The primary aim of this investigation was to determine the reliability and sensitivity of 1H magnetic resonance spectroscopy (1H-MRS) as a method for quantifying myocardial triglyceride (TG) content in humans over time and in response to metabolic perturbations. Three separate experiments were designed to quantify myocardial TG content 1) over a 90-day period, 2) after a high-fat meal, and 3) after a 48-h fast. Proton spectra were collected from a 10 x 20 x 30-mm3 voxel placed within the intraventricular septum, with measurements acquired at end-systole and end-expiration, using cardiac triggering and respiratory gating. Minimal variation was observed between myocardial TG content determined 90 days apart (r = 0.98, CV = 5%), whereas TG values were unaffected by a high-fat meal despite a significant twofold increase (P < 0.05) in serum TG. In contrast, myocardial TG content increased threefold (P < 0.05) after a 48-h fast despite a 25% reduction in serum TG. Body mass index was significantly related to myocardial TG (r = 0.58, P < 0.05) and the change in myocardial TG after a 48-h fast (r2 = 0.60). 1H-MRS is a reliable method for the determination of myocardial TG in humans and is relatively unaffected by the consumption of one high-fat meal but sensitive to changes following a prolonged fast.
"Increased myocardial lipid content (cardiac steatosis) is regarded as an important feature of disturbed myocardial substrate metabolism and thought to underlie the development of heart failure especially in patients with metabolic diseases, like diabetes (diabetic cardiomyopathy) , . In analogy to ectopic lipid deposition in liver and skeletal muscle, myocardial lipid content (MYCL) can nowadays be non-invasively assessed by 1H magnetic resonance (MR) spectroscopy , . MR imaging furthermore displays the method of choice for determining systolic cardiac function . "
[Show abstract][Hide abstract] ABSTRACT: Increased myocardial lipid accumulation has been described in patients with pre- and overt type 2 diabetes and could underlie the development of left-ventricular dysfunction in metabolic diseases (diabetic cardiomyopathy). Since women with prior gestational diabetes (pGDM) display a generally young population at high risk of developing diabetes and associated cardiovascular complications, we aimed to assess whether myocardial lipid accumulation can be detected at early stages of glucose intolerance and relates to markers of hepatic steatosis (Fatty Liver Index), cardiac function, insulin sensitivity and secretion.
Myocardial lipid content (MYCL), left-ventricular function (1H-magnetic-resonance-spectroscopy and -imaging), insulin sensitivity/secretion (oral glucose tolerance test) and the fatty liver index (FLI) were assessed in 35 pGDM (45.6±7.0 years, 28.3±4.8 kg/m2) and 14 healthy control females (CON; 44.7±9.8 years, 26.1±2.5 kg/m2), matching for age and body-mass-index (each p>0.1).
Of 35 pGDM, 9 displayed normal glucose tolerance (NGT), 6 impaired glucose regulation (IGR) and 20 had been already diagnosed with type 2 diabetes (T2DM). MYCL and cardiac function were comparable between pGDM and CON; in addition, no evidence of left-ventricular dysfunction was observed. MYCL was inversely correlated with the ejection fraction in T2DM (R = -0.45, p<0.05), while the FLI was tightly correlated with metabolic parameters (such as HbA1C, fasting plasma glucose and HDL-cholesterol) and rose along GT-groups.
There is no evidence of cardiac steatosis in middle-aged women with prior gestational diabetes, suggesting that cardiac complications might develop later in the time-course of diabetes and may be accelerated by the co-existence of further risk factors, whereas hepatic steatosis remains a valid biomarker for metabolic diseases even in this rather young female cohort.
PLoS ONE 03/2014; 9(3):e91607. DOI:10.1371/journal.pone.0091607 · 3.23 Impact Factor
"Intracellular lipid accumulation causing lipotoxicity in humans with the metabolic syndrome or type-2 diabetes mellitus, as assessed with 1H-MRS, has been associated with organ dysfunction, such as non-alcoholic fatty liver disease , cardiac diastolic dysfunction ,  and pancreatic beta cell dysfunction , . Moreover, respiratory motion compensation techniques to assess these lipid pools have been used in 1H-MRS previously, including the heart and pancreas , , . The mean percentage of renal TG content in the present study content is in line with previous, Dixon-based techniques . "
[Show abstract][Hide abstract] ABSTRACT: To assess the feasibility of renal proton magnetic resonance spectroscopy for quantification of triglyceride content and to compare spectral quality and reproducibility without and with respiratory motion compensation in vivo.
The Institutional Review Board of our institution approved the study protocol, and written informed consent was obtained. After technical optimization, a total of 20 healthy volunteers underwent renal proton magnetic resonance spectroscopy of the renal cortex both without and with respiratory motion compensation and volume tracking. After the first session the subjects were repositioned and the protocol was repeated to assess reproducibility. Spectral quality (linewidth of the water signal) and triglyceride content were quantified. Bland-Altman analyses and a test by Pitman were performed.
Linewidth changed from 11.5±0.4 Hz to 10.7±0.4 Hz (all data pooled, p<0.05), without and with respiratory motion compensation respectively. Mean % triglyceride content in the first and second session without respiratory motion compensation were respectively 0.58±0.12% and 0.51±0.14% (P = NS). Mean % triglyceride content in the first and second session with respiratory motion compensation were respectively 0.44±0.10% and 0.43±0.10% (P = NS between sessions and P = NS compared to measurements with respiratory motion compensation). Bland-Altman analyses showed narrower limits of agreement and a significant difference in the correlated variances (correlation of -0.59, P<0.05).
Metabolic imaging of the human kidney using renal proton magnetic resonance spectroscopy is a feasible tool to assess cortical triglyceride content in humans in vivo and the use of respiratory motion compensation significantly improves spectral quality and reproducibility. Therefore, respiratory motion compensation seems a necessity for metabolic imaging of renal triglyceride content in vivo.
PLoS ONE 04/2013; 8(4):e62209. DOI:10.1371/journal.pone.0062209 · 3.23 Impact Factor
"The presence of a small absolute increase in intramyocardial TG content has been demonstrated by proton magnetic resonance spectroscopy in prediabetic and diabetic humans (24,25). Although myocardial TG deposition occurs at increased rate during fasting compared with the postprandial period in healthy subjects (26), cardiac nonoxidative fatty acid metabolism is a small fraction of total myocardial fatty acid uptake (11,16), potentially explaining discordant findings between proton-magnetic resonance spectroscopy and our present method. Increased reliance on fatty acid oxidation may lead to reduced myocardial energy efficiency and predispose to increased damage if ischemia is superimposed (25,27). "
[Show abstract][Hide abstract] ABSTRACT: Impaired cardiac systolic and diastolic function has been observed in preclinical models and in subjects with type 2 diabetes. Using a recently validated positron emission tomography (PET) imaging method with 14(R,S)-[(18)F]-fluoro-6-thia-heptadecanoic acid to quantify organ-specific dietary fatty acid partitioning, we demonstrate in this study that overweight and obese subjects with impaired glucose tolerance (IGT(+)) display significant increase in fractional myocardial dietary fatty acid uptake over the first 6 h postprandial compared with control individuals (IGT(-)). Measured by [(11)C]acetate with PET, IGT(+) subjects have a significant increase in myocardial oxidative index. IGT(+) subjects have significantly reduced left ventricular stroke volume and ejection fraction (LVEF) and tend to display impaired diastolic function, as assessed by PET ventriculography. We demonstrate an inverse relationship between increased myocardial dietary fatty acid partitioning and LVEF. Fractional dietary fatty acid uptake is reduced in subcutaneous abdominal and visceral adipose tissues in IGT(+) directly associated with central obesity. Fractional dietary fatty acid uptake in skeletal muscles or liver is, however, similar in IGT(+) versus IGT(-). The current study demonstrates, for the first time, that excessive myocardial partitioning of dietary fatty acids occurs in prediabetic individuals and is associated with early impairment of left ventricular function and increased myocardial oxidative metabolism.
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