Effects of Therapy on the Nature and Quantity of Fuels Oxidized During Diabetic Ketoacidosis

Abstract

We studied seven patients, in moderate to severe diabetic ketoacidosis (DKA), measuring respiratory exchanges of O2, GO2, and acetone and urinary excretion of nitrogen, ketone bodies, and glucose to calculate the respiratory quotient (RQ), nonprotein respiratory quotient (npRQ), metabolic requirements, and calories derived from fat, carbohydrate, and protein oxidation. Results from indirect calorimetry were related to circulating concentrations of glucose, free fatty acids, ketone bodies, and amino acids over a 14-h study consisting of a 2-h period I of rehydration with saline, a 4-h period II of rehydration and insulin therapy, and an 8-h period III of rehydration, insulin, and glucose administration. During period I, of about 2 h of saline rehydration, the RQ (0.55–0.80) and npRQ (0.58–0.88) varied among the patients but in general was low. The caloric requirements were 1.24 kcal/min/1.73 m2. Initially,fat contributed 78 ± 11%, glucose 17 ± 10%, and protein 5 ± 2% of the metabolic requirements. The circulating concentrations of fuels remained constant. During period II, after about 4 h of saline and insulin therapy, the RQ (0.62–0.88) and npRQ (0.55–0.91) remained rather stable, rising in only two of seven patients. Nevertheless, in all patients, saline and insulin therapy was associated with precipitous decreases in circulating concentrations of glucose, free fatty acids, acetoacetate, and beta-hydroxybutyrate and gradual decreases in plasma amino acids. During period III, after 8–12 h of insulin therapy, the RQ (0.68–0.92) and npRQ (0.48–1.01) increased, rising in five of six patients. Heightened RQ and npRQ values were observed only after plasma free fatty acid concentrations decreased to 0.44 ± 0.12 mM and plasma acetoacetate plus beta-hydroxybutyrate concentrations decreased to 5.27 ± 1.86 mM, while plasma glucose concentration remained elevated at 13.49 ± 3.67 mM because of intravenous glucose infusion. Caloric requirements diminished progressively throughout the study, and after about 4 h of saline and insulin therapy a reciprocal relationship between the contributions of fat and glucose to metabolic requirements was evident. At the end of period III the caloric requirements were 0.77 kcal/min/1.73 m2. Fat contributed 44 ± 16%, glucose 42 ± 22%, and protein 14 ± 8% of the metabolic requirements. We have observed a dissociation between the decrease in plasma glucose, free fatty acids, ketone bodies, and amino acids and the nature of fuels oxidized. This suggests that, during the initial hours of therapy for DKA, the predominant effect of insulin is to promote fuel storage rather than to promote glucose and ketone body oxidation. It was 8–12 h in the course of therapy before the npRQ rose, reflecting heightened glucose oxidation and diminished fat oxidation. Metabolic requirements progressively decreased with therapy.