By the year 2025, it is anticipated that over 300 million individuals world wide will have type 2 diabetes, with a projected increase from 84 to 288 million (170%) in developing countries and from 51 to 72 million (42%) in developed countries. Diabetes leads to a markedly increased risk of heart disease and renal failure and to expensive and debilitating retinopathy and neuropathy. Cognitive decline is also increased. As there is accumulating evidence of the beneficial effects of moderate carbohydrate, low fat dietary patterns compared to high carbohydrate diets, this thesis will focus on the effects of moderate carbohydrate high protein dietary patterns (total carbohydrate: protein: fat ratio of 40%:34%:26%) on glycemic control, risk factors for macrovascular disease and cognitive function. Information on two key areas in type 2 diabetes will be presented, 1. Acute effects of dietary patterns, moderately carbohydrate restricted and high in protein on glucose levels assessed using continuous glucose monitoring systems (CGMS) with verification of these results through a small repeat study. 2. Chronic effects of energy restricted dietary patterns, moderately carbohydrate restricted and high in protein on glucose levels, HbA1c, cognitive function, cardiovascular disease (CVD) risk markers and renal function. In the acute study, we recruited 23 subjects with type 2 diabetes. The participants were randomized to each of 4, 3-day interventions in a cross over design with a 4 day wash out period in which the carbohydrates were distributed differently at each meal; carbohydrates evenly distributed across the day, or carbohydrates loaded at breakfast, lunch or dinner. Glucose levels were continuously measured using CGMS. Outcomes were assessed by postprandial peak glucose (Gmax), time spent above 12 mmol/L (T>12) and total area under the glucose curve (AUC20). The intervention showed that an even distribution of carbohydrates did not optimise blood glucose control, whereas carbohydrates loaded at the lunch time meal provided the most favourable postprandial profile. To verify these results we conducted a repeat study. Six of the previous participants accepted the invitation to return and complete the even distribution arm of the study after a 20 week time lag. The intervention showed that although HbA1c, fasting blood glucose (FBG), AUC, exercise and ambient temperature remained constant there was a significant effect of change in sunlight hours on Gmax, suggesting an effect of sunlight. To assess the chronic effects of energy restricted dietary patterns on the determinants of HbA1c, cognitive function, CVD risk markers and renal function under conditions of weight loss, we recruited 82 participants with type 2 diabetes. These participants were randomised to one of two high protein energy restricted dietary patterns that differed in cholesterol content, for a 12 week period, in a parallel design. A sub group of these participants completed cognitive function testing with (n=34) or without (n=17) CGMS at baseline and at 8 weeks. After 8 weeks of the intervention the determinants of HbA1c under conditions of energy restriction were evaluated. The intervention showed the change in FBG accounted for most of the variance in change in HbA1c, but % energy reduction also contributed independently of FBG. Both energy restricted high protein diets equally improved glycemic control, particularly T>12, AUC, HbA1c and FBG. Fifty one participants completed cognitive testing to evaluate the effect of weight loss and blood glucose control on cognition. Cognitive function was not altered by time, diet, baseline lipid levels. Working memory was predicted by FBG. Short term memory was predicted by FBG, Gmax and AUC24. Sixty five participants completed 12 weeks of the intervention to assess CVD risk markers and renal function. Renal function was maintained and CV markers improved on both dietary patterns, with greatest improvement in HDL-C observed in the group consuming a high protein, energy restricted dietary pattern, high in dietary cholesterol. In conclusion, in the context of a high protein, carbohydrate restricted dietary pattern, cognitive function and renal function did not change, while glycemia and CV risk profiles improved with weight loss over the short term. Under conditions of energy balance diurnal glucose profiles were optimal when the carbohydrates were loaded in the lunch meal. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1342253 / Thesis (Ph.D.) - University of Adelaide, School of Molecular and Biomedical Science, 2008

Background: Higher protein diets, especially from animal sources, have seen a rise in popularity due to potential metabolic. This may have consequences for kidney function particularly in rising middle class populations who are allocating more income towards meat. The objective of this systematic review and meta-analysis was to evaluate the effects of higher versus lower protein intake on glomerular filtration rate (GFR) in adult populations without renal impairment. Methods: Search strategies were developed and electronic databases searched: MEDLINE and EMBASE. Data were extracted up until June 3, 2015. The main outcome measure was GFR and a random effect model (Cochrane’s Review Manager Version 5.3) was used to pool mean differences in GFR values. Results: Database searches yielded 25 trials from 1914 articles that were eligible for analysis based on inclusion/exclusion criteria. 12 studies were randomized controlled trials and 11 studies were crossover trials. As a result of data presented, 2 crossover studies were treated as 4 trials to result in 25 total trials. A total of 810 subjects from 25 trials were included in this systematic review and meta-analyses. The age of participants was 24-62 years and their BMI was 21-36 kg/m2. Higher protein compared to lower protein-containing diets were associated with increased GFR values [mean difference (MD): 8.33 ml/min (95% CI 4.87 to 11.79), P < 0.00001] but this was less pronounced when assessing change from baseline GFR values [MD: 4.71 ml/min (95% CI 0.06 to 9.36), P = 0.05]. Moreover, significant heterogeneity was present and funnel plot asymmetry indicated potential publication bias in both meta-analyses. Conclusion: Higher protein diets were associated with increased GFR, however, these results were inconclusive due to significant heterogeneity and overestimation by random effect analyses. There is still no clear evidence that high protein diets negatively impact renal function in healthy populations. / Thesis / Master of Science (MSc) / Globally, the leading causes of mortality in industrialized countries are cardiovascular disease (CVD), stroke, and type 2 diabetes (T2D). Deaths from these chronic diseases now outpace deaths due to malnutrition. Being overweight and obese increases the risk of both morbidity and mortality from CVD, stroke, and T2D. Global rates of overweight and obesity have now reached ‘epidemic’ proportions and the World Health Organization has stated that, “… [a] global epidemic of overweight and obesity – ‘globesity’ – is taking over many parts of the world. If immediate action is not taken, millions will suffer from an array of serious health disorders.” Over the past 20-30 years, the popularity of higher protein energy restricted diets have grown due to the potential benefits regarding weight loss, appetite regulation, and maintenance of lean (muscle) mass. Additionally, the expansion of the global ‘middle-class’ has resulted in families allocating more income towards meat products as a primary protein source in their diet. A health concern is that higher protein intake may have an adverse effect on kidney function. In individuals with chronic kidney disease, higher protein diets have been shown to result in further renal impairment. However, the effects of increased protein intake in healthy populations are unclear. The aim of this systematic review and meta-analysis was to compare higher versus lower protein diets on kidney function in healthy populations based on the literature to date. This was accomplished by looking at changes in glomerular filtration rate (the rate at which kidneys filter blood), which is the ‘gold standard’ marker of kidney function.