Marcos M. Lima-Martínez

Tejido adiposo epicárdico y su asociación con niveles plasmáticos de adrenomedulina en pacientes con síndrome metabólico

OBJECTIVE To assess the association between epicardial adipose tissue thickness (EAT) and plasma adrenomedullin plasma levels in patients with metabolic syndrome (MS). METHODS Twenty-one patients (12 females and 9 males) with MS according to the International Diabetes Federation guidelines, aged 22-58 years, were enrolled into the study and compared to 19 age-matched control subjects without MS. Plasma glucose, lipid, and adrenomedullin levels were assessed. EAT, left ventricular mass, and carotid intima-media thickness were evaluated by transthoracic two-dimensional echocardiography. RESULTS No statistically significant differences were found between the groups in age, sex, and height. Body weight, abdominal circumference (AC), body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were significantly higher (p=0.0001) in MS patients; this group also showed significantly higher glucose (p=0.001), total cholesterol (p=0.01), LDL-C (p=0.03), VLDL-C (p=0.005), triglyceride (p=0.002), Tg/HDL ratio (p=0.0001), and plasma adrenomedullin (3.49±1.21 vs 1.69±0.92 ng/mL; p=0.0001) levels and lower HDL-C (p=0.02) levels as compared to the control group. EAT was significantly thicker in MS patients compared to the control group (8.45±3.14 vs 5.43±0.96; p=0.0001), showed a positive correlation to BMI (r=0.347; p=0.02), AC (r=0.350; p=0.02), DBP (r=0.346; p=0.02), and adrenomedullin levels (r=0.741; p=0.0001). In multiple linear regression analysis, adrenomedullin was the only parameter associated to EAT (R(2)=0.550; p=0.0001). CONCLUSION In this small patient group, a statistically significant association was found between EAT and plasma adrenomedullin levels, which may be considered as a potential biomarker of MS.

Epicardial adipose tissue thickness and its association with adiponectin in metabolic syndrome patients from Mérida, Venezuela

OBJECTIVE To study the relationship between epicardial adipose tissue (EAT) thickness and plasma levels of adiponectin in Venezuelan patients. SUBJECTS AND METHODS Thirty-one patients diagnosed with metabolic syndrome (study group) and 27 controls were selected and tested for glycemia, lipids, and adiponectin. EAT thickness, ejection fraction, diastolic function, left ventricular mass (LVM), and left atrial volume (LAV) were determined by transthoracic echocardiography. RESULTS EAT thickness was greater in metabolic syndrome patients (5.69 ± 1.12 vs. 3.52 ± 0.80 mm; p = 0.0001), correlating positively with body mass index (BMI) (r = 0.661; p = 0.0001); waist circumference (WC) (r = 0.664; p = 0.0001); systolic (SBP) (r = 0.607; p = 0.0001), and diastolic blood pressure (DBP) (r = 0.447; p = 0.0001); insulin (r = 0.505; p = 0.0001); Tg/HDL-C ratio (r = 0.447; p = 0.0001), non-HDL-C (r = 0.353; p = 0.007); LAV (r = 0.432; p = 0.001), and LVM (r = 0.469; p = 0.0001). EAT thickness correlated negatively with adiponectin (r = -0.499; p = 0.0001). CONCLUSION A significant association exists between EAT thickness and both metabolic syndrome components and adiponectin concentration, a link that might be used as a biomarker for this disease.

One year remission of type 1 diabetes mellitus in a patient treated with sitagliptin

Summary Type 1 diabetes mellitus (T1DM) is a chronic disease characterized by the autoimmune destruction of pancreatic β-cells. This paper describes the case of a 19-year-old male patient who presented with glutamic acid decarboxylase (GAD) antibody positive and diabetic ketoacidosis, which mandated intensive insulin treatment. Once the ketoacidosis was controlled, an oral dose of 100 mg of sitagliptin was administered once a day. Ketoacidosis was managed by insulin and insulin daily requirement began to dwindle after one month, until its complete withdrawal at 8 weeks, when partial remission was reached. The patient has now remained on sitagliptin treatment alone for a year, without requiring insulin. The benefit observed with this medication is possibly associated with its immunological effects. Inhibition of dipeptidyl peptidase 4 in animal models deregulates the Th1 immune response, increases secretion of Th2 cytokines, activates CD4+CD25+FoxP3+ regulatory T-cells, and prevents IL17 production. Learning points The use of insulin-dose-adjusted HbA1c constitutes the best way to define partial remission in T1DM patients. The use of sitagliptin in T1DM patients could help to decrease daily requirement of insulin by delaying β-cell loss and improving endogenous insulin production. The determination of antibodies against insulin, islet cells, and GAD permits differentiation of T1DM patients from those with atypical or ketosis-prone diabetes.

Medición ecocardiográfica de la grasa epicárdica

Resumen La grasa epicardica es un organo metabolicamente activo que genera varias moleculas que pueden afectar de forma significativa la funcion cardiaca. Ademas, el tejido adiposo epicardico puede reflejar la grasa visceral intraabdominal. Por tanto, la evaluacion ecocardiografica de este tejido podria servir como un marcador fiable de adiposidad visceral. El tejido adiposo epicardico tambien se relaciona con parametros clinicos y antropometricos del sindrome metabolico; por tanto, la evaluacion ecocardiografica de la grasa epicardica podria ser una herramienta practica y sencilla para estratificar el riesgo cardiovascular en la practica clinica.

Epicardial Fat Thickness as Cardiovascular Risk Factor and Therapeutic Target in Patients with Rheumatoid Arthritis Treated with Biological and Nonbiological Therapies

Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with high cardiovascular morbidity and mortality. Epicardial adipose tissue (EAT) thickness may act as a therapeutic target during treatments with drugs modulating the adipose tissue. We evaluate EAT thickness in RA patients treated with biological and nonbiological disease-modifying antirheumatic drugs (DMARDs). A cross-sectional study was conducted with a cohort of 34 female RA patients and 16 controls matched for age and body mass index (BMI). Plasma glucose, basal insulin, plasma lipids, and high-sensitivity C-reactive protein (hs-CRP) were assessed. EAT thickness and left ventricular mass (LVM) were measured by echocardiography. No significant differences in waist circumference (WC), blood pressure, fasting blood glucose, basal insulin, and lipid parameters were found between the groups. The control group showed lower concentrations (P = 0.033) of hs-CRP and LVM (P = 0.0001) than those of the two RA groups. Patients treated with TNF-α inhibitors showed significantly lower EAT thickness than those treated with nonbiological DMARDs (8.56 ± 1.90 mm versus 9.71 ± 1.45 mm; P = 0.04). Women with no RA revealed reduced EAT thickness (5.39 ± 1.52 mm) as compared to all RA patients (P = 0.001). Results suggest that RA patients have greater EAT thickness than controls regardless of BMI and WC.

Diabetes Care in Venezuela

BACKGROUND The incidence of type 2 diabetes (T2D) and its economic burden have increased in Venezuela, posing difficult challenges in a country already in great turmoil. OBJECTIVES The aim of this study was to review the prevalence, causes, prevention, management, health policies, and challenges for successful management of diabetes and its complications in Venezuela. METHODS A comprehensive literature review spanning 1960 to 2015 was performed. Literature not indexed also was reviewed. The weighted prevalence of diabetes and prediabetes was estimated from published regional and subnational population-based studies. Diabetes care strategies were analyzed. FINDINGS In Venezuela, the weighted prevalence of diabetes was 7.7% and prediabetes was 11.2%. Diabetes was the fifth leading cause of death (7.1%) in 2012 with the mortality rate increasing 7% per year from 1990 to 2012. In 2012, cardiovascular disease and diabetes together were the leading cause of disability-adjusted life years.T2D drivers are genetic, epigenetic, and lifestyle, including unhealthy dietary patterns and physical inactivity. Obesity, insulin resistance, and metabolic syndrome are present at lower cutoffs for body mass index, homeostatic model assessment, and visceral or ectopic fat, respectively. Institutional programs for early detection and/or prevention of T2D have not been established. Most patients with diabetes (∼87%) are cared for in public facilities in a fragmented health system. Local clinical practice guidelines are available, but implementation is suboptimal and supporting information is limited. CONCLUSIONS Strategies to improve diabetes care in Venezuela include enhancing resources, reducing costs, improving education, implementing screening (using Latin America Finnish Diabetes Risk Score), promoting diabetes care units, avoiding insulin levels as diagnostic tool, correct use of oral glucose tolerance testing and metformin as first-line T2D treatment, and reducing health system fragmentation. Use of the Venezuelan adaptation of the transcultural Diabetes Nutrition Algorithm for lifestyle recommendations and the Latin American Diabetes Association guidelines for pharmacologic interventions can assist primary care physicians in diabetes management.

Relationship between the Finnish Diabetes Risk Score (FINDRISC), vitamin D levels, and insulin resistance in obese subjects

AIM To assess the relationship between 25-hydroxyvitamin D [25(OH)D] blood concentrations in subjects with obesity and type 2 diabetes mellitus (T2D) risk according to the Finnish Diabetes Risk Score (FINDRISC) modified for Latin America (LA-FINDRISC). METHODS This study was conducted in Ciudad Bolívar, Venezuela. Eighty two women and 20 men (53 obese and 49 nonobese), with an average age of 42.6±12.30 years were enrolled. Weight, height, body mass index (BMI), waist circumference (WC), fasting glucose, basal insulin, plasma lipids, Homeostasis Model Assessment-Insulin Resistance (HOMA-IR), and 25(OH)D levels were measured. FINDRISC with WC cutoff points modified for Latin America was applied. RESULTS No difference in 25(OH)D levels between obese and nonobese subjects was found. When anthropometric, clinical, and biochemical variables according to the 25(OH)D status were compared, the only difference detected was higher LA-FINDRISC in the insufficient/low 25(OH)D group compared to normal 25(OH)D levels group (12.75±6.62; vs 10.15±5.21; p=0.031). LA-FINDRISC was negatively correlated with plasma 25(OH)D levels (r=-0.302; p=0.002) and positively correlated with the HOMA-IR index (r=0.637; p=0.0001). CONCLUSIONS The LA-FINDRISC significantly correlated with both 25(OH)D levels and insulin resistance markers in this group of patients.

Frecuencia, aspectos clínicos y moleculares de la hipercolesterolemia familiar en una unidad de endocrinología de Ciudad Bolívar, Venezuela

OBJECTIVE To assess the frequency and the clinical, biochemical, and molecular aspects of familial hypercholesterolemia (FH) in subjects attending an endocrinology unit. METHODS An observational, descriptive study evaluating 3,140 subjects attending the endocrinology unit of Centro Médico Orinoco in Ciudad Bolívar, Venezuela, from 7 January 2013 to 9 December 2016. The index cases were selected using the Dutch Lipid Clinic Network criteria. Plasma lipid levels were measured, and a molecular analysis was performed by DNA sequencing of the LDLR and APOB genes. RESULTS Ten (0.32%) of the 3,140 study patients had clinical and biochemical characteristics consistent with FH. All but one were female. Three had first-degree relatives with prior premature coronary artery; and none had a personal history of this condition. Three patients were obese; three had high blood pressure; and no one suffered from diabetes. Three patients had a history of tendon xanthomas, and one of corneal arcus. LDL-C levels ranged from 191 to 486mg/dL. Two patients were on statin therapy. The genetic causes of FH were identified in four patients, and were LDLR gene mutations in three of them and an APOB gene mutation in exon 26 in the other. CONCLUSION Approximately, one out of every 300 people attending this endocrinology unit in those four years had FH, and LDLR gene mutations were the most prevalent cause.

Bradicardia sinusal inducida por octreotide en un varón con acromegalia

La acromegalia es una enfermedad que se caracteriza por un exceso de la hormona del crecimiento (GH), la cual se inicia tras el cierre de las placas epifisarias de los huesos largos. La somatostatina es una hormona peptídica con una vida media corta (2-3 min) y es sintetizada en muchos tejidos, incluyendo el hipotálamo, con la finalidad de inhibir la secreción de la GH. Esta hormona media sus acciones a través de 5 subtipos de receptores (SSR), de los cuales el SSR2 y el SSR5 son los más expresados en los adenomas de la hipófisis1. El octreotide es un análogo sintético de la somatostatina con acción inhibitoria de la secreción de GH y de diversas hormonas tanto gastrointestinales como pancreáticas1. Presentamos el caso de un paciente varón de 37 años de edad, natural y procedente de Mérida (Venezuela), sin antecedentes personales ni familiares patológicos, que fue referido a la Unidad de Endocrinología por presentar cambios fisonómicos de 7 años de evolución, así como cefalea holocraneana de fuerte intensidad y hemianopsia heterónima bitemporal desde hacía 5 meses. El examen físico reveló un peso corporal de 102 kg, talla 185,0 cm, un índice de masa corporal (IMC) de 29,8 kg/m2, una frecuencia cardíaca de 72 lpm, presión arterial de 130/80 mmHg, rasgos faciales toscos caracterizados por el engrosamiento de la nariz, prognatismo, abultamiento frontal y pómulos prominentes. Además, se evidenció piel gruesa y de textura oleosa, cifosis dorsal superior con hiperlordosis lumbar compensatoria, prominencia de la porción inferior del esternón, manos y pies grandes y en la campimetría por confrontación se demostró la presencia de una hemianopsia heterónima bitemporal. No se encontraron alteraciones cardiovasculares ni respiratorias. En los análisis de laboratorio no se identificaron alteraciones hematológicas. La bioquímica sanguínea demostró valores normales de glucosa, función renal y hepática, calcio y fósforo. Se objetivó una concentración plasmática de GH basal de 9,7 g/L (VN: 0-2,5), una GH a las 2 h de la sobrecarga oral con 75 g de glucosa de 8,2 g/L (VN: menor de 1), IGF-1 (del inglés insulin-like growth factor) de 355 ng/mL (VN para la edad: 109-284), hormona estimulante de tiroides y t c

Epicardial adipose tissue thickness and type 2 diabetes risk according to the FINDRISC modified for Latin America

BACKGROUND The Finnish Diabetes Risk Score (FINDRISC) is a tool to predict 10-year risk of type 2 diabetes mellitus (T2DM), and visceral adiposity is associated with higher cardio-metabolic risk. The objective of the study was to assess the relationship of epicardial adipose tissue (EAT) thickness with T2DM risk according to the FINDRISC tool. METHODS The study was conducted in Ciudad Bolívar, Venezuela, and included 55 subjects of whom 37 (67.3%) were women and 18 (32.7%) men with ages between 18 and 75 years. A record was made of weight, height, body mass index (BMI), waist circumference (WC), fasting glucose, baseline insulin, plasma lipids, Homeostasis Model Assessment-Insulin Resistance (HOMA-IR), and EAT thickness. The FINDRISC tool, with WC cut-off points modified for Latin America (LA-FINDRISC) was used. RESULTS BMI, WC, plasma insulin concentration, HOMA-IR index, and EAT thickness were higher (P<0.0001) in the high-risk group compared to subjects in the low-moderate risk group according to the LA-FINDRISC. LA-FINDRISC was positively correlated with BMI (r=0.513; P=0.0001), WC (r=0.524; P=0.0001), fasting blood glucose (r=0.396; P=0.003); baseline plasma insulin (r=0.483; P=0.0001); HOMA-IR index (r=0.545; P=.0.0001); and EAT thickness (r=0.702; P=0.0001). The multivariate regression analysis showed that fasting blood glucose (P=0.023) and EAT thickness (P=0.007) remained independently associated with high T2DM risk. CONCLUSIONS LA-FINDRISC was associated with EAT thickness and insulin resistance markers. Both were independently and directly associated with high risk for diabetes in the LA-FINDRISC category.