RESUMO
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.
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Diabetes Mellitus Tipo 2/diagnóstico , Adolescente , Adulto , Idoso , Glicemia/metabolismo , Feminino , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Medição de Risco , Fatores de Risco , Inquéritos e Questionários , Venezuela , Adulto JovemRESUMO
Boucher-Neuhäuser and Gordon Holmes syndromes are clinical syndromes defined by early-onset ataxia and hypogonadism plus chorioretinal dystrophy (Boucher-Neuhäuser syndrome) or brisk reflexes (Gordon Holmes syndrome). Here we uncover the genetic basis of these two syndromes, demonstrating that both clinically distinct entities are allelic for recessive mutations in the gene PNPLA6. In five of seven Boucher-Neuhäuser syndrome/Gordon Holmes syndrome families, we identified nine rare conserved and damaging mutations by applying whole exome sequencing. Further, by dissecting the complex clinical presentation of Boucher-Neuhäuser syndrome and Gordon Holmes syndrome into its neurological system components, we set out to analyse an additional 538 exomes from families with ataxia (with and without hypogonadism), pure and complex hereditary spastic paraplegia, and Charcot-Marie-Tooth disease type 2. We identified four additional PNPLA6 mutations in spastic ataxia and hereditary spastic paraplegia families, revealing that Boucher-Neuhäuser and Gordon Holmes syndromes in fact represent phenotypic clusters on a spectrum of neurodegenerative diseases caused by mutations in PNPLA6. Structural analysis indicates that the majority of mutations falls in the C-terminal phospholipid esterase domain and likely inhibits the catalytic activity of PNPLA6, which provides the precursor for biosynthesis of the neurotransmitter acetylcholine. Our findings show that PNPLA6 influences a manifold of neuronal systems, from the retina to the cerebellum, upper and lower motor neurons and the neuroendocrine system, with damage of this protein causing an extraordinarily broad continuous spectrum of associated neurodegenerative disease.
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Ataxia Cerebelar/genética , Hormônio Liberador de Gonadotropina/deficiência , Transtornos Heredodegenerativos do Sistema Nervoso/genética , Hipogonadismo/genética , Mutação/genética , Fosfolipases/genética , Distrofias Retinianas/genética , Ataxias Espinocerebelares/genética , Adulto , Ataxia/etiologia , Ataxia/genética , Ataxia Cerebelar/fisiopatologia , DNA/genética , Exoma/genética , Família , Feminino , Hormônio Liberador de Gonadotropina/genética , Transtornos Heredodegenerativos do Sistema Nervoso/fisiopatologia , Humanos , Hipogonadismo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Mutação/fisiologia , Distrofias Retinianas/fisiopatologia , Paraplegia Espástica Hereditária/genética , Ataxias Espinocerebelares/fisiopatologiaRESUMO
The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive metabolic disorder due to an abnormal cholesterol synthesis. It was first described by Smith, Lemli and Opitz in 1964. Many cases of SLOS have been described since then, leading to the recognition as a relatively common malformation syndrome. Affected individuals have dysmorphism, microcephaly, multiple congenital malformations, mental retardation, aggressiveness and hyperactivity. The severity of physical defects correlates with the severity of the cholesterol deficiency, which is caused by an abnormally low activity of 7-dehydrocholesterol reductase, the enzyme responsible for conversion of 7-dehydrocholesterol to cholesterol. The occurrence of hypothyroidism in association with SLOS is very unusual. We describe the first Venezuelan case in which both anomalies are associated.
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Hipotireoidismo/complicações , Síndrome de Smith-Lemli-Opitz , Pré-Escolar , Humanos , Hipotireoidismo/diagnóstico , Masculino , Fenótipo , Síndrome de Smith-Lemli-Opitz/diagnóstico , VenezuelaRESUMO
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.
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COVID-19/epidemiologia , Diabetes Mellitus/epidemiologia , Hiperglicemia/complicações , Glicemia/metabolismo , COVID-19/fisiopatologia , COVID-19/virologia , Diabetes Mellitus/fisiopatologia , Hospitalização/estatística & dados numéricos , Humanos , Hiperglicemia/fisiopatologia , Prognóstico , SARS-CoV-2/isolamento & purificaçãoRESUMO
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.
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Tratamento Farmacológico da COVID-19 , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/epidemiologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Fígado/efeitos dos fármacos , Pandemias , Sistema Renina-Angiotensina/fisiologia , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do VírusRESUMO
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.
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Hiperlipoproteinemia Tipo II/prevenção & controle , Efeitos Psicossociais da Doença , Saúde Global , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/terapia , Guias de Prática Clínica como Assunto , Saúde PúblicaRESUMO
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.
Assuntos
Tecido Adiposo/metabolismo , Adiposidade/fisiologia , Diabetes Mellitus Tipo 2/epidemiologia , Pericárdio/metabolismo , Adolescente , Adulto , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Peso Corporal/fisiologia , Estudos Transversais , Feminino , Humanos , Insulina/sangue , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Risco , Venezuela , Circunferência da Cintura/fisiologia , Adulto JovemRESUMO
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.
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Tecido Adiposo/patologia , Aterosclerose/patologia , Menopausa , Pericárdio/patologia , Adulto , Antropometria , Artérias Carótidas/patologia , Espessura Intima-Media Carotídea , Estudos Transversais , Módulo de Elasticidade , Endotélio Vascular/patologia , Humanos , Pessoa de Meia-Idade , Análise de Onda de Pulso , Rigidez VascularRESUMO
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.
Assuntos
Diabetes Mellitus Tipo 2/etiologia , Resistência à Insulina , Obesidade/complicações , Inquéritos e Questionários , Deficiência de Vitamina D/complicações , Vitamina D/análogos & derivados , Adulto , Biomarcadores/sangue , Glicemia/análise , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Jejum/sangue , Feminino , Humanos , Insulina/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Venezuela , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Circunferência da CinturaRESUMO
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.
Assuntos
Hiperlipoproteinemia Tipo II/epidemiologia , Adolescente , Adulto , Antropometria , Apolipoproteínas B/genética , Criança , Comorbidade , Endocrinologia , Éxons/genética , Feminino , Unidades Hospitalares , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/genética , Hipertensão/epidemiologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Prevalência , Pró-Proteína Convertase 9/genética , Receptores de LDL/genética , Análise de Sequência de DNA , Tendões , Venezuela/epidemiologia , Xantomatose/etiologiaRESUMO
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.
Assuntos
Tecido Adiposo/diagnóstico por imagem , Cardiopatias/epidemiologia , Doenças Metabólicas/epidemiologia , Pericárdio/diagnóstico por imagem , Adolescente , Pressão Sanguínea , Criança , Ecocardiografia , Feminino , Humanos , Insulina/sangue , Masculino , Fatores de Risco , Circunferência da CinturaRESUMO
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.
Assuntos
Tecido Adiposo/patologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/patologia , Hipoglicemiantes/farmacologia , Obesidade/patologia , Pericárdio/patologia , Fosfato de Sitagliptina/farmacologia , Tecido Adiposo/efeitos dos fármacos , Adiposidade , Adolescente , Adulto , Idoso , Composição Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Quimioterapia Combinada , Impedância Elétrica , Feminino , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Humanos , Lipídeos/sangue , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Obesidade/complicações , Pericárdio/efeitos dos fármacos , Projetos Piloto , Adulto JovemRESUMO
UNLABELLED: Type 1 diabetes mellitus (T1DM) is a chronic disease characterized by the autoimmune destruction of pancreatic ß-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 100âmg 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 ß-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.
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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.
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Adiponectina/sangue , Tecido Adiposo/patologia , Síndrome Metabólica/patologia , Pericárdio/patologia , Adulto , Função do Átrio Esquerdo , Glicemia/análise , Índice de Massa Corporal , Colesterol/sangue , HDL-Colesterol/sangue , Estudos Transversais , Ecocardiografia , Feminino , Humanos , Modelos Lineares , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Tamanho do Órgão , Volume Sistólico , Triglicerídeos/sangue , Venezuela , Função Ventricular EsquerdaRESUMO
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.
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Obesity increases the risk of development of atherosclerosis. However, this risk significantly depends on adipose tissue distribution in the body and ectopic accumulation of visceral adipose tissue (VAT). Recent evidence suggests that each visceral fat deposit is anatomically and functionally different. Due to proximity to the organ, each visceral fat deposit exerts a local modulation rather than a systemic effect. Because of its unique location and biomolecular properties, a "non-traditional" fat depot - the epicardial adipose tissue - has been considered to play a causative role in atherosclerosis. Epicardial adipose tissue may be measured with imaging techniques and is clinically related to left ventricular mass, coronary artery disease, and metabolic syndrome. Therefore, epicardial fat measurement may play a role in stratification of cardiometabolic risk and may serve as a therapeutic target.
Assuntos
Tecido Adiposo/patologia , Pericárdio/patologia , Doença da Artéria Coronariana/etiologia , HumanosRESUMO
OBJECTIVE: To define an echocardiographically-assessed cut-off point for epicardial adipose tissue (EAT) thickness associated to metabolic syndrome (MS) components in Venezuelan subjects. METHODS: Fifty-two subjects aged 20-65 years diagnosed with MS according to International Diabetes Federation criteria and 45 sex- and age-matched controls were selected. Blood glucose and plasma lipids were tested; EAT thickness and left ventricular mass were measured by echocardiography. RESULTS: No significant age and sex differences were found between the two groups. Body weight, body mass index, waist circumference, and systolic and diastolic blood pressure were significantly higher (P=.0001) in the MS group. This group showed significantly higher levels of fasting blood glucose (P=.0001), total cholesterol (P=.002), LDL-C (P=.007), non-HDL-C (P=.0001), triglycerides (P=.0001), Tg-HDL-C ratio (P=.0001), and lower HDL-C levels (P=.0001) as compared to the control group. EAT thickness (P=.0001) and left ventricular mass (P=.017) were significantly higher in the MS group. The ROC curve showed an AUC of 0.852 (P=.0001) with a power of the test of 0.99. A 5-mm EAT thickness showed a sensitivity of 84.62% (95%CI: 71.9-93.1) and a specificity of 71.11% (95%CI: 55.7-83.6) for predicting MS. The odds ratio of this population for experiencing MS due to an EAT ≥ 5 mm was 8.25 (95%CI: 3.15-21.56; P=.0001). CONCLUSION: An EAT value ≥ 5 mm has good sensitivity and specificity for predicting MS in the Venezuelan population.
Assuntos
Tecido Adiposo/anatomia & histologia , Síndrome Metabólica/epidemiologia , Pericárdio/anatomia & histologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Valor Preditivo dos Testes , Venezuela , Adulto JovemRESUMO
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.
RESUMO
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.