T2D, i.e., type 2 diabetes has become a global epidemic that affects more than 380 million people around the world. However, there are some knowledge gaps when it comes to T2D and its etiology.
Type 2 diabetes is a risk factor for CHD, i.e., coronary heart disease. However, the biological pathways which explain the link are murky.
Nature Genetics published a big analysis of genetic data. The team studied what leads to type 2 diabetes. Also clarified the connection between coronary heart disease and type 2 diabetes.
These 2 diseases are the leading cause of global mortality and morbidity. Scientists have been using genome data from around 250,000 people. They identified gene variants that seem to alter the risk of heart disease and type 2 diabetes.
Scientists report that this discovery may lead to treatments that will use one single drug for both diseases.
According to statistics, around 95 % of people that have diabetes have T2D. This is a condition that develops when the body produces insulin, but the cells are not able to use it to absorb the blood sugar and use it as energy.
The other remaining 5 % of diabetes cases are T1D, i.e., type 1 diabetes. A condition that occurs when the body does not produce enough insulin.
If the diabetes is not under control, it may lead to hyperglycemia or high blood sugar. That can cause severe health problems like vision impairment, heart disease, kidney disease, and stroke.
Diabetes is the 7th leading death cause in the U.S. Around 30.3 million have diabetes. This includes 25 % of people who are without diagnosis and are not aware of it.
The Link Between Heart Disease and Diabetes
Diabetes is a risk factor for heart disease. Heart disease is the leading cause of death in the U.S. for both women and men. In fact, every year around 630,000 people die of heart disease.
Around half of these people who die because of heart disease in the United States die of CHD, i.e., coronary heart disease. CHD is induced by coronary artery disease.
Coronary artery disease is a condition in which the arteries of the heart narrow down because of plaque buildup.
The researchers in their study explain that type 2 diabetes patients are actually twice as likely to die of CHD in comparison to the patients that do not have type 2 diabetes.
However, the molecular and genetic mechanisms which induce this increased risk are poorly understood.
Thanks to the new technology by the name GWAS, (genome-wide association studies), scientists have a grasp of the “genetic architecture” of T2D and CHD.
This new technology is actually a sequencing method that can quickly scan genomes or scan complete sets of DNA of more than thousands of people. Scientists use this technology to find “loci” or sites in the genome which relate to the disease.
According to the authors, regarding coronary heart disease and type 2 diabetes GWAS was found around “several dozens” risk sites.
However, the link between the molecular pathways with which they influence the biology of the cell and the risk genes of the 2 diseases is something they still cannot grasp.
The scientists for their study examined GWAS data from around 250,000 people of European descent, South Asian, and East Asian.
They confirmed many of the familiar risk sites for diabetes. Also, they found around 16 new risks sites for T2D and 1 new site for CHD.
The scientists made further analysis. They made a discovery that most of the loci or sites on the genome which are known to be related to the increased chance of T2D are also related to the increased chance of CHD.
In fact, in 8 of the loci, the scientists identified a specific variant or spelling of letters of the genetic code which altered the risk for T2D and CHD.
The authors say that the shared variants implicate few new pathways. These pathways affect cell proliferation, immunity, and cardiovascular development.
Joint senior author of this study, assistant professor of biostatistics and epidemiology at Pennsylvania University, Danish Saleheen talks more about this topic.
He notes that the identification of these gene variants which are in relation to coronary heart disease and type 2 diabetes risk opens up new opportunities. Opportunities to reduce the risk of both outcomes and do that with only one drug.
Moreover, 7 out of 8 variants seem to increase the risk for both coronary heart disease and type 2 diabetes. However, the 8 variant (in a gene that codes for the ApoE cholesterol-transport protein) was different, and that puzzled the scientists.
This eighth variant links to increased risk for T2, but somehow it seemed to reduce the risk of CHD.
According to professor Saleheen, this probably explains why proof from statin trials found that taking drugs to reduce low-density lipoprotein cholesterol, i.e., LDL might raise the risk of developing T2D.
‘Deprioritize Pathways’ for New Drugs
The scientists came to the discovery that the genetic links which they identified between T2D and CHD seem to work only in one direction.
That means that the risk loci for T2D are more likely to be connected to increased risk of CHD than the other way around.
Also, scientists suggest that there is a possibility for pathways through which the drugs which reduce the risk of disease might increase the risk of another disease.
According to professor Saleheen, it should be possible to make drugs for T2D by using evidence from human genetics. The drugs will have either neutral or beneficial effects on the risk of CHD.
But it is crucial to identify and deprioritize pathways that lower the risk of T2D but increase CHD risk.
This team also came to the discovery that a few of the shared variants which raise the risk for type 2 diabetes seem to have different effects regarding the risk of coronary heart disease. And that also depends on which pathway they influenced.
For instance, variants that seem to exert influence through high blood pressure and obesity seem to have a stronger effect on coronary heart disease risk in comparison to variants that influence levels of insulin and blood sugar.
Benjamin F. Voight, Ph.D., co-senior author of the study and associate professor of Genetics, is hopeful about the new advanced genomic techniques.
He hopes that there will be a fast conversion of the observations of human genetics into concrete details in terms of molecular mechanisms. These mechanisms are part of both diabetes and heart disease.
Furthermore, the researchers hope to find out more about the newly found dual-risk genes and their biology. They plan to do that by studying the people with mutations in the genes.