Can we prevent heart and kidney problems in young people with type 1 diabetes?
The clinical question
Type 1 diabetes is most commonly diagnosed in children and young adults. It happens when the body can’t produce enough insulin, a hormone that controls blood glucose (sugar) levels. Young people with type 1 diabetes are at increased risk of long term health problems. This can include kidney, heart and circulatory diseases, which can reduce life expectancy by 10 to 15 years.
This risk can be reduced by improving control of blood glucose levels. But controlling blood glucose can be difficult, particularly during adolescence. At the same time, puberty seems to be a critical stress point when the first signs of eye, kidney, heart and circulatory complications appear. In adults with diabetes, blood pressure lowering drugs (such as angiotensin-converting enzyme inhibitors, or ACE inhibitors) and cholesterol lowering drugs (statins) are used to help prevent these complications. But these drugs had not been properly tested in younger people with type 1 diabetes.
The BHF co-funded the ‘Adolescent type 1 diabetes cardio-renal intervention trial’ (AdDIT), led by Professor David Dunger at the University of Cambridge. The trial aimed to find out if these medicines could help prevent or delay long-term cardiovascular complications in adolescents with type 1 diabetes. It was also important to determine if they could be safely taken by younger people.
What did the study involve?
Between 2008 and 2013 the AdDIT team screened over 4000 young people with type 1 diabetes. This included people from across the UK, Australia and Canada aged 10 to 16 years. From those screened, they identified 450 'high-risk' participants and 400 'low risk' participants.
- High risk participants were randomly allocated to take a statin, an ACE-inhibitor, a combination of both, or a placebo for 2 to 4 years.
- Their kidney, eye, heart and circulatory function were regularly monitored.
- BHF Professor John Deanfield, at University College London, led a team that assessed the structure and function of arteries in the UK participants. These measurements can help to predict the risk of heart and circulatory problems developing later on in life.
- Low risk participants took part in an observational study. This group was followed for 2 to 4 years and had similar measurements taken. However, they were not treated with ACE inhibitors or statins.
What did the study show?
- As expected, statins reduced blood cholesterol levels and ACE-inhibitors lowered blood pressure in young people with type 1 diabetes.
- These medications seemed to be safe for young people to take.
- Neither drug altered markers that reflect the risk of developing kidney, eye, heart and circulatory diseases.
- Three quarters of the participants complied with the treatment.
- Using information from the trial and observational study, the team also identified a link between the amount of a molecule, called albumin, found in the urine and predicted future cardiovascular risk.
Why is the study important?
Recruiting young people into clinical trials and asking them to take preventive medicines for long periods of time is challenging. It was a huge achievement to complete the trial successfully. And although AdDIT did not show an immediate benefit for taking statins or ACE inhibitors in this age group, it may be too soon to know whether drug therapy could reduce the long-term risk of heart and kidney complications.
It’s possible that these drugs might still reduce long-term complications through a 'legacy effect'. This is where the benefits of a drug taken during a critical period can be seen years after stopping. Legacy effects have been shown before in adults with diabetes treated with these types of medication. But it is not yet known whether this is true for young people in the AdDIT trial. In the meantime In the meantime, Professor Dunger concluded that:
Finally, this study also suggested that albumin levels in the urine, in combination with other markers, could be used to help predict heart and complications in young people with diabetes.
Study details
"Adolescent type 1 diabetes cardio-renal intervention trial (AdDIT)"
Award reference: SP/07/002/23394
Principal Investigator: Professor John Deanfield, University College London
Trial registration number: ISRCTN78168304
Publication details
Marcovecchio ML, Chiesa ST, Bond S, et al. ACE Inhibitors and Statins in Adolescents with Type 1 Diabetes. N Engl J Med. 2017;377(18):1733-1745.