Last week saw the 80th American Diabetes Association Scientific Sessions draw to a close. It’s the biggest meeting of diabetes researchers and healthcare professionals anywhere in the world, and this year it looked a little different.
12,500 attendees came together virtually to share the very latest on better treatments, advances in care and support for people living with diabetes, and new insights into the complexity and causes of all forms of the condition.
Replacing what’s lost in type 1 diabetes
The ADA kicked off with a session on one of the most promising new treatments on the horizon for type 1 diabetes – beta cell replacement.
If we could replace the insulin-producing beta cells that are destroyed in type 1 diabetes, we could help people make their own insulin again and take a massive step towards a cure. But there’s two big challenges to getting there. Although transplants using cells taken from donors already exist, there aren’t nearly enough donor cells to help everyone who could benefit. And secondly, the immune system in people with type 1 diabetes is primed to attack new beta cells.
Scientists are already making impressive progress to solve the supply problem. They’re finding ways to grow a potentially unlimited supply of beta cells in the lab, using stem cells that can be coaxed into becoming any type of cell in the body. But if these newly created beta cells are to be of any use, they need to be protected from the immune system. Dr Audrey Parent, at the University of California, gave us an update on her work that’s hoping to do just this.
A group of genes, called HLAs, are responsible for speaking to our immune system. Dr Parent is hoping to silence beta cells by genetically modifying them so that they’re missing most of their HLAs. This could allow them to fly under the immune system’s radar.
Dr Parent and her team tested if the genetically modified beta cells fare better than cells that haven’t had HLAs deleted. They transplanted the different types of beta cells into mice. After 14 days, in mice that received non-modified cells the researchers start to see a decline in the quantity of cells. This became more pronounced by 28 days. But cells with deleted HLAs did not show the same decline – more of them survived suggesting they’re protected against the immune response.
This is very early stage research. Dr Parent explained we need to explore this further with more mice and over a longer time. But so far this approach is looking promising as a potential way to 'shield' beta cells and move us closer to a cure for type 1 diabetes.
An extra three years free from type 1
Flash back to a year ago, the research world was a-buzz when TrialNet researchers announced the results of their breakthrough type 1 prevention trial. They showed that an immunotherapy drug, called teplizumaub, could delay a diagnosis of type 1 diabetes by two years, in people who have a very high risk of developing the condition. You can read more about the trial and their first results here.
At this year’s ADA, the TrialNet team gave us an update on what has happened since. They’ve now followed participants for an average of 912 days and they’re continuing to see an effect. Those taking the drug were less likely to progress to a diagnosis of type 1 diabetes than a comparison group who were given a dummy (or placebo) drug.
Their latest result show that 78% of people in the placebo group were diagnosed with type 1 diabetes during the trial, compared to 50% of participants who were treated with the drug. The median (a way of measuring the average) time for people in the placebo group to develop clinical type 1 diabetes was 2 years, while the median time in those taking teplizumab was 5 years. That’s an extra 3 years free from testing your blood sugar, carb counting, injections, hypos and the emotional toll of living with type 1 diabetes.
The TrialNet team also studied what happened in the pancreas. All of the participants started off producing similar levels of their own insulin, and were generally showing a decline in insulin production before any treatment was given. But just three months after receiving teplizumaub, the researchers saw a striking reversal of this loss of insulin production. But for people in the placebo group, insulin production continued to fall. This suggests the drug is having an early effect on preserving beta cell function.
There are still many questions, and we’re not talking about preventing type 1 diabetes entirely yet. But this research is an incredible step forward. It shows us that the course of type 1 diabetes can be altered and provides real hope for other immunotherapy research.
Turning the clock back on type 2
In type 2 diabetes the body stops responding to insulin, beta cells stop working properly and they lose their ability to produce insulin over time. But Dr Domenico Accili, of Columbia University, is asking if there’s a way to reverse this progression.
Beta cells are built to do very specific job – to produce insulin. Dr Accili explained that as type 2 progresses, beta cells go through a process known as dedifferentiation. They either revert into a less mature type of beta cell, which doesn’t have the right building blocks to be able to make insulin. Or they turn into another type of cell found in the pancreas, called an alpha cell, which again means they can’t make insulin.
To work out how we might be able to reverse this process, Dr Accili and his team first explored what drives beta cells to lose their function. They studied transcription factors – proteins that help turn genes ‘on’ or ‘off’ and identified some that seem to play an important role. As a next step, they performed experiments to find out if any of these proteins could bring beta cells, taken from people with type 2 diabetes, back to their former glory. And a couple of candidates showed real potential. One, called BAH2, could restore beta cells back to their fully mature, insulin-producing state. Another, called AFF3, helped convert alpha-like cells back to beta cells.
Dr Accili told us he feels hopeful – we can reverse beta cell failure in the lab. There’s more to understand and much more research to be done to apply this to people with type 2 diabetes. But it opens up the possibility of life-changing therapies that could one day cure the condition.
New treatments to prevent type 2
Results announced at the ADA from the eagerly anticipated DAPA-HF trial revealed that a drug used to treat type 2 diabetes may also help to prevent the condition.
DAPA-HF originally set out to investigate if an SGLT2 inhibitor, called dapagliflozin, could benefit people with chronic heart failure. The trial involved people with and without type 2 diabetes. As a sub-study, the researchers followed those who didn’t have the condition. They wanted to know if, along with protecting against heart damage, the drug could help to prevent type 2 diabetes.
Around half of the 2,600 participants without type 2 diabetes took a daily dose of dapagliflozin for 18 months. The other half received a placebo drug. The findings showed that dapagliflozin reduced new-onset type 2 diabetes by 32%. 4.9% of people in the dapagliflozin group (64 of 1,298) developed type 2 diabetes during the study, compared to 7.1% (93 of 1,307) in the placebo group.
As this drug is used to help lower blood sugar levels in people with type 2 diabetes it’s possible it’s merely masking the development of type 2. But the researchers don’t think that’s the case here. HbA1c was only minimally reduced compared to the start of the study in those taking dapagliflozin. And there wasn’t much of a difference in HbA1c between the treatment and placebo groups.
This is the first trial to show a prevention effect from an SGLT2 inhibitor. It’s good news for people with heart problems who take this drug. Not only does it help to reduce the risk of death from heart complications, but it could also reduce their risk of developing type 2 diabetes. The potential of dapagliflozin to help people live healthy lives is powerful.
But it’s important to bear in mind that all the participants in the DAPA-HF trial had heart problems. Dr Silvio Inzucchi, who presented the findings, explained that they need to do more studies to know if the drug could be helpful for other groups of people at risk of type 2 diabetes. And to figure out if the benefits last if people stop taking the drug.