COVID-19 y diabetes mellitus: una relación bidireccional / COVID-19 and diabetes: A bidirectional relationship

El coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) es el agente causal de la enfermedad por coronavirus 2019 (COVID-19). La diabetes es una de las comorbilidades más frecuentes en personas con COVID-19, con una prevalencia que varía según los estudios entre el 7 y el 30%. Los diabéticos infectados con SARS-CoV-2 tienen una tasa más alta de admisión hospitalaria, neumonía severa y mayor mortalidad en comparación con sujetos no diabéticos. La hiperglucemia crónica puede comprometer la inmunidad innata y la inmunidad humoral. Además, la diabetes se asocia con un estado inflamatorio crónico de bajo grado que favorece el desarrollo de una respuesta inflamatoria exagerada y, por tanto, la aparición del síndrome de distrés respiratorio agudo. Evidencia reciente ha demostrado que el SARS-CoV-2 también es capaz de producir un daño directo al páncreas, que podría empeorar la hiperglucemia e incluso inducir la aparición de diabetes en sujetos previamente no diabéticos. Las estrategias terapéuticas deben dirigirse a facilitar el acceso de los pacientes al sistema sanitario. El control de la glucemia y de las comorbilidades debe ser individualizado a fin de reducir la incidencia de complicaciones y disminuir la carga en los sistemas de salud. En este artículo revisaremos los mecanismos fisiopatológicos que explican la relación bidireccional entre COVID-19 y diabetes mellitus, su implicación en el pronóstico y el manejo de la hiperglucemia en este grupo de pacientes.(AU)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of coronavirus disease 2019 (COVID-19). Diabetes is one of the most frequent comorbidities in people with COVID-19 with a prevalence that varies between 7 and 30%. Diabetics infected with SARS-CoV-2 have a higher rate of hospital admission, severe pneumonia, and higher mortality compared to non-diabetic subjects. Chronic hyperglycemia can compromise innate and humoral immunity. Furthermore, diabetes is associated with a low-grade chronic inflammatory state that favors the development of an exaggerated inflammatory response and therefore the appearance of acute respiratory distress syndrome. Recent evidence has shown that SARS-CoV-2 is also capable of causing direct damage to the pancreas that could worsen hyperglycemia and even induce the onset of diabetes in previously non-diabetic subjects. Therapeutic strategies should be aimed at facilitating patient access to the healthcare system. Control of blood glucose and comorbidities must be individualized in order to reduce the incidence of complications and decrease the burden on health systems. In this article we will review the pathophysiological mechanisms that explain the bidirectional relationship between COVID-19 and diabetes mellitus, its implication in the prognosis and management of hyperglycemia in this group of patients.(AU)

COVID-19 and diabetes: A bidirectional relationship. / COVID-19 y diabetes mellitus: una relación bidireccional.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of coronavirus disease 2019 (COVID-19). Diabetes is one of the most frequent comorbidities in people with COVID-19 with a prevalence that varies between 7 and 30%. Diabetics infected with SARS-CoV-2 have a higher rate of hospital admission, severe pneumonia, and higher mortality compared to non-diabetic subjects. Chronic hyperglycemia can compromise innate and humoral immunity. Furthermore, diabetes is associated with a low-grade chronic inflammatory state that favors the development of an exaggerated inflammatory response and therefore the appearance of acute respiratory distress syndrome. Recent evidence has shown that SARS-CoV-2 is also capable of causing direct damage to the pancreas that could worsen hyperglycemia and even induce the onset of diabetes in previously non-diabetic subjects. Therapeutic strategies should be aimed at facilitating patient access to the healthcare system. Control of blood glucose and comorbidities must be individualized in order to reduce the incidence of complications and decrease the burden on health systems. In this article we will review the pathophysiological mechanisms that explain the bidirectional relationship between COVID-19 and diabetes mellitus, its implication in the prognosis and management of hyperglycemia in this group of patients.

Estatinas en COVID-19: ¿existe algún fundamento? / Statins in COVID-19: is there any foundation?

El coronavirus tipo 2 del síndrome respiratorio agudo grave (SARS-CoV-2) es el agente causal de la enfermedad por coronavirus 2019 (COVID-19). El síndrome de distress respiratorio agudo constituye la principal causa de muerte por COVID-19 y ocurre por una respuesta inflamatoria exagerada que provoca la liberación de citocinas proinflamatorias como interleucinas y factor de necrosis tumoral alfa (TNF-α). Las estatinas son fármacos hipolipemiantes con efectos pleiotrópicos. Han demostrado beneficio en el manejo de enfermedades inflamatorias y autoinmunes como el lupus eritematoso sistémico, la artritis reumatoide y la esclerosis múltiple. Además, debido a sus propiedades inmunomoduladoras se han utilizado en el tratamiento de diversas enfermedades infecciosas como neumonía adquirida en la comunidad e influenza. En esta revisión analizamos los fundamentos fisiopatológicos que apoyan el uso de estatinas como tratamiento coadyuvante en pacientes con COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of coronavirus disease 2019 (COVID-19). Acute respiratory distress syndrome is the main cause of death from COVID-19 and occurs due to an exaggerated inflammatory response that causes the release of pro-inflammatory cytokines such as interleukins and tumor necrosis factor-alpha (TNF-α). Statins are lipid lowering drugs with pleiotropic effects. They have shown benefit in the management of inflammatory and autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis. Furthermore, due to their immunomodulatory properties, they have been used in the treatment of various infectious diseases such as community-acquired pneumonia and influenza. In this review we analyze the pathophysiological foundations that support the use of statins as an adjunctive treatment in patients with COVID-19

Statins in COVID-19: is there any foundation? / Estatinas en COVID-19: ¿existe algún fundamento?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of coronavirus disease 2019 (COVID-19). Acute respiratory distress syndrome is the main cause of death from COVID-19 and occurs due to an exaggerated inflammatory response that causes the release of pro-inflammatory cytokines such as interleukins and tumor necrosis factor-alpha (TNF-α). Statins are lipid lowering drugs with pleiotropic effects. They have shown benefit in the management of inflammatory and autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis. Furthermore, due to their immunomodulatory properties, they have been used in the treatment of various infectious diseases such as community-acquired pneumonia and influenza. In this review we analyze the pathophysiological foundations that support the use of statins as an adjunctive treatment in patients with COVID-19.

Reducing the Clinical and Public Health Burden of Familial Hypercholesterolemia: A Global Call to Action.

Importance: Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder that leads to premature morbidity and mortality due to atherosclerotic cardiovascular disease. Familial hypercholesterolemia affects 1 in 200 to 250 people around the world of every race and ethnicity. The lack of general awareness of FH among the public and medical community has resulted in only 10% of the FH population being diagnosed and adequately treated. The World Health Organization recognized FH as a public health priority in 1998 during a consultation meeting in Geneva, Switzerland. The World Health Organization report highlighted 11 recommendations to address FH worldwide, from diagnosis and treatment to family screening and education. Research since the 1998 report has increased understanding and awareness of FH, particularly in specialty areas, such as cardiology and lipidology. However, in the past 20 years, there has been little progress in implementing the 11 recommendations to prevent premature atherosclerotic cardiovascular disease in an entire generation of families with FH. Observations: In 2018, the Familial Hypercholesterolemia Foundation and the World Heart Federation convened the international FH community to update the 11 recommendations. Two meetings were held: one at the 2018 FH Foundation Global Summit and the other during the 2018 World Congress of Cardiology and Cardiovascular Health. Each meeting served as a platform for the FH community to examine the original recommendations, assess the gaps, and provide commentary on the revised recommendations. The Global Call to Action on Familial Hypercholesterolemia thus represents individuals with FH, advocacy leaders, scientific experts, policy makers, and the original authors of the 1998 World Health Organization report. Attendees from 40 countries brought perspectives on FH from low-, middle-, and high-income regions. Tables listing country-specific government support for FH care, existing country-specific and international FH scientific statements and guidelines, country-specific and international FH registries, and known FH advocacy organizations around the world were created. Conclusions and Relevance: By adopting the 9 updated public policy recommendations created for this document, covering awareness; advocacy; screening, testing, and diagnosis; treatment; family-based care; registries; research; and cost and value, individual countries have the opportunity to prevent atherosclerotic heart disease in their citizens carrying a gene associated with FH and, likely, all those with severe hypercholesterolemia as well.

FINDRISC Modified for Latin America as a Screening Tool for Persons with Impaired Glucose Metabolism in Ciudad Bolívar, Venezuela.

OBJECTIVE: The Finnish Diabetes Risk Score (FINDRISC) includes anthropometric, metabolic, and lifestyle factors that predict type 2 diabetes mellitus. The objective of this study was to evaluate the FINDRISC modified for Latin America (LA-FINDRISC) as a screening tool for persons with impaired glucose metabolism in Ciudad Bolívar, Venezuela. METHODS: Subjects aged between 18 and 70 years of both sexes without known diabetes were invited to participate. After informed consent, they were screened with the LA-FINDRISC questionnaire and then given an oral glucose tolerance test, using the American Diabetes Association criteria for diagnosis. To obtain the cutoff point of LA-FINDRISC for predicting impaired glucose regulation, a receiver operating characteristic curve was constructed. RESULTS: A total of 200 subjects were evaluated, 64.5% female, with a mean age of 35.20 ± 13.84 years. Of these, 158 (79%) did not present with carbohydrate metabolism disorder, while 42 (21%) did. Age (p = 0.0001), body mass index (p = 0.011), and waist circumference (p = 0.031) were significantly higher in subjects with impaired glucose regulation when compared to those without it. There were a significantly greater number of sedentary (p = 0.039) and hypertensive subjects (p = 0.0001), as well as those with a history of glucose >100 mg/dL (p = 0.0001), in the impaired glucose metabolism group. A cutoff LA-FINDRISC of 14 points predicted a high risk of impaired glucose regulation with a sensitivity of 45.2% and a specificity of 89.9%. CONCLUSION: A LA-FINDRISC >14 points had low sensitivity but high specificity for predicting carbohydrate metabolism disorders in this group of patients from Ciudad Bolívar.

Epicardial adipose tissue thickness and type 2 diabetes risk according to the FINDRISC modified for Latin America / Espesor del tejido adiposo epicárdico y riesgo de diabetes tipo 2 de acuerdo al FINDRISC modificado para Latinoamérica

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

Introducción: La escala Finlandesa de riesgo de diabetes (FINDRISC) es una herramienta para predecir el riesgo a 10 años de diabetes tipo 2 (DMT2). La adiposidad visceral se asocia con un alto riesgo cardiometabólico. El objetivo fue evaluar la relación del espesor del tejido adiposo epicárdico (TAE) y el riesgo de DMT2 calculado según FINDRISC. Métodos: Este estudio fue realizado en Ciudad Bolívar, Venezuela. Cincuenta y cinco sujetos; 37 mujeres (67,3%) y 18 hombres (32,7%) con edades entre 18 y 75 años fueron incluidos. Peso, talla, índice de masa corporal (IMC), circunferencia abdominal (CA), glucemia, insulina basal, lípidos plasmáticos, Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) y espesor del TAE fueron medidos. Se aplicó el FINDRISC con puntos de corte de CA modificados para Latinoamérica (LA-FINDRISC). Resultados: El IMC, CA, insulina, HOMA-IR y espesor del TAE fueron mayores (p < 0,0001) en el grupo de alto riesgo comparado con el grupo de bajo-moderado riesgo según LA-FINDRISC. Esta escala se correlacionó positivamente con el IMC (r = 0,513; p = 0,0001), CA (r = 0,524; p = 0,0001), glucemia en ayuna (r = 0,396; p = 0,003); insulina (r = 0,483; p = 0,0001); HOMA-IR (r = 0,545; p = 0,0001); y espesor del TAE (r = 0,702; p = 0,0001). El análisis de regresión multivariante mostró que la glucemia en ayuna (p = 0,023) y el espesor del TAE (p = 0.007) se asociaron independientemente con alto riesgo de DMT2. Conclusiones: LA-FINDRISC se asocia tanto con el espesor del TAE como con marcadores de resistencia a la insulina. Ambos se asociaron directa e independientemente con la categoría de alto riesgo de DMT2 según LA-FINDRISC

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.

Association between endothelial dysfunction, epicardial fat and subclinical atherosclerosis during menopause / Interacción de la disfunción endotelial, la grasa epicárdica y la aterosclerosis subclínica durante la menopausia

Background: Menopausal transition is critical for the development of early, subclinical vascular damage. Multiple factors, such as atherosclerosis, increased epicardial fat, and endothelial dysfunction can play a role. Hence, the objective of this study was the comparison of epicardial adipose tissue and carotid intima media thickness in order to establish the best predictor of carotid stiffness in middle-aged women with endothelial dysfunction. Methods: A total of 43 healthy women aged 40-59 years old with endothelial dysfunction previously demonstrated by flow mediated dilation were recruited to have anthropometric, biochemical, hormonal and ultrasound determinations of carotid intima media thickness and epicardial fat thickness. Results: Carotid arterial stiffness parameters (local pulse wave velocity [4.7±0.7 vs 4.8±0.5 vs 5.6±0.5m/s, respectively, p<0.001], pressure strain elastic modulus [55.2±13.4 vs 59.2±11.8 vs 81.9±15.6kPa, respectively, p<0.001], arterial stiffness index β [4.4±1.4 vs 5.0±1.1 vs 6.4±1.3, respectively, p<0.001]) and epicardial fat thickness (2.98±1.4 vs 3.28±1.9 vs 4.70±1.0mm, respectively, p=0.007) showed a significant and proportional increase in the group of late post-menopausal women when compared to early post-menopausal and pre-menopausal groups, respectively. Among body fat markers, epicardial fat was the strongest predictor of local pulse wave velocity, independent of age. Conclusions: In menopausal women with endothelial dysfunction, menopausal transition is associated with increased carotid arterial stiffness and epicardial fat thickness, independent of age. Ultrasound measured epicardial fat was a better independent predictor of arterial stiffness than carotid intima media thickness in these women (AU)

Introducción: La transición menopáusica es crítica para el desarrollo de daño vascular subclínico precoz. Múltiples factores como la aterosclerosis, el aumento del tejido adiposo epicárdico (TAE) y la disfunción endotelial pueden desempeñar un papel en este proceso. El objetivo de este estudio fue comparar la medición del TAE y el espesor íntima media carotídeo (IMC) para establecer el mejor predictor de rigidez carotídea en mujeres de mediana edad con disfunción endotelial. Métodos: Se incluyeron 43 mujeres entre 40-50 años con disfunción endotelial demostrada por dilatación mediada por flujo. Se evaluaron variables antropométricas, bioquímicas, hormonales y se determinó por ultrasonografía el espesor de IMC y TAE. Resultados: Los parámetros de rigidez arterial carotídea (velocidad de onda del pulso local [4,7±0,7 vs 4,8±0,5 vs 5,6±0,5m/sec, p<0,001], módulo de elasticidad de deformación de presión [55,2±13,4 vs 59,2±11,8 vs 81,9±15,6 Kpa, p<0,001], índice β de rigidez arterial [4,4±1,4 vs 5,0±1,1 vs 6,4±1,3 p<0,001]) y el espesor del TAE (2,98±1,4 vs 3,28±1,9 vs 4,70±1,0mm, p=0,007) mostraron un incremento significativo y proporcional en el grupo de mujeres en posmenopausia tardía comparado con los grupos de posmenopausia temprana y premenopausia respectivamente. Entre los marcadores de adiposidad el TAE fue el mejor predictor de la velocidad de onda del pulso independientemente de la edad. Conclusiones: En mujeres menopáusicas con disfunción endotelial la transición menopáusica se asoció con un incremento en la rigidez arterial y espesor del TAE, independiente de la edad. El espesor del TAE fue mejor predictor independiente de rigidez arterial que el espesor IMC en estas mujeres (AU)

Association between endothelial dysfunction, epicardial fat and subclinical atherosclerosis during menopause.

BACKGROUND: Menopausal transition is critical for the development of early, subclinical vascular damage. Multiple factors, such as atherosclerosis, increased epicardial fat, and endothelial dysfunction can play a role. Hence, the objective of this study was the comparison of epicardial adipose tissue and carotid intima media thickness in order to establish the best predictor of carotid stiffness in middle-aged women with endothelial dysfunction. METHODS: A total of 43 healthy women aged 40-59 years old with endothelial dysfunction previously demonstrated by flow mediated dilation were recruited to have anthropometric, biochemical, hormonal and ultrasound determinations of carotid intima media thickness and epicardial fat thickness. RESULTS: Carotid arterial stiffness parameters (local pulse wave velocity [4.7±0.7 vs 4.8±0.5 vs 5.6±0.5m/s, respectively, p<0.001], pressure strain elastic modulus [55.2±13.4 vs 59.2±11.8 vs 81.9±15.6kPa, respectively, p<0.001], arterial stiffness index ß [4.4±1.4 vs 5.0±1.1 vs 6.4±1.3, respectively, p<0.001]) and epicardial fat thickness (2.98±1.4 vs 3.28±1.9 vs 4.70±1.0mm, respectively, p=0.007) showed a significant and proportional increase in the group of late post-menopausal women when compared to early post-menopausal and pre-menopausal groups, respectively. Among body fat markers, epicardial fat was the strongest predictor of local pulse wave velocity, independent of age. CONCLUSIONS: In menopausal women with endothelial dysfunction, menopausal transition is associated with increased carotid arterial stiffness and epicardial fat thickness, independent of age. Ultrasound measured epicardial fat was a better independent predictor of arterial stiffness than carotid intima media thickness in these women.

Frecuencia, aspectos clínicos y moleculares de la hipercolesterolemia familiar en una unidad de endocrinología de Ciudad Bolívar, Venezuela / Frequency and clinical and molecular aspects of familial hypercholesterolemia in an endocrinology unit in Ciudad Bolívar, Venezuela

Objetivo: Describir la frecuencia, los aspectos clínicos, bioquímicos y moleculares de la hipercolesterolemia familiar (HF) en sujetos que acuden a una unidad de endocrinología. Métodos: Estudio observacional, descriptivo en el que se evaluaron 3.140 sujetos que fueron atendidos en la Unidad de Endocrinología del Centro Médico Orinoco en Ciudad Bolívar, Venezuela, desde el 7 de enero del 2013 al 9 de diciembre del 2016. Los casos índice fueron seleccionados de acuerdo con los criterios de la Red de Clínicas de Lípidos de Holanda. Se midieron lípidos plasmáticos. El análisis molecular se realizó por medio de secuenciación de ADN de los genes LDLR y APOB. Resultados: De los 3.140 sujetos evaluados, 10 (0,32%) tuvieron características clínicas y bioquímicas compatibles con HF. Todos, excepto uno, eran de sexo femenino. Tres pacientes tuvieron antecedente familiar en primer grado de enfermedad coronaria prematura y ninguno antecedente personal de esta patología. Tres pacientes tuvieron obesidad, 3 hipertensión arterial y ninguno tuvo diabetes. Tres pacientes presentaban xantomas tendinosos y solo uno arco corneal. Los valores de c-LDL oscilaron entre 191 y 486mg/dl. Solo 2 recibían tratamiento con estatinas. En 4 pacientes se identificó la causa genética de la HF: 3 de ellos por mutaciones en el gen LDLR y uno por mutación en el exón 26 del gen APOB. Conclusión: Aproximadamente una de cada 300 personas que acuden a consulta en esta unidad de endocrinología presentan HF. Las mutaciones en el gen LDLR son las principales causantes de HF en este grupo de pacientes (AU)

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 (AU)

Frequency and clinical and molecular aspects of familial hypercholesterolemia in an endocrinology unit in Ciudad Bolívar, Venezuela. / 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.

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.

Metreleptina: Tratamiento para las complicaciones metabólicas de la Lipodistrofia Generalizada / Metreleptin: Treatment for metabolic complications of generalized lipodystrophy

La metreleptina es un análogo de leptina que ha sido probado en pacientes con patologías derivadas del déficit de leptina. Las lipodistrofias representan un grupo de enfermedades caracterizadas por deficiencia de leptina, y se asocian con formas severas de síndrome metabólico que incluyen hiperglucemia, hipertrigliceridemia y esteatosis hepática. Estas complicaciones metabólicas pueden posteriormente progresar a diabetes mellitus, pancreatitis aguda y cirrosis hepática. Para el manejo de estas anormalidades, usualmente se requieren diversos tratamientos, pero en estadíos avanzados tienden a ser de difícil manejo. La metreleptina es el producto farmacéutico aprobado por la Administración de Alimentos y Fármacos de los Estados Unidos (FDA) para tratar las complicaciones metabólicas de las lipodistrofias generalizadas. En este artículo, se revisa el perfil farmacólogico de metreleptina y los aspectos clínicos de las lipodistrofias generalizadas. Además, se describen algunos estudios que evaluaron la eficacia y seguridad de metreleptina en pacientes con lipodistrofias generalizadas.

Metreleptin is a synthetic leptin analog that has been trialed in patients with leptin-deficient conditions. Lipodystrophies represent a class of diseases characterized by leptin deficiency, which is associated with a severe form of the metabolic syndrome characterized by hyperglycemia, hypertriglyceridemia, and hepatic steatosis. These metabolic complications can progress to diabetes mellitus, acute pancreatitis, and hepatic cirrhosis. For the management of these abnormalities, multiple therapies are usually required, and advances stages may be progressively difficult to treat. Metreleptin is the pharmaceutical derived product that has been approved by the US Food and Drug Administration (FDA) to treat the severe metabolic abnormalities of the generalized forms of lipodystrophy. Herein, we review the pharmacological profile of metreleptin, and clinical aspects of generalized lipodystrophies. Further, we examine studies that assessed the efficacy and safety of metreleptin in generalized lipodystrophies.

Espesor del tejido adiposo epicárdico en niños y adolescentes con factores de riesgo cardiometabólico / Epicardial adipose tissue thickness in children and adolescents with cardiometabolic risk factors

Objetivo: Determinar la relación del espesor del tejido adiposo epicárdico (TAE) con factores de riesgo cardiometabólico (FRC) en niños y adolescentes. Métodos: Se seleccionaron 77 sujetos de ambos sexos entre 7 y 18 años. Se realizó anamnesis y evaluación de parámetros clínicos, determinación de glucemia, insulina y lípidos y se calculó el HOMA-IR. Se determinó el espesor del TAE mediante ecocardiografía transtorácica. Se formaron 2 grupos, participantes con menos de 2 FRC (cero o un FRC) y participantes con 2 o más FRC. Resultados: El grupo con 2 o más FRC presentó mayores valores de espesor del TAE, insulina y HOMA-IR (p < 0,05). El espesor del TAE mostró una correlación positiva estadísticamente muy significativa con el índice de masa corporal (IMC) (r = 0,561; p = 0,0001), la circunferencia abdominal (r = 0,549; p = 0,0001), la presión arterial sistólica (PAS) (r = 0,256; p = 0,028), la insulina (r = 0,408; p = 0,0001) y el HOMA-IR (r = 0,325; p = 0,005), sin embargo, estas correlaciones fueron no significativas al ajustar para el IMC. El punto de corte para el espesor del TAE como predictor de 2 o más FRC fue de 3,17 mm. El riesgo (odds ratio) de tener 2 o más FRC si presenta un espesor de TAE > 3,17 mm fue de 3,1 (IC: 1,174-8,022, p = 0,02). El IMC fue la variable independiente que más influyó sobre los valores del espesor del TAE y la presencia de 2 o más FRC (AU)

Conclusión: En este grupo de niños y adolescentes se encontró que la relación del TAE con los FRC es dependiente del IMC. Objective: To assess the relationship of epicardial adipose tissue (EAT) thickness with cardiometabolic risk factors (CRFs) in children and adolescents. Methods: Seventy-seven subjects of both sexes aged 7-18 years were selected. Medical history, clinical parameters, and glucose, insulin, and lipid levels were collected. EAT thickness was measured using transthoracic echocardiography. Study subjects were divided into two groups based on whether they had less than two or two or more CRFs. Results: The group with two or more CRFs had higher EAT thickness, insulin, and HOMA-IR values (P < .05). EAT thickness showed a statistically significant positive correlation with body mass index (BMI) (r = 0.561, P = .0001), waist circumference (r = .549, P = .0001), systolic blood pressure (SBP) (r = .256, P = .028), insulin (r = 0.408, P = .0001), and HOMA-IR (r = .325, P = .005). However, these correlations were not significant after adjustment for BMI. The cut-off point for EAT thickness as predictor of two or more CRFs was 3.17 mm. The risk (odds ratio) of having two or more CRFs if EAT thickness was > 3.17 mm was 3.1 (95% CI: 1.174-8.022). BMI was the independent variable that most affected EAT thickness and the presence of two or more CRFs. Conclusion: In this group of children and adolescents, the relationship of EAT thickness with CRFs was found to be dependent on BMI (AU)

Síndrome de hiperquilomicronemia primaria tratado con ciprofibrato en la infancia / Primary hyperchylomicronemia syndrome treated with ciprofibrate in childhood

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Effect of sitagliptin on epicardial fat thickness in subjects with type 2 diabetes and obesity: a pilot study.

The aim of the study was to assess the effect of sitagliptin addition on the epicardial adipose tissue (EAT) thickness in subjects with type 2 diabetes mellitus inadequately controlled on metformin monotherapy. This was a 24-week interventional pilot study in 26 consecutive type 2 diabetic patients, 14 females and 12 males average age of 43.8 ± 9.0 years, with Hemoglobin A1c (HbA1c) ≥ 7% on metformin monotherapy. Subjects who met the inclusion criteria were added on sitagliptin and started on sitagliptin/metformin combination at the dosage of 50 mg/1000 mg twice daily. EAT and visceral and total body fat were measured, respectively, with echocardiography and bioelectrical impedance analysis at baseline and after 24 weeks of sitagliptin/metformin treatment in each subject. HbA1c and plasma lipids were also measured. EAT decreased significantly from 9.98 ± 2.63 to 8.10 ± 2.11 mm, p = 0.001, accounting for a percentage of reduction (∆%) of -15% after 24 weeks of sitagliptin addition, whereas total body fat percentage, visceral fat, and body mass index (BMI), decreased by 8, 12, and 7%, respectively (p = 0.001 for all). After 6 month, EAT ∆% was significantly correlated with ∆% of visceral fat (r = 0.456; p = 0.01), whereas no correlation with either BMI ∆% (r = 0.292; p = 0.147) or HbA1c ∆% was found. The addition of Sitagliptin produced a significant and rapid reduction of EAT, marker of organ-specific visceral fat, in overweight/obese individuals with type 2 diabetes inadequately controlled on metformin monotherapy. EAT as measured with ultrasound can serve as no invasive and accurate marker of visceral fat changes during pharmaceutical interventions targeting the fat.

Epicardial adipose tissue thickness in children and adolescents with cardiometabolic risk factors.

OBJECTIVE: To assess the relationship of epicardial adipose tissue (EAT) thickness with cardiometabolic risk factors (CRFs) in children and adolescents. METHODS: Seventy-seven subjects of both sexes aged 7-18 years were selected. Medical history, clinical parameters, and glucose, insulin, and lipid levels were collected. EAT thickness was measured using transthoracic echocardiography. Study subjects were divided into two groups based on whether they had less than two or two or more CRFs. RESULTS: The group with two or more CRFs had higher EAT thickness, insulin, and HOMA-IR values (P<.05). EAT thickness showed a statistically significant positive correlation with body mass index (BMI) (r=0.561, P=.0001), waist circumference (r=.549, P=.0001), systolic blood pressure (SBP) (r=.256, P=.028), insulin (r=0.408, P=.0001), and HOMA-IR (r=.325, P=.005). However, these correlations were not significant after adjustment for BMI. The cut-off point for EAT thickness as predictor of two or more CRFs was 3.17mm. The risk (odds ratio) of having two or more CRFs if EAT thickness was >3.17mm was 3.1 (95% CI: 1.174-8.022). BMI was the independent variable that most affected EAT thickness and the presence of two or more CRFs. CONCLUSION: In this group of children and adolescents, the relationship of EAT thickness with CRFs was found to be dependent on BMI.

Tratamiento con cirugía bariátrica en el paciente obeso: Guías clínicas del Servicio de Endocrinología del Instituto Autónomo Hospital Universitario de Los Andes

La incidencia de obesidad ha incrementado en forma significativa, constituyendo en la actualidad un grave problema de salud pública por su asociación frecuente con condiciones médicas tales como diabetes mellitus, hipertensión arterial sistémica y dislipidemias, que constituyen factores de riesgo cardiovascular. Los resultados de las intervenciones terapéuticas tradicionales (dieta, actividad física y tratamiento farmacológico), no han resultado exitosos en alcanzar y mantener la pérdida de peso, lo cual ha generado, en las últimas décadas, el desarrollo de otras modalidades terapéuticas con mejores tasas de respuesta como la cirugía bariátrica. Se requiere una adecuada selección de los posibles candidatos para cirugía bariátrica y conocimiento del manejo post-operatorio a corto y largo plazo.

The incidence of obesity has increased significantly, currently constituting a serious public health problem because of its frequent association with medical conditions such as diabetes mellitus, hypertension and dyslipidemia, which are cardiovascular risk factors. The results of traditional therapeutic interventions (diet, physical activity and drug treatment), have not been successful in achieving and maintaining weight loss, which has generated in recent decades the development of other therapeutic modalities with better response rates as bariatric surgery. Proper selection of potential candidates for bariatric surgery and post-operative knowledge of short and long-term management is required.