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.
Highlights
According to 2011 Centers for Disease Control (CDC) data 25.8 million children and adults in the United States (8.3% of the population) have diabetes mellitus [3]
Pyruvate derived from glucose, glycogen, lactate and exogenous pyruvate is oxidized by pyruvate dehydrogenase localized within the inner mitochondrial membrane as a secondary substrate for normal myocardial energy production, if sufficient intramitochondrial CoA is available
This study demonstrated an apparent reduction of myocardial function in diabetic animals with excess circulating glucose and fatty acids when the serum free carnitine level was low and the E/F ratio elevated
Summary
According to 2011 Centers for Disease Control (CDC) data 25.8 million children and adults in the United States (8.3% of the population) have diabetes mellitus [3]. Because of reduced glucose uptake, cardiomyocytes of diabetic subjects must increase fatty acid β-oxidation to almost 100% for sufficient ATP production [12]. By controlling the influx of fatty acids into the mitochondria, regulates the substrate supply for β-oxidation which produces the ATP required for normal cardiac function [13]. Efficient mitochondrial energy production requires the free L-carnitine inside the mitochondria to esterify fatty acid acyl-groups for transport out of the mitochondria to leave sufficient free CoA in the mitochondria for continued ATP generation from any available substrate [14]. 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. 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
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