Metabolism, endocrinology and bone

Key areas of focus

  • Research into causes of obesity, insulin resistance and related conditions; translation of new knowledge into advances in treatment and prevention, including establishing an NHS England service for people with severe insulin resistance
  • Pioneering the development of the ‘artificial pancreas’ in Type 1 diabetes that automatically replaces missing insulin in exactly the amount required to control glucose levels.
  • Advancing the diagnosis and treatment of endocrine diseases including tumours of endocrine glands such as the pituitary and adrenal

Welcome to the Metabolism, Endocrinology and Bone theme. Our research is helping to translate basic scientific research into real advances in understanding, treatment and prevention of human
metabolic, endocrine and musculoskeletal diseases.

We work on common conditions such as obesity and diabetes, which are responsible for widespread, major health problems. We also research rare diseases that can have devastating consequences such as lysosomal storage disorders, extreme insulin resistance and congenital hypothyroidism. Our research into musculoskeletal diseases including arthritis and osteoporosis helps to advance treatments for back and joint pain – the main cause of work related illness in the UK.

A main link between obesity and ill health is a significant increase in the likelihood of developing Type 2 diabetes, insulin resistance and cardiovascular disease. Our investigators have identified several genetic causes of obesity, including defects in genes which normally act in the brain to control appetite and energy balance. Together with advances in behavioural neuroscience these studies highlight the crucial role of the brain and specifically the hypothalamus in regulating appetite and satiety.

Insulin resistance, in which people are unable to respond normally to insulin, is a major link between obesity and diseases such as Type 2 diabetes, fatty liver disease, coronary artery disease and some cancers. Our theme has world-leading strengths in the genetics of both common and rare forms. Detailed physiological studies are also helping us understand why these genetic changes lead to insulin resistance, to aid development of preventative strategies and therapies. We have also developed expertise in conditions where insulin signalling is excessive in parts of the body leading to disfiguring overgrowth syndromes.

In Type 1 diabetes the pancreas is unable to produce insulin. Our team is pioneering the development and use of the ‘artificial pancreas’. This replaces the missing insulin in exactly the amount required to control glucose levels, for example reducing the risk of night-time hypoglycaemia. In collaboration with industry partners, we have developed a prototype system that is being tested by people in their own homes.

Endocrine disorders affect up to 10% of people in the UK, with thyroid problems being particularly common. Our Theme has established a world-leading centre for evaluating unusual forms of thyroid disorders, including discovering new genetic causes and using this information to develop novel therapies. We have also developed novel imaging techniques with the potential to greatly improve diagnosis and treatment of pituitary and adrenal tumours.

Osteoporosis is the major risk factor for disabling fractures that cost an estimated £1.8 billion annually. Our research has led to the development of novel imaging tools to identify people at high risk of osteoporotic fracture and predict the likelihood of developing osteoarthritis. These tools are being tested to determine their effectiveness in ‘real world’ situations.

Lysosomal storage diseases such as Tay-Sachs and Sandhoff are rare, recessive disorders resulting in severe mental retardation and early death. The work of our theme has led to improvements in how these diseases are diagnosed and managed. While there are no effective treatments yet, we are working to develop novel forms of gene therapy.