Age of diagnosis as a factor in the heterogeneity of type 2 diabetes: a clinical and molecular study

Abstract

The age range at which type 2 diabetes develops has recently expanded. Thus chronological age and age of onset are now important variables in this already heterogeneous disease. The increasing prevalence of early-onset diabetes in particular raises clinical and societal concerns. Such individuals have a longer life-time disease duration and potentially can develop more diabetes related complications, at a relatively young age, perhaps during the most productive periods of their lives. The determinants of, and impact on outcome of age of onset as a clinical variable are unclear. Therefore studies using both clinical data and molecular techniques are employed to answer questions in this area.

Whether the factors that impact on the development of type 2 diabetes are specifically different for those with younger onset as compared to older onset disease is not clear. By way of three studies, the first part of this thesis explores the general question of ‘what determines the age of type 2 diabetes onset?’

The specific impact of the metabolic syndrome, insulin resistance and body weight on the age of type 2 diabetes onset is examined in two different ethnic groups. This is in recognition of the paucity of specific data in this area and the differing prevalence of the metabolic syndrome in different ethnicities. This is examined in Chapter 2. The ‘accelerators’ of disease onset were quite different, dependent on ethnicity. Weight, insulin resistance and a high prevalence of the metabolic syndrome are associated with early-onset disease in Anglo-Celtics, but not so in Chinese. The mechanistic and public health implications of these observations are discussed.