title: Elevated Glucose Oxidation, Reduced Insulin Secretion, and a Fatty Heart May Be Protective Adaptions in Ischemic CAD.
abstract: Insulin resistance, β-cell dysfunction, and ectopic fat deposition have been implicated in the pathogenesis of coronary artery disease (CAD) and type 2 diabetes, which is common in CAD patients. We investigated whether CAD is an independent predictor of these metabolic abnormalities and whether this interaction is influenced by superimposed myocardial ischemia.
  
  
  
  We studied CAD patients with (n = 8) and without (n = 14) myocardial ischemia and eight non-CAD controls. Insulin sensitivity and secretion and substrate oxidation were measured during fasting and oral glucose tolerance testing. We used magnetic resonance imaging/spectroscopy, positron emission and computerized tomography to characterize CAD, cardiac function, pericardial and abdominal adipose tissue, and myocardial, liver, and pancreatic triglyceride contents. Ischemic CAD was characterized by elevated oxidative glucose metabolism and a proportional decline in β-cell insulin secretion and reduction in lipid oxidation. Cardiac function was preserved in CAD groups, whereas cardiac fat depots were elevated in ischemic CAD compared to non-CAD subjects. Liver and pancreatic fat contents were similar in all groups and related with surrounding adipose masses or systemic insulin sensitivity.
  
  
  
  In ischemic CAD patients, glucose oxidation is enhanced and correlates inversely with insulin secretion. This can be seen as a mechanism to prevent glucose lowering because glucose is required in oxygen-deprived tissues. On the other hand, the accumulation of cardiac triglycerides may be a physiological adaptation to the limited fatty acid oxidative capacity. Our results underscore the urgent need of clinical trials that define the optimal/safest glycemic range in situations of myocardial ischemia.
authors.affiliation: Turku PET Center (J.C.H., R.L., J.P.P., M.B., S.K., T.T., J.K., P.I.), University of Turku, 20014 Turku, Finland; Heart Center (R.L.), Turku University Hospital, 20520 Turku, Finland; Institute of Neuroscience (A.M.), National Research Council, 35127 Padua, Italy; and Institute of Clinical Physiology (M.A.G., P.I.), National Research Council, 56124 Pisa, Italy.
authors.forename: J C
authors.initials: JC
authors.lastname: Hannukainen
authors.affiliation: Turku PET Center (J.C.H., R.L., J.P.P., M.B., S.K., T.T., J.K., P.I.), University of Turku, 20014 Turku, Finland; Heart Center (R.L.), Turku University Hospital, 20520 Turku, Finland; Institute of Neuroscience (A.M.), National Research Council, 35127 Padua, Italy; and Institute of Clinical Physiology (M.A.G., P.I.), National Research Council, 56124 Pisa, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Lautamäki
authors.affiliation: Turku PET Center (J.C.H., R.L., J.P.P., M.B., S.K., T.T., J.K., P.I.), University of Turku, 20014 Turku, Finland; Heart Center (R.L.), Turku University Hospital, 20520 Turku, Finland; Institute of Neuroscience (A.M.), National Research Council, 35127 Padua, Italy; and Institute of Clinical Physiology (M.A.G., P.I.), National Research Council, 56124 Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Mari
authors.affiliation: Turku PET Center (J.C.H., R.L., J.P.P., M.B., S.K., T.T., J.K., P.I.), University of Turku, 20014 Turku, Finland; Heart Center (R.L.), Turku University Hospital, 20520 Turku, Finland; Institute of Neuroscience (A.M.), National Research Council, 35127 Padua, Italy; and Institute of Clinical Physiology (M.A.G., P.I.), National Research Council, 56124 Pisa, Italy.
authors.forename: J P
authors.initials: JP
authors.lastname: Pärkkä
authors.affiliation: Turku PET Center (J.C.H., R.L., J.P.P., M.B., S.K., T.T., J.K., P.I.), University of Turku, 20014 Turku, Finland; Heart Center (R.L.), Turku University Hospital, 20520 Turku, Finland; Institute of Neuroscience (A.M.), National Research Council, 35127 Padua, Italy; and Institute of Clinical Physiology (M.A.G., P.I.), National Research Council, 56124 Pisa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bucci
authors.affiliation: Turku PET Center (J.C.H., R.L., J.P.P., M.B., S.K., T.T., J.K., P.I.), University of Turku, 20014 Turku, Finland; Heart Center (R.L.), Turku University Hospital, 20520 Turku, Finland; Institute of Neuroscience (A.M.), National Research Council, 35127 Padua, Italy; and Institute of Clinical Physiology (M.A.G., P.I.), National Research Council, 56124 Pisa, Italy.
authors.forename: M A
authors.initials: MA
authors.lastname: Guzzardi
authors.affiliation: Turku PET Center (J.C.H., R.L., J.P.P., M.B., S.K., T.T., J.K., P.I.), University of Turku, 20014 Turku, Finland; Heart Center (R.L.), Turku University Hospital, 20520 Turku, Finland; Institute of Neuroscience (A.M.), National Research Council, 35127 Padua, Italy; and Institute of Clinical Physiology (M.A.G., P.I.), National Research Council, 56124 Pisa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Kajander
authors.affiliation: Turku PET Center (J.C.H., R.L., J.P.P., M.B., S.K., T.T., J.K., P.I.), University of Turku, 20014 Turku, Finland; Heart Center (R.L.), Turku University Hospital, 20520 Turku, Finland; Institute of Neuroscience (A.M.), National Research Council, 35127 Padua, Italy; and Institute of Clinical Physiology (M.A.G., P.I.), National Research Council, 56124 Pisa, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Tuokkola
authors.affiliation: Turku PET Center (J.C.H., R.L., J.P.P., M.B., S.K., T.T., J.K., P.I.), University of Turku, 20014 Turku, Finland; Heart Center (R.L.), Turku University Hospital, 20520 Turku, Finland; Institute of Neuroscience (A.M.), National Research Council, 35127 Padua, Italy; and Institute of Clinical Physiology (M.A.G., P.I.), National Research Council, 56124 Pisa, Italy.
authors.forename: J
authors.initials: J
authors.lastname: Knuuti
authors.affiliation: Turku PET Center (J.C.H., R.L., J.P.P., M.B., S.K., T.T., J.K., P.I.), University of Turku, 20014 Turku, Finland; Heart Center (R.L.), Turku University Hospital, 20520 Turku, Finland; Institute of Neuroscience (A.M.), National Research Council, 35127 Padua, Italy; and Institute of Clinical Physiology (M.A.G., P.I.), National Research Council, 56124 Pisa, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Iozzo
mesh_terms: D050153:Abdominal Fat / Q000378:metabolism; D000222:Adaptation, Physiological; D050154:Adiposity / Q000502:physiology; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000378:metabolism / Q000517:prevention & control*; D019610:Cytoprotection; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006321:Heart; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D014280:Triglycerides; D005947:Glucose