The Clinical Utility of Zinc Transporter 8 Autoantibody Measurement in Diabetes

Abstract

Maturity onset diabetes of the young (MODY) is caused by single gene mutations that are of autosomal dominant inheritance. Mutations are highly penetrant, and patients often develop a phenotype similar to type 1 or type 2 diabetes. Glucokinase, Hepatic nuclear factor 1a and 4a mutations consists of 80% of MODY cases. Approximately 1% of patients with diabetes have MODY, and it is often misdiagnosed. Diagnosis is important as patients with MODY often have a good prognosis and glycaemic control if they are treated appropriately. The aim of this thesis was to explore the use of islet autoantibodies, in particular a new autoantibody against Zinc Transporter 8, as biomarkers to identify MODY.

A literature review of MODY and its important subtypes are discussed. It highlights the major mutation that cause MODY and the management of patients with MODY is also explored. Islet autoantibodies will also be reviewed in the same chapter, with a discussion on established autoantibodies and ZnT8 autoantibodies in relation to type 1 diabetes.

Chapter 1 aims to investigate whether ZnT8 autoantibodies are similar to established autoantibodies against GAD and IA-2 as a biomarker in differentiating T1D patients from MODY patients. The prevalence of ZnT8 autoantibodies in MODY patients and the effect of disease duration on antibody prevalence and discriminative power would also be investigated.

In Chapter 2, a study was performed to investigate whether islet autoantibodies are useful in the MODY referral setting in ruling out patients for genetic testing. This is a way to rationalise genetic testing at the Exeter molecular genetics referral service. Additionally, other biomarkers will also be investigated, namely C-peptide levels and Type 1 Diabetes Genetic Risk score. Results from the study will have implications to how MODY is diagnosed at the referral service.

A discussion of the findings of each chapter, implications and plans for future research will be explored in chapter 3.