Cardiac lipid content is unresponsive to a physical activity training intervention in type 2 diabetic patients, despite improved ejection fraction

Background: Increased cardiac lipid content has been associated with diabetic cardiomyopathy. We recently showed that cardiac lipid content is reduced after 12 weeks of physical activity training in healthy overweight subjects. The beneficial effect of exercise training on cardiovascular risk is well established and the decrease in cardiac lipid content with exercise training in healthy overweight subjects was accompanied by improved ejection fraction. It is yet unclear whether diabetic patients respond similarly to physical activity training and whether a lowered lipid content in the heart is necessary for improvements in cardiac function. Here, we investigated whether exercise training is able to lower cardiac lipid content and improve cardiac function in type 2 diabetic patients. Methods: Eleven overweight-to-obese male patients with type 2 diabetes mellitus (age: 58.4 +/- 0.9 years, BMI: 29.9 +/- 0.01 kg/m(2)) followed a 12-week training program (combination endurance/strength training, three sessions/week). Before and after training, maximal whole body oxygen uptake (VO2max) and insulin sensitivity (by hyperinsulinemic, euglycemic clamp) was determined. Systolic function was determined under resting conditions by CINE-MRI and cardiac lipid content in the septum of the heart by Proton Magnetic Resonance Spectroscopy. Results: VO2max increased (from 27.1 +/- 1.5 to 30.1 +/- 1.6 ml/min/kg, p = 0.001) and insulin sensitivity improved upon training (insulin stimulated glucose disposal (delta Rd of glucose) improved from 5.8 +/- 1.9 to 10.3 +/- 2.0 mu mol/kg/min, p = 0.02. Left-ventricular ejection fraction improved after training (from 50.5 +/- 2.0 to 55.6 +/- 1.5%, p = 0.01) as well as cardiac index and cardiac output. Unexpectedly, cardiac lipid content in the septum remained unchanged (from 0.80 +/- 0.22% to 0.95 +/- 0.21%, p = 0.15). Conclusions: Twelve weeks of progressive endurance/strength training was effective in improving VO(2)max, insulin sensitivity and cardiac function in patients with type 2 diabetes mellitus. However, cardiac lipid content remained unchanged. These data suggest that a decrease in cardiac lipid content in type 2 diabetic patients is not a prerequisite for improvements in cardiac function.Cardiovascular Aspects of Radiolog

Inhibition of sarcolemmal FAT/CD36 by sulfo-N-succinimidyl oleate rapidly corrects metabolism and restores function in the diabetic heart following hypoxia/reoxygenation.

AIMS: The type 2 diabetic heart oxidizes more fat and less glucose, which can impair metabolic flexibility and function. Increased sarcolemmal fatty acid translocase (FAT/CD36) imports more fatty acid into the diabetic myocardium, feeding increased fatty acid oxidation and elevated lipid deposition. Unlike other metabolic modulators that target mitochondrial fatty acid oxidation, we proposed that pharmacologically inhibiting fatty acid uptake, as the primary step in the pathway, would provide an alternative mechanism to rebalance metabolism and prevent lipid accumulation following hypoxic stress. METHODS AND RESULTS: Hearts from type 2 diabetic and control male Wistar rats were perfused in normoxia, hypoxia and reoxygenation, with the FAT/CD36 inhibitor sulfo-N-succinimidyl oleate (SSO) infused 4 min before hypoxia. SSO infusion into diabetic hearts decreased the fatty acid oxidation rate by 29% and myocardial triglyceride concentration by 48% compared with untreated diabetic hearts, restoring fatty acid metabolism to control levels following hypoxia-reoxygenation. SSO infusion increased the glycolytic rate by 46% in diabetic hearts during hypoxia, increased pyruvate dehydrogenase activity by 53% and decreased lactate efflux rate by 56% compared with untreated diabetic hearts during reoxygenation. In addition, SSO treatment of diabetic hearts increased intermediates within the second span of the Krebs cycle, namely fumarate, oxaloacetate, and the FAD total pool. The cardiac dysfunction in diabetic hearts following decreased oxygen availability was prevented by SSO-infusion prior to the hypoxic stress. Infusing SSO into diabetic hearts increased rate pressure product by 60% during hypoxia and by 32% following reoxygenation, restoring function to control levels. CONCLUSIONS: Diabetic hearts have limited metabolic flexibility and cardiac dysfunction when stressed, which can be rapidly rectified by reducing fatty acid uptake with the FAT/CD36 inhibitor, SSO. This novel therapeutic approach not only reduces fat oxidation but also lipotoxicity, by targeting the primary step in the fatty acid metabolism pathway

Heart-type Fatty acid-binding protein in Acute Myocardial infarction Evaluation (FAME): Background and design of a diagnostic study in primary care

<p>Abstract</p> <p>Background</p> <p>Currently used biomarkers for cardiac ischemia are elevated in blood plasma after a delay of several hours and therefore unable to detect acute coronary syndrome (ACS) in a very early stage. General practitioners (GPs), however, are often confronted with patients suspected of ACS within hours after onset of complaints. This ongoing study aims to evaluate the added diagnostic value beyond clinical assessment for a rapid bedside test for heart-type fatty-acid binding protein (H-FABP), a biomarker that is detectable as soon as one hour after onset of ischemia.</p> <p>Methods</p> <p>Participating GPs perform a blinded H-FABP rapid bedside test (Cardiodetect^®) in patients with symptoms suggestive of ACS such as chest pain or discomfort at rest. All patients, whether referred to hospital or not, undergo electrocardiography (ECG) and venapunction for a plasma troponin test within 12–36 hours after onset of complaints. A final diagnosis will be established by an expert panel consisting of two cardiologists and one general practitioner (blinded to the H-FABP test result), using all available patient information, also including signs and symptoms. The added diagnostic value of the H-FABP test beyond history taking and physical examination will be determined with receiver operating characteristic curves derived from multivariate regression analysis.</p> <p>Conclusion</p> <p>Reasons for presenting the design of our study include the prevention of publication bias and unacknowledged alterations in the study aim, design or data-analysis. To our knowledge this study is the first to assess the diagnostic value of H-FABP <it>outside </it>a hospital-setting. Several previous hospital-based studies showed the potential value of H-FABP in diagnosing ACS. Up to now however it is unclear whether these results are equally promising when the test is used in primary care. The first results are expected in the end of 2008.</p

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Evaluating possible acute coronary syndrome in primary care:the value of signs, symptoms, and plasma heart-type fatty acid-binding protein (H-FABP). A diagnostic study

BACKGROUND: Additional diagnostic means could be of added value when evaluating possible acute coronary syndrome (ACS) in primary care. AIM: To determine whether heart-type fatty acid-binding protein (H-FABP)-based point-of-care (POC) biomarker testing, embedded in a clinical decision rule (CDR), is helpful to the GP when evaluating possible ACS. DESIGN & SETTING: A prospective, non-randomised, double-blinded, diagnostic derivation study was undertaken, with a delayed-type cross-sectional diagnostic model among GPs in the Netherlands and Belgium. METHOD: Signs and symptoms predicting acute myocardial infarction (AMI) or ACS were identified using both logistic regression analysis, and classification and regression trees (CART). Diagnostic values of the POC H-FABP test (cut-off value 4 ng/ml) alone and as part of a CDR were determined. RESULTS: A total of 303 participants (48.8% male) with chest pain or discomfort who had consulted a GP were enrolled. ACS was found in 32 (10.6%) of these 303 patients. For ACS, sensitivity and negative predictive value (NPV) of the POC H-FABP test was 25.8% (95% confidence interval [CI] = 12.5 to 44.9) and 91.6% (95% CI = 87.6% to 94.5%), respectively. The area under the receiver operating curve of the optimal CDR was 0.78 for ACS. CONCLUSION: Sensitivity of the current H-FABP POC test (cut-off value 4 ng/ml) as a stand-alone test is poor, either owing to limitations of the marker or of the test device. Usability of a CDR derived from these results is doubtful: the number of ACS cases missed by the GP is reduced but, as a consequence, disproportionally more ACS-negative patients are referred

Heart-type Fatty acid-binding protein in Acute Myocardial infarction Evaluation (FAME): Background and design of a diagnostic study in primary care-1

The clinical score is based on ref. 13. ** Measurements are performed by qualified GP laboratory personnel.<p><b>Copyright information:</b></p><p>Taken from "Heart-type Fatty acid-binding protein in Acute Myocardial infarction Evaluation (FAME): Background and design of a diagnostic study in primary care"</p><p>http://www.biomedcentral.com/1471-2261/8/8</p><p>BMC Cardiovascular Disorders 2008;8():8-8.</p><p>Published online 15 Apr 2008</p><p>PMCID:PMC2358877.</p><p></p

Heart-type Fatty acid-binding protein in Acute Myocardial infarction Evaluation (FAME): Background and design of a diagnostic study in primary care-0

The clinical score is based on ref. 13. ** Measurements are performed by qualified GP laboratory personnel.<p><b>Copyright information:</b></p><p>Taken from "Heart-type Fatty acid-binding protein in Acute Myocardial infarction Evaluation (FAME): Background and design of a diagnostic study in primary care"</p><p>http://www.biomedcentral.com/1471-2261/8/8</p><p>BMC Cardiovascular Disorders 2008;8():8-8.</p><p>Published online 15 Apr 2008</p><p>PMCID:PMC2358877.</p><p></p