Clinical implications of persistent beta cell function in long duration type 1 diabetes

Abstract

Type 1 diabetes was thought to be a disease of absolute insulin deficiency. However, recent evidence has shown that most people with Type 1 diabetes have persistent endogenous insulin production, even those with long disease duration. Close to diagnosis preserved beta cell function is associated with reduced HbA1c, hypoglycaemia and complication rates. However, very little is known about the clinical impact of persistent endogenous insulin in long duration diabetes. This thesis aims to assess the clinical impact of preserved beta cell function in long duration type 1 diabetes.

During this analysis we identified the potential for glucagon to be used as a biomarker of hypoglycaemic risk. Intensive treatment is an integral part of diabetes management and is key to reducing the risk of both development and progression of microvascular complications. However, treatment induced hypoglycaemia poses a significant barrier to intensive treatment. Currently, prediction of those most at risk of hypoglycaemia is based on clinical information, such as diabetes duration, with no biomarkers used to assess hypoglycaemic risk. As such, this finding prompted an additional aim: to investigate the relationship between meal stimulated glucagon and hypoglycaemia in long duration type 1 diabetes.

In Chapter 1 I review current evidence on the role and importance of persistent beta cell function in type 1 diabetes.

In Chapter 2 I outline the methods of the TIGI Study, which provided the data for this project.

In Chapter 3 I demonstrate that preserved beta cell function is associated with significantly reduced reported hypoglycaemia in long duration type 1 diabetes.

In Chapter 4 I show that higher meal stimulated glucagon is associated with reduced hypoglycaemia rate in long duration type 1 diabetes, independent of HbA1c, C-peptide and disease duration.

Chapter 5 discusses the findings of Chapters 3 and 4 and highlights areas for future research.