Diabetic Cardiovascular Risk and Carnitine Deficiency <br/>—Carnitine Deficiency in Clinical Diabetes Mellitus
- 1 Department of Internal Medicine, The University of South Florida Morsani College of Medicine, Tampa, FL, USA
- 2 Charlotte Heart and Vascular Institute, Port Charlotte, FL, USA
- 3 Department of Internal Medicine, The University of South Florida Morsani College of Medicine, Tampa, FL, USA
Abstract
Background: Type 1 diabetes mellitus increases the risk of coronary heart disease. The Pittsburgh IDDM morbidity and mortality study reported greater than 10 fold coronary heart disease mortality compared with US national data [1] . Adults with diabetes have heart disease death rates 2 to 4 times higher than adults without diabetes [2] . Diabetic cardiomyopathy explains much of this survival difference and carnitine deficiency is a cause of cardiomyopathy. Research Design and Methods: Adult subjects (40) with type 1 diabetes mellitus were seen for a routine annual visit having no clinical complaints. Fasting serum samples were collected for annual chemistries and the measurement of carnitine. Results: The mean total (40.8 ± 8.8) [40 - 80 nmol/ml] and free (32.9 ± 7.9) [30 - 60 nmol/ml] carnitine levels for this group included 43% low total and 28% low free carnitine. The mean esterified/free (E/F) carnitine ratio (0.25 ± 0.09) for this group was elevated indicating carnitine insufficiency. Conclusions: Fatty acids are the primary energy source for diabetic heart muscle, and carnitine is essential for intracellular fatty acid transport and ATP production. Therefore, mild carnitine deficiency can compromise fatty acid energy production in a failing heart. Carnitine deficiency in subjects at high risk for cardiovascular failure is a possible unrecognized reason for the 4 fold increased death rate in patients with type 1 diabetes. Supplementation with oral carnitine could reduce that increased risk of heart failure, in patients with type 1 diabetes. Intravenous carnitine may be life saving when managing acute cardiac failure in patients with diabetes mellitus. Normal carnitine levels in patients with type 1 diabetes may provide a biochemical environment that prevents the long recognized idiopathic heart failure that occurs in insulin requiring diabetics as first reported in the 1974 Framingham Study.
- Orchard, T.J., Kretowski, A., Costacou, T. and Nesto, R.W. (2006) Type 1 Diabetes and Coronary Artery Disease. Diabetes Care, 55, 3556-3565.
- Stone, P.H., Muller, J.E., Hartwell, T., et al. (1989) The Effect of Diabetes Mellitus on Prognosis and Serial Left Ventricular Function after Acute Myocardial Infarction: Contribution of Both Coronary Disease and Diastolic Left Ventricular Dysfunction to the Adverse Prognosis. The MILIS Study Group. Journal of the American College of Cardiology, 14, 49-57. http://dx.doi.org/10.1016/0735-1097(89)90053-3
- Centers for Disease Control and Prevention (2011) National Diabetes Fact Sheet: National Estimates and General Information on Diabetes and Prediabetes in the United States. US Department of Health and Human Services, Centers for Disease Control and Prevention, Atlanta.
- Grundy, S.M., Benjamin, I.J., Burke, G.L., et al. (1999) Diabetes and Cardiovascular Disease a Statement for Healthcare Professionals from the American Heart Association. Circulation, 100, 1134-1146. http://dx.doi.org/10.1161/01.CIR.100.10.1134
- Singer, D.E., Moulton, A.W. and Nathan, D.M. (1989) Diabetic Myocardial Infarction: Interaction of Diabetes with Other Preinfarction Risk Factors. Diabetes, 38, 350-357. http://dx.doi.org/10.2337/diab.38.3.350
- Smith, J.W., Marcus, F.I. and Serokman, R. (1984) Prognosis of Patients with Diabetes Mellitus after Acute Myocardial Infarction. American Journal of Cardiology, 54, 718-721. http://dx.doi.org/10.1016/S0002-9149(84)80196-4
- Fang, Z.Y., Prins, J.B. and Marwick, T.H. (2004) Diabetic Cardiomyopathy: Evidence, Mechanisms, and Therapeutic Implications. Endocrine Reviews, 25, 543-567. http://dx.doi.org/10.1210/er.2003-0012
- Bing, R.J., Siegel, A., Ungar, I. and Gilbert, M. (1954) Metabolism of the Human Heart: II. Studies on Fat, Ketone and Amino Acid Metabolism. American Journal of Medicine, 16, 504-515. http://dx.doi.org/10.1016/0002-9343(54)90365-4
- Li, S.H. and McNeill, J.H. (2001) In Vivo Effects of Vanadium on GLUT 4 Translocation in Cardiac Tissue of STZ-Diabetic Rats. Molecular and Cellular Biochemistry, 217, 121-129. http://dx.doi.org/10.1023/A:1007224828753
- Garvey, W.T., Hardin, D., Juhaszova, M. and Dominguez, J.H. (1993) Effects of Diabetes on Myocardial Glucose Transport System in Rats: Implications for Diabetic Cardiomyopathy. American Journal of Physiology, 264, H837-H844.
- Chatham, J.C., Gao, Z.P., Bonen, A. and Forder, J.R. (1999) Preferential Inhibition of Lactate Oxidation Relative to Glucose Oxidation in the Rat Heart Following Diabetes. Cardiovascular Research, 43, 96-106. http://dx.doi.org/10.1016/S0008-6363(99)00056-5