Effects of regular insulin or insulin LISPRO on glucose metabolism after an oral glucose load in patients with type 2 diabetes mellitus.

Seven obese Type 2 diabetic patients were studied for two 4-h periods after ingestion of a glucose load to determine the effects of preprandial subcutaneous injection of Insulin Lispro (5 min before the meal) or regular insulin (20 min before the meal) on glucose metabolism. Glucose production and utilisation were measured using a dual isotope method. After Lispro, the mean postprandial increase in plasma glucose was 29% lower and the increase in insulin concentration 25% higher than after regular insulin (p < 0.05). Suppression of endogenous glucose production was similar with both types of insulin. Thus, preprandial injection of Lispro reduced postprandial glucose increments in Type 2 diabetic patients as compared to regular insulin. This effect is best explained by the increased postprandial bioavailability of Lispro.

[Arginine aspartate and muscular activity. II]. / Aspartate d'arginine et activité musculaire. Partie II.

We measured the effect of a 4-weeks treatment with arginine aspartate on 21 athletes. By a double blind methodology, we were able to show that the treatment group had an enhanced maximal oxygen consumption as well as a significantly decreased plasma lactate concentration at a work intensity of 200, 300 and 400 W on the treadmill. By the same token, 5 and 20 minutes after completion of the test run, blood lactate levels were significantly lower in the group receiving arginine aspartate. Nevertheless, at the 4 mmol lactate threshold, power and total work output were the same for both controls and treatment groups. These results show a favourable effect of arginine aspartate on blood lactate levels.

Modifications of glucose storage and oxidation in nonobese diabetics, measured by continuous indirect calorimetry.

A new application of continuous indirect calorimetry is described for measuring the disposal of a glucose load. In a group of 10 normal subjects, 3 h after a 100 g oral glucose load, 20 g glucose was oxidized at basal rate, 19 g in response to the load and 63 g stored, while a decrease of 2 g was observed in the glucose space (GS). In a group of four type I, insulin-dependent diabetics, both glucose oxidation (9 g at the basal rate and 4 g in response to the load) and glucose storage (9 g) were markedly decreased, with the remainder either being lost in the urine (36 g) or remaining in the glucose space (42 g). In a group of eight nonobese type II, non-insulin-dependent diabetics, glucose oxidation both in the basal rate and in response to the load was slightly decreased (13 and 14 g, respectively) and glucose storage decreased to 40 g. These results suggest that, in type I diabetics, complete insulin deficiency seriously impairs two major mechanisms regulating glucose homeostasis, i.e., glucose storage and oxidation, while, in type II diabetics, the remaining insulin secretion attentuates these disturbances.

Energy expenditure during oxygen deficit of submaximal concentric and eccentric exercise.

Aerobic (MR) and anaerobic (Man) energy production was determined in five subjects during the 1st min of concentric and eccentric exercise (steady-state energy expenditure approximately 415 W in both situations). Man was obtained by solving the heat balance equation, MR + Man - S = (R + C + E) +/- parallel to W parallel to, all other variables of which could be measured [S is heat storage; (R + C + E) are the radiative, convective, and evaporative heat losses; and W is work output]. The size of the O2 deficit was similar whatever the type of exercise (99 +/- 19 W concentric and 102 +/- 19 W eccentric). MR + Man was lower than the steady-state MR in both types of exercise (concentric; 364 +/- 19 and 407 +/- 24 W, respectively, and eccentric; 346 +/- 25 and 430 +/- 21 W, respectively). The size of the O2 deficit during the 1st min of muscular exercise is imposed by the steady-state energy requirement whatever the type of exercise. The smaller energy expenditure during this phase is probably due to less energy being released when creatinge phosphate is split without resynthesis (O2 deficit) than during splitting and resynthesis of high-energy phosphate bonds (steady state).

Energy expended during oxygen deficit period of submaximal exercise in man.

Aerobic (MR) and anaerobic (Man) metabolism was determined during the transition from mild (50 W external work) to heavier exercise (50% VO2max) in six subjects. The overall exercise efficiency was calculated during the oxygen deficit period and during steady-state exercise. MR was obtained by indirect calorimetry and Man by solving the heat balance equation: MR + Man - S = (R + C + E) + W, where radiative, convective, and evaporative heat losses (R + C + E) were measured by direct calorimetry, work output (W) by ergometry, and heat storage (S) by thermometry. (MR + Man) during the oxygen deficit period was found to be lower than MR during steady state. In the 1st min of exercise, mean mixed work efficiency (aerobic + anaerobic) was 33%, which was greater than aerobic efficiency (26.6%) during steady state. The mean anaerobic efficiency efficiency was 41%. This difference reflects the fact that the energy released by splitting of preformed high-energy bonds (i.e., creatine phosphate) is less than the energy released when high-energy bonds expended during mechanical work are continuously regenerated through oxidative phosphorylation. The reported measurements of overall energy metabolism in man provide means for estimating in vivo the coupling efficiency of physical work (i.e., 41%) as well as the efficiency with which energy released by substrate oxidations is recovered in the form of high-energy bonds (i.e., phosphorylation efficiency = 64%).

Carbohydrate utilization in obese subjects after an oral load of 100 g naturally-labelled [13C] glucose.

1. Total carbohydrate (CHO) and ingested glucose oxidation was measured in five obese subjects with normal glucose tolerance after an oral load of 100 g naturally-labelled [13C]glucose using indirect calorimetry and mass spectrometry respectively. 2. CHO utilization rate (107 +/- 14 mg/min in the post-absorptive state) increased 30 min after the glucose load to reach a plateau (245 +/- 25 mg/min) between 90 and 120 min. It then decreased to basal values at 330 min. Cumulative CHO oxidation over 480 min was 66 +/- 7 g and the CHO oxidized above basal levels was 26 +/- 7 g. 3. Enrichment of expired carbon dioxide with 13C began at 45 min and maximum values were observed between 210 and 300 min. At 480 min, cumulative oxidation of the ingested glucose was 24 +/- 2 g. 4. Compared with controls, the obese subjects exhibit an impairment of CHO utilization which precedes glucose intolerance. This impairment can be explained by an increased availability of free fatty acids which favours lipid oxidation at the expense of ingested [13C]glucose oxidation.

Substrate utilization during prolonged exercise after ingestion of 13C-glucose in obese and control subjects.

This study was performed to investigate whether the difference in substrate utilization observed between obese and control individuals at rest still exists during prolonged exercise. Using a combination of respiratory exchange and tracer techniques, six obese and six control subjects were investigated while exercising for 2 h on a bicycle ergometer, 1 h after ingesting 100 g naturally-enriched 13C-glucose. Oxidation rates of protein, lipid and carbohydrate (CHO) were measured by indirect calorimetry and that of exogenous glucose by mass spectrometry (13CO2). Before exercise the obese subjects presented a lower rate of CHO utilization with a mean respiratory quotient of .803 compared to .858 for the controls. This impairement of CHO utilization disappeared during exercise where total CHO oxidation was found to be comparable for the obese (94.0 +/- 8.4 g) and the control group (94.3 +/- 6.1g). Exogenous-glucose oxidation was even slightly more elevated in the obese subjects (33.6 +/- 2.5 g compared with 28.1 +/- 2.3 g). Two hypotheses have been proposed to explain the improvement in CHO utilization during exercise after a glucose load: (1) The fall in FFA is sufficient to suppress the inhibition of CHO uptake and oxidation; (2) The insulin resistance decreases during exercise. In conclusion, this study supports the concept that exercise performed by obese individuals stimulates CHO utilization with a concomitant improvement in glucose tolerance.

[Changes in storage and oxydation of ingested glucose in obesity and diabetes mellitus]. / Altération du stockage et de l'oxydation du glucose ingéré dans l'obésité et le diabète.

Indirect calorimetric studies were performed during a 100 g oral glucose tolerance test in diabetic patients with varying degrees of endocrine pancreatic dysfunction and in a control group of normal subjects. In 3 obese diabetics the study was repeated after a 3 day protein sparing modiefied fast. In diabetic patients the results show alterations of oxidation and storage of carbohydrates, related to insulin secretion deficiency on the one hand, and to overweight on the other. Endocrine pancreatic insufficiency may account directly for alterations observed in individuals with decreased or absent insulin response to glucose load, wheras metabolic factors such as adipose mass, hepatic steatosis, and peripheral insulin resistance appear to be responsible for alterations in carbohydrate oxidation and storage in subjects with relative endocrine pancreatic insufficiency, particularly obese diabetics.