Background 18 F-NaF positron emission tomography (PET) targets microcalcifications. We compared in vitro microPET assessed 18 F-NaF uptake between culprit and non-culprit human carotid plaques. Furthermore, we compared 18 F-NaF uptake with calcification visualized on microcomputed tomography (microCT). Methods Carotid plaques from stroke patients undergoing surgery were incubated in 18 F-NaF and scanned using a microPET and a microCT scan. The average PET assessed 18 F-NaF uptake was expressed as percentage of the incubation dose per gram (%Inc/g). 18 F-NaF PET volume of interest (VOI) was compared with CT calcification VOI. Results 23 carotid plaques (17 culprit, 6 non-culprit) were included. The average 18 F-NaF uptake in culprit carotid plaques was comparable with the uptake in non-culprit carotid plaques (median 2.32 %Inc/g [IQR 1.98 to 2.81] vs. median 2.35 %Inc/g [IQR 1.77 to 3.00], P = 0.916). Only a median of 10% (IQR 4 to 25) of CT calcification VOI showed increased 18 F-NaF uptake, while merely a median of 35% (IQR 6 to 42) of 18 F-NaF PET VOI showed calcification on CT. Conclusions 18 F-NaF PET represents a different stage in the calcification process than CT. We observed a similar PET assessed 18 F-NaF uptake and pattern in culprit and non-culprit plaques of high-risk patients, indicating that this method may be of more value in early atherosclerotic stenosis development. Electronic supplementary material The online version of this article (10.1007/s12350-018-1325-5) contains supplementary material, which is available to authorized users.
OBJECTIVEType 2 diabetes is accompanied by premature atherosclerosis and arterial stiffness. The underlying association remains incompletely understood. The possible relationship between subclinical arterial inflammation assessed by 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and arterial stiffness was investigated in patients with early type 2 diabetes. RESEARCH DESIGN AND METHODSPatients with type 2 diabetes (n = 44), without cardiovascular disease and any type of antidiabetic medication, were studied (median age 63 years [interquartile range 54-66], men:women 27:17). Arterial inflammation was quantified as the FDG uptake maximal standardized uptake value (SUV max ). SUV max was corrected for the prescan glucose level. A target-to-background ratio (TBR) was calculated by dividing the SUV max of the arteries by the SUV mean of the caval veins (blood pool). TBRs were calculated for four individual segments (carotid arteries, ascending aorta and aortic arch, descending and abdominal aorta, and iliac and femoral arteries) and averaged for the total aortic tree ( mean TBR). Arterial stiffness was assessed as central systolic blood pressure (cSBP), carotid-femoral pulse wave velocity (PWV), and augmentation index (AIx). RESULTSThe mean TBR was significantly associated with PWV (R = 0.47, P = 0.001) and cSBP (R = 0.45, P = 0.003) but not with AIx. TBR of each separate segment was also significantly associated with PWV and cSBP. In a multiple linear regression model including age, sex, BMI, hemoglobin A 1c (HbA 1c ), hs-CRP, cholesterol, cSBP, and PWV, PWV was the strongest determinant of mean TBR. CONCLUSIONSIn patients with type 2 diabetes, FDG-PET/CT-imaged subclinical arterial inflammation is positively associated with determinants of arterial stiffness.
Linagliptin decreased aortic PWV in people with early-stage type 2 diabetes as compared with placebo after 26 weeks of treatment. These results suggest that linagliptin has a favourable effect on arterial stiffness.
Background Glucagon-like peptide-1 receptor agonists (GLP-1 RA) added to insulin in type 2 diabetes patients have shown to lower body weight, improve glycaemic control and reduce total daily insulin dose in short term studies, although the individual response greatly varies. Objective To evaluate GLP-1 RA treatment on body weight, glycaemic control and total daily insulin dose in obese, insulin-using type 2 diabetes patients after 2 years follow-up in a real life setting and to explore a possible relation with eating behaviour. Setting The Martini Hospital and the University Medical Center in Groningen in the Netherlands. Methods Eligible patients were at least 18 years of age, were on insulin therapy and obese (BMI > 30 kg/m2), started GLP-1 RA treatment. At baseline eating behaviour was classified according to the validated Dutch Eating Behaviour Questionnaire. A 2 years follow-up was performed. Main outcome measures Body weight, HbA1c and total daily insulin dose. Results 151 Patients started with exenatide or liraglutide. 120 patients completed the 2 years follow-up. From baseline to 2 years, body weight (mean ± SD) changed from 117.9 ± 22.1 to 107.9 ± 22.9 kg (P < 0.0001), HbA1c (median, IQR) changed from 7.9 (7.2–8.9) to 7.6 (6.9–8.3) % [63 (55–74) to 60 (52–67) mmol/mol] (P < 0.0001), total daily insulin dose changed from 90 (56–150) to 60 (0–100) Units/day (P < 0.0001). Weight change differed between eating behaviour groups (P < 0.001) in which external eating behaviour (n = 17) resulted in the smallest decline (−3.1 %) and restrained (n = 41) in the greatest (−10.3 %) in comparison with emotional (n = 37, −8.5 %) and indifferent (n = 25, −9.6 %) eating behaviours. Conclusion Two year of GLP-1 RA treatment resulted in a sustained reduction of weight, HbA1c and total daily insulin dose in obese, insulin-using type 2 diabetes patients in a real life setting. Largest weight loss was achieved in patients with a predominant restraint eating pattern while a predominant external eating pattern resulted in the smallest weight reduction.Electronic supplementary materialThe online version of this article (doi:10.1007/s11096-015-0219-8) contains supplementary material, which is available to authorized users.
Visceral adipose tissue volume is associated with premature atherosclerosis in early type 2 diabetes mellitus independent of traditional risk factors.
Background While [18F]-fluordeoxyglucose ([18F]FDG) uptake is associated with arterial inflammation, [18F]-sodium fluoride ([18F]NaF) is a marker for arterial micro-calcification. We aimed to investigate the prospective correlation between both PET markers over time and whether they are prospectively ([18F]FDG) and retrospectively ([18F]NaF) related to progression of systemic arterial disease in a longitudinal study in patients with type 2 diabetes mellitus (T2DM). Methods Baseline [18F]FDG PET/Low Dose (LD) Computed Tomography (CT) scans of ten patients with early T2DM without cardiovascular history (70% men, median age 63 years) were compared with five-year follow-up [18F]NaF/LDCT scans. Systemic activity was expressed as mean target-to-background ratio (meanTBR) by dividing the maximal standardized uptake value (SUVmax) of ten arteries by SUVmean of the caval vein. CT-assessed macro-calcifications were scored visually and expressed as calcified plaque (CP) score. Arterial stiffness was assessed with carotid-femoral pulse wave velocity (PWV). Five-year changes were expressed absolutely with delta (Δ) and relatively with %change. Results Baseline meanTBR[18F]FDG was strongly correlated with five-year follow-up meanTBR[18F]NaF (r = 0.709, P = .022). meanTBR[18F]NaF correlated positively with ΔCPscore, CPscore at baseline, and follow-up (r = 0.845, P = .002 and r = 0.855, P = .002, respectively), but not with %change in CPscore and PWV. Conclusion This proof-of-concept study demonstrated that systemic arterial inflammation is an important pathogenetic factor in systemic arterial micro-calcification development.
Purpose: Severity of abdominal obesity and possibly levels of metabolic activity of abdominal visceral adipose tissue (VAT) are associated with an increased risk for cardiovascular disease (CVD). In this context, the purpose of the current study was to evaluate the reproducibility and repeatability of a semi-automated method for assessment of the metabolic activity of VAT using 2-deoxy-2-[ PET/low-dose (LD) CT scans within 1 week were included. Abdominal VAT was automatically segmented using CT between levels L1-L5. The initial CT-based segmentation was further optimized using PET data with a standardized uptake value (SUV) threshold approach (range 1.0-2.5) and morphological erosion (range 0-5 pixels). The [ 18 F]FDG uptake in SUV that was measured by the automated method was compared with manual analysis. The reproducibility and repeatability were quantified using intraclass correlation coefficients (ICCs).Results: The metabolic assessment of VAT on [ 18 F]FDG PET/LDCT scans expressed as SUV mean , using an automated method showed high inter and intra observer (all ICCs 9 0.99) and overall repeatability (ICC = 0.98). The manual method showed reproducible inter observer (all ICCs 9 0.92), but less intra observer (ICC = 0.57) and less overall repeatability (ICC = 0.78) compared with the automated method.
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