Mental health and the progression from normal glucose levels, to prediabetes, and to type 2 diabetes

Type 2 diabetes is a chronic state of elevated blood glucose that leads to the destruction of the insulin-producing beta cells of the pancreas. According to the International Diabetes Federation (2019), type 2 diabetes affects approximately 9% of the global population, with approximately half of diabetes cases being undiagnosed. The prevalence of T2D is projected to continue to increase in Europe and around the world (Global Burden of Disease Study 2013 Collaborators, 2015; Whiting, Guariguata, Weil, & Shaw, 2011). The global prevalence of prediabetes, a subthreshold state of heightened blood glucose that can begin more than 10 years prior to the onset of type 2 diabetes, is approximately 7.7%, and thus almost 17% of the population have impairments in glucose control. Prediabetes, a condition characterized by blood glucose levels that are above the normal range but that do not reach the threshold for a diagnosis of type 2 diabetes, is a well-established risk factor for type 2 diabetes (Bonora et al., 2011) that is also increasing in prevalence (Mainous, Tanner, Baker, Zayas, & Harle, 2014). Though not everyone with prediabetes will develop type 2 diabetes, reported rates of progression from prediabetes to type 2 diabetes have been estimated at around 11% annually (Knowler et al., 2009). Identifying predictors of the progression from prediabetes to type 2 diabetes could have important implications for reducing the incidence of type 2 diabetes. 
Mental health conditions such as depression and anxiety have been shown to accelerate the progression from prediabetes to type 2 diabetes. Among people with prediabetes, the likelihood of reverting to normal glucose levels can be increased with healthy lifestyle changes (Knowler et al., 2009; Tabak et al., 2012). However, lifestyle behaviours such as smoking, unhealthy eating habits, and physical inactivity are common in people with depressive and anxiety symptoms (Strine et al., 2008) and depression/anxiety symptoms might increase the risk of progressing from prediabetes to type 2 diabetes. Stress associated with depression and anxiety might also lead to biological changes and increase the likelihood of developing prediabetes or progressing from prediabetes to type 2 diabetes (Rosmond & Björntorp, 2000). We have previously shown that depression and anxiety moderate the association between prediabetes and the progression to T2D in a sample of middle-aged adults (Deschênes, Burns, Graham, & Schmitz, 2016). However, many knowledge gaps remain, as the biopsychosocial mechanisms for these associations are lacking and it is not clear if these associations exist in younger or older adults. In particular, there is a lack of information about how mental health and psychosocial factors influence this transition at an earlier stage, when glucose dysregulation begins to appear and when reverting to normal glucose levels is most likely to be achieved. Poor cognitive functioning is also associated with type 2 diabetes (Umegaki, 2014) and recent cross-sectional evidence suggests that cognitive impairment is evident amongst adults with prediabetes (Dybjer, Nilsson, Engström, Helmer & Nägga, 2018). However, it is unknown if prediabetes status interacts with cognitive status to increase the risk of developing incident type 2 diabetes.  
The goal of the study is to examine the interaction between prediabetes status and mental health (depression/anxiety and cognitive function) at baseline and the risk of developing prediabetes or type 2 diabetes during the follow-up period. The present study will allow us to examine the prospective associations between mental health, prediabetes, and type 2 diabetes in adults from age 18 onwards, with age-stratified analyses. We will also be able to examine a broad range of potential biopsychosocial mechanisms for these associations.