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

Abstract

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.