A growing body of research shows that diabetes can be stratified into five different subgroups. Researchers at Lund University have now investigated whether a person's genetic predisposition to different diabetes subgroups can help assess the risk of developing coronary artery disease. The team created genetic risk scores and found that the scores for one subgroup could predict coronary artery disease, even before onset of diabetes.
Diabetes increases the risk of developing coronary artery disease, a common form of cardiovascular disease, often caused by atherosclerosis. Andreas Edsfeldt, who works as cardiologist, meets many patients with coronary artery disease who also turn out to have type 2 diabetes. Myocardial infarction is one example of coronary artery disease.
"Type 2 diabetes is a silent disease which is often detected when the patient is seeking care for complications, such as coronary artery disease. We need to identify individuals with a high risk of developing diabetes and coronary artery disease at a much earlier stage, as this may allow us to improve prevention of complications, such as myocardial infarction. In our new study, we have identified a group that we may be able to help at an earlier stage than we do today," says Andreas Edsfeldt, associate professor in cardiology at Lund University Diabetes Centre and cardiologist at Skåne University Hospital in Malmö.
Diabetes and coronary artery disease
The new study, published in Diabetes Care, builds on research at Lund University Diabetes Centre, which has shown that it is possible to divide type 1 diabetes into one subgroup and type 2 diabetes into four subgroups. Previous research on these subgroups has been done on the ANDIS (All New Diabetics in Skåne) study, which aims to register new cases of diabetes diagnosed in southern Sweden. The new study has been conducted on participants within Malmö Diet Cancer (MDC), a population study with a long follow-up time and randomly selected participants from the general population.
The researchers have developed genetic risk scores based on previous genome-wide association studies (GWAS) of the five subgroups to predict participants' genetic risk to develop diabetes and coronary artery disease. Their analysis included 24 025 participants from the MDC cohort and 4 105 participants developed diabetes during the follow-up time. The new study shows that the genetic risk score for the five subgroups could predict diabetes. Furthermore, the genetic risk score could predict coronary artery disease in individuals with increased risk for MOD, even before onset of diabetes. MOD is characterised by obesity and early onset of type 2 diabetes.
"Diabetes is a heterogeneous disease and the risk to develop coronary artery disease can differ greatly between individuals. Our DNA is inherited and largely stable across life, therefore genetic risk scores can help determine a person's risk of developing diabetes and coronary artery disease early in life," says Jiangming Sun, associate professor at Lund University.
Early detection of disease
The study contributes with new evidence that may make it possible to offer more tailored risk prediction of coronary artery disease and diabetes. The research team hopes that genetic risk scores can be used for early detection of individuals at high risk of developing diabetes and coronary artery disease.
"I hope that genetic risk scores can be used to identify individuals who are at risk of developing diabetes and coronary artery disease long before early signs of disease. This would give us a better opportunity to delay or prevent onset of the disease," says Andreas Edsfeldt.
Since the study shows a genetic association between MOD and coronary artery disease, the researchers plan to move forward with studies where they investigate the biological mechanisms behind coronary artery disease in this group. The new article in Diabetes Care is part of a thesis project by Mengyu Pan, who is investigating associations between type 2 diabetes and atherosclerosis.
"A limitation of our study is that it has been conducted on population studies where most participants are of European descent, which means that the findings may not be generalisable to other populations. Future studies in diverse populations are warranted to validate and extend these findings," says Mengyu Pan, doctoral student in bioinformatics at Lund University.
Coronary artery disease
Coronary artery disease is a common term for the buildup of plaque in the heart's arteries that can lead to myocardial infarction or stroke. Plaques first grow within the walls of the coronary arteries until the blood flow to the heart's muscle is limited, which prevents the heart muscle from receiving enough oxygen. Coronary artery disease may be chronic or acute. Diabetes increases the risk of developing coronary artery disease.
Source: American Heart Association
The five subgroups
SAID (severe autoimmune diabetes)
SAID includes patients traditionally referred to as type 1 diabetes and latent autoimmune diabetes in adults (LADA). SAID is defined by the presence of GAD autoantibodies and characterised by early onset, poor metabolic control and low insulin secretion.
SIDD (severe insulin-deficient diabetes)
SIDD is characterised by early onset of type 2 diabetes, impaired insulin secretion, moderate obesity, and poor blood-sugar control.
SIRD (severe insulin-resistant diabetes)
SIRD is characterised by late onset of type 2 diabetes, obesity, insulin resistance, high risk of non-alcoholic fatty liver disease, and nephropathy.
MOD (moderate obesity-related diabetes)
MOD has early onset of type 2 diabetes, obesity, and a relatively moderate disease progression.
MARD (moderate age-related diabetes)
MARD is characterised by late onset of type 2 diabetes. Patients in this group have relatively good blood sugar control.
