Myocardial Glucose Uptake In Patients Research Articles

Relationship of Ketosis With Myocardial Glucose Uptake Among Patients Undergoing FDG PET/CT for Evaluation of Cardiac Sarcoidosis.

Fluorine-18 fluorodeoxyglucose (FDG) with positron emission tomography (PET) is the standard for detecting myocardial inflammation in cardiac sarcoidosis, requiring preparation with the ketogenic diet (KD) to achieve myocardial glucose suppression. Despite this, incomplete myocardial glucose suppression remains a significant issue, and strategies to reduce myocardial glucose uptake (MGU) and identify incomplete myocardial glucose suppression are required. This study sought to understand the relationship between point-of-care beta-hydroxybutyrate (BHB) and different patterns of MGU and between KD and fasting duration with MGU in patients undergoing evaluation for cardiac sarcoidosis. We prospectively included 471 outpatients who underwent FDG-PET for cardiac sarcoidosis evaluation, followed the KD for 1 (n=100), 2 (n=29), and ≥3 days (n=342), fasted for at least 12 hours, and had BHB levels measured immediately before FDG injection. Images were classified as (1) no MGU (negative), (2) focal/multifocal (positive), (3) diffuse (nondiagnostic), or (4) nonspecific uptake (NS-MGU). Cardiac FDG-PET scans were interpreted as the following: 376 (79.83%) negative; 61 (12.95%) positive; 14 (2.97%) diffuse; and 20 (4.25%) NS-MGU. There was a strong negative relationship between BHB levels and MGU (P<0.0001). BHB levels increased significantly with KD duration (P<0.0001) and fasting time (P=0.0067). The combined rate of diffuse, NS-MGU, and positive scans (34%, 28%, 16%) decreased inversely with KD duration (1, 2, and ≥3 days, respectively). However, MGU was not different across different fasting times (P=0.6). Blood glucose levels were not associated with MGU (P=0.17) and only weakly associated with BHB levels (R2=0.03; P<0.001). We observed a strong inverse relationship between ketosis and patterns of MGU. Longer KD and fasting durations are associated with higher ketosis. However, only KD duration was associated with lower rates of MGU. Measurement of BHB levels before FDG-PET using point-of-care testing is feasible and may facilitate the management of patients referred for myocardial inflammation.

Non-alcoholic fatty liver disease with reduced myocardial FDG uptake is associated with coronary atherosclerosis

BackgroundNon-alcoholic fatty liver disease (NAFLD) has a significant role in the development of coronary atherosclerosis, independent of traditional cardiovascular and metabolic risk factors. However, the role of myocardial glucose uptake in NAFLD patients who develop coronary atherosclerosis was unclear. The aim of the present study thus was to investigate the association between NAFLD with characteristic of coronary atherosclerotic plaque and myocardial glucose uptake measured by using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). Methods and ResultsA total of 418 consecutive subjects who had undergone FDG PET/computed tomography (CT) and coronary computed tomography angiography (CCTA) were retrospectively investigated. Fatty liver was assessed by unenhanced CT. Coronary atherosclerotic plaques and stenosis on CCTA were evaluated. The metabolic parameters were measured on PET images. The ratio of the maximum myocardium FDG value to the mean standardized uptake value of liver (SUVratio) was calculated to estimate myocardial glucose uptake. The association of myocardial glucose uptake with NAFLD and coronary atherosclerosis was determined by multivariate logistic regression analysis. The proportion of low SUVratio in patients with NAFLD was significantly higher compared to those without NAFLD (45.00% vs 19.82%, P < .001). There was a significantly negative correlation between myocardial FDG uptake and hepatic steatosis in association trend analysis (P < .001). When the proportion of individuals with non-calcified plaque on CCTA is stratified by quartiles of SUVratio, patients with low quartiles of SUVratio were more likely to have higher proportion of non-calcified plaque than those with high quartiles of SUVratio (Q1 and Q2 vs Q3 and Q4, P = .003). The trend analysis presented correlated inversely relationship between non-calcified plaque and myocardial SUVratio (P = .001). Moreover, multivariate regression analysis showed that the low SUVratio was independently associated with NAFLD, non-calcified plaque, and significant stenosis after adjusting for clinically important factors. ConclusionWe demonstrated that the presence of reduced myocardial glucose uptake in patients with NAFLD was independently associated with non-calcified plaque and significant stenosis, suggesting an increased risk of coronary atherosclerosis and future cardiovascular events.

Nonalcoholic fatty liver disease, diastolic dysfunction, and impaired myocardial glucose uptake in patients with type 2 diabetes

To investigate whether degree of nonalcoholic fatty liver disease (NAFLD) is associated with myocardial dysfunction related to impaired myocardial glucose uptake in patients with type 2 diabetes. In total, 131 patients with type 2 diabetes from a tertiary care hospital were included in this study. Myocardial glucose uptake was assessed using [18 F]-fluorodeoxyglucose-positron emission tomography. Hepatic steatosis and fibrosis were determined using transient liver elastography. Echocardiography was performed to evaluate cardiac structure and function. Patients with NAFLD had cardiac diastolic dysfunction with higher left ventricular filling pressure (E/e' ratio) and left atrial (LA) volume index than patients without NAFLD (all P < 0.05). Hepatic steatosis correlated with E/e' ratio and LA volume index, and hepatic fibrosis also correlated with E/e' ratio (all P < 0.05). Even after adjusting for confounding factors, a higher degree of hepatic steatosis (r2 = 0.409, P = 0.041) and a higher degree of fibrosis (r2 = 0.423, P = 0.009) were independent contributing factors to a higher E/e' ratio. Decreased myocardial glucose uptake was associated with a higher degree of steatosis (P for trend = 0.084) and fibrosis (P for trend = 0.012). At the same time, decreased myocardial glucose uptake was an independent contributing factor for a higher E/e' ratio (r2 = 0.409; P = 0.040). Hepatic steatosis and fibrosis were significantly associated with diastolic heart dysfunction in patients with type 2 diabetes coupled with impaired myocardial glucose uptake.

422-P: Association between Nonalcoholic Fatty Liver Disease and Diastolic Myocardial Dysfunction and Myocardial Insulin Resistance in Patients with Type 2 Diabetes

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes and associated with cardiovascular risks. We investigated whether degree of NAFLD was associated with myocardial dysfunction in relation to myocardial glucose uptake in patients with type 2 diabetes. A total of 131 patients with type 2 diabetes were included from a tertiary care hospital. Myocardial glucose uptake was assessed using [18F]-FDG-PET scan. Hepatic steatosis and fibrosis were determined using transient liver elastography (Fibroscan). Echocardiogram was performed to evaluate cardiac structure and function. Patients with NAFLD revealed cardiac diastolic dysfunction with increased left ventricular filling pressure (E/e’ ratio) and left atrial volume index (LAVI) compared with patients without NAFLD (all p&amp;lt;0.05). Hepatic steatosis was correlated with E/e’ ratio and LAVI, and hepatic fibrosis was also correlated with E/e’ ratio (all p &amp;lt; 0.05). In linear regression analyses, degree of hepatic steatosis and fibrosis were independent determinant factors for a higher E/e’ ratio even after adjusting for confounding factors (r2=0.409, p=0.041 for steatosis and r2=0.423, p=0.009 for fibrosis). Higher degree of steatosis and fibrosis were associated with decreased myocardial glucose uptake (p for trends=0.084 and 0.012 for steatosis and fibrosis, respectively). Furthermore, decreased myocardial glucose uptake was an independent determinant factor for a higher E/e’ ratio (r2=0.409, p=0.04). In conclusion, hepatic steatosis and fibrosis are significantly associated with diastolic heart dysfunction in patients with type 2 diabetes coupled with decreased myocardial glucose uptake. Disclosure Y. Kim: None. M. Lee: None. S. Lee: None. B. Cha: None. E. Kang: None.

Clinical significance of quantitative assessment of right ventricular glucose metabolism in patients with heart failure with reduced ejection fraction

Dynamic 18F-fluorodeoxyglucose (FDG) PET can be used to quantitatively assess the rate of myocardial glucose uptake (MRGlu). The aim of this study was to evaluate the clinical significance and prognostic value of right ventricular (RV) MRGlu in patients with coronary artery disease and heart failure with reduced ejection fraction. Patients with left ventricular ejection fraction (LVEF) ≤ 40% were consecutively enrolled for FDG PET between November 2012 and May 2017. Global LV and RV MRGlu (μmol/min/100g) were analyzed. Outcome events were independently assessed using electronic medical records to determine hospitalization for revascularization, new-onset ischemic events, heart failure, cardiovascular, and all-cause death. Differences between LV and RV MRGlu and associations with clinical characteristics and echocardiographic data were evaluated. Associations among FDG PET findings and outcomes were analyzed using Kaplan-Meier survival analysis. Seventy-five patients (mean age 62.2 ± 12.7years, male 85.3%, LVEF 19.3 ± 8.6%) were included for analysis. The mean glucose utilization ratio of RV-to-LV (RV/LV MRGlu) was 89.5 ± 264.9% (r = 0.77, p < 0.001). Positive correlations between RV MRGlu and maximal tricuspid regurgitation peak gradient (r = 0.28, p = 0.033) and peak tricuspid regurgitation jet velocity (r = 0.29, p = 0.021) were noted. LVEF was positively correlated with LV MRGlu (r = 0.27, p = 0.018), but negatively correlated with end-diastolic volume (r = - 0.37, p = 0.001), end-systolic volume (r = - 0.54, p < 0.001), and RV/LV MRGlu (r = - 0.40, p < 0.001). However, RV MRGlu was not well correlated with LVEF. Forty-three patients received revascularization procedures after FDG PET, and 13 patients died in a mean follow-up period of 496 ± 453days (1-1788days), including nine cardiovascular deaths. Higher RV and LV MRGlu values, LVEF ≤ 16% and LV end-diastolic volume ≥ 209ml of gated-PET were associated with poor overall survival and cardiac outcomes. In patients with coronary artery disease and ischemic cardiomyopathy, RV glucose utilization was positively correlated with RV pressure overload, but not LVEF. Global LV and RV MRGlu, LVEF, and LV end-diastolic volume showed significant prognostic value.

Effect of liraglutide on myocardial glucose uptake and blood flow in stable chronic heart failure patients: A double-blind, randomized, placebo-controlled LIVE sub-study

BackgroundThe glucagon-like peptide-1 analog liraglutide increases heart rate and may be associated with more cardiac events in chronic heart failure (CHF) patients. We studied whether this could be ascribed to effects on myocardial glucose uptake (MGU), myocardial blood flow (MBF) and MBF reserve (MFR). Methods and ResultsCHF patients with left ventricular ejection fraction ≤45% and without type 2 diabetes were randomized to liraglutide (N = 18) 1.8 mg once daily or placebo (N = 18) for 24 weeks in a double-blinded design. Changes in MGU during an oral glucose tolerance test (OGTT) and changes in MBF and MFR from baseline to follow-up were measured quantitatively by 18F-FDG and 15O-H2O positron emission tomography. Compared with placebo, liraglutide reduced weight (P = 0.03), HbA1c (P = 0.03) and the 2-hour glucose value during the OGTT (P = 0.004). Despite this, changes in MGU (P = 0.98), MBF (P = 0.76) and MFR (P = 0.89) from baseline to follow-up did not differ between groups. Furthermore, there was no association between the level of insulin resistance at baseline and changes in MGU in patients treated with liraglutide. ConclusionLiraglutide did not affect MGU, MBF, or MFR in non-diabetic CHF patients. Any potential increase in cardiac events in these patients seems not to involve changes in MGU, MBF, or MFR. Trial RegistrationTrial registry: http://www.ClinicalTrials.org. Identifier: NCT01472640. Url: https://clinicaltrials.gov/ct2/show/NCT01472640?term=NCT01472640&rank=1

Dipeptidyl Peptidase 4 Inhibition Increases Myocardial Glucose Uptake in Nonischemic Cardiomyopathy

BackgroundGlucose and fatty acids comprise the primary substrates for myocardial energy metabolism. The normal myocardium switches toward glucose metabolism in the setting of stress; the inability to affect such a switch is a fundamental mechanism behind “diabetic” or “insulin-resistant” cardiomyopathy. The purpose of this mechanistic study was to evaluate the effects of treatment with the dipeptidyl peptidase (DPP) 4 inhibitor sitagliptin on myocardial glucose uptake in patients with nonischemic cardiomyopathy. Methods and ResultsTwelve nondiabetic subjects with nonischemic cardiomyopathy underwent metabolic testing and assessment of myocardial glucose uptake by 18F-fluorodeoxyglucose positron-emission tomographic/computerized tomographic imaging at baseline and after 4 weeks of sitagliptin therapy. Sitagliptin therapy resulted in a significant increase in myocardial glucose uptake (19% increase; P = .04). Although most patients had at least a slight increase in glucose uptake, there was an overall bimodal response, with 6 patients (“responders”) demonstrating large increases (>20%) in glucose uptake and 6 patients (“nonresponders”) demonstrating <5% increases or slight decreases. Triglyceride–high-density lipoprotein ratios significantly dropped in the 6 responders compared with the 6 nonresponders (P < .02). ConclusionsTherapy with the DPP-4 inhibitor sitagliptin results in increased myocardial glucose uptake in nondiabetic patients with nonischemic cardiomyopathy.

Therapy With a DPP-4 Inhibitor Increases Myocardial Glucose Uptake in Nonischemic Cardiomyopathy

Introduction: Glucose and fatty acids comprise the primary substrates for myocardial energy metabolism. Because glucose is the more efficient fuel, the normal myocardium switches metabolism toward glucose in the setting of stress the inability to affect such a switch is a fundamental mechanism behind “diabetic” or “insulin-resistant” cardiomyopathy. We sought to evaluate the effects of treatment with the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin on myocardial glucose uptake in patients with nonischemic cardiomyopathy. Methods: Twelve patients with nonischemic dilated cardiomyopathy on stable medical therapy were enrolled in the trial. Because the goal of the study was to assess the direct actions of sitagliptin on myocardial glucose uptake rather than sitagliptin’s effects as a hypoglycemic therapy for diabetes, diabetic patients were excluded. At baseline, all subjects underwent fasting metabolic testing (glucose, insulin, lipids) and assessment of myocardial glucose uptake by 18F-FDG-PET/CT imaging. All subjects were then treated with sitagliptin (100 mg orally once daily) for four weeks, and metabolic testing and PET-CT imaging was repeated. The primary endpoint of the study was change in myocardial glucose uptake preand post-sitagliptin therapy, measured 10-30 minutes post-FDG injection. Results: Sitagliptin therapy resulted in a significant increase in myocardial glucose uptake (19% increase, P50.04). While most patients had at least a slight increase in glucose uptake, there was an overall bimodal response e with six patients (“responders”) demonstrating large increases (O20%) in glucose uptake and six patients (“nonresponders”) demonstrating !5% increases or slight decreases. There were no associations between increases in glucose uptake and levels of serum/plasma glucose, insulin, or insulin resistance. Triglyceride:HDL ratios significantly dropped in the six “responders” compared with the six “nonresponders” (P!0.02). Conclusions: Therapy with sitagliptin results in increased myocardial glucose uptake in nondiabetic patients with nonischemic cardiomyopathy. These results provide mechanistic evidence to support a trial assessing clinical heart failure endpoints.

Rosiglitazone increases myocardial glucose uptake in patients with type 2 diabetes mellitus and coronary artery disease,

Rosiglitazone increases myocardial glucose uptake in patients with type 2 diabetes mellitus and coronary artery disease,

Rosiglitazone Improves Myocardial Glucose Uptake in Patients With Type 2 Diabetes and Coronary Artery Disease

Rosiglitazone therapy improves insulin sensitivity and glucose uptake in patients with uncomplicated type 2 diabetes. In coronary artery disease (CAD), glucose is an important source of energy and preserved myocardial glucose uptake is essential for the viability of jeopardized myocardium. The aim was to test whether rosiglitazone changes myocardial metabolism in type 2 diabetic patients with CAD. We studied 54 patients (38 men and 16 women) with type 2 diabetes (HbA(1c) 7.2 + 0.9%) and CAD. Myocardial glucose uptake was measured with [(18)F]fluoro-2-deoxy-d-glucose positron emission tomography in ischemic (evaluated by single-photon emission tomography and coronary angiography) and nonischemic regions during euglycemic-hyperinsulinemic clamp before and after a 16-week intervention period with rosiglitazone (n = 27) or placebo (n = 27). Rosiglitazone significantly improved glycemic control (P < 0.0001) and whole-body insulin sensitivity (P < 0.0001). Rosiglitazone increased myocardial glucose uptake from 20.6 +/- 11.8 to 25.5 +/- 12.4 micromol . 100 g(-1) . min(-1) (P = 0.038 vs. baseline, P = 0.023 vs. placebo) in ischemic regions and from 21.7 +/- 12.1 to 28.0 +/- 12.7 micromol . 100 g(-1) . min(-1) (P = 0.014 vs. baseline, P = 0.003 vs. placebo) in nonischemic regions. The increase in myocardial glucose uptake was partly explained by the suppression of free fatty acid levels during clamp. Rosiglitazone therapy significantly increased insulin sensitivity and improved myocardial glucose uptake in type 2 diabetic patients with CAD. These results suggest that rosiglitazone therapy may facilitate myocardial glucose storage and utilization in these patients.

Enhancement of insulin‐stimulated myocardial glucose uptake in patients with Type 2 diabetes treated with rosiglitazone

Peroxisome proliferator-activated receptor gamma (PPARgamma) activators have recently been identified as regulators of cellular proliferation, inflammatory responses and lipid and glucose metabolism. These agents prevent coronary arteriosclerosis and improve left ventricular remodelling and function in heart failure after myocardial infarction. Improvement in myocardial metabolic state may be one of the mechanisms behind these findings. The aim of this study was to investigate the effects of rosiglitazone on myocardial glucose uptake in patients with Type 2 diabetes. Placebo and metformin were used as control treatments. Forty-four patients were randomized to treatment with rosiglitazone (4 mg b.i.d.), metformin (1 g b.i.d.) or placebo in a 26-week double-blinded trial. Myocardial glucose uptake was measured using [(18)F]-2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) and positron emission tomography (PET) during euglycaemic hyperinsulinaemia before and after the treatment. Rosiglitazone increased insulin-stimulated myocardial glucose uptake by 38% (from 38.7 +/- 3.4 to 53.3 +/- 3.6 micromol 100 g(-1) min(-1), P = 0.004) and whole body glucose uptake by 36% (P = 0.01), while metformin treatment had no significant effect on myocardial (40.5 +/- 3.5 vs. 36.6 +/- 5.2, NS) or whole body glucose uptake. Myocardial work as determined by the rate-pressure-product was similar between the groups. Neither treatment had any significant effect on fasting serum free fatty acids (FFA) but the FFA levels during hyperinsulinaemia were more suppressed in the rosiglitazone group (-47%, P = 0.02). Myocardial glucose uptake correlated inversely to FFA concentrations both before (r =-0.54, P = 0.002) and after (r = -0.43, P = 0.01) the treatment period in the pooled data. Furthermore, the increase in myocardial glucose uptake correlated inversely with interleukin-6 (IL-6) concentrations (r = -0.58, P = 0.03). In addition to the improvement in whole body insulin sensitivity, rosiglitazone treatment enhances insulin stimulated myocardial glucose uptake in patients with Type 2 diabetes, most probably due to its suppression of the serum FFAs.

Exercise training improves insulin-stimulated myocardial glucose uptake in patients with dilated cardiomyopathy

Background The effects of exercise training on myocardial substrate utilization have not previously been studied in patients with idiopathic dilated cardiomyopathy and mild heart failure. Methods and results Myocardial glucose uptake was studied in 15 clinically stable patients with dilated cardiomyopathy (New York Heart Association class I-II, ejection fraction 34% ± 8%) with the use of 2-[fluorine 18]fluoro-2-deoxy- d-glucose ([F-18]FDG) and positron emission tomography under euglycemic hyperinsulinemia. Eight of these patients participated in a 5-month endurance and strength training program, whereas seven patients served as nontrained subjects. Left ventricular function was assessed by 2-dimensional echocardiography before and after the intervention. After the training period, insulin-stimulated myocardial fractional [F-18]FDG uptake and glucose uptake rates were significantly increased in the anterior, lateral, and septal walls ( P < .01) in the trained subjects but remained unchanged in the nontrained subjects. In the trained patients, whole-body insulin-stimulated glucose uptake was enhanced and serum free fatty acid levels were suppressed during hyperinsulinemia compared with the baseline study ( P < .05). No changes were observed in the nontrained group. Conclusions These results indicate that exercise training in patients with dilated cardiomyopathy improves insulin-stimulated myocardial glucose uptake. This improvement in glucose uptake may be indicative of a switch in myocardial preference to a more energy-efficient substrate.

Myocardial glucose uptake in patients with NIDDM and stable coronary artery disease

Myocardial glucose uptake in patients with NIDDM and stable coronary artery disease

Myocardial glucose uptake in patients with NIDDM and stable coronary artery disease.

Whole body insulin resistance characterizes patients with NIDDM, but it is not known whether insulin also has impaired ability to stimulate myocardial glucose uptake (MGU) in these patients. This study was designed to evaluate MGU as measured by 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET) in patients with NIDDM and stable coronary artery disease (CAD) under standardized metabolic conditions. Eight patients with NIDDM, 11 nondiabetic patients with CAD, and 9 healthy control subjects were enrolled in the study. MGU was quantitated in the normal myocardial regions with [18F]FDG and PET and the whole body glucose disposal by glucose-insulin clamp technique (serum insulin, -430 pmol/l). Plasma glucose and serum insulin concentrations were comparable in all groups during PET studies. The whole body glucose uptake was 45% lower in NIDDM patients (22 +/- 9 micromol x min(-1) X kg(-1) body wt [mean +/- SD]), compared with healthy control subjects (40 +/- 17 micromol x min(-1) x kg(-1) body wt, P < 0.05). In CAD patients, whole body glucose uptake was 30 +/- 9 micromol x min(-1) x kg(-1) body wt (NS between the other groups). MGU was similar in the normal segments in all three groups (69 +/- 28 micromol x min(-1) x 100 g(-1) in NIDDM patients, 72 +/- 17 micromol x min(-1) x 100 g(-1) in CAD patients, and 76 +/- 10 micromol x min(-1) x 100 g(-1) in healthy control subjects, NS). No correlation was found between whole body glucose uptake and MGU. As studied by [18F]FDG PET under stable normoglycemic hyperinsulinemic conditions, MGU is not reduced in patients with NIDDM and CAD in spite of peripheral insulin resistance. These findings suggest that there is no significant defect in MGU in patients with NIDDM.

Myocardial glucose uptake in patients with insulin-dependent diabetes mellitus assessed quantitatively by dynamic positron emission tomography.

Animal studies have demonstrated reduced myocardial glucose utilization in the diabetic heart, suggesting abnormalities in glucose transport. This study was designed to evaluate myocardial glucose uptake as assessed by 2-fluoro-(fluorine-18)2-deoxy-D-glucose (FDG) and positron emission tomography (PET) in patients with insulin-dependent diabetes mellitus (IDDM) under standardized metabolic conditions. A hyperinsulinemic-euglycemic clamp technique was used during PET data acquisition in nine healthy male volunteers and seven young male patients with a history of IDDM for less than 5 years. Oxidative metabolism was assessed with C-11 acetate, and glucose uptake was quantitatively measured with FDG using Patlak graphic analysis. Hemodynamic data and C-11 acetate kinetics were comparable. Myocardial glucose uptake averaged 0.44 +/- 0.12 mumol.g-1.min-1 in normal subjects and 0.43 +/- 0.16 mumol.g-1.min-1 in patients with IDDM (P = NS). Blood tracer clearance was also similar in both groups as determined by the ratio of peak blood tracer activity to the activity at 55 to 60 minutes after tracer injection. F-18 activity ratio between myocardium and blood pool averaged 7.2 +/- 3.4 in the normal heart and 7.5 +/- 3.0 in the diabetic heart (P = NS). These data indicate that metabolic standardization and supplementation with insulin in young patients with IDDM is associated with myocardial glucose uptake similar to that observed in the normal heart. Chronic therapy with insulin may prevent the metabolic abnormalities observed in diabetic animal models.