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; 298:526-530March 9, 1978
Dichloroacetate is known to reduce plasma glucose and triglycerides in diabetic and starved animals and to lower plasma lactate under various experimental conditions. To investigate its metabolic effects in man, we administered oral doses (3 to 4 g) of dichloroacetate as the sodium salt to patients with diabetes mellitus or hyperlipoproteinemia or both for six to seven days. Dichloroacetate significantly reduced fasting hyperglycemia an average of 24 per cent (P<0.01) from base line and produced marked, concomitant falls in plasma lactate (73 per cent; P<0.05 to <0.01) and alanine (82 per cent; P<0.01 to <0.001). In addition, it significantly decreased plasma cholesterol (22 per cent; P<0.01 to <0.001) and triglyceride (61 per cent; P<0.01) levels while increasing (71 per cent; P<0.01) plasma ketone-body concentrations. Plasma insulin, free fatty acid and glycerol levels were not affected. Serum uric acid rose, whereas excretion and renal clearance fell. Some patients experienced mild sedation, but no other laboratory or clinical evidence of adverse effects was noted during or immediately after the treatment phase. (N Engl J Med 298:526–530, 1978)
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.
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).
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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