Obesity has long been associated with a higher risk for heart disease, but recent research by the SOPHIA project found that there are five subgroups of people that have a high risk of having a cardiovascular event even though they may be slim.
The project then went one step further to see whether this might also hold true for people with type 1 diabetes, for whom heart attacks are the leading cause of death.
“Despite the fact that the care for people with type 1 diabetes has improved, we still see that on average they live 10 years less and that the cause of them dying is usually a cardiovascular event. They remain at a much higher risk of cardiovascular disease than the average population,” says Bart van der Schueren of the University of Leuven, who led SOPHIA’s work on the relationship between obesity and type 1 diabetes.
The SOPHIA study in the general population identified five groups of people who were at risk of heart disease more than would be expected based on their degree of overweight: people with high blood sugar, inflammation linked to excess body fat, high blood pressure, unhealthy blood fat levels that increase the risk of clogged arteries, and abnormal liver enzyme levels suggesting fat build-up in the liver.
Three of these risk profiles were seen in the type 1 diabetes study, and the proportion of people with type 1 diabetes in each risk profile was different compared to the general population. The vast majority of people with type 1 diabetes (55-76%) were in the hyperglycaemic subgroup, compared to only 2.5% of the general population. However, glycaemia is only part of the puzzle.
“Even at equal body mass index (BMI) [to a regular person without type 1 diabetes], they are still intrinsically at a higher risk,” says Van der Schueren.
“In this study, we identified the fact that if you are better controlled in terms of glycaemia, then your cardiovascular risk is more likely to be explained by your BMI and normal risk factors. Whereas, if you’re hyperglycaemic, then your risk increases. This is a call to improve glycaemia in people living with type 1 diabetes,” says Van der Schueren.
A range of factors, other than glucose, that the researchers examined worked differently in people living with type 1 diabetes compared to the general population. In women, differences in systolic blood pressure were seen, while in men, levels of low-density lipoprotein (LDL), a type of protein that carries cholesterol through the bloodstream, were altered.
“This study provides new insight into commonly measured markers,” says Sofia Pazmino Lucio, the lead author of the study. “We want to exploit to the maximum what we’re already collecting. We can get more valuable information without adding any extra burden to the healthcare system. It is true that if you have greater glycaemic control, you can reduce your cardiovascular risk. But for people that are already controlling their glycaemic levels well, you can then see which other markers could be targeted to continue to lower their risk.”
SOPHIA also developed an app called the Obesity Phenotype Explorer, to make it simple and easy for clinicians to calculate the risk of cardiovascular disease in patients. The app can be used to translate the observed biomarkers into a risk profile on the spot, helping clinicians to rapidly evaluate whether a person is at risk of cardiovascular events or not, regardless of their weight.
Highlighting the gap between care for type 1 and type 2 diabetes
While a high risk of heart complications is well known in people living with type 2 diabetes, there are far fewer studies done on people with type 1 diabetes which could be why risk factors for cardiovascular diseases in this population are so often overlooked.
“We have less research on type ones, because even if they're incorporated into the clinical trials, they're a minority group,” says Pazmino Lucio.
People with type 2 diabetes are often prescribed statins or lipid lowering medications readily, which reduces their cardiovascular risk. However, people with type 1 diabetes tend not to be given access to those treatments so easily.
One key reason for this is late diagnosis, and another is the fact that clinicians do not yet associate slim people with high cardiovascular risk. However, a key factor is the additional complications that people with type 1 diabetes live with, the ever-present risk of hypoglycaemic attacks and – if diabetes is not under control – life-threatening diabetic ketoacidosis. These complications can make it less attractive for pharmaceutical companies to test their medications on type 1 diabetes, because it might be trickier for drugs to pass through clinical trials without side effects.
The knock-on result of this is that fewer treatments for cardiovascular events have been approved on the market for people with type 1 diabetes, and that needs to change.
“It feels like the population with type 1 diabetes has been left a bit aside,” says Van der Schueren. “This is a call for action to take this cardiovascular risk in people with type 1 diabetes more seriously, and to jump more regulatory hurdles for drugs that do exist for people with type 2 diabetes and might not exist or are not approved for people with type 1.”
Pazmino Lucio also stresses the importance of these results to identify more people at risk of developing cardiovascular disease. “It’s not just a higher BMI, a higher risk. It’s a way of profiling everyone, not just those that have overweight or obesity.”
SOPHIA is supported by the Innovative Medicines Initiative, a partnership between the European Union and the European pharmaceutical industry.