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Title: Effects of testosterone levels on mortality and cardiovascular risk in men with Type 2 diabetes
Author: Muraleedharan, Vakkat
ISNI:       0000 0004 7431 1450
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2018
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There is increased prevalence of low testosterone level in men with type 2 diabetes. There is growing evidence that low testosterone levels has adverse cardio-metabolic outcome in the long term. The mortality and morbidity in men with type 2 diabetes and low testosterone has not been studied previously. Chapter 1 reviews the relationship between low testosterone and cardiovascular mortality and morbidity and discusses about metabolic pathways which could be affected in low testosterone state. Chapter 2 is the first study to look into the mortality of type 2 diabetic men with low testosterone. The results demonstrated an increase in mortality with low testosterone state and a beneficial effect of testosterone replacement therapy in hypogonadal men with type 2 diabetes on long-term follow up. Chapter 3 and 4 looked at the longitudinal and cross sectional studies studying the effects of low testosterone on cardio-metabolic risk profile. The results demonstrated an adverse cardiometabolic risk profile in type 2 diabetic men with low testosterone and an inverse relationship between the SHBG levels and cardio-metabolic risk profile in men with type 2 diabetes independent of testosterone levels. Chapter 5 examined at the relationship between androgen receptor sensitivity as assed by CAG repeat polymorphism (AR CAG) and cardio-metabolic risk profile in men with type 2 diabetes. The results showed no significant direct relation between AR CAG and cardiometabolic risk profile. However there was a significant correlation between the ratio of testosterone and AR CAG (T/AR CAG or BioT/ CAG) and cardio-metabolic risk profile with the higher ratio predicting favourable cardio-metabolic profiles for glycaemic control and anthropometric measurements. In chapter 6 the different effects of testosterone on metabolic pathways in key tissues were investigated using testicular feminised mouse (Tfm) model which has an inactive AR and low circulating testosterone levels. The results demonstrated that a low testosterone state was associated with adverse cardio-metabolic profile by affecting major enzymes and receptors involved in the carbohydrate and lipid metabolism in liver, muscle and adipose tissues. Physiological replacement of testosterone partially reversed the expression of some of these parameters which provide evidence that some of the actions of testosterone in metabolic pathways are independent of androgen receptor. Chapter 7 draws together the results and conclusions are discussed.
Supervisor: Jones, Thomas Hugh ; Ross, Richard Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available