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Title: Aspects of energy expenditure in diabetic and non-diabetic man : the role of brown adipose tissue
Author: Leslie, P. J.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1988
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INTRODUCTION: Abnormalities of energy expenditure (EE) in obesity and type II diabetes mellitus have been described in animal models and adult man and it has been suggested that these abnormalities predispose to weight gain. In rodents there is evidence for a requirement for insulin in regulatory thermogenesis mediated via brown adipose tissue (BAT). The hypotheses that, firstly, insulin has a role in the control of EE and, secondly, that this is mediated by BAT in adult man were tested in the present studies. METHODS: Three components of daily EE resting metabolic rate (RMR), and the thermic responses to a mixed liquid meal (32.6 KJ/kg) and to an infusion of noradrenaline (NA), 0.1 μg/kg/min, were measured using indirect calorimetry in type I and type II diabetic subjects. The components of EE were measured in 9 lean type I diabetics initially while poorly controlled on conventional therapy (CT), HbA_1 12.1±0.7%; (mean±SEM), and then when optimally controlled on continuous subcutaneous insulin infusion (CSII) (HbA_1 7.5±0.2%). The response to fat supplementation for one week (5.23 MJ/day) was assessed and the results compared to 8 non-diabetic control subjects. These parameters were also measured in 8 type II diabetics controlled on diet and oral hypoglycaemic agents (HbA1 8.6±0.7%) in order to ascertain whether the alterations in body weight during metformin therapy (weight loss) or sulphonylurea therapy (weight gain) were reflected in alterations of EE. An estimation of the thermogenic potential of BAT in adult man was attempted by histological (light and electron microscopy) and biochemical (GDP binding, cytochrome c oxidase activity and respiration of isolated mitochondria and adipocytes) studies on perirenal BAT obtained at post mortem and during surgery. RESULTS: Poorly controlled type I diabetic subjects had a significantly (p< .01)) raised RMR (4.92±0.27 KJ/min) which returned to predicted value (4.6±0.34 KJ/min) on attainment of optimal glycaemic control. This decrease in RMR may partly explain the mean gain in weight (3.5 kg) observed during CSII. The thermic response to infused NA was decreased by over 50% during CT (27.1±3.4 KJ controls vs. 11.1±3.7 KJ diabetic CT; p< 01) and did not significantly improve during CSII (13.4±3.7 KJ). A blunted thermic response to a meal was observed during fat supplementation with CT (44.8±14.0 KJ) but CSII corrected this (71±9.9 KJ). Hence insulin has a role in the control of EE but precise replacement does not correct all these abnormalities in Type I diabetes mellitus. 2. Type II diabetic subjects had a normal RMR and thermic responses and these were similar whether on metformin or sulphonylurea therapy. This suggests that alterations in EE do not account for the changes in weight during treatment with these agents. 3. Histological and biochemical studies demonstrated the presence of functional BAT in adult man with activity equivalent to the partially cold-adapted guinea pig suggesting some potential for thermogenesis in adult man. However, it was calculated that this tissue can account for only 0.2% of the rise in oxygen consumption during NA infusion and suggests that this tissue has little energetic significance in adult man. CONCLUSIONS: These data suggest that although type I diabetes mellitus may be associated with abnormalities of EE these are unlikely to be mediated through BAT metabolism in man.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available