Lack of demonstrable harmful effect of higher protein weight loss diets on bone health and nephropathy in type 2 diabetes.

The optimal macronutrient composition of diets to maximize weight loss has been a subject of great interest in obesity research. High protein weight loss diets have gained widespread popularity. However their safety regarding osteoporosis risk and progression of diabetic nephropathy has been questioned. With regard to bone, higher dietary protein could cause a low grade metabolic acidosis, leading to hypercalciuria with loss of calcium from bone, causing osteoporosis. Recent studies suggest the situation is more complicated. The interaction with other dietary components such as calcium, fruit and vegetables is important. Historically, nephrologists have advocated lower protein diets in subjects with renal impairment to slow the decline in glomerular filtration rate. Whether this could be extrapolated to subjects with nephropathy from type 2 diabetes remains unclear. These subjects are often obese and potential candidates for high protein diets. If weight loss was achieved, this should slow the deterioration in renal function both directly as well as by improving lipid, blood pressure and glycaemic control which are risk factors for diabetic nephropathy. This thesis aims to test the hypothesis that higher protein diets are harmful to bone and renal health. We designed two clinical trials to test the effect of higher protein weight loss diets compared to lower protein weight loss diets on bone health, in overweight but otherwise healthy post-menopausal women over 2 years and on decline in glomerular filtration rate over 1 year in subjects with early nephropathy from type 2 diabetes. These two trials were conducted at the Commonwealth Scientific and Industrial Research Organisation in collaboration with the Centre of Clinical Research Excellence in Human Nutrition at the University of Adelaide. As a separate sub-study, I analysed the accuracies of the three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations using creatinine, cystatin C and both, compared to radioisotope methods in our obese subjects from the renal study. These results and accompanying discussion are presented in a combined narrative and publication format as per University of Adelaide guidelines. The results of my studies did not demonstrate any signal of increased bone loss from higher protein diets; our results are consistent with a modest beneficial effect based on lower bone turnover with higher dietary protein. With the renal study, there was no evidence that the higher protein diet accelerated decline in GFR in type 2 diabetes. The main benefit came from weight loss; subjects who hyperfiltered (estimated GFR greater than 120 ml/min/1.73m²) had a decrease in eGFR. Subjects with a baseline eGFR between 40-120 ml/min/1.73m² had an increase in GFR with weight loss. I also demonstrated that after weight loss, the CKD-EPI equations using cystatin C or both cystatin C and creatinine had higher precision compared to the equation using creatinine alone. This reflected the loss of lean mass with weight loss, which has a bigger influence on serum creatinine than cystatin C. Therefore, in post-menopausal women and subjects with early type 2 diabetic nephropathy, higher protein weight loss diets are not harmful to bone and renal health.Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 201