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Diabetes Publish Ahead of Print published online ahead of print October 3, 2007
DOI: 10.2337/db07-1199
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Original Research

FATTY ACIDS AND INSULIN MODULATE MYOCARDIAL SUBSTRATE METABOLISM IN HUMANS WITH TYPE 1 DIABETES MELLITUS

Linda R. Peterson, MD1,,2, Pilar Herrero, MS3, Janet McGill, MD4, Kenneth B. Schechtman, PhD5, Zulfia Kisrieva-Ware, MD, PhD3, Donna Lesniak, RN3, and Robert J. Gropler, MD1,,3

Cardiovascular Division1,
the Division of Geriatrics and Nutritional Sciences2,
and Division of Endocrinology3
in the Department of Internal Medicine, Mallinckrodt Institute Department of Radiology4
and the Division of Biostatistics5 at the Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, Missouri, 63110, USA

Objective: Normal human myocardium switches substrate metabolism preference, adapting to the prevailing plasma substrate levels and hormonal milieu, but in type 1 diabetes mellitus (T1DM), the myocardium relies heavily on fatty acid (FA) metabolism for energy. Whether conditions that affect myocardial glucose use and FA utilization, oxidation, and storage in nondiabetic subjects alter them in T1DM is not well known.

Research Design and Methods: To test the hypotheses that in humans with T1DM myocardial glucose and FA can be manipulated by altering plasma free fatty acid (FFA) and insulin levels, we quantified myocardial MVO2, glucose and FA metabolism in nondiabetics and 3 groups of T1DM subjects (euglycemic, hyperlipidemic, and hyperinsulinemic/euglycemic clamp) using positron emission tomography.

Results: T1DM subjects had higher MVO2 and lower glucose utilization rate/insulin than controls. In T1DM, glucose utilization increased with increasing plasma insulin and decreasing FFA levels. Myocardial FA utilization, oxidation, and esterification rates and the percent of utilization accounted for by esterification increased with increasing plasma FFA. Increasing plasma insulin levels decreased myocardial FA esterification rates but increased the percentage of FAs going into esterification.

Conclusion: T1DM myocardium has increased MVO2 and is insulin resistant during euglycemia. However, its myocardial glucose and FA metabolism still responds to changes in plasma insulin and plasma FFA levels. Moreover, insulin and plasma FFA levels can regulate the intramyocardial fate of FAs in humans with T1DM.

Correspondence: lpeterso{at}im.wustl.edu


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Copyright © 2007 by the American Diabetes Association.