For individuals living with diabetes, the risk of developing cardiovascular disease – particularly coronary artery disease – is significantly elevated. Now, research from Lund University in Sweden suggests a more personalized approach to assessing that risk may be on the horizon. Scientists have discovered that genetic predispositions to different subtypes of diabetes can be used to predict the likelihood of developing coronary artery disease, even before a diabetes diagnosis is made. This offers a potential pathway to earlier intervention and preventative care for those most vulnerable.
The findings, published in the journal Diabetes Care, build upon growing recognition that diabetes isn’t a single condition, but rather a collection of distinct subtypes. Understanding these subtypes, and a person’s genetic susceptibility to them, could revolutionize how we approach diabetes prevention and treatment. The research team developed “genetic risk scores” to evaluate an individual’s likelihood of developing both diabetes and coronary artery disease, and found that scores related to one specific subtype were particularly predictive of future heart problems.
Coronary artery disease, often caused by a buildup of plaque in the arteries (atherosclerosis), can lead to heart attack and stroke. As Andreas Edsfeldt, a cardiologist at Skåne University Hospital in Malmö, Sweden, and a researcher at Lund University Diabetes Centre, explains, “Type 2 diabetes is often a silent disease, frequently discovered when patients seek care for complications like coronary artery disease.” Identifying those at high risk earlier is crucial, he emphasizes, to prevent these life-threatening complications. “In our new study, we’ve identified a group we could potentially aid at an earlier stage than we do today.”
Unraveling the Complexity of Diabetes
For years, diabetes has been broadly categorized as type 1 and type 2. However, research at the Lund University Diabetes Centre has demonstrated that type 1 diabetes can be further divided into one subtype, while type 2 diabetes encompasses at least four distinct subtypes. This work stemmed from the ANDIS (All New Diabetics in Skåne) study, which aims to include all new cases of diabetes in the Skåne region of Sweden. The current study leveraged data from the Malmö Kost Cancer (MKC) study, a long-term population study involving 24,025 participants randomly selected from the general population.
The researchers developed genetic risk scores based on a previous genome-wide association study (GWAS) examining the five diabetes subtypes. These scores were used to estimate an individual’s genetic risk for developing both diabetes and coronary artery disease. Analysis of the MKC cohort, which included 4,105 individuals who developed diabetes during the follow-up period, revealed that the genetic risk scores could accurately predict the onset of diabetes. Importantly, the scores too predicted coronary artery disease in individuals at increased risk for a subtype known as MOD (moderate obesity-related diabetes) – and this prediction occurred before a diabetes diagnosis.
“Diabetes is a heterogeneous disease, and the risk of developing cardiovascular disease can vary greatly between individuals,” explains Jiangming Sun, Associate Professor at Lund University. “We inherit our DNA, and it remains largely intact throughout life. Genetic risk scores can be used to assess an individual’s risk of developing diabetes and coronary artery disease early in life.”
The Promise of Early Detection
This study provides new evidence that could pave the way for more personalized risk assessments for both coronary artery disease and diabetes. The hope is that genetic risk scores will allow healthcare providers to identify individuals at high risk at an earlier stage, enabling proactive interventions.
“My hope is that genetic risk scores will allow us to identify individuals who are at risk of developing diabetes and coronary artery disease long before there are any signs of disease,” says Edsfeldt. “Then we have better opportunities to delay or prevent the progression of the disease.”
The finding of a genetic link between MOD and coronary artery disease is prompting further research into the underlying biological mechanisms driving heart disease in this specific subgroup. The research is part of an ongoing doctoral dissertation by Mengyu Pan, who is investigating the relationship between type 2 diabetes and atherosclerosis.
However, the researchers acknowledge limitations. Pan notes that the study was conducted on populations with predominantly European ancestry, meaning the findings may not be generalizable to other populations. “Future studies on other populations are needed to confirm and expand our findings,” she says.
The American Heart Association defines coronary artery disease as a common form of heart disease caused by plaque buildup in the arteries, potentially leading to heart attack and stroke.
Understanding the Five Diabetes Subtypes
Here’s a brief overview of the five identified diabetes subtypes:
- SAID (Severe Autoimmune Diabetes): Corresponds to type 1 diabetes and LADA (latent autoimmune diabetes in adults). Characterized by early onset, poor blood sugar control, impaired insulin production, and the presence of GADA antibodies.
- SIDD (Severe Insulin-Deficient Diabetes): Characterized by early-onset type 2 diabetes, impaired insulin production, moderate obesity, and poor blood sugar control.
- SIRD (Severe Insulin-Resistant Diabetes): Affects individuals diagnosed with type 2 diabetes later in life, often with obesity, severe insulin resistance, and an increased risk of fatty liver disease and diabetic nephropathy.
- MOD (Moderate Obesity-Related Diabetes): Includes individuals with significant obesity who develop type 2 diabetes at a relatively young age, with a moderate disease course.
- MARD (Moderate Age-Related Diabetes): The largest group, comprising older individuals with type 2 diabetes and relatively good blood sugar control.
This research represents a significant step toward a more nuanced understanding of diabetes and its cardiovascular consequences. The next phase of research will focus on unraveling the biological mechanisms linking MOD to increased heart disease risk, potentially leading to targeted therapies and preventative strategies.
Disclaimer: This article provides information for general knowledge and informational purposes only, and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.
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