Characterisation of Turner Syndrome with focus on the pathogenesis of diabetes mellitus

Introduction: Turner Syndrome (TS) is a complex condition, affecting every system in the body (Elsheikh, Conway, & Wass, 1999; Gravholt et al., 2017). Caused by a complete or partial lack of one X chromosome TS is associated with a variety of morbidities such as diabetes mellitus (DM). A literature review found that DM is poorly characterised in TS and DM risk is reported to be higher than that of females in the general population (Gravholt, Juul, Naeraa, & Hansen, 1998). The results from glucose homeostasis reports have been conflicting reporting both insulin deficiency (V. K. Bakalov et al., 2004) and resistance (Salgin et al., 2006) to be the mechanism behind pathogenesis as well as a possible association with the isochromosome karyotype (V. K. Bakalov, Cheng, C., Zhou, J., and Bondy, C.A., 2008). Furthermore, those with established DM have often been excluded from analysis and therefore remain largely unexplored. The overall aim my doctoral research was to identify the factors involved in TS-associated DM using a multipronged approach. Methodologies A series of methodologies were implemented to address the characterisation of the DM phenotype experienced by women with TS. Studies 1 & 2 Statistical characterisation of adult health parameter data derived from the Turner Syndrome Life Course Project against; karyotype, paediatric treatments and long-term oestrogen use. Study 3 A prospective study of the characterisation of glucose homeostasis and DM-risk factors in affected and women with an unknown DM status. Study 4 Pilot array study of T2DM-associated SNP to assess if there was an over-represented in those with Impaired Glucose Tolerance or DM. Conclusions TS-associated DM was found to have a unique profile that has features of both T2DM and LADA such as genetic influences, insulin resistance and a degree of autoimmunity.