLDL fue muy pequeño, especialmente en sujetos con elevado riesgo cardiovascular como los diabéticos

Sobrecarga oral de glucosa como herramienta para la mejora tras intervencionismo coronario percutáneo / Oral glucose tolerance test as a tool for patient improvement after percutaneous coronary intervention

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Tolerancia a la glucosa y concentraciones plasmáticas de testosterona en varones. Resultados del Estudio Asturias / Glucose tolerance and plasma testosterone concentrations in men. Results of the Asturias Study

Antecedentes y objetivo Diversos estudios realizados en varones han demostrado la existencia de una correlación entre las concentraciones séricas de andrógenos así como de proteína transportadora de hormonas sexuales (sex hormone binding globulin o SHBG), y la presencia de alteraciones de la tolerancia a la glucosa, diabetes y síndrome metabólico. El objetivo de este estudio fue evaluar las concentraciones séricas de testosterona total, SHBG y testosterona biodisponible en la cohorte del Estudio Asturias, y su asociación con el grado de tolerancia a la glucosa y el síndrome metabólico. Pacientes y métodos Se estudiaron 282 varones adultos de 36 a 85 años de edad con concentraciones séricas normales de testosterona total, evaluándose tanto su grado de tolerancia a la glucosa como la presencia o no de síndrome metabólico. Resultados Las concentraciones en suero de testosterona y testosterona biodisponible se correlacionaron negativamente con la edad, el índice de masa corporal, el perímetro de cintura, la glucemia, las concentraciones de hemoglobina glucosilada y la insulinemia. Los hombres con intolerancia a la glucosa o diabetes mellitus tenían concentraciones en suero de testosterona total, SHBG y testosterona biodisponible inferiores a las de los que tenían tolerancia normal a la glucosa. Tras el análisis multivariable, la edad y las concentraciones de testosterona (..) (AU)

Background and objective Studies in men have demonstrated a correlation between serum concentrations of androgens and sex hormone binding globulin (SHBG) with the presence of impaired glucose tolerance, diabetes and metabolic syndrome. The aim of this study was to evaluate circulating levels of total testosterone, SHBG, and bioavailable testosterone in the cohort of the Asturias Study and their association with the degree of glucose tolerance and metabolic syndrome. Patients and methods The study population consisted of 282 men aged 36 to 85 years old with normal concentrations of total testosterone. The degree of glucose tolerance and the presence of metabolic syndrome were evaluated. Results Serum concentrations of testosterone and bioavailable testosterone were negatively correlated with age, body mass index, waist circumference, blood glucose, glycated hemoglobin levels and insulin. Serum concentrations of total testosterone, bioavailable testosterone and SHBG were lower in men with glucose intolerance or diabetes than in those with normal glucose tolerance. After multivariate analysis, age and total testosterone levels were independent predictors of the presence of diabetes or glucose intolerance. The risk of glucose intolerance or diabetes mellitus was over 2.5 times higher in men with total testosterone levels in the lowest quartile than in those with total testosterone in the top quartile. Conclusions In this general population sample from Asturias, men with lower plasma concentrations of total testosterone – even when within the normal range – have an increased risk of glucose intolerance or diabetes, regardless of age and body mass index (AU)

Rendimiento de la glucohemoglobina y un modelo de riesgo para la detecci¨®n de diabetes desconocida en pacientes coronarios / Performance of glycated hemoglobin and a risk model for detection of unknown diabetes in coronary patients

Introducción y objetivos: Clásicamente, la sobrecarga oral de glucosa ha diagnosticado la diabetes desconocida. Recientemente, la American Diabetes Association ha aceptado un valor de glucohemoglobina ≥ 6,5% como criterio de diabetes desconocida. Pretendemos conocer la rentabilidad que tiene la glucohemoglobina para la detección de diabetes desconocida y validar un modelo que permita ajustar la realización de la sobrecarga oral de glucosa en enfermos coronarios. Métodos: Se estudia el perfil glucémico de 338 enfermos coronarios sin diabetes conocida. Se usan los criterios de la American Diabetes Association de 2010 y, mediante regresión logística, se construye un modelo predictor de diabetes desconocida. Se valida el modelo en otra cohorte. Resultados: Se diagnosticó diabetes desconocida a 26 enfermos mediante glucohemoglobina y/o glucemia basal. Los demás presentaban, tras realizar sobrecarga oral de glucosa: diabetes desconocida, 53 (17%); prediabetes, 144 (46,2%), y normoglucemia, 115 (36,8%). Método diagnóstico de diabetes desconocida: glucemia basal, 25,3%; glucohemoglobina, 7,6%, y sobrecarga oral de glucosa, 67,1%. Un modelo que incluye glucemia basal, glucohemoglobina, fracción de eyección de ventrículo izquierdo, edad y enfermedad vascular no coronaria resultó eficaz como predictor de diabetes desconocida tras sobrecarga oral de glucos: área bajo la curva ROC, 0,8 (intervalo de confianza del 95%, 0,74-0,87). Realizando sobrecarga oral de glucosa sólo a la población con puntuación del modelo > 6 (el 31% del total), podemos localizar al 83% de los casos de diabetes desconocida reales (sensibilidad, 75%; especificidad, 73%; valor predictivo positivo, 40%; valor predictivo negativo, 93%). El modelo se validó correctamente en otra cohorte de 115 pacientes (área bajo la curva ROC, 0,84 [intervalo de confianza del 95%, 0,74-0,95]). Conclusiones: La glucohemoglobina diagnostica aisladamente pocos casos de diabetes desconocida. Sin embargo, su incorporación a un modelo de riesgo permite optimizar la indicación de la sobrecarga oral de glucosa, con un aprovechamiento óptimo (AU)

Introduction and objectives: Traditionally, the oral glucose tolerance test has been useful to diagnose unknown diabetes. Recently, the American Diabetes Association committee has accepted glycated hemoglobin ≥6.5% as a criterion for unknown diabetes. The aim was to determine the benefit of glycated hemoglobin for diagnosing unknown diabetes and also create a predictive model that adjusts the indication for oral glucose tolerance test in coronary patients. Methods: We examined the glycemic profile of 338 coronary patients without previous diagnosis of diabetes, applying 2010 American Diabetes Association criteria. A unknown diabetes risk predictive model was developed using logistic regression analysis, and then validated in another cohort. Results: Using the glycated hemoglobin criteria and/or fasting plasma glucose, unknown diabetes was diagnosed in 26 patients. The remaining patients were classified according to oral glucose tolerance test as follows: unknown diabetes 53 (17%), prediabetes 144 (46.2%), and normoglycemic 115 (36.8%). The diagnostic method for unknown diabetes was fasting plasma glucose in 25.3%, glycated hemoglobin in 7.6%, and oral glucose tolerance test in 67.1%. A risk model including fasting plasma glucose, glycated hemoglobin, left ventricular ejection fraction, age, and noncoronary vascular disease was shown to effectively predict unknown diabetes after oral glucose tolerance test: area under the ROC curve 0.8 (95% interval confidence: 0.74-0.87). When the oral glucose tolerance test is restricted to patients with a risk score >6 (31% of our sample) we properly identify 83% of unknown diabetes cases (sensitivity: 75%, specificity: 73%, positive predictive value: 40%, negative predictive value: 93%). The model was adequately validated in another cohort of 115 patients (area under the ROC curve 0.84 [95% interval confidence: 0.74-0.95]). Conclusions: In coronary patients, glycated hemoglobin alone failed to detect many cases of unknown diabetes. However, its inclusion in a risk prediction model leads to optimizing the usefulness of oral glucose tolerance test (AU)

Riesgo de mortalidad en diabetes diagnosticada, diabetes no diagnosticada y prediabetes en población adulta española. Estudio Asturias 1998-2004 / Mortality risk in spanish adults with diagnosed diabetes, undiagnosed diabetes or pre-diabetes. The Asturias Study 1998–2004

Introducción y objetivos. Aunque la diabetes mellitus DM tipo 2 es una causa establecida de mortalidad, el riesgo de mortalidad asociado a DM no diagnosticada y a estadios previos de disglucemia no está claramente definido. Métodos. El estudio incluyó a 1.015 individuos de 30-75 años de edad que participaron en la primera fase del Estudio Asturias (1998-1999), realizando encuesta, exploración física y SOG. Se registraron los fallecimientos en la cohorte durante 6 años de seguimiento (diciembre de 1998 a diciembre de 2004). Resultados. Se clasificó a los sujetos en cuatro grupos según el resultado de la SOG en la primera fase del estudio: normoglucemia, prediabetes, DM ignorada y DM conocida (criterios de la OMS 1999). Se registraron 42 muertes durante el seguimiento. Respecto al grupo control con normoglucemia, el riesgo relativo (RR) de mortalidad en el modelo multivariable fue 2,5 (intervalo de confianza [IC] del 95%, 1-6,3) en el grupo con DM conocida, RR = 2,7 (IC del 95%, 1,1-6,7) en el grupo con DM ignorada y RR = 1,6 (IC del 95%, 0,7-4) en el grupo con prediabetes. Conclusiones. Tanto los individuos con DM conocida como los que tenían DM no diagnosticada presentaron un riesgo de mortalidad alrededor de 2,5-3 veces superior al de los individuos con normoglucemia. En individuos con prediabetes también se encontró un incremento de mortalidad frente al grupo control, aunque no estadísticamente significativo (AU)

Introduction and Objectives. Although type-2 diabetes is a well-known cause of death, the mortality associated with undiagnosed diabetes and early-stage dysglycemia has not been clearly determined. Methods. This study included 1015 individuals aged 30-75 years who took part in the first phase of the Asturias study (1998-1999). Participants completed a questionnaire and underwent a physical examination and an oral glucose tolerance test (OGTT). All deaths that occurred in the cohort within 6 years of follow-up (ie December 1998 to December 2004) were recorded. Results. Participants were divided into four groups according to the condition indicated by their OGTT result in the first phase of the study: normoglycemia, pre-diabetes, undiagnosed diabetes, or diagnosed diabetes (World Health Organization 1999 criteria). A total of 42 deaths were recorded during follow-up. With normoglycemic individuals acting as a control group, multivariate analysis showed that the relative risk of mortality was 2.5 (95% CI, 1-6.3) in the group with diagnosed diabetes, 2.7 (95% CI, 1.1-6.7) in the group with undiagnosed diabetes, and 1.6 (95% CI, 0.7-4) in the group with pre-diabetes. Conclusions. Both individuals with diagnosed diabetes and those with undiagnosed diabetes had a risk of mortality around 2.5-3 times greater than individuals with normoglycemia. Those with pre-diabetes also had increased mortality relative to the control group, though the difference was not significant. multivariate analysis showed that the relative risk of mortality was 2.5 (95% CI, 1-6.3) in the group with diagnosed diabetes, 2.7 (95% CI, 1.1-6.7) in the group with undiagnosed diabetes and 1.6 (95% CI, 0.7-4) in the group with pre-diabetes. Conclusions. Both individuals with diagnosed diabetes and those with undiagnosed diabetes had a risk of mortality around 2.5-3 times greater than individuals with normoglycemia. Those with pre-diabetes also had increased mortality relative to the control group, though the difference was not significant (AU)