No abstract

We have investigated whole body protein turnover in the fasted state in five normal men, five male Type 1 diabetic patients off insulin therapy, and five obese women, using IV 13C-leucine as a tracer. In diabetic patients, there was, as expected, a greater net loss of protein in the fasted state than in normal subjects. However, contrary to animal and studies in vitro, our diabetic patients in the fasted state showed a greater rate of protein synthesis than normal subjects (p less than 0.01). The increased net loss of protein in diabetic patients compared with normal subjects arose because, in the diabetic patients, protein breakdown was increased even more than protein synthesis under the conditions of this study. Plasma leucine concentration was higher in diabetic and in insulin-insensitive obese patients than in normal subjects (p less than 0.01), and higher in diabetic than in obese patients (p less than 0.05). The rate of protein synthesis per kg lean body mass was also higher in diabetic patients than in obese or normal subjects (p less than 0.01), and higher in obese than normal subjects (p less than 0.05). We conclude that, in human subjects, whole body leucine and protein metabolism are very sensitive to the action of insulin.

The basal energy expenditure of 10 Type 1 (insulin-dependent) C-peptide-negative diabetic patients (2042 +/- 62 kcal/24 h) was found to be significantly higher than the 1774 +/- 52 kcal/24 h predicted from their age, sex and body surface area (p less than 0.01). Intravenous insulin treatment significantly reduced energy expenditure to 1728 +/- 19 kcal/24h (p less than 0.01), which matched predicted values. The observed increase in metabolic rate in uncontrolled diabetic patients is associated with increased protein turnover, increased plasma glucagon, but no significant increase in cortisol, growth hormone or triiodothyronine concentrations in plasma. It may be accounted for by the energy cost of protein synthesis, or gluconeogenesis, or possibly increased sympathetic activity. This increased energy expenditure will contribute to the weight loss seen in Type 1 diabetic patients.

The thermic response of five lean and five obese subjects was measured by indirect calorimetry before, and for 157.5 min after a meal of protein, carbohydrate or fat, each of which provided 1.25 MJ. The change in plasma glucose, insulin and (in the case of the carbohydrate meal) the rate of exogenous glucose oxidation was also measured. There was no significant difference between the lean and obese groups in the magnitude of the thermic response to any of the three meals. In both weight groups the response was largest and most prolonged after the protein meal (P less than 0.01). The obese group showed a higher concentration of fasting plasma insulin (P less than 0.01) and a larger increase in plasma glucose (P less than 0.05) after the carbohydrate meal, but there was no significant difference in the oxidation of exogenous glucose when compared with the lean group. Previous studies on dietary-induced thermogenesis in lean and obese subjects have given conflicting results. In general reports of decreased thermogenesis in obese subjects are characterized by either (a) high pre-meal metabolic rates in the obese group, especially in diabetic subjects, or (b) a group classified as 'normal' who have been selected for their high thermogenic capacity.

The effect of increased physical activity on energy intake and balance was investigated in six obese women (mean 167% above ideal body weight) voluntarily hospitalized for metabolic balance studies. Three 19-day treatments-one sedentary and two with treadmill exercise which increased daily expenditure to 110% (mild) and 125% (moderate) of sedentary expenditure-were imposed on each subject. Individual daily expenditure and ad libitum intake were determined by activity diaries and covert monitoring, respectively. Subjects selected and did not not change an intake level which allowed for energy balance during the sedentary period only. Therefore, the difference between intake and expenditure between treatments was significantly different (sedentary 11, mild -114, and moderate -369 kcal/day). The negative balance observed with mild and moderate exercise was obtained because while expenditure was raised with exercise, no compensatory increase in intake occurred. Moderate, realistic levels of activity did not regulate intake.