Research: LYONS and COLLEAGUES,

Listed in Issue 243

Abstract

LYONS and COLLEAGUES,  (1)Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri set out to determine whether 1) sex affects the myocardial metabolic response to lipid lowering in type 2 diabetes (T2DM), 2) altering lipid [fatty acid (FA) or triglyceride] delivery to the heart would lower the elevated myocardial lipid metabolism associated with T2DM, and 3) decreasing lipid delivery improves diastolic dysfunction in T2DM.

Background

Increased myocardial lipid delivery is a determinant of myocardial substrate metabolism and function in animal models of type 2 diabetes (T2DM). Sex also has major effects on myocardial metabolism in the human heart. The authors’ aims were to determine whether 1) sex affects the myocardial metabolic response to lipid lowering in T2DM, 2) altering lipid [fatty acid (FA) or triglyceride] delivery to the heart would lower the elevated myocardial lipid metabolism associated with T2DM, and 3) decreasing lipid delivery improves diastolic dysfunction in T2DM.

Methodology

To this end, the authors studied 78 T2DM patients (43 women) with positron emission tomography, echocardiography, and whole body tracer studies before and 3 mo after randomization to metformin (MET), metformin + rosiglitazone (ROSI), or metformin + Lovaza (LOV).

Results

No treatment main effects were found for myocardial substrate metabolism, partly because men and women often had different responses to a given treatment. In men, MET decreased FA clearance, which was linked to increased plasma FA levels, myocardial FA utilization and oxidation, and lower myocardial glucose utilization. In women, ROSI increased FA clearance, thereby decreasing plasma FA levels and myocardial FA utilization. Although LOV did not change triglyceride levels, it improved diastolic function, particularly in men. Group and sex also interacted in determining myocardial glucose uptake.

Conclusion

Thus, in T2DM, different therapeutic regimens impact myocardial metabolism and diastolic function in a sex-specific manner. This suggests that sex should be taken into account when designing a patient's diabetes treatment.

References

Lyons MR(1), Peterson LR, McGill JB, Herrero P, Coggan AR, Saeed IM, Recklein C,  Schechtman KB, Gropler RJ. Impact of sex on the heart's metabolic and functional responses to diabetic therapies.  Am J Physiol Heart Circ Physiol. 305(11):H1584-91. doi: 10.1152/ajpheart.00420.2013. Dec 1 2013. Epub Sep 16 2013.

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