Acetone Metabolism During Diabetic Ketoacidosis

Abstract

The presence and the importance of acetone and its metabolism in diabetic ketoacidosis has largely been ignored. Therefore, we studied acetone metabolism in nine diabetic patients in moderate to severe ketoacidosis. The concentration of acetone in plasma, urine, and breath, and the rates of acetone production and elimination in breath and urine were determined and the rates of vivo metabolism were calculated. Plasma acetone concentrations (1.55–8.91 mM) were directly related and were generally > acetoacetate concentrations (1.16–6.08 mM). The rates of acetone production ranged from 68 to 581 μmol/min/1.73 m2, indicating the heterogeneous nature of the patients studied. The average acetone production rate was 265 μmol/min/1.73 m2 and accounted for about 52% of the estimated acetoacetate production rate. Urinary excretion of acetone remained constant and accounted for about 7% of the acetone production rate in all patients. There was a positive linear relationship between the percentage of the acetone production rate accounted for by excretion in breath and the plasma acetone concentration. At low plasma acetone concentrations, ∼ 20%, and at high plasma acetone concentrations, ∼ 80% of the production rate was accounted for by breath acetone. In contrast, there was a negative linear relationship between the percentage of acetone production rate undergoing in vivo metabolism and plasma acetone concentration. At low plasma acetone concentrations, ∼ 75%, and at high concentrations, ∼ 20% of acetone production rate was accounted for by in vivo metabolism. Radioactivity from 2-[14C]-acetone was variably present in plasma acetone, glucose, lipids and proteins. No radioactivity was found in plasma acetoacetate, beta-hydroxy butyrate or free fatty acids or other anionic compounds. Exchange rates of acetone into other metabolites could not be estimated because of non-steady-state precursor product relationships in these patients.