Increased Myocardial Fatty Acid Metabolism in Patients With Type 1 Diabetes Mellitus

Herrero, Pilar; Peterson, Linda R.; McGill, Janet B.; Matthew, S; Lesniak, Donna; Dence, Carmen S.; Gropler, Robert J.

doi:10.1016/j.jacc.2005.09.030

Cited by 228 publications

(166 citation statements)

References 44 publications

(41 reference statements)

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“…In patients with idiopathic cardiomyopathy, cardiac muscle fatty acid uptake and oxidation decrease, while glucose metabolism increases ( 39 ). Patients with type 1 and type 2 diabetes, major risk factors for CVD, have increased myocardial fatty acid uptake and oxidation and reduced glucose oxidation (40)(41)(42). Such changes in cardiac fatty acid uptake and metabolism refl ect the plasticity of cardiac muscle metabolism for fuel utilization for energy production ( 42 ).…”

Section: Downloaded Frommentioning

confidence: 99%

Omega-3 fatty acid supplementation and cardiovascular disease

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Depner

Tripathy

2012

Journal of Lipid Research

192

118

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Section: Downloaded Frommentioning

confidence: 99%

Omega-3 fatty acid supplementation and cardiovascular disease

Jump

Depner

Tripathy

2012

Journal of Lipid Research

192

118

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“…Because of its inherent quantitative capabilities and diversity of metabolic radiotracers, PET has played a key role in characterizing perturbations in myocardial carbohydrate use associated with all of these conditions (7)(8)(9)(10)(11). To date, however, measurements of myocardial carbohydrate metabolism in humans have focused solely on glucose use because of the availability of excellent PET tracers of glucose uptake and metabolism such as 18 F-FDG (8,10) and 1-11 Cglucose (7,9,11).…”

mentioning

confidence: 99%

L-3-11C-Lactate as a PET Tracer of Myocardial Lactate Metabolism: A Feasibility Study

Herrero¹,

Dence²,

Coggan³

et al. 2007

Journal of Nuclear Medicine

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Lactate is a key myocardial energy source. Lactate metabolism is altered in a variety of conditions, such as exercise and diabetes mellitus. However, to our knowledge, noninvasive quantitative measurements of myocardial lactate metabolism have never been performed because of the lack of an adequate radiotracer. In this study we tested L-3-11 C-lactate ( 11 C-lactate) as such a tracer. Methods: Twenty-three dogs were studied under a wide range of metabolic interventions. 11 C-Lactate and 13 C-lactate were injected as boluses and PET data were acquired for 1 h. Concomitant arterial and coronary sinus (ART/CS) blood samples were collected to identify 13 C-lactate metabolites and to measure fractional myocardial extraction/production of 11 C metabolite fractions ( 11 C acidic: 11 CO 2 and 11 C-lactate; 11 C basic: 11 C-labeled amino acids; and 11 C neutral: 11 C-glucose). Lactate metabolism was quantified using 2 PET approaches: monoexponential clearance analysis (oxidation only) and kinetic modeling of PET 11 C-myocardial curves. Results: Arterial 11 C acidic, neutral, and basic metabolites were identified as primarily 11 C-labeled lactate 1 pyruvate, glucose, and alanine, respectively. Despite a significant contribution of 11 C-glucose (23%-45%) and 11 C-alanine (,11%) to total arterial 11 C activity, both were minimally extracted (1)/produced(2) by the heart (1.7% 6 1.0% and 20.12% 6 0.84%, respectively). Whereas extraction of 11 C-lactate correlated nonlinearly with that of unlabeled lactate extraction (r 5 0.86, P , 0.0001), 11 CO 2 production correlated linearly with extraction of unlabeled lactate (r 5 0.89, P , 0.0001, slope 5 1.20 6 0.13). In studies with physiologic free fatty acids (FFA) (415 6 216 nmol/mL), 11 C-lactate was highly extracted (32% 6 12%) and oxidized (26% 6 14%), and PET monoexponential clearance and kinetic modeling analyses resulted in accurate estimates of lactate oxidation and metabolism. In contrast, supraphysiologic levels of plasma FFA (4,111 6 1,709 nmol/mL) led to poor PET estimates of lactate metabolism due to negligible lactate oxidation (1% 6 2%) and complete backdiffusion of unmetabolized 11 C-lactate into the vasculature (28% 6 22%). Conclusion: Under conditions of net lactate extraction, L-3-11 Clactate faithfully traces myocardial metabolism of exogenous lactate. Furthermore, in physiologic substrate environments, noninvasive measurements of lactate metabolism are feasible with PET using myocardial clearance analysis (oxidation) or compartmental modeling. Thus, L-3-11 C-lactate should prove quite useful in widening our understanding of the role that lactate oxidation plays in the heart and other tissues and organs.

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“…Under deranged metabolic milieu, inclusive of diabetes, heart use relatively more fat than normal heart (Herrero et al, 2006;Carley & Severson, 2005). The shift towards increased fatty acids and decreased glucose utilization is linked to elevated circulating levels of FFA and triglycerides as a consequence of enhanced adipose tissue lipolysis, increased FFA uptake as well as high tissue FFAs caused by hydrolysis of augmented myocardial triglyceride stores.…”

Section: Altered Fuel Supply and Altered Substrate Utilizationmentioning

confidence: 99%

The Evolving Face of Heart Failure Associated with Elevated Cardio-Metabolic Risk Factors

Dutt¹,

Chauthaiwale²,

Mohanan³

et al. 2012

Cardiomyopathies - From Basic Research to Clinical Management

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Increased Myocardial Fatty Acid Metabolism in Patients With Type 1 Diabetes Mellitus

Abstract: Humans with diabetes mellitus exhibit increased MFAU and MFAO and reduced MGU consistent with observations obtained in experimental models of diabetes.

Cited by 228 publications

References 44 publications

Omega-3 fatty acid supplementation and cardiovascular disease

Omega-3 fatty acid supplementation and cardiovascular disease

L-3-11C-Lactate as a PET Tracer of Myocardial Lactate Metabolism: A Feasibility Study

The Evolving Face of Heart Failure Associated with Elevated Cardio-Metabolic Risk Factors

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