Safety and efficacy of P2Et extract from Caesalpinia spinosa in breast cancer patients: study protocol for a randomized double blind phase II clinical trial (CS003-BC).

BACKGROUND: Chemotherapy in breast cancer is effective but can generate significant toxicity and lead to tumor resistance. Joint treatment with standardized plant extracts can be an alternative to improve the response and allow an effective activation of the antitumor immune response that favors recovery in the short and long term. The P2Et extract of Caesalpinia spinosa presents antitumor activity in cells and animal models of breast cancer, improves the tumor microenvironment, and induces activation of the specific immune response against the tumor and is synergistic when used together with anthracyclines, which makes it a good candidate for evaluation in patients. METHODS: Conducted at a single center, this phase II study is a randomized, double-blind, placebo-controlled trial aimed at assessing the safety and efficacy of P2Et extract in patients diagnosed with stage II and III breast cancer, who are eligible for neoadjuvant treatment. The study aims to determine the safety profile at the previously established optimal biological dose from phase I trial while investigating various efficacy outcomes. These outcomes include improvements in quality of life, immunomodulation, metabolic profile, microbiome, as well as clinical indicators such as tumor reduction, disease-free survival, and pathological response, assessed at different stages of the treatment regimen. DISCUSSION: Treatment with the P2Et extract in breast cancer patients is hypothesized to enhance overall well-being, positively influencing their quality of life, while also triggering an antitumor immune response and enhancing immune infiltration. These combined effects have the potential to contribute to improved long-term survival outcomes for patients receiving the phytomedicine alongside neoadjuvant chemotherapy treatment. TRIAL REGISTRATION: This trial was registered in the US National Library of Medicine with identifier NCT05007444. First Registered August 16th, 2021. Last Updated: August 9th, 2022.

Exploring the safety and efficacy of phytomedicine Petiveria alliacea extract (Esperanza) in patients with metastatic gastrointestinal tumors and acute leukemias: study protocol for a phase Ib/randomized double blind phase II trial (PA001).

BACKGROUND: The energy metabolism of drug-resistant tumor cells can provide a survival advantage during therapy, and treatment itself may influence metabolic reprogramming. Petiveria alliacea (Traditional name: Anamu) could inhibit glycolysis and OXPHOX modulating tumor metabolism, making it a potential treatment for tumors with altered metabolism. This clinical study aims to evaluate the safety and efficacy of a standardized Anamu phytomedicine called Esperanza in treating gastric tumors and acute leukemias. METHODS: This is a prospective, open label, phase I/ randomized, double-blind single-center phase II study designed to evaluate the safety and efficacy of Esperanza extract in patients with metastatic gastrointestinal tumors and acute leukemias. In stage 1, the study will determine the MTD and assess safety. In stage 2, safety at the MTD will be evaluated, and the efficacy of Esperanza extract will be explored in both metastatic gastric tumors and acute leukemias. Quality of life improvement will be the primary outcome in the gastric tumor group, while different efficacy outcomes will be assessed in the acute leukemia group. A placebo group will be used for comparison in the gastric tumor group, and a historical control group will be used in the acute leukemia arm. DISCUSSION: This clinical trial aims to evaluate the safety profile of the Esperanza extract in patients with metastatic gastrointestinal tumors and acute leukemias, while exploring its potential efficacy in conjunction with standard treatment for these pathologies. TRIAL REGISTRATION: This trial was registered in the US National Library of Medicine with identifier NCT05587088. Registered October 19th, 2022.

Randomized double-blind clinical study in patients with COVID-19 to evaluate the safety and efficacy of a phytomedicine (P2Et).

Background: It has been proposed that polyphenols can be used in the development of new therapies against COVID-19, given their ability to interfere with the adsorption and entrance processes of the virus, thus disrupting viral replication. Seeds from Caesalpinia spinosa, have been traditionally used for the treatment of inflammatory pathologies and respiratory diseases. Our team has obtained an extract called P2Et, rich in polyphenols derived from gallic acid with significant antioxidant activity, and the ability to induce complete autophagy in tumor cells and reduce the systemic inflammatory response in animal models. Methods: In this work, a phase II multicenter randomized double-blind clinical trial on COVID-19 patients was designed to evaluate the impact of the P2Et treatment on the clinical outcome and the immunological parameters related to the evolution of the disease. The Trial was registered with the number No. NCT04410510*. A complementary study in an animal model of lung fibrosis was carried out to evaluate in situ lung changes after P2Et in vivo administration. The ability of P2Et to inhibit the viral load of murine and human coronaviruses in cellular models was also evaluated. Results: Patients treated with P2Et were discharged on average after 7.4 days of admission vs. 9.6 days in the placebo group. Although a decrease in proinflammatory cytokines such as G-CSF, IL-15, IL-12, IL-6, IP10, MCP-1, MCP-2 and IL-18 was observed in both groups, P2Et decreased to a greater extent G-CSF, IL-6 and IL-18 among others, which are related to lower recovery of patients in the long term. The frequency of T lymphocytes (LT) CD3+, LT double negative (CD3+CD4-CD8-), NK cells increased in the P2Et group where the population of eosinophils was also significantly reduced. In the murine bleomycin model, P2Et also reduced lung inflammation and fibrosis. P2Et was able to reduce the viral replication of murine and human coronaviruses in vitro, showing its dual antiviral and anti-inflammatory role, key in disease control. Conclusions: Taken together these results suggest that P2Et could be consider as a good co-adjuvant in the treatment of COVID-19. Clinical trail registration: https://clinicaltrials.gov/ct2/show/NCT04410510, identifier: NCT04410510.

Validation of the Finnish Type 2 Diabetes Risk Score (FINDRISC) with the OGTT in Health Care Practices in Europe.

AIMS: /hypothesis. To determine the best cut-off threshold value of the Finnish Diabetes Risk Score (FINDRISC) for the detection of diabetes and non-diabetic hyperglycaemia in people 35 years or older at primary health care settings in Europe. METHODS: Cross-sectional study in 11,444 adults from primary health care centres using community and opportunistic screening approaches. All participants completed the FINDRISC questionnaire and underwent a 2-hour oral glucose tolerance test (OGTT). The FINDRISC performance was assessed by the area under the curve (AUC) using receiver operating characteristics (ROC) analysis. The sensitivity, specificity, Youdens index, positive and negative prediction values for different FINDRISC cut-offs were calculated. RESULTS: The optimal FINDRISC value for detecting both diabetes or glucose impairment in the community - screened sample was 14 point with the associated AUC 0.75,5 (95 %CI 0.73,7-0.77,3). The optimal score in the opportunistic screening sample was 16 with the associated AUC only 0.60,4 (95% CI 0.56, 4-0.64, 4). CONCLUSIONS/INTERPRETATION: The FINDRISC is a non-invasive tool useful for detecting people with unknown diabetes and glucose impairment in people visiting primary health centres in Europe.

Screening, prevalence, treatment and control of kidney disease in patients with type 1 and type 2 diabetes in low-to-middle-income countries (2005-2017): the International Diabetes Management Practices Study (IDMPS).

AIMS/HYPOTHESIS: Diabetes is the leading cause of kidney disease worldwide. There is limited information on screening, treatment and control of kidney disease in patients with diabetes in low-to-middle-income countries (LMICs). METHODS: The International Diabetes Management Practices Study is an ongoing, non-interventional study of clinical profiles and practices among patients receiving outpatient care mainly by internal medicine physicians and endocrinologists in LMICs. We examined screening, prevalence, treatment and control of kidney disease across seven waves (W) of data collection between 2005 and 2017. RESULTS: Among 15,079 patients with type 1 and 66,088 patients with type 2 diabetes, screening for kidney disease increased between W2 and W3 followed by a plateau (type 1 diabetes: W2, 73.7%; W3, 84.1%; W7, 83.4%; type 2 diabetes: W2, 65.1%; W3, 82.6%; W7, 86.2%). There were also decreasing proportions of patients with microalbuminuria (type 1 diabetes: W1, 27.1%; W3, 14.7%; W7, 13.8%; type 2 diabetes: W1, 24.5%; W3, 12.6%; W7, 11.9%) and proteinuria (type 1 diabetes: W1, 14.2%; W3, 8.7%; W7, 8.2%; type 2 diabetes: W1, 15.6%; W3, 9.3%; W7, 7.6%). Fewer patients were reported as receiving dialysis for both type 1 diabetes (W2, 1.4%; W7, 0.3%) and type 2 diabetes (W2, 0.9%; W7, 0.2%) over time. While there was no change in mean HbA1c or prevalence of diagnosed hypertension (type 1 diabetes: W1, 22.7%; W7, 19.9%; type 2 diabetes: W1, 60.9%; W7, 66.2%), the use of statins had increased among patients diagnosed with dyslipidaemia (type 1 diabetes: W1, 77.7%; W7, 90.7%; type 2 diabetes: W1, 78.6%; W7, 94.7%). Angiotensin II receptor blockers (type 1 diabetes: W1, 18.0%; W7, 30.6%; type 2 diabetes: W1, 24.2%; W7, 43.6%) were increasingly used over ACE inhibitors after W1 (type 1 diabetes: W1, 65.0%; W7, 55.9%; type 2 diabetes: W1, 55.7%, W7, 41.1%) among patients diagnosed with hypertension. CONCLUSIONS/INTERPRETATION: In LMICs, real-world data suggest improvement in screening and treatment for kidney disease in patients with type 1 and type 2 diabetes attending non-nephrology clinics. This was accompanied by decreasing proportions of patients with microalbuminuria and proteinuria, with fewer patients who reported receiving dialysis over a 12-year period.

Transculturalizing Diabetes Prevention in Latin America.

BACKGROUND: Type 2 diabetes (T2D) imposes a heavy burden in developing countries, requiring effective primary prevention policies. Randomized clinical trials have identified successful strategies in T2D prevention. However, translating these results to real-life scenarios and adapting to ethnocultural differences is a major challenge. Transculturalization allows incorporating cultural factors to diabetes prevention strategies to optimize implementation of clinical trials results. The purpose of this paper is to review the transcultural adaptations developed for T2D prevention in Latin America (LA). METHODS: A comprehensive literature review spanning 1960-2016 was performed, using "Diabetes," "Latin America," "Prevention," "Screening," and "Tools" as key words. RESULTS: Two major tasks are underway in LA: adaptation of screening tools for high-risk individuals, and implementation of diabetes prevention programs. The Finnish Diabetes Risk Score (FINDRISC) is the most widely used screening tool to detect new cases of T2D and people with prediabetes, and it has been adapted (LA-FINDRISC) to include the waist circumference cutoff values appropriate for LA population (≥94 cm for men and ≥90 cm for women). The validation of the LA-FINDRISC performance depends on the local characteristics. A LA-FINDRISC score >10 may be the best cutoff to identify individuals with impaired glucose regulation in population-based studies, but a higher score (>12-14) might be more appropriate in a clinical setting. A shorter version of the FINDRISC using only the 4 variables with highest impact has been developed and validated in Colombia (ColDRISC). The translation of the Diabetes Prevention Program study in a Latino population in Venezuela found a significant improvement in cardiometabolic risk factors. An adaptation of the Diabetes Prevention Study in the DEMOJUAN study in Barranquilla, Colombia, reduced 2-hour postload glucose. CONCLUSION: Successful transculturalization strategies have been implemented in screening tools and prevention programs in LA.

Recent advances in understanding/managing type 2 diabetes mellitus.

The treatment of type 2 diabetes mellitus has evolved in the present century toward safer and maybe more effective drugs, which in some cases can also reduce the risk of cardiovascular and renal outcomes. Nevertheless, we still need better strategies to reduce excess body weight in order to achieve diabetes remission, which is now a feasible target, as has been demonstrated with bariatric surgery. This review focuses on the significant advances in the management of blood glucose in type 2 diabetes mellitus, including the current understanding of the mechanisms of drug action but keeping in mind that the treatment of the disease is multifactorial.

Cardio-Metabolic Health Venezuelan Study (EVESCAM): Design and Implementation / Estudio Venezolano de Salud Cardio-Metabólica (EVESCAM): Diseño e Implementación

The EVESCAM (EstudioVenezolano de Salud Cardio-Metabólica) is the first national, population survey in Venezuela, designed to examine the prevalence of diabetes and cardio-metabolic risk factors and its relationship with lifestyle. It is a cross-sectional, cluster sampling study, which recruited 4454 participants aged ≥ 20 years. The data were collected in community health-care centers by trained health professionals and medical students. The data collected from each subject included, after informed consent, structured questionnaires (clinical, demographic, physical activity, nutritional and psychological), anthropometric measurements (weight, height and waist circumference), body fat by bioelectrical impedance, hand grip, blood pressure, electrocardiogram, and biochemical measurements (standard 75 g oral glucose tolerance test, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). The data will be used to estimate the prevalence of overweight, obesity, prediabetes, diabetes, hypertension, dyslipidemias, sarcopenia and metabolic syndrome; and to examine their relationships with lifestyle factors. The risk of coronary heart disease and impaired glucose regulation will be estimated using the Framingham Coronary Heart Disease Risk Score and the Latin America adaptation of the Finnish Diabetes Risk Score (LA-FINDRISC), respectively. These results will guide national cardiovascular and diabetes prevention strategies, and will be available for government agencies to help in the implementation of public health policies.

El EVESCAM (Estudio Venezolano de Salud Cardio-Metabólica) es el primer estudio poblacional de muestreo nacional en Venezuela diseñado para examinar la prevalencia de diabetes y factores de riesgo cardio-metabólico, y su relación con el estilo de vida. Se trata de un estudio transversal de muestreo por conglomerados, reclutando 4454 participantes de 20 años o más. Los datos fueron recogidos en centros de salud de la comunidad por profesionales de salud y estudiantes de medicina entrenados. Después del consentimiento infor mado, los datos recolectados en cada sujeto incluyeron: cuestionarios estructurados (clínico, demográfico, actividad física, nutricional y psicológico), medidas antropométricas (peso, talla y circunferencia de cintura), grasa corporal por impedancia bioeléctrica, fuerza de aprehensión de la mano, presión arterial, electrocardiograma y medidas bioquímicas (prueba de tolerancia a la glucosa oral estándar con 75 g de glucosa, colesterol total, colesterol HDL, colesterol LDL y triglicéridos). Los datos se utilizarán para estimar la prevalencia de sobrepeso, obesidad, prediabetes, diabetes, hipertensión arterial, dislipidemias, sarcopenia y síndrome metabólico; y para examinar sus relaciones con factores de estilo de vida. El riesgo de cardiopatía coronaria y de alteración de la regulación de la glucosa se calculará utilizando la puntuación de riesgo de la enfermedad coronaria de Framingham y la adaptación para Latinoamérica de la puntuación finlandesa del riesgo de diabetes (LA-FINDRISC), respectivamente. Estos resultados guiarán las estrategias nacionales de prevención cardiovascular y diabetes, y estarán disponibles para que las agencias gubernamentales ayuden en la implementación de las políticas de salud pública.

Pancreatic Safety of Sitagliptin in the TECOS Study.

OBJECTIVE: We evaluated the incidence of acute pancreatitis and pancreatic cancer in patients with type 2 diabetes and cardiovascular disease who were treated with sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4i). RESEARCH DESIGN AND METHODS: In the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) study, a cardiovascular safety study of sitagliptin, all suspected cases of acute pancreatitis and pancreatic cancer were collected prospectively for 14,671 participants during a median follow-up time of 3 years, and were adjudicated blindly. RESULTS: Baseline differences were minimal between participants confirmed to have no pancreatic events, acute pancreatitis, or pancreatic cancer. Among those participants randomized to receive sitagliptin, 23 (0.3%) (vs. 12 randomized to receive placebo [0.2%]) had pancreatitis (hazard ratio 1.93 [95% CI 0.96-3.88], P = 0.065; 0.107 vs. 0.056/100 patient-years), with 25 versus 17 events, respectively. Severe pancreatitis (two fatal) occurred in four individuals allocated to receive sitagliptin. Cases of pancreatic cancer were numerically fewer with sitagliptin (9 [0.1%]) versus placebo (14 [0.2%]) (hazard ratio 0.66 [95% CI 0.28-1.51], P = 0.32; 0.042 vs. 0.066 events/100 patient-years). Meta-analysis with two other DPP-4i cardiovascular outcome studies showed an increased risk for acute pancreatitis (risk ratio 1.78 [95% CI 1.13-2.81], P = 0.01) and no significant effect for pancreatic cancer (risk ratio 0.54 [95% CI 0.28-1.04], P = 0.07). CONCLUSIONS: Pancreatitis and pancreatic cancer were uncommon events with rates that were not statistically significantly different between the sitagliptin and placebo groups, although numerically more sitagliptin participants developed pancreatitis and fewer developed pancreatic cancer. Meta-analysis suggests a small absolute increased risk for pancreatitis with DPP-4i therapy.

TRANSCULTURALIZATION RECOMMENDATIONS FOR DEVELOPING LATIN AMERICAN CLINICAL PRACTICE ALGORITHMS IN ENDOCRINOLOGY--PROCEEDINGS OF THE 2015 PAN-AMERICAN WORKSHOP BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY.

The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) convened their first Workshop for recommendations to optimize Clinical Practice Algorithm (CPA) development for Latin America (LA) in diabetes (focusing on glycemic control), obesity (focusing on weight loss), thyroid (focusing on thyroid nodule diagnostics), and bone (focusing on postmenopausal osteoporosis) on February 28, 2015, in San Jose, Costa Rica. A standardized methodology is presented incorporating various transculturalization factors: resource availability (including imaging equipment and approved pharmaceuticals), health care professional and patient preferences, lifestyle variables, socio-economic parameters, web-based global accessibility, electronic implementation, and need for validation protocols. A standardized CPA template with node-specific recommendations to assist the local transculturalization process is provided. Participants unanimously agreed on the following five overarching principles for LA: (1) there is only one level of optimal endocrine care, (2) hemoglobin A1C should be utilized at every level of diabetes care, (3) nutrition education and increased pharmaceutical options are necessary to optimize the obesity care model, (4) quality neck ultrasound must be part of an optimal thyroid nodule care model, and (5) more scientific evidence is needed on osteoporosis prevalence and cost to justify intervention by governmental health care authorities. This 2015 AACE/ACE Workshop marks the beginning of a structured activity that assists local experts in creating culturally sensitive, evidence-based, and easy-to-implement tools for optimizing endocrine care on a global scale.

Guía de práctica clínica para la prevención, detección temprana, diagnóstico, tratamiento y seguimiento de las dislipidemias: evaluación del riesgo cardiovascular / Clinical practice guidelines for the prevention, early detection, diagnosis, treatment and follow up of dyslipidemia: cardiovascular risk assessment

Objetivo: El tratamiento de la dislipidemia debe ser acorde con el riesgo individual de cada paciente. Existen múltiples ecuaciones de predicción de riesgo cardiovascular, sin embargo, es necesario determinar cuál es la más adecuada para ser utilizada en la población colombiana. Métodos: La alianza CINETS, comisionada por el Ministerio de la Protección Social y Colciencias, revisó la evidencia disponible con respecto a qué métodos de evaluación de riesgo cardiovascular son válidos en la población colombiana. Se generaron recomendaciones utilizando la metodología GRADE. Población: Población adulta con diagnóstico de dislipidemia o en riesgo de desarrollarla. Recomendaciones: En la población de prevención primaria o sin enfermedad cardiovascular clínicamente manifiesta se recomienda utilizar la escala de Framingham recalibrada para Colombia para clasificar el riesgo (Recomendación fuerte a favor de la intervención). Existen personas con condiciones que por sí mismas implican un riesgo mayor y ameritan manejo farmacológico directo.

Aim: The treatment of dyslipidemia must be related with patient's individual risk. There are multiple functions for predicting cardiovascular risk; however, it is necessary to determine the most appropriate for being used in Colombian population. Methods: The CINETS alliance, endorsed by the Colombian Social Protection Ministry and Colciencias, reviewed the evidence available about the validity of cardiovascular risk evaluation methods in Colombian Population. Recommendations were generated using GRADE methodology. Population: General adult population with or at risk of dyslipidemia. Recommendations In primary prevention population, or without clinically evident cardiovascular disease, Framingham risk function recalibrated for Colombia must be used to calculate cardiovascular risk (Strong recommendation). In patients with an especial condition increasing cardiovascular risk, direct pharmacologic treatment must be used.

Guía de práctica clínica para la prevención, detección temprana, diagnóstico, tratamiento y seguimiento de las dislipidemias: tratamiento farmacológico con estatinas / Clinical practice guidelines for prevention, early detection, diagnose, treatment and follow-up of dyslipidemias: farmacological treatment with statins

Objetivo: Evaluar el impacto del tratamiento con estatinas sobre la incidencia y la recurrencia de los eventos cardiovasculares y los cerebrovasculares (prevención primaria y secundaria), los niveles de las fracciones lipídicas y la incidencia de efectos secundarios (el cáncer y la diabetes mellitus) en personas con hipercolesterolemia. Métodos: Se elaboró una guía de práctica clínica siguiendo los lineamientos de la guía metodológica del Ministerio de Salud y Protección Social para recolectar de forma sistemática la evidencia científica y formular las recomendaciones utilizando la metodología GRADE. Resultados: Se evidenció un efecto benéfico del tratamiento farmacológico con estatinas tanto en población de prevención primaria como en prevención secundaria, logrando reducciones clínica y estadísticamente significativas en la mortalidad y en los eventos cardiovasculares y cerebrovasculares. Adicionalmente, el tratamiento intensivo con estatinas mostró mayor reducción en los eventos cardiovasculares y cerebrovasculares ateroscleróticos al compararlo con el tratamiento de intensidad moderada. No se encontraron diferencias significativas en el riesgo de desarrollar cáncer al comparar estatinas frente a placebo pero sí se encontró un incremento de nueve por ciento en el riesgo de presentar diabetes mellitus asociado al tratamiento con estatinas. Conclusiones: Se formulan recomendaciones a favor del uso de estatinas como primera línea de tratamiento de hipercolesterolemia, y se establecen criterios para definir la intensidad de la terapia (alta o moderada respuesta) según el riesgo cardiovascular a 10 años, el nivel de colesterol LDL (cLDL), la edad y los antecedentes personales y los familiares.

Objective: To evaluate the impact of statin therapy on the incidence and recurrence of cardiovascular and cerebrovascular events (primary and secondary prevention), the levels of lipid fractions and the incidence of side effects (cancer and diabetes mellitus) 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 systematically collect the evidence and make recommendations using the GRADE methodology. Results: A beneficial effect of pharmacological treatment with statins in both primary prevention and secondary prevention was evident, achieving clinically and statistically significant reductions in mortality and cardiovascular and cerebrovascular events. Additionally, intensive statin therapy showed greater reduction in atherosclerotic cardiovascular and cerebrovascular events as compared to the treatment of moderate intensity. No significant differences in the risk of developing cancer by comparing statins versus placebo were found, but a 9% increase in the risk of diabetes mellitus associated with statin therapy was found. Conclusions: Recommendations for the use of statins as first-line treatment of hypercholesterolemia are formulated, and criteria to define the intensity of therapy (high or moderate response) as cardiovascular risk at 10 years, level of LDL (LDLc), age and personal and family history were established.

Estudio venezolano de salud cardiometabólica (EVESCAM): descripción general y muestreo / Venezuelan cardiometabolic health study (EVESCAM): overview and sampling

El Estudio Venezolano de Salud Cardio-Metabólica (EVESCAM) es el primer estudio multicéntrico sobre la Salud cardiometabólica del venezolano. Evaluar la prevalencia de diabetes y Factores de Riesgo Cardio-Metabólico (FRCM), y su relación con el estilo de vida en Venezuela. Es un estudio poblacional, transversal, con muestreo por conglomerados, cuyo objetivo es evaluar a 4200 participantes ≥ 20 años de las 8 regiones de Venezuela. Los datos serán recolectados en centros asistenciales por profesionales de la salud y estudiantes de medicina previamente capacitados y certificados. Después de obtener el consentimiento informado, en cada participante se realizarán: a. Cuestionarios estructurados para obtener datos clínicos, demográficos, de actividad física, nutricionales, psicológicos y estratos sociales; b. examen físico (peso, talla, grasa corporal por bioimpedancia, circunferencia de la cintura, fuerza de aprehensión de la mano, presión arterial y electrocardiograma) y c. Pruebas bioquímicas (Prueba de Tolerancia a la Glucosa -PTGO- estándar 75 g, colesterol total, HDL-colesterol, LDL-colesterol y triglicéridos). Además se calculará el riesgo de enfermedad cardíaca coronaria (por puntaje de Framingham) y la regulación de la glucosa alterada (por puntaje FINDRISC modificado). Se estimará la prevalencia de sobrepeso, obesidad, prediabetes, diabetes, hipertensión, dislipidemias, sarcopenia, síndrome metabólico y su relación con los factores de estilo de vida (nutrición, actividad física, estrés psicosocial, uso de tabaco y alcohol). En esta primera parte se explica la metodología y la aplicación del muestreo a la Ciudad de Barquisimeto.

This is the first cardiometabolic multicentric study of the Venezuelan people cardiometabolic health. To evaluate the relationship of the prevalence of diabetes and risk factors with Venezuelan lifestyle. This is a population, transverse, with conglomerates of 4200 of 20 or more years-old in 8 areas of Venezuela. Data were colected in different health centers by physicians and medical students, who had been enabled for this. After obtaining consented inform, to each participant the following was applied: 1) structured questionaires for clinical data, demography, physical activity, nutrition, psicological traits and social status. 2. complete physical examination, including EKG). 3. Glucose tolerance test, lipid profile, Framingham score and FINDRISK modified score. Prevalence of overweight, obesity, prediabetes, hypertension, dyslipidemia, sarcopenia, metabolic syndrome and their relationship with lifestyle factors. This is the first parte in the city of Barquisimeto.

La importancia de estimar la obesidad abdominal / The importance of estimating abdominal obesity

Desde mediados del siglo pasado se viene demostrando que la distribución de la grasa corporal es tan o quizás más importante que su acumulación en todo el cuerpo. Los estudios del grupo canadiense liderado por JP Després, han encontrado que la grasa acumulada dentro del abdomen en forma de tejido adiposo visceral (Vat por sus siglas en inglés) medido mediante tomografía axial computadorizada (TAC), se asocia con resistencia a la insulina e hiperinsulinemia compensatoria que pueden conducir a diabetes, así como a dislipidemia, hipertensión arterial y mayor riesgo cardiovascular (1). La mejor forma de estimar la cantidad de Vat en la práctica clínica, es la medición del perímetro de cintura (PC) a nivel de la línea media entre la cresta ilíaca y el reborde costal, utilizando un metro que rodee la cintura en posición horizontal. Tener un PC que indique un exceso de Vat se ha considerado diagnóstico de obesidad abdominal (oa), pero la forma de determinar el punto de corte de PC se ha prestado a controversia y aún no existe un método estandarizado para hacerlo. El panel de tratamiento del colesterol en adultos (ATP iii) fue el primero que propuso un valor de PC para definir OA, que para entonces se había establecido como uno de los componentes fundamentales del síndrome metabólico (sm). Ellos adoptaron un PC >102 cm en hombres y >88 cm en mujeres, porque tenían una óptima sensibilidad y especificidad para identificar personas con un índice de masa corporal (IMC) ≥ 30 kg/m2 en un estudio escocés, donde la correlación entre PC e IMC fue muy alta (2). Basado en ese mismo estudio, el grupo europeo de resistencia a la insulina (EGIR) prefirió usar un PC >94 cm en hombres y >80 cm en mujeres por su capacidad para identificar personas con IMC ≥ 25 kg/m2.

Estudio IDEA (International Day for Evaluation of Abdominal Obesity): prevalencia de obesidad abdominal y factores de riesgo asociados en atención primaria en Colombia / IDEA Study (International Day for the Evaluation of Abdominal Obesity): Primary care study of the prevalence of abdominal obesity and associated risk factors in Colombia

Introducción. La obesidad está asociada con factores de riesgo para enfermedades cardiovasculares y metabólicas. La obesidad central, marcador de adiposidad intraabdominal aumentada, es mejor factor de riesgo para aterosclerosis y diabetes que el índice de masa corporal (IMC), y buen predictor de riesgo de morbimortalidad cardiovascular, síndrome metabólico y diabetes. Objetivo. Estimar prevalencias de obesidad por IMC y de obesidad abdominal por circunferencia abdominal en pacientes de atención primaria en Colombia. Materiales y métodos. Como parte de un estudio internacional, 105 médicos de atención primaria elegidos al azar reclutaron consecutivamente a pacientes de 18 a 80 años, que consultaran por cualquier razón, en dos medios días especificados previamente. Se registraron edad, sexo, tabaquismo, antecedentes cardiovasculares, diabetes, altura, peso y circunferencia abdominal mediante métodos estandarizados. Se excluyeron mujeres embarazadas y quienes no quisieran participar. Resultados. Se evaluaron 3.795 pacientes, con edad promedio de 45 años (69 % mujeres). El 60,7 % de los hombres y el 53,9 % de las mujeres tenían sobrepeso u obesidad según el IMC. El 24,6 % de los hombres y el 44,6 % de las mujeres tenían obesidad abdominal (según las guías del National Cholesterol Education Program), pero las cifras cambiaban a 62,5 % y 67,0 %, respectivamente, si se consideraban las guías de la International Diabetes Federation. La obesidad, determinada por el IMC o por la circunferencia abdominal, se asoció con mayor prevalencia de diabetes, hipertensión y dislipidemia. Conclusiones. El aumento de la circunferencia abdominal es un marcador práctico y útil para enfermedades cardiovasculares y metabólicas. La prevalencia de obesidad abdominal en pacientes de atención primaria en Colombia fue alta, y más frecuente en mujeres.

Introduction. Obesity is frequently associated with risk factors for cardiovascular and metabolic diseases. Central obesity is a marker of increased intra-abdominal adiposity and a known risk factor for atherosclerosis and diabetes; it is also a good predictor of risk for coronary events, cardiovascular mortality, diabetes and metabolic syndrome. A less predictive alternate measurement is known as the body mass index (BMI). Objective. Obesity prevalence was estimated first by BMI and then by abdominal obesity (measured by waist circumference, WC) in primary care patients. Materials and methods. As part of an international study, primary care physicians recruited consecutive patients aged 18 to 80 years who consulted for any reason on two pre-specified half-days. Age, gender, smoking status and history of cardiovascular disease or diabetes were recorded. Height, weight and WC were measured using standard methods. Pregnant women and subjects unwilling to participate were excluded. Results. A total of 3,795 patients from 105 primary care centers located throughout Colombia were evaluated. The mean age was 45 years (69% females). Of these, 60.7% of males and 53.9% of females were overweight or obese according to their BMI; 24.6% of males and 44.6% of females had abdominal obesity when National Cholesterol Education Program guidelines were used, but numbers changed to 62.5% and 67.0% when the International Diabetes Federation guidelines were used. Obesity, either determined by BMI or by WC, was associated with higher prevalence of diabetes, hypertension and dyslipidemia. Conclusions. Increased waist circumference is a practical and useful marker for cardiovascular and metabolic conditions. The prevalence of abdominal obesity in Colombian primary care patients is high and more frequent in females.

[IDEA study (International Day for the Evaluation of Abdominal Obesity): primary care study of the prevalence of abdominal obesity and associated risk factors in Colombia]. / Estudio IDEA (International Day for Evaluation of Abdominal Obesity): prevalencia de obesidad abdominal y factores de riesgo asociados en atención primaria en Colombia.

INTRODUCTION: Obesity is frequently associated with risk factors for cardiovascular and metabolic diseases. Central obesity is a marker of increased intra-abdominal adiposity and a known risk factor for atherosclerosis and diabetes; it is also a good predictor of risk for coronary events, cardiovascular mortality, diabetes and metabolic syndrome. A less predictive alternate measurement is known as the body mass index (BMI). OBJECTIVE: Obesity prevalence was estimated first by BMI and then by abdominal obesity (measured by waist circumference, WC) in primary care patients. MATERIALS AND METHODS: As part of an international study, primary care physicians recruited consecutive patients aged 18 to 80 years who consulted for any reason on two pre-specified half-days. Age, gender, smoking status and history of cardiovascular disease or diabetes were recorded. Height, weight and WC were measured using standard methods. Pregnant women and subjects unwilling to participate were excluded. RESULTS: A total of 3,795 patients from 105 primary care centers located throughout Colombia were evaluated. The mean age was 45 years (69% females). Of these, 60.7% of males and 53.9% of females were overweight or obese according to their BMI; 24.6% of males and 44.6% of females had abdominal obesity when National Cholesterol Education Program guidelines were used, but numbers changed to 62.5% and 67.0% when the International Diabetes Federation guidelines were used. Obesity, either determined by BMI or by WC, was associated with higher prevalence of diabetes, hypertension and dyslipidemia. CONCLUSIONS: Increased waist circumference is a practical and useful marker for cardiovascular and metabolic conditions. The prevalence of abdominal obesity in Colombian primary care patients is high and more frequent in females.

Comparación de la función pulmonar de pacientes con diabetes mellitus tipo 2 sometidos a tratamiento de insulina inyectada versus tratamiento con hipoglucemiantes orales / Comparison of the pulmonary function of patients with type 2 diabetes mellitus treated with insulin injections versus that of patients treated with oral hypoglucemic agents

Introducción: la potencial asociación entre el tipo de tratamiento de la diabetes mellitus tipo 2 (DM2) y alteración de la función pulmonar es algo poco estudiado hasta ahora. Objetivos: comparar la función pulmonar de pacientes con DM2 que reciben tratamiento con insulina inyectable versus hipoglicemiantes orceles (HO). Determinar si niveles de marcadores de inflamación en pacientes con tratamiento basado en insulina son diferentes a los de los tratados con HO. Métodos: estudio observacional analítico de corte transversal a partir de una muestra de conveniencia de 369 pacientes con diagnóstico de DM2, y tratamiento con insulina o HO. Se realizaron espirometrías, y se obtuvieron valores residuales promedios para VEF1, CVF y relación VEF1/CVF. Mediante regresión lineal múltiple, se ajustó por diferencias en determinantes conocidos de la función pulmonar, así como por control de la diabetes y tiempo desde el diagnóstico. Adicionalmente, se midieron niveles de marcadores inflamatorios sanguíneos para cada grupo de tratamiento. Resultados: 63 pacientes (17%) recibían tratamiento con insulina y 306 (83%) con HO. La diferencia en residuales favoreció a los tratados con HO. Para VEF1, CVF y VEF1/CVF la diferencia fue 57.6 mL (IC95% 32.45-82.74; P 0.0047), 45.6 mL (IC95% 20.84-70.39; P 0.0231) y 0.017, (IC95% 0.01- 0.02, P<0.0001), respectivamente. No hubo cambios estadísticamente significativos en marcadores de inflamación. Conclusiones: los pacientes en tratamiento con HO presentaron mejor función pulmonar que los tratados con insulina. Este hallazgo de diferencias en función pulmonar pudiera tener implicación clínica en el manejo de los pacientes diabéticos, pero debe confirmarse en estudios prospectivos (Acta Med Colom; 2010: 35: 113-118).

Introduction: the potential association between the type of treatment of type 2 diabetes mellitus (DM2) and impaired lung function is something rarely studied so far. Objectives: to compare the lung function of patients with DM2 who are treated with injectable insulin versus HO. To determine whether levels of inflammatory markers in patients with insulin-based treatment are different from those treated with HO. Methods: an observational, analytical, cross-sectional study from a convenience sample of 369 patients diagnosed with DM2 and treated with insulin or HO. Spirometry was performed, and residual values were averaged for FEV1, FVC and FEV1/FVC ratios. Multiple linear regression results were adjusted by differences in known determinants of lung function, as well as control of diabetes and time since diagnosis. Additionally, we measured blood levels of inflammatory markers for each treatment group. Results: 63 patients (17%) were treated with insulin and 306 (83%) with OH. The difference in residual favored those treated with HO. For FEV1, FVC and FEV1/FVC the difference was 57.6 mL (95% CI 32.45 to 82.74, P 0.0047), 45.6 mL (95% CI 20.84 to 70.39, P 0.0231) and 0.017 (95% CI 0.01 to 0.02, P <0.0001), respectively. There were no statistically significant changes in inflammation markers. Conclusions: patients treated with HO showed better lung function than those treated with insulin. This finding of differences in lung function may have clinical implications in the management of diabetic patients, but needs to be confirmed in prospective studies (Acta Med Colom; 2010: 35: 113-118).

Inadequate glucose control in type 2 diabetes is associated with impaired lung function and systemic inflammation: a cross-sectional study.

BACKGROUND: Inadequate glucose control may be simultaneously associated with inflammation and decreased lung function in type 2 diabetes. We evaluated if lung function is worse in patients with inadequate glucose control, and if inflammatory markers are simultaneously increased in these subjects. METHODS: Subjects were selected at the Colombian Diabetes Association Center in Bogotá. Pulmonary function tests were performed and mean residual values were obtained for forced expiratory volume (FEV1), forced vital capacity (FVC) and FEV1/FVC, with predicted values based on those derived by Hankinson et al. for Mexican-Americans. Multiple least-squares regression was used to adjust for differences in known determinants of lung function. We measured blood levels of glycosylated hemoglobin (HBA1c), interleukin 6 (IL-6), tumor necrosis factor (TNF-alpha), fibrinogen, ferritin, and C-reactive protein (C-RP). RESULTS: 495 diabetic patients were studied, out of which 352 had inadequate control (HBA1c > 7%). After adjusting for known determinants of lung function, those with inadequate control had lower FEV1 (-75.4 mL, IC95%: -92, -59; P < 0.0001) and FVC (-121 mL, IC95%: -134, -108; P < 0,0001) mean residuals, and higher FEV1/FVC (0.013%, IC95%: 0.009, 0.018, P < 0.0001) residuals than those with adequate control, as well as increased levels of all inflammatory markers (P < 0.05), with the exception of IL-6. CONCLUSIONS: Subjects with type 2 diabetes and inadequate control had lower FVC and FEV1 than predicted and than those of subjects with adequate control. It is postulated that poorer pulmonary function may be associated with increased levels of inflammatory mediators.

Diabetes mellitus tipo 2 y deterioro de la función pulmonar / Diabetes mellitus type 2 and deterioration of pulmonary function

Introducción: un aspecto poco estudiado de la diabetes mellitus tipo 2 (DM 2), es su posible asociación con alteraciones de la función pulmonar. Estudios recientes han mostrado niveles mayores de marcadores de inflamación sistémica de bajo nivel en pacientes con DM 2, lo que también podría afectar la función pulmonar. El objetivo de este estudio fue determinar si la función pulmonar de personas con DM 2 es diferente de la función pulmonar de un grupo control sin DM.Población y método: se realizó un estudio observacional transversal, comunitario, en diabéticos y en controles sanos, apareados por estratos de edad y sexo. Los controles fueron vecinos de cada diabético, del mismo sexo y grupo de edad, sin DM. La muestra de diabéticos se seleccionó de la población de pacientes que consultan a la Asociación Colombiana de Diabetes (ACD) en Bogotá. Se comprobó el estatus de diabético y de control sano mediante las pruebas de glucemia en ayunas y glucemia poscarga de glucosa. Se realizaron curvas de flujo volumen tanto para los diabéticos como para los controles, y de acuerdo con los valores de referencia obtenido por Hankinson para mexicoamericanos se obtuvieron valores residuales promedios (observado – esperado) para VEF1, CVF y relación VEF1/CVF. Mediante regresión lineal múltiple se ajustó por diferencias en determinantes conocidos de la función pulmonar (edad, sexo, talla, tabaquismo, exposición a humo de leña)...

Sitagliptin, a DPP-4 inhibitor for the treatment of patients with type 2 diabetes: a review of recent clinical trials.

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of oral antihyperglycemic agents that enhance the body's ability to regulate blood glucose by increasing the active levels of incretins, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). There are numerous DPP-4 inhibitors in development with sitagliptin as the first approved agent for the treatment of patients with type 2 diabetes. OBJECTIVE: The purpose of this review is to provide an overview of the clinical trial results with sitagliptin. METHODS: Clinical trials published between January 2005 (first sitagliptin publication) and November 2007 were included in this review. Medline was searched using the search terms: MK-0431 or sitagliptin. FINDINGS: Sitagliptin, an oral, once-daily, and highly selective DPP-4 inhibitor, has been evaluated in clinical trials as monotherapy, as add-on therapy, or as initial combination therapy with metformin. Sitagliptin provided effective fasting and postprandial glycemic control in a wide range of patients with type 2 diabetes. Markers of beta-cell function (HOMA-beta and proinsulin/insulin ratio) were improved with sitagliptin treatment. In these clinical trials, sitagliptin was generally well tolerated with an overall incidence of adverse experiences comparable to placebo, a low risk of hypoglycemia or gastrointestinal adverse experiences, and a neutral effect on body weight. The findings presented in this review are limited to the specific patient population enrolled in each clinical trial and for durations for up to 1 year. Future clinical studies should evaluate whether this class of agents has the potential to delay progression and/or prevent type 2 diabetes. CONCLUSIONS: Sitagliptin has been shown to be effective and well-tolerated in various treatment regimens and may be considered for both initial therapy and as add-on therapy for patients with type 2 diabetes.