Reducing the risk of Type 2 Diabetes

Working with researchers in Leicester, they recruited 1,368 people – including more than 300 of south Asian ethnicity – to take part in the NIHR-funded PROPELS study.

Study participants all had blood glucose (sugar) levels that were higher than normal, and this put them at risk of developing T2D.

Participants were allocated to one of three groups. The first group received detailed advice on how to reduce their risk of T2D. The second group received the same information, a pedometer (step counter), encouragement to walk 2,000-3,000 steps more each day and an annual 4-hour education programme about diet and physical activity. The final group received all this plus follow-on support through personalised text-messaging and telephone calls to encourage behaviour change and monitoring of physical activity by a pedometer.

After 12 months and then again at 4 years, participants provided blood samples and their physical activity was measured. The data is being analysed and the results should provide new evidence for the long-term effectiveness of a tailored programme to reduce T2D risk in high-risk groups.

Reviewing the NHS Health Check programme

The NHS Health Check programme offers people information on how to reduce their risk and/or early treatment. Many of the recommended lifestyle changes also lower the risk of other diseases, such as cancer and lung disease.

Under the current ‘one size fits all’ guidelines, the checks are available to all apparently healthy people every five years until they reach 75. However, within this group some will be at higher risk of future disease and may benefit from earlier and more frequent health checks – while those at lower risk will need fewer checks.

To identify people with greatest health needs, researchers have been developing methods to use data from electronic health records (which all patients have), including measurements of the “risk factors” that are known to be linked with greater risk of disease. These include smoking, being older, being overweight, and having high blood pressure and high cholesterol.

GPs will be able to use this tool to estimate when individuals should next be invited for an NHS health check. This may help increase the cost-effectiveness of the programme while directly benefiting those at highest risk of future disease.

Predicting the breech baby

A baby is ‘breech’ when they have not turned to a ‘head down’ position for birth. When breech babies are spotted in the final stages of pregnancy, clinicians will attempt to turn the baby safely ready for a vaginal birth. Babies remaining in the breech position are usually delivered by caesarean to avoid the risks of breech delivery. However, not all breech babies are discovered before delivery under standard care.

Researchers wanted to investigate whether providing an extra scan late in pregnancy will help identify babies who are in a breech position earlier and reduce the risk of complications before labour or the number of emergency caesareans. Nearly 4,000 pregnant women were invited to have an extra ultrasound at 36 weeks. Almost 5 per cent of babies were found to be breech and in about half of these cases the baby had been thought to be in a head first position. Identifying these previously undiagnosed cases enabled clinicians to intervene or plan for a caesarean section. On day of delivery, there were no undiagnosed breech deliveries by women participating in the study. Women whose scans showed their baby was breech had their baby turned or delivered by planned caesarean.

Researchers used the Cambridge data to estimate what might happen if such a scan was introduced nationally. They showed that it could prevent ~4000 emergency caesareans each year in the UK and prevent 5-10 baby deaths. The findings led to questions in Parliament and the research team is working with the NHS makers policy to construct the case that late pregnancy ultrasound is part of normal care for pregnant women.

Investigating whether a cancer drug can help MS patients

MS is a chronic, degenerative auto-immune disease, where the immune system attacks the myelin (fatty protective cover) that surrounds nerve cells, causing disability.

At first, the body is able to rebuild the myelin (remyelination) but over time, the damage becomes harder to repair, causing progressive and permanent disability.

Currently, there are no treatments that can boost myelin repair in MS. Researchers in Cambridge and Edinburgh had already shown that Bexarotene targets a protein in the brain that encourages myelin repair. Encouraged by this result, a study has been set up to see whether the drug could help the brain regenerate myelin in people with MS.

Fifty patients took part in the nine-month trial, which ended in May 2019; will help researchers understand if Bexarotene has potential as an MS treatment. To stop MS we need to find treatments that repair the damage to the protective myelin coating around nerves.

Cambridge researchers supported by the NIHR Cambridge BRC are also looking at the potential of diabetes drug Metformin to promote myelin repair in patients with progressive MS. This trial is due to open in 2020.

How do our genes affect our weight

Researchers in Cambridge have discovered genetic variants (small changes in DNA) that help protect people from obesity, type 2 diabetes and heart disease. These findings could help researchers to develop drugs for people who have weight problems.

Obesity is a serious problem; it can lead to heart disease, type 2 diabetes, stroke and mobility problems.

Cambridge researchers studied a gene called ‘MC4R’ which is known to regulate weight by acting like an ‘off’ switch for appetite. By looking at samples from half a million volunteers in the UK, they found that in naturally lean people small changes in the MC4R gene were able to limit their appetite to prevent weight gain. They also found that some people had a version of the gene that defended against the risk of diseases associated with obesity such as type 2 diabetes and heart disease.

These findings help explain the genetics of why slim people have an advantage when managing their weight. The research could now help researchers to develop new treatments to help people reduce excess weight.

Testing whether an anti-inflammatory drug can help people with depression

In a nationwide study led from Cambridge, researchers will be testing a new anti-inflammatory drug, specifically designed to reduce levels of inflammation in the brain. Patients with depression will be asked to take the new drug or a placebo (a pill that is inactive) in addition to their regular anti-depressant medication for 8 weeks.

Researchers will then measure whether the new anti-inflammatory drug reduces depressive symptoms by asking participants to complete questionnaires. They will also collect blood and saliva samples, and take images of the brain using MRI, to understand more precisely how the drug works on the immune system and the brain.

This study is currently running in Cambridge and will shortly also be open for recruitment in London, Oxford, Cardiff and Glasgow. It is due to finish in 2022.

A swift ‘kick and kill’ for the HIV virus

A new approach to wake this latent virus and destroy it ‘kick and kill’ was the approach of researchers from Cambridge, Oxford and London. Cambridge developed a novel assay to detect whether the latent virus had been depleted, without which it would be difficult to validate any curative effect.

Clinicians, virologists, immunologists and molecular biologists ran a large clinical trial to try and eradicate HIV from infected patients.

The trial which lasted three years looked at 60 men recently diagnosed with HIV. All of them showed a good response to conventional therapy, however, the ‘kick and kill’ approach was not strong enough to reduce the amount of latent virus as measured by Cambridge researchers, and other, assays.

The study however has provided a benchmark from which to trial different combinations of therapies to tackle HIV and investigate new strategies to destroy dormant virus. Meanwhile patients continue to benefit from advances in suppressive therapy which, when successful is giving them a normal lifespan.

New test to help personalise IBD medicine

IBD is a term used to describe two conditions, Crohn’s disease and Ulcerative Colitis. These lifelong illnesses mostly affect young adults and flare at intervals, producing debilitating symptoms including cramping abdominal pains, anaemia, weight loss and diarrhoea.

Previous Cambridge research showed that studying an immune cell called a CD8 T-cell could help doctors to identify which patients would go on to experience more aggressive disease and which patients would have a better outcome. This initial technical approach, however, is too complicated to be performed in routine clinical use.

Looking at nearly 70 people with the condition, the team developed a simpler blood test – using a method that is widely available in the NHS called  qPCR – to identify the same patient subgroups as were found using the more complicated CD8 T-cell test.

They found the test was able to predict the strength of the condition in the patient and a patient’s likely outcome. This research can now help newly diagnosed people with IBD to identify the strength of their disease and enable their doctors to provide a personalised treatment plan – ensuring they receive the medication that is right for them, rather than a ‘one size fits all’ approach.

The research has been so successful that the test has been licenced by Cambridge Enterprise to a company, PredictImmune Ltd, who are making it available to patients in the UK to provide better outcomes, while in parallel it is being assessed by NICE to determine whether they recommend it can be used in the NHS.

How a chance meeting inspired a rare disease research project

This was the question a mum of a daughter with the rare inflammatory bone disease CRMO asked rheumatologist Dr Jagtar Singh Nijjar at the Rare Disease Day evening lecture, which took place in 2017.

Two years on, Dr Nijjar gave a talk at the 2019 Rare Disease Day evening lecture, hosted by the NIHR BioResource and the Cambridge Rare Disease Network, about what followed from that chance meeting.

Listen to this edited transcript of his talk (3:13 mins). Click to listen to the full lecture.

Cambridge researchers develop new tool to map beginnings of heart disease

Researcher Dr Dirk Paul said: “We previously discovered that certain gene variants are more common in people with heart disease. Now the challenge is to find out how exactly these gene variants contribute to the risk of heart disease.”

Using stem cells from 200 healthy volunteers, the team grew them in the laboratory into macrophages, which are specialist cells responsible for sweeping up harmful particles, such as cholesterol in the arteries.

Dr Paul said: “Macrophages are part of the biological machinery that clears away fatty material inside the arteries – but in individuals who carry these gene variants, the machinery doesn’t work properly leading to a build-up of cholesterol.

“This in turn leads to atherosclerosis, the condition that causes most heart attacks and strokes.

“We fed the macrophages with cholesterol and then studied them in minute molecular detail to see what happened. This will improve our understanding of how atherosclerosis develops.

“This new approach will help us see how the gene variants affect disease risk and translate this knowledge into new treatments.”

Well-planned patient preparation before their scans improves imaging quality and cancer detection rates

Multiparametric magnetic resonance imaging (mpMRI) is a special type of scan that creates more detailed pictures of the prostate. It plays an essential role in the diagnosis of prostate cancer (PCa), and can help doctors decide if tumours are clinically significant (that is, likely to impact on a patient’s life and therefore needing treatment); it is now performed in up to 75% of men with suspicion of PCa in the UK.

Existing guidelines on its use, while they address technical hardware and software and diagnostic considerations, have not to date adequately covered patient-related factors which also can affect the quality of the imaging.

This review from Cambridge radiologists Dr Tristan Barrett and Dr Iztok Caglič looked at how some simple steps can help to further optimise the image quality of mpMRI.

Before mpMRI the authors therefore recommend:

  • Using antiperistaltic agents to minimise spasm in the intestines and associated movement (which can result in blurring of image)
  • Asking patients to empty their bowels prior to examination to minimise image distortion
  • Asking patients to refrain from ejaculation for three days before their scans
  • Using an additional scan sequence called PROPELLER to improve image quality in patients with hip metalwork.

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