Myocardial fatty acid oxidation in patients with impaired glucose tolerance

Abstract

On the basis of both experimental and human studies, it has been shown that diabetes could be associated with alterations in the myocardial glucose and the non-esterified fatty acid (NEFA) metabolism, which could further contribute to the deterioration of cardiac function [1]. The results of the recent studies with positron emission tomography (PET) have, however, shown that myocardial glucose uptake during euglycaemic hyperinsulinaemia both in patients with Type I (insulin-dependent) and II (non-insulin-dependent) diabetes is normal during controlled metabolic conditions (euglycaemic hyperinsulinaemia), confirming that the heart is not insulin-resistant in diabetes [2,3].Studies on myocardial NEFA metabolism are sparse. A study with [ ]HDA) and single-photon emission tomography (SPET) found myocardial NEFA uptake and b-oxidation to be reduced in patients with impaired glucose tolerance (IGT) [4]. Surprisingly, the same study found that NEFA metabolism was normal in patients with Type II diabetes. We recently measured the myocardial uptake of NEFA in patients with IGT Diabetologia (2001) Abstract Aims/hypothesis. Fatty acids are an important source of energy in the myocardium. Abnormal myocardial fatty acid metabolism could contribute to the deterioration of cardiac function frequently observed in patients with Type II (non-insulin-dependent) diabetes mellitus. In our previous study, myocardial total uptake of non-esterified fatty acid (NEFA) was measured in patients with impaired glucose tolerance and found to be normal. This study aimed to investigate the subsequent metabolic steps and b-oxidation of NEFA.

Effect of Obesity and Insulin Resistance on Myocardial Substrate Metabolism and Efficiency in Young Women

“…36 Therefore, it is possible that the alterations in fatty acid metabolism observed in young obese women in the present study may not apply to men studied previously by other investigators. 34,35 We found that MGU tended to be inversely associated with BMI and plasma glucose AUC, but the relationship was not statistically significant even though MFAUp, MFAU, and MFAO correlated significantly with BMI, plasma glucose AUC, or both. This pattern of substrate metabolism parallels that seen in obese animals that are studied early in the course of their progression from insulin resistance to type II diabetes and in isolated working rat heart models that are infused with leptin.…”

“…In those studies, MFAUp and MFAO were not different between normal volunteers and subjects with impaired glucose tolerance. 34,35 However, differences in study subject sex, age, and endogenous myocardial fat content and the choice of tracers between studies may have affected the results. Data from studies conducted in experimental animals suggest that estrogens increase MFAO.…”

Kinetic models for analysing myocardial [11C]palmitate data

“…Some data on fatty acid metabolism in the heart has been published however, using a more simplified biexponential model [10]. For comparison, the patient data in this study were also analysed with the biexponential model: average uptake indices (±SD) were 0.08±0.02 vs. 0.11±0.01, and clearance half-times were 19.1±3.1 min vs. 17.6±1.6 min for this study and the study by Knuuti et al [10], respectively.…”

“…Although kinetics of this tracer were originally studied using a six-compartment model, the limited time resolution of a PET study forced a reduction to a simplified two-tissue compartment model describing uptake (and back diffusion) and (irreversible)Finally, [ 11 C]palmitate can be used to study uptake and utilization of long-chain fatty acids, which play a dominant role in delivering energy to the heart. Since fatty acid metabolism [8] is affected by a number of pathophysiological conditions, [ 11 C]palmitate has been used to study myocardial metabolism in various diseases such as viral infections and diabetes [5,10]. Most studies involving [ 11 C]palmitate used semiquantitative analyses to describe its kinetics.…”

“…Most studies involving [ 11 C]palmitate used semiquantitative analyses to describe its kinetics. Tracer washout is commonly described using a biexponential function with a rapid phase reflecting fast oxidation of fatty acid in the mitochondria and a slower phase, appearing later, representing incorporation of extracted fatty acids into neutral lipid pools [10]. However, a simpler single-exponential model, only describing oxidation of the tracer has also been used [11].…”