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CLINICAL RESEARCH: DIABETES AND OBESITY

Increased Myocardial Fatty Acid Metabolism in Patients With Type 1 Diabetes Mellitus

Pilar Herrero, MS^_*, Linda R. Peterson, MD^,, Janet B. McGill, MD, Stanley Matthew, MD, Donna Lesniak, RN^_*, Carmen Dence, MS^_* and Robert J. Gropler, MD^_*,,_*

^_* Division of Radiological Sciences, Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri
Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri
Division of Geriatrics and Nutritional Sciences, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri
Division of Endocrinology and Metabolism, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri

Manuscript received January 11, 2005; revised manuscript received August 15, 2005, accepted September 12, 2005.

^_* Reprint requests and correspondence: Dr. Robert J. Gropler, Cardiovascular Imaging Laboratory, Mallinckrodt Institute of Radiology, 510 South Kingshighway, St. Louis, Missouri 63110 (Email: Groplerr{at}mir.wustl.edu).

OBJECTIVES: The purpose of this study was to determine if myocardial fatty acid utilization (MFAU) and myocardial fatty acid oxidation (MFAO) are increased in diabetic patients.

BACKGROUND: Experimental models of diabetes mellitus demonstrate that MFAU and MFAO are increased, and that this dependence on myocardial fatty acid metabolism may be detrimental to cardiac function. Whether similar metabolic changes occur in humans with diabetes mellitus is unclear.

METHODS: Eleven healthy non-diabetic control patients (5 women, ages 25 ± 5 years) and 11 otherwise healthy patients with type 1 diabetes mellitus (T1DM) (8 women, ages 36 ± 10 years, HbA1c 8.4 ± 1.9%) underwent positron emission tomography for the determination of myocardial blood flow (MBF); myocardial oxygen consumption (MVO₂); myocardial glucose utilization (MGU); and MFAU, MFAO, and %MFAO.

RESULTS: Plasma lactate, insulin, and MBF levels were similar between the two groups. However, plasma glucose (5.71 ± 0.98 µmol/ml vs. 5.28 ± 0.65 µmol/ml, p = 0.04), free fatty acid levels (0.60 ± 0.24 µmol/ml vs. 0.19 ± 0.07 µmol/ml, p < 0.0001), and MVO₂ (6.64 ± 2.21 vs. 4.51 ± 1.39 µmol/g/min, p = 0.007) levels were higher in the T1DM subjects. Furthermore, compared with control patients, T1DM subjects exhibited higher MFAU (213 ± 135 nmol/g/min vs. 57 ± 28 nmol/g/min, p = 0.0004), MFAO (206 ± 131 nmol/g/min s. 50 ± 26 nmol/g/min, p = 0.0002), and %MFAO (94 ± 6% vs. 81 ± 19%, respectively, p = 0.04). In contrast, MGU was lower in T1DM subjects than in controls (207 ± 108 nmol/g/min vs. 403 ± 191 nmol/g/min, p = 0.0008).

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

Abbreviations and Acronyms   FFA = free fatty acid   MBF = myocardial blood flow (ml/g/min)   MFAEF = myocardial fatty acid extraction fraction   MFAO = myocardial fatty acid oxidation (nmol/g/min)   MFAU = myocardial fatty acid utilization (nmol/g/min)   MGEF = myocardial glucose extraction fraction   MGU = myocardial glucose utilization (nmol/g/min)   MVO2 = myocardial oxygen consumption (µmol/g/min)   PET = positron emission tomography   PPAR = peroxisome proliferator-activated receptor   T1DM/T2DM = type 1 diabetes mellitus/type 2 diabetes mellitus

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