Humans of health research

Dr Shivani Misra is a Consultant Physician in Diabetes & Metabolic Medicine at Imperial College Healthcare NHS Trust and an Honorary Senior Clinical Lecturer in the department of Metabolism, Digestion and Reproduction at Imperial College London.

Dr Misra’s research focuses on rare types of diabetes, such as maturity onset diabetes of the young (MODY) – a genetic form of diabetes that runs in families and is caused by a mutation in a single gene. 

“When I was a registrar working in a Charing Cross diabetes clinic I frequently saw people from South Asian or African Caribbean ethnic backgrounds who were labelled as having type 2 diabetes but when you dug deeper there were features in their history and presentation that didn’t fit for example, being relatively lean and diagnosed at young age. We would often discuss these cases in our post-clinic meeting with consultant colleagues and wonder if they could have MODY.

“When I examined the scientific literature about the prevalence of MODY in ethnic minority groups, I realised it was rarely reported and there was a real knowledge gap. I wanted to do a PhD and I thought – this is a good research question to answer.

“I applied for funding and was awarded a one year fellowship from the Imperial Health Charity which I used to get some data on how many people had MODY.

“We recruited about 30 people initially from south Asian ethnic backgrounds in our local area and we did find some MODY cases that had been misdiagnosed.  We used this data to apply for funding to expand the study. I secured a bigger three year PhD Fellowship from the Diabetes Research & Wellness Foundation to look for MODY in people from Black and South Asian backgrounds across the UK. The National Institute for Health and Care Research Imperial Biomedical Research Centre (NIHR Imperial BRC) provided the infrastructure support.

“Our study recruited over 1700 people and found that cases of MODY  were being missed in South Asian and African Caribbean individuals compared with white European individuals.  People misdiagnosed may not be getting the right treatment, which depends on the gene affected, so we now need to improve selection of the right cases for genetic testing.

“One of the most rewarding aspects of this research is that it helped support set up a special genetic diabetes service at St Mary’s Hospital where cases of MODY are being identified more accurately and which has grown to accommodate other people with unusual and rare forms of diabetes such as my patient Rodney Brooks.

“Looking back at the project, a lot of people said ‘I think you are really going to struggle to recruit’; there is a stereotype that people from ethnic minority backgrounds are less engaged in research. I have to say that I saw the compete opposite. We set out to recruit across the whole of London and at the peak we were recruiting at 40 NHS Trusts across England.  There was a phenomenal response from people of south Asian and African-Caribbean heritage in the UK.

“I think improving diversity in clinical studies is extremely important.  I find it a bit frustrating when the next latest advance is reported on and it was studied in an exclusively white European population. Of course we must start somewhere, but we need to ensure that there is sufficient diversity in clinical research studies to reflect the population we are trying to help.

“One of the things I enjoy about research is being able to give a participant information that they didn’t have before, that they have only got because they have participated in the research, and that information either fills a knowledge gap they had about their diabetes, changes how they feel about their diabetes or changes their treatment. That is extremely powerful for me and the MODY project has been very rewarding in this regard.”

Rodney Brooks has a very rare type of diabetes called Type B insulin resistance, which is an autoimmune disorder. It is so rare that the number of cases are unknown but is estimated to be fewer than 100 worldwide. 

Autoimmune diseases arise when the immune system mistakes parts of the body as being unfamiliar and mounts an immune response against the body’s healthy cells, tissues, and organs damaging function.  People with type B insulin resistance develop antibodies that block the insulin receptor and this results in high blood sugars that are hard to control, even with very high doses of insulin and it can be a life-threatening condition.

When presented with rare diseases, patients and healthcare teams must work collaboratively to decide on the best treatment approach because guidelines are usually not available and key knowledge may only be available from small research studies.

For Rodney this meant regular meetings between him and his clinical team members with review of the scientific literature and discussions with collaborators.

“I met Dr Shivani Misra four years ago when I was admitted to Hammersmith Hospital with very high glucose levels and doctors couldn’t control it even with intravenous insulin. Dr Misra was called over because of her expertise in rare diabetes.

“It was a very challenging time as I was called in on Christmas Eve 2018 and was frustrated by my condition and not being in control of when I could leave hospital. 

“I was given hundreds of units of insulin per day but my glucose levels were stuck between 25-30 millimoles per litre which is extremely high.

“Dr Misra and her team decided the best approach to manage my condition was to give higher strength insulin, which is imported from abroad. She prescribed over 1000 units of insulin per day, with the hope that it would override my system and bring my blood sugars down. I didn't realise this at the time but this was a huge dose of insulin compared to typical doses used to treat type 1 or type 2 diabetes.  

“I realised how important research was for people with rare diseases – had other doctors not published case reports on this condition, we would not know what had worked or what to try. 

"I learnt that my condition is more common in people from Black backgrounds, for example. With my type of diabetes there aren’t any clinical guidelines so Dr Misra had to review published studies and also discussed with scientific collaborators around the world to develop a plan personalised for me.

“It was frustrating initially to know my condition was rare but I was happy to go along with treatment plans because I trusted the team and I understood that options were limited.

“As part of my initial treatment plan, I would get advice from Dr Misra about insulin doses to take with my meals per day and her team also applied for funding for continuous glucose monitoring as people with my condition are at risk of low glucose levels. With time, I was able to adjust my doses independently. 

“The best part was seeing my glucose level gradually come under control and the numbers come right down from where it was, to a near normal level.  It was life changing.

“My condition continues to evolve and there are times where my treatment plans have had to change as result.  It will always be an ongoing process managing my condition but being in a research active clinic that has expertise in rare diseases, I have learned lots of things about myself, my body, and the way it responds to insulin treatment.”

Dr Sumeet Hindocha is a Clinical Research Fellow in the Department of Surgery & Cancer at Imperial College London and a Clinical Oncology Specialist Registrar at the Royal Marsden Hospital NHS Foundation Trust. 

Dr Hindocha’s research focuses on machine learning methods to predict lung cancer patients at risk of their cancer returning, following treatment.

“I am a PhD candidate at the Artificial Intelligence for Healthcare centre for doctoral training at Imperial College London.  My research is looking at how we can use artificial intelligence to predict which patients are at risk of their cancer coming back after they have radiotherapy treatment for non-small cell lung cancer.

“Lung cancer is the leading cause of cancer deaths around the world and 85 per cent of all lung cases are attributed to non-small lung cancer.

Lung cancer is curable if detected early enough but in up to 36 per cent of patients their cancers return.  If we can identify patients which are at risk of their cancers coming back, we can personalise their follow-up and hopefully detect the recurrence sooner. We can then offer these patients the next line of treatments and hopefully improve their outcomes.

“As a doctor you have the privilege of helping the patient in front of you and those who are in your waiting room. However, research offers you the opportunity to potentially  positively impact the lives of hundreds of thousands of patients around the world. You can contribute to something which has a much bigger reach and it is a really rewarding thing to participate in.

“It also offers variety and that’s something I really value in my job.  No one day is the same in my working week.  Another thing that attracted me to research is that it is a team sport, as you have the opportunity to work with colleagues across different academic and clinical fields, as well as patients.  What I have enjoyed is meeting so many different people who all have the same values, goals and are contributing different work to meet a shared vision.

“A recent research highlight for me was having my paper published in the Lancet’s eBioMedicine Journal.  It was really rewarding to see our hard work in print.  Not only that, but soon after, a friend who works in another hospital told me that my paper had just been discussed in their journal club. It was great to hear of other academics valuing my contribution. Another highlight is when you hear patients’ stories on how much they value the impact of research, it’s things like this that make you want to keep going.

“The end goal of my research is to have something in the clinic that other doctors can use to help identify and support patients that are at risk of their cancer returning.  I don’t think my research is finished until we reach that goal.”