High protein diets, weight loss, glycaemic control and renal function in type 2 diabetes mellitus.

Abstract

The evidence for the efficacy of weight loss diets with a higher protein to carbohydrate (CHO) ratio has increased. However, the long-term effect of higher protein diets (HPD) on renal function in individuals with type 2 diabetes is lacking. The studies in this thesis focus on the effect of altering the macronutrient composition towards a higher protein to carbohydrate ratio on renal function, HbA1c and lipids in individuals with type 2 diabetes mellitus (T2DM) and microalbuminuria. The main study was a 12 month randomized weight loss study in 56 volunteers. A 6 MJ high protein diet (HPD: protein 30% total energy (TE) equal to 90-120g/d, carbohydrate [CHO] 40%TE, fat 30%TE) was contrasted with a 6 MJ standard protein diet (SPD: protein 20%TE equal to 55-70g/d, CHO 50%TE, fat 30%TE). This study showed a significant decrease in weight (-10.5kg HPD and -7.5kg SPD), fat mass (-9% HPD and -8% SPD) and increased fat free mass (+6% in both groups) with no significant difference between diets. Renal function, measured as isotope GFR, calculated GFR and serum cystatin C, was unaffected by either diet. Microalbuminuria was reduced in HPD (AER: -12.0±9.1 μg/min and + 1.0±17.0 μg/min in SPD) with a borderline significant treatment effect after adjustment for baseline values (p=0.059). Glycaemic control (HbA1c -0.9 HPD and -0.5 SPD), high density lipoprotein cholesterol (+ 0.1 mmol/L in both groups), and triglycerides (HPD -0.8 and SPD -0.5mmol/L), improved similarly in both groups. There was a decreased diastolic BP in the HPD group (-2.5 mmHg) and an increase in SPD ( +5.2 mmHg; p=0.03). The major contributor to diabetes nephropathy is hyperglycaemia. In study 2 (a sub-study to the main study) and study 3, a short term meal intervention study, we investigated the effect of changing macronutrient composition and CHO timing on glycaemic control using a continuous glucose monitoring system. These studies showed a significant decrease in time spent with blood glucose (BG) above 10 mmol/L, maximal BG level and area under the BG curve indicating an overall beneficial effect of altering the CHO to protein ratio on glycaemic control. Changing the CHO content of breakfast had no effect on lunch glucose levels. In conclusion: This study is the first to examine the long-term efficacy and safety of higher protein diets in individuals with T2DM and microalbuminuria. Both diets had positive effects on cardiovascular risk factors with no changes in renal function.