Medicine (Austin & Northern Health) - Theses
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ItemClinical and physiological differences in obese individuals with and without diabetes mellitus undergoing a very-low-calorie diet program.( 2012)In Australia, the rising prevalence of obesity and type 2 diabetes mellitus represents the major health challenge of the 21st Century. Weight reduction is a cornerstone of modern management of overweight and obese patients with type 2 diabetes; however, management of the obese diabetic patient remains one of the most challenging in clinical medicine. Very-low-calorie diets (VLCDs) – defined as diets limiting energy intake to 800 kcal (3.35 MJ) per day while providing at least 50 g of high-quality protein and amino acids, essential fatty acids and daily requirements of trace elements, vitamins and minerals – have been advanced as a therapeutic intervention for weight loss in overweight and obese individuals with type 2 diabetes mellitus. However, whether obese individuals with diabetes lose as much weight as non-diabetic individuals using VLCDs remains uncertain, as earlier studies had significant limitations. The aim of this thesis was to examine the question: are obese individuals with type 2 diabetes mellitus as “successful” as obese individuals without diabetes participating in a VLCD program? Success may variably be defined in terms of weight loss, decreases in anthropometric measurements such as waist circumference, improvements in body composition such as reductions in percentage body fat or visceral adipose tissue, improvements in metabolic parameters or insulin dosage, or improvements in renal and cardiac function. While previous studies have been primarily focused upon weight loss, the focus of this thesis is to explore the effects of VLCDs in this broader context of successes that may be attributable to participation in these weight loss programs. Importantly, the comparison of diabetic and non-diabetic individuals using VLCDs is an area hitherto under-investigated. Chapter 2 presents the results of a single centre, prospective, case-control study investigating change in weight and body composition in obese subjects with type 2 diabetes mellitus or normal fasting glucose concentrations undergoing a 24-week VLCD program. It was found that while following a 24-week VLCD program, obese subjects with and without diabetes achieved comparable weight loss but the decrease in adiposity per unit weight loss was attenuated in diabetic subjects. Hyperinsulinemia may have inhibited lipolysis in the diabetic group; however, other factors may also have contributed. Chapter 3 extends the findings of Chapter 2 by reporting on change in abdominal adipose tissue compartments, namely visceral and subcutaneous adipose tissue depots, and the changes in adipokines associated with change in visceral fat. In diabetic subjects, increased VAT volume at baseline, not baseline BMI, predicted greater weight loss. Reduction in VAT relative to abdominal SAT was attenuated in the diabetic compared to control group. Differences between the groups related to insulin and adiponectin concentrations may have contributed to this observation. Chapter 4 reports on a pilot study of abdominal magnetic resonance imaging, originally performed to image visceral adiposity, to measure skeletal muscle area at the 3rd lumbar vertebral level, allowing estimation of whole body skeletal muscle mass derived by dual-energy X-ray absorptiometry. The use of formulae previously developed in a cancer patient population was verified, with suggestions for improving these calculations for use in an obese population. Chapters 5, 6 and 7 present data on changes in renal and cardiac function and reproductive hormone profiles. Renal function was measured using the plasma clearance of the radioisotope 99mTc-diethylene-triamine-penta-acetic acid (DTPA) technique, with the Brochner-Mortensen correction. Change in advanced glycation end-products was also documented. Cardiac function was measured using transthoracic echocardiography, adding to the existing literature which is largely derived from studies of bariatric surgery. In summary, the efficacy of VLCDs in facilitating weight loss was shown to be preserved in obese individuals with diabetes. However, significant differences in the change in body composition including reductions in body fat and visceral adiposity were found. The findings of this study have implications for the management of obese individuals with diabetes undergoing intensive dietary therapies, with a greater clinical focus on fat reduction and attention to antidiabetic and weight loss pharmacotherapies mandatory in this difficult to treat population.