RESUMEN
BACKGROUND: We have previously found that pioglitazone attenuates inflammation in the left main trunk of coronary artery (LMT), evaluated as target-to-background ratio (TBR) by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in patients with impaired glucose tolerance or type 2 diabetes. OBJECTIVES: We assessed which clinical variables could predict the change in TBR in the LMT after 4-month add-on therapy with oral hypoglycemic agents (OHAs). METHODS: A total of 38 type 2 diabetic patients with carotid atherosclerosis who had already received OHAs except for pioglitazone was enrolled. At baseline and 4 months after add-on therapy with pioglitazone or glimepiride, all patients underwent 75 g oral glucose tolerance test, blood chemistry analysis, and FDG-PET/CT. RESULTS: Fasting plasma glucose, 30-, 60-, 90-, 120-minutes postload plasma glucose, HbA1c, and LMT-TBR values were significantly decreased by add-on therapy, whereas high-density lipoprotein-cholesterol and adiponectin levels were increased. Increased serum levels of pigment epithelium-derived factor (PEDF), a marker of insulin resistance and non-use of aspirin at baseline could predict the favorable response of LMT-TBR to add-on therapy. Moreover, Δ120-minutes postload plasma glucose and ΔPEDF were independent correlates of ΔLMT-TBR. CONCLUSIONS: Our present study suggests that 120-minutes postload plasma glucose and PEDF values may be markers and potential therapeutic targets of coronary artery inflammation in type 2 diabetic patients. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov . Unique identifier: NCT00722631. New markers for diabetes and CAD is on the horizon! Two-hour postload plasma glucose and pigment epithelium derived factor are markers of coronary artery inflammation in type 2 diabetic patients.
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Glucemia/análisis , Enfermedad de la Arteria Coronaria/diagnóstico , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/diagnóstico , Proteínas del Ojo/sangre , Inflamación/diagnóstico , Factores de Crecimiento Nervioso/sangre , Serpinas/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Enfermedad de la Arteria Coronaria/sangre , Diabetes Mellitus Tipo 2/sangre , Angiopatías Diabéticas/sangre , Femenino , Humanos , Inflamación/sangre , Masculino , Persona de Mediana EdadRESUMEN
We have developed a high-speed vision chip using 3D stacking technology to address the increasing demand for high-speed vision chips in diverse applications. The chip comprises a 1/3.2-inch, 1.27 Mpixel, 500 fps (0.31 Mpixel, 1000 fps, 2 × 2 binning) vision chip with 3D-stacked column-parallel Analog-to-Digital Converters (ADCs) and 140 Giga Operation per Second (GOPS) programmable Single Instruction Multiple Data (SIMD) column-parallel PEs for new sensing applications. The 3D-stacked structure and column parallel processing architecture achieve high sensitivity, high resolution, and high-accuracy object positioning.
RESUMEN
OBJECTIVE: Endothelial dysfunction is an initial step in atherosclerotic cardiovascular disease. However, involvement of vascular inflammation in endothelial dysfunction is not fully investigated in humans because of the lack of diagnostic modality to noninvasively evaluate vascular inflammation. We assessed the relationship between endothelial function and vascular inflammation evaluated by [(18)F]-fluorodeoxyglucose-positron emission tomography/computed tomographic imaging. APPROACH AND RESULTS: We examined endothelial function and vascular inflammation by flow-mediated dilation (FMD) of the brachial artery and [(18)F]-fluorodeoxyglucose-positron emission tomography/computed tomographic imaging of carotid arteries, respectively, in 145 subjects (95 men and 50 women; mean age, 61.8±9.5 years) who underwent a risk-screening test for cardiovascular disease in Kurume University Hospital. Vascular inflammation was measured by blood-normalized standardized uptake value, known as a target:background ratio (TBR). We investigated whether absolute changes from baseline of %FMD after antihypertensive treatment for 6 months (Δ%FMD) were correlated with those of TBR in 33 drug-naive patients with essential hypertension. Multiple logistic regression analysis revealed that age (odds ratio, 1.767 for 10-year increase), male sex (odds ratio, 0.434), low-density lipoprotein-cholesterol (odds ratio, 1.630 for 26-mg/dL increase), and TBR values (odds ratio, 1.759 for 0.2 increase) were independently associated with %FMD in 145 patients. There was an inverse correlation between Δ%FMD and ΔTBR; ΔTBR was a sole independent associate of Δ%FMD in hypertensive patients (r=-0.558; P<0.001). CONCLUSIONS: The present study showed that vascular inflammation in the carotid arteries evaluated by [(18)F]-fluorodeoxyglucose-positron emission tomography/computed tomography was one of the independent correlates of decreased %FMD, thus suggesting the association of vascular inflammation with endothelial dysfunction in humans.
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Arteria Braquial/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Endotelio Vascular/diagnóstico por imagen , Fluorodesoxiglucosa F18/administración & dosificación , Hipertensión/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos/administración & dosificación , Vasculitis/diagnóstico por imagen , Vasodilatación , Anciano , Antihipertensivos/uso terapéutico , Biomarcadores/sangre , Arteria Braquial/efectos de los fármacos , Arteria Braquial/fisiopatología , Enfermedades de las Arterias Carótidas/fisiopatología , Grosor Intima-Media Carotídeo , LDL-Colesterol/sangre , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Japón , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Valor Predictivo de las Pruebas , Flujo Sanguíneo Regional , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Resultado del Tratamiento , Vasculitis/fisiopatología , Vasodilatación/efectos de los fármacosRESUMEN
Trimethylamine (TMA), an intestinal microflora-dependent metabolite formed from phosphatidylcholine- and L-carnitine-rich food, such as red meat, is further converted to trimethylamine-N-oxide (TMAO), which could play a role in cardiometabolic disease. Red meat-derived products are one of the major environmental sources of advanced glycation end products (AGEs) that may also contribute to the pathogenesis of cardiometabolic disorders through the interaction with receptor for AGEs (RAGE). However, the relationship among AGEs, soluble form of RAGE (sRAGE) and TMAO in humans remains unclear. Non-diabetic subjects underwent a physical examination, determination of blood chemistry and anthropometric variables, including AGEs, sRAGE, TMA and TMAO. Multiple regression analyses revealed that HbA1c, uric acid and AGEs were independently associated with log TMA, whereas log AGEs to sRAGE ratio and statin non-use were independently correlated with log TMAO. Our present findings indicated that AGEs to sRAGE ratio was correlated with log TMAO, a marker of cardiometabolic disorders.
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Productos Finales de Glicación Avanzada/sangre , Metilaminas/sangre , Receptor para Productos Finales de Glicación Avanzada/sangre , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoAsunto(s)
Síndrome de Behçet/patología , Estenosis Carotídea/patología , Síndrome de Behçet/complicaciones , Grosor Intima-Media Carotídeo , Estenosis Carotídea/complicaciones , Femenino , Fluorodesoxiglucosa F18 , Humanos , Angiografía por Resonancia Magnética , Imagen Multimodal , Tomografía de Emisión de Positrones , Radiofármacos , Adulto JovenAsunto(s)
Ecocardiografía Tridimensional , Imagenología Tridimensional , Insuficiencia de la Válvula Mitral/complicaciones , Taquicardia Supraventricular/etiología , Anciano de 80 o más Años , Apéndice Atrial , Cicatriz/complicaciones , Cicatriz/diagnóstico , Cicatriz/patología , Femenino , Atrios Cardíacos/patología , Hemorreología , Humanos , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/fisiopatología , Imagen Multimodal , Venas Pulmonares , Tomografía Computarizada por Rayos XRESUMEN
CONTEXT: Body fat distribution and inflammation may play a role in metabolic derangements and cardiovascular disease in obesity. OBJECTIVE: The aim of this study is to investigate clinical and biochemical factors associated with area and metabolic activity in the visceral and subcutaneous adipose tissues (VAT and SAT). PARTICIPANTS: (18)F-fluorodeoxyglucose-positron emission tomography and computed tomography imaging was performed in 251 consecutive subjects (62.6 ± 9.3 y) for risk screening. MAIN OUTCOME MEASURES: We examined which clinical, anthropometric, metabolic, and inflammatory variables including advanced glycation end products (AGEs) and pigment epithelium-derived factor (PEDF) were independently associated with area and metabolic activity in VAT and SAT. Adipose tissue area was determined with computed tomography, whereas metabolic activity was assessed by (18)F-fluorodeoxyglucose uptake expressed as a target to background ratio (TBR) of blood-normalized standardized uptake. RESULTS: Serum levels of AGEs and PEDF were 9.81 ± 3.21 U/mL and 14.0 (range 10.8-17.7) µg/mL, respectively. Although the area in VAT and SAT was associated with waist circumference and sex, each adipose tissue area and TBR had different metabolic risk profiles. The TBR value in VAT was higher than that in SAT. In a multiple stepwise regression analysis, AGEs and medication for hypertension were independently associated with VAT TBR (R(2) = 0.102), whereas medication for diabetes, mean intima-media thickness, AGEs, and PEDF were the independent correlates of SAT TBR (R(2) = 0.132). CONCLUSIONS: The present study demonstrated that area and metabolic activity in VAT and SAT could be differently regulated, suggesting the involvement of AGEs and PEDF in adipose tissue inflammation.
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Enfermedades Cardiovasculares/metabolismo , Grasa Intraabdominal/diagnóstico por imagen , Síndrome Metabólico/metabolismo , Obesidad/metabolismo , Grasa Subcutánea/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Distribución de la Grasa Corporal , Enfermedades Cardiovasculares/diagnóstico por imagen , Grosor Intima-Media Carotídeo , Proteínas del Ojo/sangre , Femenino , Productos Finales de Glicación Avanzada/sangre , Humanos , Masculino , Síndrome Metabólico/diagnóstico por imagen , Persona de Mediana Edad , Factores de Crecimiento Nervioso/sangre , Obesidad/diagnóstico por imagen , Radiografía , Cintigrafía , Factores de Riesgo , Serpinas/sangre , Circunferencia de la CinturaRESUMEN
Atherosclerosis and its thrombotic complications represent the major cause of morbidity and mortality in the industrialized countries. Despite recent advances in the diagnosis and management of cardiovascular disease, a substantial number of patients still die from acute coronary syndromes. Recently, atherosclerotic plaque composition rather than the degree of arterial stenosis has been shown to reflect the plaque vulnerability, thus contributing to the pathogenesis of cardiovascular disease. Vulnerable plaques have a large lipidrich necrotic core, a thin-fibrous cap and numerous inflammatory cells. Among them, macrophage activation plays a central role in vascular inflammation and plaque instability within the atherosclerosis, being strongly involved in acute coronary syndromes. Various morphologic features of plaque vulnerability have been described by computed tomography angiography, magnetic resonance imaging, intravascular ultrasound, and optical coherence tomography. Molecular imaging is the tool best suited for identifying metabolically active macrophages. Indeed, positron emission tomography (PET) imaging with 18F-fluorodeoxyglucose (FDG) is capable of identifying and quantifying vascular inflammation characterized by macrophage activation within the atherosclerotic plaques. So, FDG-PET might be a feasible clinical tool for detecting vulnerable plaques and evaluating the efficacy of drugs in plaque instability. In this paper, we review the clinical utility of FDG-PET imaging in identifying patients at risk of plaque rupture and resultantly prone to cardiovascular disease.
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Aterosclerosis/diagnóstico , Imagen Molecular/métodos , Enfermedades Vasculares/diagnóstico , Animales , Aterosclerosis/fisiopatología , Diagnóstico por Imagen/métodos , Diagnóstico por Imagen/tendencias , Humanos , Inflamación/diagnóstico , Inflamación/fisiopatología , Imagen Molecular/tendencias , Enfermedades Vasculares/fisiopatologíaRESUMEN
OBJECTIVE: The purpose of this study was to investigate the relationship between serum levels of malondialdehyde-modified low-density lipoprotein cholesterol (MDA-LDL) and vascular inflammation evaluated by fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT). METHODS/RESULTS: The study involved 106 consecutive patients (75 males and 31 female, mean age 62.5 ± 7.7 years) who visited our hospital for cardiovascular risk screening and underwent carotid ultrasonography, (18)F-FDG PET/CT, complete history, physical examinations, and determination of blood chemistry including high-sensitivity C-reactive protein (hsCRP), asymmetric dimethylarginine (ADMA), and MDA-LDL. Vascular inflammation, was measured as blood-normalized standardized (18)F-FDG uptake value, known as the target-to-background ratio (TBR) of carotid arteries. Univariate and multiple stepwise regression analyses were performed for determining independent correlates of carotid TBR values. Median MDA-LDL, mean carotid TBR values and carotid intima-media thickness (IMT) were 127.5 (IQR 92.0-147.8) U/l, 1.55 ± 0.22, and 0.72 ± 0.15 mm, respectively. Univariate analysis revealed that carotid TBR values positively correlated with MDA-LDL (p = 0.043) and carotid IMT (p = 0.049). Multiple stepwise regression analysis demonstrated that MDA-LDL (p = 0.043) and carotid IMT (p = 0.038) were independently associated with carotid TBR values. CONCLUSION: The present study reveals that serum levels of MDA-LDL are independently associated with vascular inflammation evaluated by (18)F-FDG PET/CT. Circulating MDA-LDL may be a more useful clinical biomarker for vascular inflammation within the atherosclerotic plaques than hsCRP or ADMA.
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LDL-Colesterol/sangre , Fluorodesoxiglucosa F18/química , Inflamación/sangre , Malondialdehído/química , Anciano , Biomarcadores , Proteína C-Reactiva/metabolismo , Arterias Carótidas/diagnóstico por imagen , Arterias Carótidas/patología , Grosor Intima-Media Carotídeo , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Estudios Prospectivos , Encuestas y Cuestionarios , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVES: The aim of this study was to compare the effect of pioglitazone with glimepiride on coronary arterial inflammation with serial (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) combined with computed tomography (CT) angiography. BACKGROUND: Recent studies have shown that FDG-PET combined with CT is a reliable tool to visualize and quantify vascular inflammation. Although pioglitazone significantly prevented the progression of coronary atherosclerosis and reduced the recurrence of myocardial infarction in patients with type 2 diabetes mellitus (DM), it remains unclear whether pioglitazone could attenuate coronary artery inflammation. METHODS: Fifty atherosclerotic patients with impaired glucose tolerance or type 2 DM underwent determination of blood chemistries, anthropometric and inflammatory variables, and FDG-PET/CT angiography, and then were randomized to receive either pioglitazone or glimepiride for 16 weeks. Effects of the treatments on vascular inflammation of the left main trunk were evaluated by FDG-PET/CT angiography at baseline and end of the study. Vascular inflammation of the left main trunk was measured by blood-normalized standardized uptake value, known as a target-to-background ratio. RESULTS: Three patients dropped out of the study during the assessment or treatment. Finally, 25 pioglitazone-treated patients and 22 glimepiride-treated patients (37 men; mean age: 68.1 ± 8.3 years; glycosylated hemoglobin: 6.72 ± 0.70%) completed the study. After 16-week treatments, fasting plasma glucose and glycosylated hemoglobin values were comparably reduced in both groups. Changes in target-to-background ratio values from baseline were significantly greater in the pioglitazone group than in the glimepiride group (-0.12 ± 0.06 vs. 0.09 ± 0.07, p = 0.032), as well as changes in high-sensitivity C-reactive protein (pioglitazone vs. glimepiride group: median: -0.24 [interquartile range (IQR): -1.58 to -0.04] mg/l vs. 0.08 [IQR: -0.07 to 0.79] mg/l, p = 0.031). CONCLUSIONS: Our study indicated that pioglitazone attenuated left main trunk inflammation in patients with impaired glucose tolerance or DM in a glucose-lowering independent manner, suggesting that pioglitazone may protect against cardiac events in patients with impaired glucose tolerance or DM by suppressing coronary inflammation. (Anti-Inflammatory Effects of Pioglitazone; NCT00722631).
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Glucemia/efectos de los fármacos , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Vasos Coronarios/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Angiopatías Diabéticas/tratamiento farmacológico , Fluorodesoxiglucosa F18 , Hipoglucemiantes/uso terapéutico , Imagen Multimodal/métodos , Tomografía de Emisión de Positrones , Radiofármacos , Tiazolidinedionas/uso terapéutico , Tomografía Computarizada por Rayos X , Anciano , Biomarcadores/sangre , Glucemia/metabolismo , Proteína C-Reactiva/metabolismo , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/etiología , Vasos Coronarios/diagnóstico por imagen , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/diagnóstico , Angiopatías Diabéticas/etiología , Hemoglobina Glucada/metabolismo , Humanos , Japón , Masculino , Persona de Mediana Edad , Pioglitazona , Valor Predictivo de las Pruebas , Estudios Prospectivos , Compuestos de Sulfonilurea/uso terapéutico , Factores de Tiempo , Resultado del TratamientoRESUMEN
CONTEXT: Excess visceral fat is associated with chronic systemic inflammation and cardiovascular complications. Pioglitazone has been reported to variably influence visceral fat volume; however, its effect on metabolic activity of the visceral fat remains uncharacterized. OBJECTIVE: The aim of this study was to assess the effects of pioglitazone on glucose metabolism of fat tissue by using (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) and computed tomography imaging. DESIGN, SETTING, AND PARTICIPANTS: FDG-PET and computed tomography imaging were performed in 56 patients with impaired glucose tolerance or type 2 diabetes mellitus; lipid and glycemic profiles and inflammatory biomarkers were obtained in all patients. These patients were randomized to treatment with either pioglitazone or glimepiride for 16 weeks. MAIN OUTCOME MEASURES: The metabolic activity of the visceral fat tissues as assessed by FDG uptake was expressed as a target-to-background ratio (TBR) of blood-normalized standardized uptake value. RESULTS: The study was completed in 32 pioglitazone-treated and 21 glimepiride-treated patients (40 men and 13 women; mean age, 67.7 ± 8.1 y; body mass index, 25.0 ± 3.6 kg/m(2); glycated hemoglobin, 6.78 ± 0.70%). Both treatments were well-tolerated and comparably improved glycemic control. At baseline, visceral fat exhibited a higher TBR value than subcutaneous fat (0.55 ± 0.14 vs 0.30 ± 0.07, P < .001). Pioglitazone, but not glimepiride, significantly decreased the visceral fat volume (130.5 ± 53.0 to 122.1 ± 51.0 cm(2), P = .013) and TBR values (0.57 ± 0.16 to 0.50 ± 0.11, P = .007). Neither pioglitazone nor glimepiride treatment showed any effect on the volume or TBR values of subcutaneous fat. After 16 weeks of treatment with pioglitazone, reduction in visceral fat TBR was correlated to the increase in high-density lipoprotein cholesterol levels. CONCLUSIONS: Our study indicated that pioglitazone decreased the visceral fat volume and its metabolic activity in patients with impaired glucose tolerance or type 2 diabetes mellitus. The beneficial effects of pioglitazone on visceral fat may be independent of its glucose-lowering effect.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Intolerancia a la Glucosa/tratamiento farmacológico , Grasa Intraabdominal/efectos de los fármacos , Grasa Intraabdominal/metabolismo , Compuestos de Sulfonilurea/administración & dosificación , Tiazolidinedionas/administración & dosificación , Administración Oral , Anciano , Distribución de la Grasa Corporal , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Fluorodesoxiglucosa F18 , Intolerancia a la Glucosa/diagnóstico por imagen , Intolerancia a la Glucosa/metabolismo , Humanos , Hipoglucemiantes/administración & dosificación , Grasa Intraabdominal/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Imagen Multimodal , Pioglitazona , Tomografía de Emisión de Positrones , Grasa Subcutánea/diagnóstico por imagen , Grasa Subcutánea/efectos de los fármacos , Grasa Subcutánea/metabolismo , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Advanced glycation end products (AGEs) evoke oxidative stress generation and inflammatory reactions, thus being involved in vascular complications in diabetes. Since oxidative stress and inflammation impair insulin actions as well, it is conceivable that AGEs may play some role in insulin resistance. However, there is no clinical study to examine the relationship between serum levels of AGEs and insulin resistance. This study investigated whether serum AGE levels were independent correlates of insulin resistance in humans. METHODS: Three hundred twenty-two nondiabetic Japanese subjects (216 male and 106 female; mean age 61.5 ± 9.1 years) underwent a complete history and physical examination, determinations of blood chemistries, anthropometric and metabolic variables, including AGEs. Serum AGE levels were examined with an enzyme-linked immunosorbent assay. RESULTS: Mean serum AGE levels were 8.96 ± 2.57 U/mL. In univariate analysis, waist circumference, diastolic blood pressure (BP), mean BP, AGEs, low-density lipoprotein (LDL) cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol (inversely), hemoglobin A1c (GHb), creatinine clearance, uric acid, and high sensitivity C-reactive protein were significantly associated with insulin resistance evaluated by homeostasis model assessment of insulin resistance (HOMA-IR) index. After performing multiple regression analysis, waist circumference (P < 0.001), GHb (P < 0.001), triglycerides (P < 0.001), and AGEs (P < 0.01) still remained significant independently. When age-adjusted HOMA-IR levels stratified by AGE tertiles were compared using ANCOVA, a significant trend was demonstrated in both males and females. CONCLUSION: The present study demonstrated for the first time that serum AGE levels were one of the independent correlates of HOMA-IR index, thus suggesting that AGEs may play some pathological role in insulin resistance in humans.
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Productos Finales de Glicación Avanzada/sangre , Resistencia a la Insulina , Anciano , Biomarcadores/sangre , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Análisis Multivariante , Análisis de Regresión , Medición de Riesgo , Factores de RiesgoRESUMEN
OBJECTIVE: Advanced glycation end products (AGEs) evoke inflammatory reactions, contributing to the development and progression of atherosclerosis. We investigated the relationship between serum AGE level and vascular inflammation. RESEARCH DESIGN AND METHODS: The study involved 275 outpatients at Kurume University, Japan (189 males and 86 females; mean age 61.2 ± 8.8 years) who underwent complete history and physical examinations and determinations of blood chemistry and anthropometric variables, including AGEs. Serum AGE level was examined by enzyme-linked immunosorbent assay. Vascular [(18)F]fluorodeoxyglucose (FDG) uptake, an index of vascular inflammation, was measured as blood-normalized standardized uptake value, known as the target-to-background ratio (TBR), by FDG-positron emission tomography (FDG-PET). Furthermore, we examined whether the changes in serum AGE level after treatment with oral hypoglycemia agents (OHAs) were correlated with those of TBR in another 18 subjects whose AGE value was >14.2 units/mL (mean ± 2 SD). RESULTS: Mean serum AGE level and carotid TBR values were 9.15 ± 2.53 and 1.43 ± 0.22 units/mL, respectively. Multiple stepwise regression analysis revealed that TBR was independently correlated with AGEs (P < 0.001), carotid intima-media thickness (P < 0.01), and BMI (P < 0.02). When age- and sex-adjusted AGE values stratified by TBR tertiles were compared using ANCOVA, a significant trend was observed (P < 0.01). In addition, the changes in AGEs after OHA treatment were positively (r = 0.50, P < 0.05) correlated with those in TBR value. CONCLUSIONS: The current study reveals that serum AGE level is independently associated with vascular inflammation evaluated by FDG-PET, suggesting that circulating AGE value may be a biomarker that could reflect vascular inflammation within an area of atherosclerosis.
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Fluorodesoxiglucosa F18 , Productos Finales de Glicación Avanzada/sangre , Tomografía de Emisión de Positrones/métodos , Anciano , Antineoplásicos/uso terapéutico , Aterosclerosis/sangre , Aterosclerosis/diagnóstico , Aterosclerosis/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Pigment epithelium-derived factor (PEDF) could play a protective role against atherosclerosis. However, there is no clinical study to examine the relationship between serum level of PEDF and atherosclerosis in humans. METHODS/RESULTS: The study involved 317 consecutive outpatients in Kurume University Hospital (220 male and 97 female) with a mean age of 62.1±9.1. We examined whether serum level of PEDF were independently associated with vascular inflammation evaluated by [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET) and intima-media thickness (IMT) in carotid artery in humans. Carotid [(18)F]-FDG uptake, an index of vascular inflammation within the atherosclerotic plaques, was measured as standardized uptake value (SUV). Mean serum PEDF level, carotid SUV and IMT values were 13.5±1.1 µg/mL, 1.34±0.19, and 0.71±0.15 mm, respectively. In multiple stepwise regression analysis, estimated glomerular filtration rate (p<0.001), males (p<0.001), homeostasis model assessment of insulin resistance index (p<0.05), heart rate (p<0.05), triglycerides (p<0.05), carotid IMT (p<0.05), waist circumference (p<0.05) and carotid SUV (p<0.05) were independently correlated to PEDF level (R(2)=0.332). CONCLUSION: The present study reveals that serum level of PEDF is independently associated with vascular inflammation and IMT, thus suggesting that PEDF level is a novel biomarker that could reflect atherosclerosis in humans.
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Aterosclerosis/diagnóstico , Proteínas del Ojo/sangre , Factores de Crecimiento Nervioso/sangre , Serpinas/sangre , Anciano , Aterosclerosis/sangre , Biomarcadores , Arterias Carótidas/metabolismo , Grosor Intima-Media Carotídeo , Estudios Transversales , Femenino , Fluorodesoxiglucosa F18 , Humanos , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones/métodosRESUMEN
OBJECTIVES: The aim of this study was to compare the effect of pioglitazone, an insulin sensitizer, with glimepiride, an insulin secretagogue, on atherosclerotic plaque inflammation by using serial (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. BACKGROUND: Atherosclerosis is intrinsically an inflammatory disease. Although hyperglycemia is associated with an increased risk of atherosclerotic cardiovascular disease, there are no clinical data to show the preference of any specific oral hypoglycemic agents to prevent atherosclerotic plaque inflammation. METHODS: A total of 56 impaired glucose tolerant or diabetic patients with carotid atherosclerosis underwent a complete history, determinations of blood chemistries, anthropometric variables, and FDG-PET. They were randomly assigned to receive either pioglitazone (15 to 30 mg) or glimepiride (0.5 to 4.0 mg) for 4 months with titration to optimal dosage. Effects of the drugs on atherosclerotic plaque inflammation were evaluated by FDG-PET at study completion. Plaque inflammation was measured by blood-normalized standardized uptake value, known as a target-to-background ratio. RESULTS: The study was completed in 31 pioglitazone-treated patients and 21 glimepiride-treated patients. Although both treatments reduced fasting plasma glucose and hemoglobin A1c values comparably, pioglitazone, but not glimepiride, decreased atherosclerotic plaque inflammation. Compared with glimepiride, pioglitazone significantly increased high-density lipoprotein cholesterol level. High-sensitivity C-reactive protein was decreased by pioglitazone, whereas it was increased by glimepiride. Multiple stepwise regression analysis revealed that the increase in high-density lipoprotein cholesterol level was independently associated with the attenuation of plaque inflammation. CONCLUSIONS: Our present study suggests that pioglitazone could attenuate atherosclerotic plaque inflammation in patients with impaired glucose tolerance or in diabetic patients independent of glucose lowering effect. Pioglitazone may be a promising strategy for the treatment of atherosclerotic plaque inflammation in impaired glucose tolerance or diabetic patients. (Detection of Plaque Inflammation and Visualization of Anti-Inflammatory Effects of Pioglitazone on Plaque Inflammation in Subjects With Impaired Glucose Tolerance and Type 2 Diabetes Mellitus by FDG-PET/CT; NCT00722631).
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Antiinflamatorios/uso terapéutico , Enfermedades de la Aorta/tratamiento farmacológico , Aortografía , Enfermedades de las Arterias Carótidas/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Angiopatías Diabéticas/tratamiento farmacológico , Fluorodesoxiglucosa F18 , Intolerancia a la Glucosa/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Inflamación/tratamiento farmacológico , Imagen Multimodal , Tomografía de Emisión de Positrones , Radiofármacos , Compuestos de Sulfonilurea/uso terapéutico , Tiazolidinedionas/uso terapéutico , Tomografía Computarizada por Rayos X , Anciano , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades de la Aorta/etiología , Biomarcadores/sangre , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Proteína C-Reactiva/metabolismo , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/etiología , HDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/diagnóstico por imagen , Angiopatías Diabéticas/etiología , Femenino , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/complicaciones , Hemoglobina Glucada/metabolismo , Humanos , Inflamación/diagnóstico por imagen , Inflamación/etiología , Japón , Masculino , Persona de Mediana Edad , Pioglitazona , Valor Predictivo de las Pruebas , Estudios Prospectivos , Análisis de Regresión , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVES: This study evaluated the usefulness of fasting (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in the diagnosis and management of cardiac sarcoidosis (CS) and compared it with FDG uptake in dilated cardiomyopathy (DCM). BACKGROUND: Cardiac sarcoidosis may clinically present as DCM but is amenable to systemic corticosteroid therapy if disease activity is high. Although alterations of FDG uptake have been reported in CS, limited information is available on the quantitative estimates of FDG uptake. METHODS: Fasting FDG-PET was performed in 24 systemic sarcoidosis patients and was compared with 8 age-matched DCM patients. FDG-PET was also performed in 15 age-matched healthy control subjects. Twelve of the 24 sarcoidosis patients had cardiac involvement based on criteria established by the Japanese Ministry of Health and Welfare; the remaining 12 of 24 patients revealed no evidence of cardiac involvement. The myocardial FDG uptake was quantified by measuring the standardized uptake value in 17 myocardial segments in each subject. Coefficient of variation (COV), which equals the standard deviation of uptake divided by the average uptake of 17 segments, was calculated as an index of heterogeneity in the heart. RESULTS: The FDG uptake was distinctly heterogeneous in CS patients. The COV value was significantly greater in CS patients (0.25 ± 0.05) than control subjects (0.14 ± 0.03, p < 0.01), sarcoidosis patients without cardiac involvement (0.14 ± 0.03, p < 0.01), or DCM patients (0.15 ± 0.02, p < 0.01). The COV value in DCM patients was similar to control subjects or sarcoidosis patients without cardiac involvement. The cutoff COV value for the diagnosis of CS was 0.18 (sensitivity: 100%; specificity: 97%). After corticosteroid therapy in CS patients, the COV value was decreased to 0.14 ± 0.06 (p < 0.05) and became essentially similar to the other groups. CONCLUSIONS: Heterogeneous myocardial FDG uptake may be a useful diagnostic marker of disease activity for CS.