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DOI: 10.1055/s-0043-119076
Effect of Diabetes on the Assessment Role of 2-Oxoglutarate to the Severity of Chronic Heart Failure
Publication History
received 18 May 2017
revised 03 August 2017
accepted 30 August 2017
Publication Date:
08 November 2017 (online)
![](https://www.thieme-connect.de/media/eced/201808/lookinside/thumbnails/05-2017-0191-dia_10-1055-s-0043-119076-1.jpg)
Abstract
Background Serum 2-oxoglutarate can reflect the severity of chronic heart failure (CHF) in patients without diabetes. Whether this predictive role persists in type 2 diabetes mellitus (T2DM) patients is unclear. In this study, we investigated this predictive role in T2DM patients and whether 2-oxoglutarate can indicate the diastolic or systolic function of left ventricle.
Methods One hundred eighty CHF patients (76 with T2DM) and 66 healthy controls were studied. 2-Oxoglutarate was assayed by liquid chromatography-mass spectrometry/mass spectrometry. Echocardiographic parameters, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and other parameters were measured.
Results 2-Oxoglutarate was increased in CHF patients with or without T2DM compared with controls (both P<0.01). Patients with a lower left ventricular ejection fraction or a higher NT-proBNP or left ventricular end-diastolic volume index had higher levels of 2-oxoglutarate (median, 18.77 μg/mL versus 11.25 μg/mL; median, 14.06 µg/ml versus 9.39 µg/ml; median, 18.06 µg/mL versus 11.60 µg/mL, all P<0.05) in nondiabetic patients but not in T2DM patients. In multiple logistic regression analysis, NT-proBNP (OR=3.445, 95% CI=1.098 to 10.816, P=0.034) and left ventricular end-diastolic diameter (OR=2.544, 95% CI=1.033 to 6.268, P=0.042) were independently associated with increased 2-oxoglutarate in nondiabetic patients.
Conclusions The levels of 2-oxoglutarate can reflect the clinical severity of CHF in nondiabetic patients but not in those with T2DM, and it can be used as a potential indicator of the systolic dysfunction of the left ventricle.
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References
- 1 Kadkhodayan A, Coggan AR, Peterson LR. A "PET" area of interest: myocardial metabolism in human systolic heart failure. Heart Fail Rev 2013; 18: 567-574
- 2 Mori J, Basu R, McLean BA. et al. Agonist-induced hypertrophy and diastolic dysfunction are associated with selective reduction in glucose oxidation: a metabolic contribution to heart failure with normal ejection fraction. Circ Heart Fail 2012; 5: 493-503
- 3 Nasir S, Aguilar D. Congestive heart failure and diabetes mellitus: Balancing glycemic control with heart failure improvement. Am J Cardiol 2012; 110: 50B-57B
- 4 Aneja A, Tang WH, Bansilal S. et al. Diabetic cardiomyopathy: Insights into pathogenesis, diagnostic challenges, and therapeutic options. Am J Med 2008; 121: 748-757
- 5 Liu JE, Palmieri V, Roman MJ. et al. The impact of diabetes on left ventricular filling pattern in normotensive and hypertensive adults: The Strong Heart Study. J Am Coll Cardiol 2001; 37: 1943-1949
- 6 Vasu S, Morgan TM, Kitzman DW. et al. Abnormal stress-related measures of arterial stiffness in middle-aged and elderly men and women with impaired fasting glucose at risk for a first episode of symptomatic heart failure. J Am Heart Assoc 2015; 4: e000991
- 7 From AM, Scott CG, Chen HH. The development of heart failure in patients with diabetes mellitus and pre-clinical diastolic dysfunction a population-based study. J Am Coll Cardiol 2010; 55: 300-305
- 8 Zile MR, Baicu CF, Gaasch WH. Diastolic heart failure–abnormalities in active relaxation and passive stiffness of the left ventricle. N Engl J Med 2004; 350: 1953-1959
- 9 Dunn WB, Broadhurst DI, Deepak SM. et al. Serum metabolomics reveals many novel metabolic markers of heart failure, including pseudouridine and 2-oxoglutarate. Metabolomics 2007; 3: 413-426
- 10 Samara MA, Tang WH, Cikach Jr F. et al. Single exhaled breath metabolomic analysis identifies unique breathprint in patients with acute decompensated heart failure. J Am Coll Cardiol 2013; 61: 1463-1464
- 11 Chen PA, Xu ZH, Huang YL. et al. Increased serum 2-oxoglutarate associated with high myocardial energy expenditure and poor prognosis in chronic heart failure patients. Biochim Biophys Acta 2014; 1842: 2120-2125
- 12 McKee PA, Castelli WP, McNamara PM. et al. The natural history of congestive heart failure: the Framingham study. N Engl J Med 1971; 285: 1441-1446
- 13 Ma YC, Zuo L, Chen JH. et al. Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease. J Am Soc Nephrol 2006; 17: 2937-2944
- 14 Schiller NB, Shah PM, Crawford M. et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American society of echocardiography committee on standards, subcommittee on quantitation of two-dimensional echocardiograms. J Am Soc Echocardiogr 1989; 2: 358-367
- 15 Devereux RB, Alonso DR, Lutas EM. et al. Echocardiographic assessment of left ventricular hypertrophy: Comparison to necropsy findings. Am J Cardiol 1986; 57: 450-458
- 16 Pallant J. SPSS survival manual: a step by step guide to data analysis using SPSS for windows (version 10). UK: Open University Press; 2001: 23-101
- 17 Buchanan J, Mazumder PK, Hu P. et al. Reduced cardiac efficiency and altered substrate metabolism precedes the onset of hyperglycemia and contractile dysfunction in two mouse models of insulin resistance and obesity. Endocrinology 2005; 146: 5341-5349
- 18 Kato T, Niizuma S, Inuzuka Y. et al. Analysis of metabolic remodeling in compensated left ventricular hypertrophy and heart failure. Circ Heart Fail 2010; 3: 420-430
- 19 Lopatin YM, Rosano GM, Fragasso G. et al. Rationale and benefits of trimetazidine by acting on cardiac metabolism in heart failure. Int J Cardiol 2016; 203: 909-915
- 20 Fragasso G, Perseghin G, De Cobelli F. et al. Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine/adenosine triphosphate ratio in patients with heart failure. Eur Heart J. 2006; 27: 942-948
- 21 Neijssel OM, Tempest DW. The role of energy-spilling reactions in the growth of Klebsiella aerogenes NCTC 418 in aerobic chemostat culture. Arch Microbiol 1976; 110: 305-311
- 22 Weiss RG, Gerstenblith G, Bottomley PA. ATP flux through creatine kinase in the normal, stressed, and failing human heart. Proc Natl Acad Sci USA 2005; 102: 808-813
- 23 Phan TT, Abozguia K, Nallur Shivu G. et al. Heart failure with preserved ejection fraction is characterized by dynamic impairment of active relaxation and contraction of the left ventricle on exercise and associated with myocardial energy deficiency. J Am Coll Cardiol 2009; 54: 402-409
- 24 Senni M, Paulus WJ, Gavazzi A. et al. New strategies for heart failure with preserved ejection fraction: The importance of targeted therapies for heart failure phenotypes. Eur Heart J 2014; 35: 2797-2815
- 25 Hoenig MR, Bianchi C, Rosenzweig A. et al. The cardiac microvasculature in hypertension, cardiac hypertrophy and diastolic heart failure. Curr Vasc Pharmacol 2008; 6: 292-300
- 26 Paulus WJ, Tschöpe C. A novel paradigm for heart failure with preserved ejection fraction: Comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol 2013; 62: 263-271
- 27 Fonarow GC, Stough WG, Abraham WT. et al. Characteristics, treatments, and outcomes of patients with preserved systolic function hospitalized for heart failure: A report from the OPTIMIZE-HF Registry. J Am Coll Cardiol 2007; 50: 768-777
- 28 Mentz RJ, Kelly JP, von Lueder TG. et al. Noncardiac comorbidities in heart failure with reduced versus preserved ejection fraction. J Am Coll Cardiol 2014; 64: 2281-2293
- 29 Siddiqi N, Singh S, Beadle R. et al. Cardiac metabolism in hypertrophy and heart failure: Implications for therapy. Heart Fail Rev 2013; 18: 595-606
- 30 Lee L, Horowitz J, Frenneaux M. Metabolic manipulation in ischaemic heart disease, a novel approach to treatment. Eur Heart J 2004; 25: 634-641
- 31 Fukushima A, Lopaschuk GD. Cardiac fatty acid oxidation in heart failure associated with obesity and diabetes. Biochim Biophys Acta. 2016; 1860: 1525-1534
- 32 Ménard SL, Croteau E, Sarrhini O. et al. Abnormal in vivo myocardial energy substrate uptake in diet-induced type 2 diabetic cardiomyopathy in rats. Am J Physiol Endocrinol Metab 2010; 298: E1049-E1057
- 33 Sonenshein AL. Control of key metabolic intersections in Bacillus subtilis. Nat Rev Microbiol 2007; 5: 917-927
- 34 Snaith CD, Wright G, Lofkin M. The effects of aspartate and 2-oxoglutarate upon glycolytic energy metabolites and mechanical recovery following global ischaemia in isolated rat hearts. J Mol Cell Cardiol 1992; 24: 305-315
- 35 Patel SG, Hsu JW, Jahoor F. et al. Pathogenesis of A−β+ ketosis-prone diabetes. Diabetes 2013; 62: 912-922
- 36 Fillmore N, Mori J, Lopaschuk GD. Mitochondrial fatty acid oxidation alterations in heart failure, ischaemic heart disease and diabetic cardiomyopathy. Br J Pharmacol 2014; 171: 2080-2090