Sex differences in myocardial oxygen and glucose metabolism

Peterson, Linda R.; Soto, Pablo; Herrero, Pilar; Schechtman, Kenneth B.; Dence, Carmen S.; Gropler, Robert J.

doi:10.1016/j.nuclcard.2007.03.001

Cited by 69 publications

(63 citation statements)

References 38 publications

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“…Peterson and colleagues (1,3) found that women had significantly higher myocardial oxidative metabolism compared with men, which may have explained increased myocardial NEFA uptake and oxidation. The latter observations were performed during fasting and may not necessarily apply to the postprandial state, however.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Sex and Impaired Glucose Tolerance on Organ-Specific Dietary Fatty Acid Metabolism in Humans

et al. 2014

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Oral 14(R,S)-[18 F]-fluoro-6-thia-heptadecanoic acid was used to determine whether an increase in cardiac dietary fatty acid (DFA) metabolism in impaired glucose tolerance (IGT) is different in men and women. Myocardial DFA partitioning after 6 h was higher in IGT versus control subjects (P = 0.006) in both men (2.14 [95% CI sex difference. Men had higher net myocardial DFA uptake between time 90 and 120 min driven by higher chylomicrontriglyceride (TG) levels. IGT-associated increased cardiac DFA partitioning was directly related to obesity in women, whereas it was associated with IGT per se in men. We conclude that early cardiac DFA uptake is higher in men driven by change in postprandial chylomicron-TG level but that increase in 6-h postprandial cardiac DFA partitioning nevertheless occurs with IGT both in men and women.Sex, obesity, and insulin resistance appear to act independently but also in concert on myocardial metabolism, structure, and function. Studies conducted in the fasting state show that women have greater myocardial oxygen consumption (1), which increases with obesity (2). In addition, female sex appears to be an important predictor of higher diabetes-associated cardiac plasma nonesterified fatty acid (NEFA) utilization (3). Excess exposure of lean tissues to fatty acids may stem from a disordered storage of dietary fatty acids (DFAs) in adipocytes (4-7). We recently developed a novel method for noninvasive measurement of organ-specific DFA uptake and partitioning using 14(R,S)-[ 8). Using this method, we found that subjects with impaired glucose tolerance (IGT) displayed increased myocardial DFA partitioning and fractional uptake that correlated negatively with left ventricular ejection fraction (9). Subjects with IGT also displayed reduced DFA partitioning in abdominal adipose tissues (9), in accordance with findings using conventional tracer methods (10-12).Due to the small sample size at the time of our previous report, it was not possible to assess whether any sexrelated differences in organ-specific DFA metabolism were present and could modulate the effect of IGT on cardiac metabolism. Based on previous reports on cardiac NEFA metabolism (3), the hypothesis of the current study was that elevated DFA uptake and partitioning observed with IGT would be worsened in women versus men. A secondary exploratory objective of our study was to determine sexrelated differences in liver, skeletal muscle, and adipose tissue DFA partitioning according to IGT status. RESEARCH DESIGN AND METHODS Study ParticipantsForty-one Caucasian individuals (see Table 1) with normal (IGT 2 ) and IGT (IGT + ), defined as having a 2-h post 75-g

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Section: Discussionmentioning

confidence: 99%

“…Studies conducted in the fasting state show that women have greater myocardial oxygen consumption (1), which increases with obesity (2). In addition, female sex appears to be an important predictor of higher diabetes-associated cardiac plasma nonesterified fatty acid (NEFA) utilization (3).…”

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confidence: 99%

Effect of Sex and Impaired Glucose Tolerance on Organ-Specific Dietary Fatty Acid Metabolism in Humans

et al. 2014

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“…If a treatment effect was found among the three groups, paired comparisons were used to evaluate the differences between any two groups' responses to therapy. Because of known sex effects on myocardial metabolism, we performed subgroup analyses of the treatment effects within each sex using paired t-tests (19,20 …”

Section: Methodsmentioning

confidence: 99%

Impact of sex on the heart's metabolic and functional responses to diabetic therapies

Lyons

Peterson

McGill

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Lyons MR, 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: H1584 -H1591, 2013. First published September 16, 2013 doi:10.1152/ajpheart.00420.2013.-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. Our 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. To this end, we 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 ϩ rosiglitazone (ROSI), or metformin ϩ Lovaza (LOV). 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. 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.sex; type 2 diabetes; myocardial metabolism; metformin; rosiglitazone; Lovaza TYPE 2 DIABETES (T2DM) IS a risk factor for heart failure even in the absence of coronary disease. Sex plays an important role in the interaction between T2DM and heart failure. Diabetic women have a higher heart failure risk than diabetic men, and the women's risk of death from heart failure is greater than that of the men (3, 9).To understand why sex may impact heart failure in diabetes, it is important to understand how abnormalities in myocardial substrate metabolism contribute to the diabetic cardiomyopathic process. In animal models of T2DM, excessive fatty acid (FA) delivery to the myocardium is an important causative event in the development of cardiomyopathy (25). Conversely, lowering plasma FA levels in animals with T2DM prevents heart lipid accumulation and cardiac dysfunction (25). Animals with T2DM treated with omega-3E fatty acids, which typically lower plasma triglyceride levels, also improved cardiac dysfunction, but only in the males (22). A study in T2DM men showed that lowering plasma FA levels (via weight l...

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“…Sex-related differences in myocardial flow, oxygen consumption, efficiency, and metabolism have also been observed in prior PET-related studies in healthy and obese subjects, patients with type 2 diabetes, and patients with nonischemic cardiomyopathy. [6][7][8] In several studies of healthy and obese individuals, women tended to have higher myocardial blood flow than men. [7][8][9] This is similar to the results from the current study by Duvernoy et al 5 Myocardial blood flow was also higher in women with type 2 diabetes compared with men with the same disease.…”

mentioning

confidence: 99%

“…[6][7][8] In several studies of healthy and obese individuals, women tended to have higher myocardial blood flow than men. [7][8][9] This is similar to the results from the current study by Duvernoy et al 5 Myocardial blood flow was also higher in women with type 2 diabetes compared with men with the same disease. This is consistent with prior literature, which has been fairly consistent in demonstrating that oxygen consumption is generally higher in womennormal, obese, and with type 2 diabetes mellitus, than in comparable groups of men.…”

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confidence: 99%

‘SeXX’ matters: In the myocardium of patients with type 1 diabetes

Mikhalkova

McGill

Peterson

2016

Journal of Nuclear Cardiology

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Sex differences in myocardial oxygen and glucose metabolism

Abstract: Background-Both physiologic and pathophysiologic conditions affect the myocardium's substrate use and consequently, its structure, function, and adaptability. The effect of sex on myocardial oxygen, glucose, and fatty acid metabolism in humans is unknown.

Cited by 69 publications

References 38 publications

Effect of Sex and Impaired Glucose Tolerance on Organ-Specific Dietary Fatty Acid Metabolism in Humans

Effect of Sex and Impaired Glucose Tolerance on Organ-Specific Dietary Fatty Acid Metabolism in Humans

Impact of sex on the heart's metabolic and functional responses to diabetic therapies

‘SeXX’ matters: In the myocardium of patients with type 1 diabetes

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