Metabolic Effects of Dichloroacetate in Patients with Diabetes Mellitus and Hyperlipoproteinemia

Metabolic Effects of Dichloroacetate in Patients with Diabetes Mellitus and Hyperlipoproteinemia

Peter W. Stacpoole, Ph.D., M.D., George W. Moore, M.D., and David M. Kornhauser, M.D.

New England Journal of Medicine 1978; 298:526-530 March 9, 1978

Abstract

Dichloroacetate is known to lower plasma lactate under various experimental circumstances and to lower plasma glucose and triglycerides in diabetic and malnourished animals. We gave individuals with diabetes mellitus, hyperlipoproteinemia, or both oral dosages (3 to 4 g) of dichloroacetate as the sodium salt for six to seven days in order to study its metabolic effects in humans. Dichloroacetate generated large, concurrent drops in plasma lactate (73%) and alanine (82%) as well as a mean reduction in fasting hyperglycemia of 24% (P0.01) and 82% (P0.01 to 0.001), respectively. Additionally, it markedly increased plasma ketone-body concentrations (71%) while decreasing triglyceride levels (61%; P0.01 to 0.001) and cholesterol levels (22%; P0.01 to 0.001). Glycerol, free fatty acid, and plasma insulin levels were unaffected. While excretion and renal clearance decreased, serum uric acid increased. Mild drowsiness was encountered by a few patients, but no further clinical or laboratory evidence of unfavorable effects was discovered during or right after the therapy phase. 1978; N Engl J Med 298:526–530

Presented in part at the annual meeting of the American Diabetes Association, San Francisco, CA, June 19–23, 1976.

Supported in part by research grants (GM-15431, 5–M01-RR 95, AM 17076 and AM 19587) from the National Institutes of Health (Dr. Moore is an endocrinology fellow sponsored by the U.S. Air Force, and Dr. Kornhauser was the recipient of a fellowship for careers in clinical pharmacology from the Pharmaceutical Manufacturers Association Federation).

We are indebted to Dr. William W. Lacy for the plasma amino acid measurements, to Dr. Henry G. Wilcox for the lipoprotein fractionation, to Dr. Ulrich Keller for the plasma free fatty acid and glycerol determinations and to Drs. David Rabinowitz, Oscar B. Crofford and John A. Oates for continued support.

Source Information

From the Diabetes-Endocrinology Research Center and the divisions of Endocrinology and Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine (address reprint requests to Dr. Stacpoole at the Department of Medicine, Vanderbilt University Hospital, Nashville, TN 37232).

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Figure 1Effect of Dichloroacetate (DCA) on Fasting Plasma Glucose (Broken Vertical Lines Indicate Period of Treatment).

Figure 2Effect of Dichloroacetate (DCA) on Fasting Plasma Lactate and Alanine (Broken Vertical Lines Indicate Period of Treatment).

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