A B S T R A C T Although alcoholism is a leading cause of morbidity and mortality of middle-aged Americans, there are no data available pertaining to the consequences of Laennec's cirrhosis on total body energy requirements or mechanisms for maintaining fuel homeostasis in this patient population. Therefore, we simultaneously used the techniques of indirect calorimetry and tracer analyses of ["4C]palmitate to measure the nature and quantity of fuels oxidized by patients with biopsy-proven alcoholic cirrhosis and compared the results with values obtained from healthy volunteers. Cirrhotic patients were studied after an overnight fast (10-12 h). Normal volunteers were studied after an overnight fast (12 h) or after a longer period of starvation (36-72 h).Total basal metabolic requirements were similar in overnight fasted cirrhotic patients (1.05±0.06 kcal/ min per 1.73 m2), overnight fasted normal subjects (1.00±0.05 kcal/min per 1.73 m2), and 36-72-h fasted normal volunteers (1.10±0.06 kcal/min per 1.73 m2).Indirect calorimetry revealed that in cirrhotic patients the percentages of total calories derived from fat (69±3%), carbohydrate (13±2%), and protein (17±4%) were comparable to those found in 36-72-h fasted subjects, but were clearly different from those of overnight fasted normal individuals who derived 40±6, 39±4, and 21±2% from fat, carbohydrate, and protein, respectively.These data are strikingly similar to data obtained through tracer analyses of ['4C]palmitate, which showed that in overnight fasted patients with alcoholic cir-

To study the mechanism of the diabetogenic action of ethanol, ethanol (0.75 g/kg over 30 min) and then glucose (0.5 g/kg over 5 min) were infused intravenously into six normal males. During the 4-h study, 21.8±2.1 g of ethanol was metabolized and oxidized to CO2 and H20. Ethanol decreased total body fat oxidation by 79% and protein oxidation by 39%, and almost completely abolished the 249% rise in carbohydrate (CHO) oxidation seen in controls after glucose infusion. Ethanol decreased the basal rate of glucose appearance (GR.) by 30% and the basal rate of glucose disappearance (GR,) by 38%, potentiated glucose-stimulated insulin release by 54%, and had no effect on glucose tolerance. In hyperinsulinemic-euglycemic clamp studies, ethanol caused a 36% decrease in glucose disposal. We conclude that ethanol was a preferred fuel preventing fat, and to lesser degrees, CHO and protein, from being oxidized. It also caused acute insulin resistance which was compensated for by hypersecretion of insulin.

A B S T R A C T The metabolism of acetone was studied in lean and obese humans during starvation ketosis. Acetone concentrations in plasma, urine, and breath; and rates of endogenous production, elimination in breath and urine, and in vivo metabolism were determined. There was a direct relationship between plasma acetone turnover (20-77 ,Umol/m2 per min) and concenitration (0.19-1.68 mM). Breath and urinary excretion of acetone accounted for a 2-30% of the endogenous production rate, and in vivo metabolism accounted for the remainder. Plasma acetone oxidation accounted for -60% of the production rate in 3-d fasted subjects and about 25% of the production rate in 21-d fasted subjects. About 1-2% ofthe total CO2 production was derived from plasma acetone oxidation and was not related to the plasma concentration or production rate. Radioactivity from [14C]acetone was not detected in plasma free fatty acids, acetoacetate, ,-hydroxybutyrate, or other anionic compounds, but was present in plasma glucose, lipids, and proteins. If glucose synthesis from acetone is possible in humans, this process could account for 11% of the glucose production rate and 59% of the acetone production rate in 21-d fasted subjects. During maximum acetonemia, acetone productioni from acetoacetate could account for 37% of the anticipated acetoacetate production, which implies that a significant fraction of the latter compound does not undergo immediate terminal oxidation.

A B S T R A C T Plasma acetate turnover and oxidation were determined in 11 healthy subjects by the constant infusion of a trace amount of [1_-4C]acetate for 6 h. The subjects ages ranged from 22 to 57 yr. There was a positive correlation (P < 0.001) between plasma acetate concentration and turnover rate, and a negative correlation (P < 0.001) between turnover and age. The plasma acetate concentration in the subjects 22-28 yr old was 0.17 vs. 0.13 mM (P < 0.02) in subjects 40-57 yr old. The plasma acetate turnover rate was also greater in the younger age group (8.23+0.66 vs. 4.98+0.64 ,umol/ min -kg, P < 0.01). Approximately 90% of the plasma acetate turnover was immediately oxidized to CO2 in both age groups, however, 13.2±+0.89% of the CO2 output in the younger group was derived from plasma acetate oxidation compared to 7.9+0.94% in the older group (P < 0.01). The mean plasma acetate concentration, turnover, and oxidation in six cancer patients 47-63 yr old were similar to the values observed in the age-matched healthy subjects.

Plasma acetone turnover rates were measured with the primed continuous infusion of 2-[14C]acetone in patients with moderate to severe diabetic ketoacidosis. Plasma acetone turnover rates ranged from 1.52 to 15.9 mumol X kg-1 X min-1 (108-1038 mumol X 1.73 m-2 X min-1) and were directly related to the plasma acetone concentrations that ranged from 0.47 to 7.61 mM. The average acetone turnover rate was 6.45 mumol X kg-1 X min-1 (533 mumol X 1.73 m-2 X min-1), a value twice that obtained in a similar group of diabetic ketoacidotic patients via the single-injection technique of 2-[14C]acetone administration. Degradation of urine glucose revealed that 14C from administered 2-[14C )acetone was principally located in carbons 1, 2, 5, and 6 of the glucose molecule in five of six patients. This distribution is similar to that expected from 2-[14C]pyruvate, suggesting that acetone was converted to glucose through pyruvate. In one patient, label was located predominantly in glucose carbons 3 and 4, indicating that acetone metabolism may be different in some patients. Acetol (1-hydroxyacetone) and 1,2-propanediol (PPD), two possible metabolites of acetone, were detected in plasma of the patients. The concentrations of Acetol ranged from 0 to 0.48 mM and of PPD ranged from 0 to 0.53 mM. The concentrations of each metabolite were directly related to the plasma acetone concentrations. During the continuous infusion of 2-[14C]acetone, the specific activities of plasma glucose and PPD rose continuously but did not reach constant values. Estimates of the minimal percent plasma glucose and PPD derived from plasma acetone averaged 2.1 and 74%, respectively.