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Metabolic diseases, such as obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD) are extremely common. In north-west London, with a diverse population of 2.4 million, there are 1.44 million people (60%) who are obese or overweight, 140,000 who have diabetes, and 600,000 (one in four) with NAFLD. Evidence has shown that the NHS spends around – around 10% of its entire budget.

Metabolic disease also affects cardiovascular health (heart attacks, strokes), neurological health (strokes, dementia), kidney disease and infectious disease. For example, the mortality from COVID-19 pandemic respiratory infection is magnified by obesity and diabetes.

For endocrine disease, this theme focuses uniquely on infertility and subfertility, which are linked to obesity. This condition affects one in seven couples in the UK and current treatments such as IVF are expensive and difficult to access through the NHS.

Our metabolic research focuses on diagnosis and treatment of obesity, diabetes and fatty liver disease and our endocrine research focuses on therapies for reproductive and other endocrine diseases.

Detailed Theme objectives can be found

• Novel hormones (Glucagon like peptide – 1 (GLP-1)/glucagon, kisspeptin, insulin) are effective treatments for NAFLD – we will look at early diagnosis and precision medicine approaches to NAFLD, using machine learning and artificial intelligence. We will develop new treatments (such as the hormones GLP-1/glucagon, kisspeptin, insulin) for NAFLD that help reduce fat in the liver.

• Interrogation of large clinical and genetic datasets will identify individuals at high risk of early-onset type 2 diabetes (T2D) and rapid progression to adverse outcomes – people of South Asian descent living in the UK are at a higher risk of developing Type 2 Diabetes at a younger age. This can lead to serious health problems like heart attacks, strokes, kidney failure, blindness, and amputations. We will look at early diagnosis and precision medicine approaches to improve outcomes using medical records from doctors to identify people who are at high risk of developing early-onset Type 2 Diabetes.

• Aptamer technology can be used for early and more precise diagnosis of subfertility in patients with obesity – infertility is difficult to diagnose because we can’t measure certain hormone changes. We will develop a tool that can measure these changes more easily and turn this tool into a tiny wireless sensor that can be implanted in the body.

• Weight loss interventions will improve fertility in people with obesity – obesity is a leading cause of infertility:

– Infertility in obese males is linked to sperm DNA damage – we will conduct the first randomised study of a low energy diet (LED) on sperm function in obese men as the first ever potential therapy for male infertility.
– Women with obesity often suffer from infertility. We will conduct a clinical study, looking at interventions such as diet, exercise and psychological support to optimise fertility and pregnancy, and to address the mental health issues facing women undergoing weight loss and fertility treatment.

Pilot Projects

Following an open call in the spring of 2024 the following pilot projects were funded from the Theme:

• Evaluation of Kisspeptin-54 as a test to improve the diagnosis and treatment of women who have irregular periods –
•  Understanding the impact of amylin receptor genetic mutations on the responses to new weight loss drugs –
• Avoidance of insulin-induced lipohypertophy in people with diabetes: A feasibility study of implementation of ultrasound scanning within diabetes clinics –
• Investigating Intranasal Kisspeptin as a Novel and Effective Delivery Route for Stimulating Reproductive Hormone Secretion in Humans –
• A state-of-the-art method for functional imaging of the brainstem and hypothalamus to accelerate treatment development for obesity and reproductive disorders –

Our theme will work closely with our newly recruited community partners who represent individuals based in north-west London who have lived experience relevant to our research areas. Community Partners will take on a strategic and governance role, advising us on ways to make our research more relevant and impactful, as well as helping us to engage and involve the wider north-west London.

Professor Waljit Dhillo (co-theme lead) co-wrote the Imperial BRC EDI policy. EDI will be a core part of all activities in the theme, including:

• Membership of the theme governance committee
• Appointment of all staff
• EDI consideration in presentations at theme meetings.