Fatty acids and insulin modulate myocardial substrate metabolism in humans with type 1 diabetes.
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.


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 (MVo(2)), 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 MVo(2) 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 MVo(2) 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.
Peterson
Linda R
LR
Cardiovascular Division, Department of Internal Medicine, Mallinckrodt Institute, Washington University School of Medicine, St. Louis, Missouri, USA. lpeterso@im.wustl.edu
Herrero
Pilar
P
McGill
Janet
J
Schechtman
Kenneth B
KB
Kisrieva-Ware
Zulfia
Z
Lesniak
Donna
D
Gropler
Robert J
RJ
D000328:Adult; D001783:Blood Flow Velocity; D002096:C-Peptide / Q000097:blood; D002250:Carbon Radioisotopes; D003922:Diabetes Mellitus, Type 1 / Q000000981:diagnostic imaging / Q000378:metabolism*; D004452:Echocardiography; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006321:Heart / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D018579:Patient Selection; D049268:Positron-Emission Tomography; D012016:Reference Values
D002096:C-Peptide; D002250:Carbon Radioisotopes; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005947:Glucose