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Carbohydrate and lipid oxidation was measured in normal and diabetic human beings by means of continuous indirect calori metry in the course of a 100-gm. oral glucose tolerance test. After the glucose load, the carbohydrate (CHO) oxidation rate of 10 control subjects gradually rose, from 30 to 180 minutes, during the decline of plasma glucose and immunoreactive insulin (IRI). The lipid oxidation rate decreased during the same period. Diabetics were divided into two groups. In a group of six nonobese maturity-onset diabetics with a slight IRI response to glucose load and a fall in plasma free fatty acid (FFA) levels, the CHO oxidation rate was found to be of the same order of magnitude as in normal subjects, but this occurred at a high plasma concentration of glucose. The lipid oxidation rate decreased as in normal subjects. Conversely, in a group of four juvenile-type diabetics with no IRI response to glucose load and no fall in FFA levels, the CHO oxidation rate was markedly diminished and the lipid oxidation rate presented only a slight fall after glucose load. In the group of maturity-onset diabetics, a slight insulin secretion seemed to be sufficient to prevent lipolysis and to allow normal rates of lipid and CHO oxidation in response to glucose load. On the other hand, in the group of juvenile-type diabetics, the lack of endogenous insulin secretion seemed to be responsible for increased lipolysis, leading to decreased responses of lipid and CHO oxidation to glucose load.

In ten normal male subjects, the influence of amino acid and carbohydrate infusions on the plasma concentrations of glucose, free fatty acids, inorganic phosphate, insulin, glucagon, and growth hormone was studied. The molar insulin:glucagon ratio was calculated. Three different solutions were used: A mixture of 13 amino acids (50 g/l) = group I, solution (1) plus sorbitol (50 g/l) plus xylitol (50 g/l) = group II, and solution (1) plus glucose (100 g/l) = group III. According to Unger, the relative concentrations of insulin and glucagon control the hepatic glucose balance and the organism’s energy requirement. The insulin:glucagon ratio is inversely correlated with increased glucose production of the liver. A high ratio indicates glucose storage and increased protein synthesis, whereas a low one is a sign of increased gluconeogenesis from amino acids. Our data are in agreement with the clinical observation that, in parenteral nutrition, amino acids should be given together with carbohydrates to produce an anabolic effect. The insulin:glucagon ratio remained unchanged in group I and showed a rise from 6.4 to 14.8 in group II. In group III, a marked increase in the ratio was observed with a maximum of 46 after 60 minutes. Thus, in normal subjects, the combination of amino acids and glucose has a stronger effect on glucose storage and protein synthesis than the combination of amino acids and sorbitol and xylitol. The determination of the insulin:glucagon ratio can be useful for evaluating the anabolic effect of carbohydrate and amino acid solutions in parenteral nutrition.

During fructose, sorbitol, and xylitol perfusions, carbohydrate utilization was studied by continuous indirect calorimetry and compared with glucose utilization during pharmacologic inhibition of endogenous insulin secretion. The experiment was performed in 28 normal volunteers divided into 5 groups (glucose, fructose, sorbitol, xylitol, and saline), each subject being its own control. Insulin suppression was obtained by means of a constant infusion of epinephrine (6 microgram/min) and propranolol (0.08 mg/min). After 90 min, during plasma insulin steady state, each sugar or polyol was infused at a rate of 6 mg/kg/min for 120 min. In contrast with a rise in plasma glucose from 161 +/- 6 mg/dl) to 291 +/- 14 mg/dl during glucose infusion, glucose levels remained unchanged during infusion of the glucose substitutes. Carbohydrate oxidation showed a rise of 24, 65, 76, and 44 mg/min during infusions of glucose, fructose, sorbitol, and xylitol, respectively. Lipid oxidation rates decreased by 7, 20, 33, and 23 mg/min during the same infusions. These results indicate that fructose, sorbitol, and xylitol are oxidized at a higher rate than glucose during suppression of endogenous insulin secretion, without any significant rise in glycemia.

Oral tolerance tests with 30 and 50 g of xylitol were performed in 10 normal subjects adapted to taking this pentitol. A 50 g oral glucose tolerance test served as control. Continuous indirect calorimetry was carried out in 7 of these subjects to measure the effects on the metabolic rate and on the oxidation rates of carbohydrate and fat. A small and short rise in serum xylitol and low quantities of xylitol excretion in urine were observed in both xylitol tests. Xylitol caused a small but statistically significant increase in blood glucose and plasma insulin concentrations. Plasma free glycerol diminished significantly. After xylitol the metabolic rate rose throughout the test period but the total increase was only half of that after glucose administration. There was no significant influence of xylitol on the oxidation rates of carbohydrate and lipids. The total increase in carbohydrate oxidation during 2/2 hours amounted to one fourth of that caused by glucose. It is suggested that xylitol, during the first two hours after ingestion, charges the body’s metabolism much less than equal amounts of glucose. Therefore, the use of xylitol as a sweetener in the diet of diabetic patients seems to be justified.

The influence of peripherally administered adrenaline on the secretion of human growth hormone (HGH) and cortisol was investigated in 14 normal subjects. In a control group, HGH and cortisol release was stimulated by insulin infusion for 30 min (0.1 IU/kg). This procedure was compared with a similar insulin infusion which was started 60 min after initiating an adrenaline infusion for 150 min (6 μg/min). Adrenaline did not significantly alter the basal levels of HGH and cortisol. The mean maximal HGH rise during insulin hypoglycaemia (38.9 ± 7.2 ng/ml) was significantly (P < 0.005) inhibited by simultaneously administered adrenaline (9.6 ± 3.0 ng/ml). The same action of adrenaline was also found to be effective on cortisol release. The rise in plasma cortisol after insulin infusion (16.0±1.4 μg/100ml) was suppressed by adrenaline to 6.4 ± 2.2μg/100 ml (P < 0.005). Blood glucose and plasma free fatty acids (FFA), increased by adrenaline administration, were decreased significantly after insulin infusion. These results suggest an inhibitory effect of peripheral adrenaline on insulin-induced secretion of HGH. Blood glucose and plasma FFA levels seem to have no effect on this action. Whether there is a negative feedback between HGH and adrenaline should be considered. It is possible that the inhibition of cortisol release by adrenaline is mediated by an inhibiting effect on ACTH release, in the same manner as on the release of HGH.