The role of residual beta-cell function on glycaemic and vascular outcomes at rest and post exercise in people with type 1 diabetes

Abstract

Within patients with type 1 diabetes (T1D), residual ꞵ-cell function and endogenous insulin secretion occurs in a substantial number of individuals. The role this ꞵ-cell function plays in glycaemic control in individuals with T1D is currently not fully understood. This is especially true around exercise, where maintaining glycaemic control is challenging and a large inter-individual variation exists. Micro amounts of endogenous insulin secretion appears to offer some protection against vascular damage and diabetes complications. Endothelial progenitor cells (EPCs) are important for the repair and growth of blood vessels, with circulating numbers increased by exercise. However, the count of EPCs appear to be reduced in individuals with T1D. It is unknown whether residual ꞵ-cell function in individuals with T1D influences these circulating cells. Therefore, this thesis aimed to investigate the effects of residual ꞵ-cell function in individuals with T1D and its influence on glycaemic control under free-living conditions and after an acute bout of aerobic exercise, as well as on the count of circulating EPCs at rest and after exercise mobilisation. Chapter 3 demonstrated that under free-living conditions, increased endogenous insulin secretion was associated with improved continuous glucose monitoring measures, including increased time spent in euglycaemia. The results of Chapter 4 revealed that within a cohort who had comparable glycaemic control under free-living conditions, individuals with higher residual ꞵ-cell function displayed a substantially greater amount of time spent in euglycaemia in the hours following a bout of moderate intensity exercise compared to those with undetectable or lower endogenous insulin secretion. Lastly, Chapter 5 assessed the number of circulating EPCs at rest and after mobilisation with a bout of moderate intensity exercise. In comparison to matched non-diabetes controls, all markers of EPCs were lower in the T1D group, with some markers having attenuated mobilisation with exercise. Despite comparable resting counts, only the high residual ꞵ-cell function group had mobilisation of these cells with exercise within the T1D participants. In conclusion, the findings of this thesis demonstrate that residual ꞵ-cell function impacts upon individuals with longer duration T1D. Increased C-peptide secretion is associated with improved glycaemic control under free-living conditions and after an acute bout of exercise, as well as increasing the count of circulating EPCs that are mobilised with exercise.