Humans with diabetes mellitus exhibit increased MFAU and MFAO and reduced MGU consistent with observations obtained in experimental models of diabetes.

In the short term, hyperglycemia has a deleterious effect on myocardial vasodilator function, which outweighs the beneficial effect of hyperinsulinemia.

OBJECTIVE-Normal human myocardium switches substrate metabolism preference, adapting to the prevailing plasma substrate levels and hormonal milieu, but in type 1 diabetes, the myocardium relies heavily on fatty acid metabolism for energy. Whether conditions that affect myocardial glucose use and fatty acid utilization, oxidation, and storage in nondiabetic subjects alter them in type 1 diabetes is not well known.RESEARCH DESIGN AND METHODS-To test the hypotheses that in humans with type 1 diabetes, myocardial glucose and fatty acid metabolism can be manipulated by altering plasma free fatty acid (FFA) and insulin levels, we quantified myocardial oxygen consumption (MVO 2 ), glucose, and fatty acid metabolism in nondiabetic subjects and three groups of type 1 diabetic subjects (those studied during euglycemia, hyperlipidemia, and a hyperinsulinemic-euglycemic clamp) using positron emission tomography.RESULTS-Type 1 diabetic subjects had higher MVO 2 and lower myocardial glucose utilization rate/insulin than control subjects. In type 1 diabetes, glucose utilization increased with increasing plasma insulin and decreasing FFA levels. Myocardial fatty acid utilization, oxidation, and esterification rates increased with increasing plasma FFA. Increasing plasma insulin levels decreased myocardial fatty acid esterification rates but increased the percentage of fatty acids going into esterification. CONCLUSIONS-Type 1 diabetes myocardium has increasedMVO 2 and is insulin resistant during euglycemia. However, its myocardial glucose and fatty acid metabolism still responds to changes in plasma insulin and plasma FFA levels. Moreover, insulin and plasma FFA levels can regulate the intramyocardial fate of fatty acids in humans with type 1 diabetes. Diabetes 57: [32][33][34][35][36][37][38][39][40] 2008 A growing literature suggests that impaired cardiac metabolism in diabetes contributes to cardiac dysfunction, leading to overt heart failure, a so-called "diabetic cardiomyopathy" (1-4). Results from studies in animal models of type 1 diabetes show that myocardial substrate metabolic alterations may play a key role in the development of diabetic cardiomyopathy (5). Specifically, in diabetes, there is increased lipid delivery to the myocardium, myocardial fatty acid utilization and oxidation, and decreased myocardial glucose uptake and triglyceride hydrolysis (2,6,7). This excessive myocardial fatty acid utilization may be detrimental to cardiac function via impairing glucose utilization (particularly when glucose is required, e.g., ischemia), decreasing transsarcolemmal calcium flux-induced contractility and/or increasing free radical production (8 -11). Moreover, decreasing free fatty acid (FFA) delivery to the myocardium in animal models decreases its fat storage and improves function (12). These results suggest that metabolic modulation of myocardial substrate metabolism may be a new paradigm for treatment of diabetic cardiomyopathy (12,13).There is little data on the effects of altering FFA or hormonal delivery to the ...

Objective To determine in the hearts of women with type-1 diabetes mellitus (T1DM), if the fate of extracted glucose is altered and if so what is the impact of dobutamine on myocardial substrate metabolism. Background In experimental models of T1DM, myocardial glycolysis and glucose oxidation are reduced with the impairment becoming more pronounced with dobutamine. Whether similar changes in occur in humans with T1DM is unknown. Methods Myocardial perfusion, oxygen consumption, glucose and fatty acid metabolism were measured with PET in 19 women, 7 normal volunteers (NV) and 12 with T1DM. The NV and 6 T1DM (DM1) were studied under baseline metabolic conditions and 6 T1DM studied during hyperinsulinemic-euglycemic clamp (DM1-C) both at rest and during dobutamine. Results At rest, myocardial glucose uptake, glycolysis, glycogen storage and oxidation were reduced by similar levels in DM1 compared with NV (P < .05). During dobutamine, although myocardial glucose uptake was not different from DM1 at rest, fractional glycolysis was lower compared with NV or DM1-C and reflected a lower glucose oxidation rate (P < .001). Measurements of myocardial glucose metabolism at rest and during dobutamine were comparable between NV and DM1-C. During dobutamine, myocardial fatty acid uptake and oxidation increased in all 3 groups. Conclusions In women with T1DM, 1) myocardial glucose metabolism is impaired downstream from initial uptake, 2) these abnormalities become more pronounced with dobutamine and are paralleled by an increase in myocardial fatty acid metabolism, and 3) insulin restores glucose metabolism to levels observed in normal controls.

PurposeTo assess the feasibility of our newly developed cardiovascular magnetic resonance (CMR) methods to quantify global and/or regional myocardial oxygen consumption rate (MVO2) at rest and during pharmacologically-induced vasodilation in normal volunteers.MethodsA breath-hold T2 quantification method is developed to calculate oxygen extraction fraction (OEF) and MVO2 rate at rest and/or during hyperemia, using a two-compartment model. A previously reported T2 quantification method using turbo-spin-echo sequence was also applied for comparison. CMR scans were performed in 6 normal volunteers. Each imaging session consisted of imaging at rest and during adenosine-induced vasodilation. The new T2 quantification method was applied to calculate T2 in the coronary sinus (CS), as well as in myocardial tissue. Resting CS OEF, representing resting global myocardial OEF, and myocardial OEF during adenosine vasodilation were then calculated by the model. Myocardial blood flow (MBF) was also obtained to calculate MVO2, by using a first-pass perfusion imaging approach.ResultsThe T2 quantification method yielded a hyperemic OEF of 0.37 ± 0.05 and a hyperemic MVO2 of 9.2 ± 2.4 μmol/g/min. The corresponding resting values were 0.73 ± 0.05 and 5.2 ± 1.7 μmol/g/min respectively, which agreed well with published literature values. The MVO2 rose proportionally with rate-pressure product from the rest condition. The T2 sensitivity is approximately 95% higher with the new T2 method than turbo-spin-echo method.ConclusionThe CMR oxygenation method demonstrates the potential for non-invasive estimation of myocardial oxygenation, and should be explored in patients with altered myocardial oxygenation.