Background: Endothelial dysfunction is an initial step for atherosclerotic cardiovascular disease. However, involvement of vascular inflammation in endothelial dysfunction is not fully investigated in humans. We assessed the relationship between endothelial function and vascular inflammation evaluated by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging. Methods and Results: We examined endothelial function and vascular inflammation, which were evaluated by flow-mediated dilation (FMD) of the brachial artery functionally and FDG-PET imaging of carotid arteries, respectively, in 128 subjects (83 males and 45 females; mean age 61.8 ± 10.0 years) who underwent a risk-screening test for cardiovascular disease in Kurume University Hospital. Vascular inflammation of the carotid arteries was measured by blood-normalized standardized uptake value, known as a target-to-background ratio (TBR). Mean percent change in vasodilation (percent change over the baseline values; %FMD) and carotid TBR were 5.60 ± 2.24 % and 1.43 ± 0.22, respectively. %FMD was less in men than in women. In univariate analysis, %FMD was inversely correlated with age (p=0.011), systolic blood pressure (p=0.014), carotid artery maximum intima-media thickness (p=0.014), HbA1c (p=0.020), visceral fat volume (p=0.005), or TBR values (p<0.001). Multiple stepwise regression analysis revealed that age (p=0.034), visceral fat volume (p=0.002), and TBR values (p<0.001) were independently associated with decreased %FMD (R2=0.245). Conclusions: We found here that vascular inflammation in the carotid arteries evaluated by FDG-PET was one of the independent association of decreased %FMD, thus suggesting that vascular inflammation might contribute to endothelial dysfunction in humans.
Body fat distribution and inflammation may play a role in metabolic derangements and cardiovascular disease in obesity.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).(18)F-fluorodeoxyglucose-positron emission tomography and computed tomography imaging was performed in 251 consecutive subjects (62.6 ± 9.3 y) for risk screening.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.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).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.
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.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.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.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.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.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.
Advanced glycation end products (AGEs) are involved in cardiovascular disease. Low testosterone level is associated with increased risks of cardiometabolic disorders as well. However, which anthropometric and metabolic variables, including AGEs, are independently correlated with low testosterone is largely unknown. In this study, we investigated whether high serum level of AGEs is one of the independent determinants of low testosterone in non-diabetic men. One hundred thirteen non-diabetic men who did not receive any drugs for hypertension and dyslipidemia underwent a complete history and physical examination, determination of blood chemistries, including serum AGEs and testosterone. Univariate analysis showed that testosterone levels were associated with waist circumference (inversely), diastolic blood pressure (BP) (inversely), mean BP (inversely), triglycerides (inversely), HDL-cholesterol, fasting plasma glucose (inversely), fasting insulin (inversely), homeostasis model assessment of insulin resistance (HOMA-IR) (inversely), AGEs (inversely) and uric acid (inversely). By the use of multiple stepwise regression analyses, HOMA-IR (p = 0.005) and triglycerides levels (p < 0.05) remained significant and were independently related to testosterone levels (R(2) = 0.168). HOMA-IR index was one of the independent determinants of serum levels of AGEs as well. The present study demonstrated for the first time that HOMA-IR was independently associated with high serum levels of AGEs and low testosterone in non-diabetic men. Insulin resistance could link elevation of AGEs to testosterone deficiency in non-diabetic men.
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