We take a look at some of the exciting diabetes research developments announced in August, and what the findings could mean for people living with or affected by diabetes.
In this month's article:
- Why insulin-making cells fail in type 2 diabetes
- Uncovering new ‘core’ proteins for type 1 diabetes
- Identifying the most important prediabetes research questions
Why insulin-making cells fail in type 2 diabetes
Scientists in Barcelona have uncovered a new reason why the pancreas struggles to make enough insulin in people with type 2 diabetes.
Type 2 diabetes develops for many complex reasons, but our genes are one important contributor. This new study focused on a gene called HNF1A.
The researchers discovered HNF1A plays a crucial role in keeping hundreds of other genes that support insulin release working properly. When they deactivated HNF1A inside beta cells, this chain of command collapsed, causing insulin production to fail.
When the team studied human pancreas tissue, they found that people with type 2 diabetes had around eight times more dysfunctional beta cells with low HNF1A activity compared to people without diabetes.
These findings reveal a hidden control system inside beta cells that may explain why they fail in type 2 diabetes. It suggests looking for problems with HNF1A could help spot people at higher risk of type 2 diabetes earlier. The findings also offer hope for new treatments designed to repair this faulty system and restore the beta cell’s ability to produce insulin.
Mutations in HNF1A can also cause a rarer form of genetic diabetes called Maturity Onset Diabetes of the Young, or MODY. So, these discoveries may help to inform new approaches to its treatment as well.
Uncovering new ‘core’ proteins for type 1 diabetes
The causes of type 1 diabetes involve a complex mix of genetic factors combined with environmental triggers. With our funding, Professors Helen Colhoun and Paul McKeigue at the University of Edinburgh have previously identified nine ‘core’ genes linked to the immune system that directly and strongly influence the risk of developing type 1 diabetes.
But that’s only part of the picture. In the body, genes can act as commanders, issuing instructions. Their messages are translated into proteins, which actually carry out the functions. The team’s next step was to identify the ‘core’ proteins that could be at the root of type 1 diabetes.
In their latest Diabetes UK-funded study, the researchers analysed data from more than 420,000 people, both with and without type 1 diabetes. They looked at how small differences in people’s genes influence the levels of more than 5,000 proteins in the blood. They then compared those protein levels in people with and without type 1 diabetes.
The researchers identified 27 proteins that appear to play a direct role in the development of type 1 diabetes. Interestingly, although these proteins seem to be important contributors to type 1 diabetes, only one of them – called PDCD1 – had been linked to the condition before.
Several of the proteins showing the strongest link with type 1 are key components of the immune system itself. Some others – including PDCD1 – are known as immune checkpoints. They act as brakes to prevent the immune system from overreacting and attacking the body’s own tissues.
These findings point to new potential immunotherapy drug targets for treating or even preventing type 1 diabetes. If we can fix or block those proteins, we might stop the immune system’s attack. Drugs that activate PDCD1 to restore immune balance are already in development for other autoimmune conditions, and this study suggests they may also be worth testing for type 1 diabetes.
Identifying the most important prediabetes research questions
Researchers in Denmark have pinpointed the most important research questions in prediabetes, according to people living with prediabetes or type 2 diabetes, their families, researchers, and healthcare professionals.
Prediabetes is when blood sugar levels are higher than usual, but still below the diabetes range, and people are at higher risk of developing type 2 diabetes. An estimated 6.3 million people in the UK are living with prediabetes.
The researchers ran a Priority Setting Partnership (PSP). This is a rigorous way to collect the views of people affected by health conditions and use them to set the direction of future research. 405 people took part in the prediabetes PSP.
Their input was used to narrow down to a top 10 priority questions:
- What are the best ways to prevent type 2 diabetes, and will intervening earlier mean less people develop the condition?
- Why do people with prediabetes progress to type 2 diabetes and can this knowledge be used to tailor treatments to different groups?
- How does our biology, like blood pressure, cholesterol, hormones, weight, age, and gender impact the development of prediabetes and progression to type 2 diabetes?
- Which non-medical approaches are most effective at preventing type 2 diabetes and when should they be used?
- How can we target dietary advice and nutrition guidelines to people with prediabetes that are simple to follow and easy to use in the long-term?
- How do different types of pharmaceutical treatments, like diabetes medications and weight loss medications, affect the development of prediabetes and long-term complications?
- How can we improve management of prediabetes, and can collaboration among medical doctors, nurses, dietitians and other relevant people, improve prevention?
- Can temporary use of continuous glucose monitoring (CGM) help people living with prediabetes to better understand how diet and physical activity impact their blood sugar levels, helping to prevent progression to type 2 diabetes?
- Can prediabetes screening be targeted to people who are at high risk of the condition to improve early identification of prediabetes, and how can screening methods be used in the clinic?
- What links exist between other conditions and prediabetes, including autoimmune and hormone conditions?
The researchers also shared the top 10 list with people representing the UK, USA, Netherlands, Sweden, and Denmark. They scored the questions similarly to the Danish study, suggesting that the list is relevant globally.
Researchers, funders, and the healthcare industry should now work together to help answer the top 10 questions, to make sure future research will make the greatest possible difference for people with prediabetes. This could transform their long-term health and prevent them progressing to type 2.
