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Fatty Acids and Insulin Modulate Myocardial Substrate Metabolism in Humans With Type 1 Diabetes

¹ Cardiovascular Division, Department of Internal Medicine, Mallinckrodt Institute, Washington University School of Medicine, St. Louis, Missouri
² Division of Geriatrics and Nutritional Sciences, Department of Internal Medicine, Mallinckrodt Institute, Washington University School of Medicine, St. Louis, Missouri
³ Mallinckrodt Institute, Department of Radiology, Washington University, St. Louis, Missouri
⁴ Division of Endocrinology, Department of Medicine, Washington University, St. Louis, Missouri
⁵ Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri

Address correspondence and reprint requests to Linda R. Peterson, MD, Campus Box 8086, 660 S. Euclid Ave., St. Louis, MO 63110. E-mail: lpeterso{at}im.wustl.edu

Key Words: FFA, free fatty acids • HIEG, hyperinsulinemic euglycemic • MVO₂, myocardial oxygen consumption • PET, positron emission tomography

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 (MVO₂), 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 MVO₂ 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 increased MVO₂ 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.

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