Research Description
People with pre-diabetes and diabetes often have elevated lipid levels that increase their risk of heart diseases such as atherosclerotic cardiovascular disease or the build-up of lipids in the vessel wall in addition to their elevated blood sugar. To reduce the risk of atherosclerotic cardiovascular disease, many people with diabetes are treated with a class of lipid-lowering medications called statins. However, statin therapy only targets certain aspects of the elevated lipids in people with diabetes. It does so at the cost of increasing the risk of new-onset diabetes and worsening established diabetes. The part of the dyslipidemia not targeted by statins is called triglyceride-rich lipoprotein (TRL). We have recently demonstrated that a critical regulator of TRL levels, apolipoprotein C3 (APOC3), is important in diabetes-accelerated atherosclerotic cardiovascular disease. Intriguingly, reducing APOC3 also improves blood sugar control in models of prediabetes and diabetes. The hypothesis is that TRLs affect insulin-producing cells (insulin is the hormone that lowers blood sugar), resulting in dysfunction and loss of these cells. This can be prevented by reducing levels of APOC3, which will be in contrast to the effects of lowering lipids with statins. This hypothesis will be tested by silencing APOC3 in a mouse model of diabetes with human-like changes in lipids. Targeting APOC3 and, therefore, TRLs could offer people at risk for diabetes and people with diabetes an alternative to statin therapy that may offer heart disease and blood sugar control benefits.Research Profile
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?Our research aims to understand how elevated lipids contribute to the increased risk of diabetes. People with pre-diabetes and diabetes often have elevated lipid levels that increase their risk of heart diseases such as atherosclerotic cardiovascular disease or the build-up of lipids in the vessel wall. To reduce the risk of atherosclerotic cardiovascular disease, many people with diabetes are treated with a class of lipid-lowering medications called statins. Yet, people with diabetes have an elevated risk of heart disease. However, statin therapy only targets certain aspects of the elevated lipids seen in people with diabetes. It does so at the cost of increasing the risk of new-onset diabetes and worsening established diabetes. The part of dyslipidemia that is not targeted by statins is called triglyceride-rich lipoproteins, which we want to target in this research. Targeting this type of dyslipidemia could offer people at risk for diabetes and those with diabetes an alternative to statin therapy that may offer heart disease and blood sugar control benefits.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?Although this research mainly focuses on the fundamental mechanism(s) whereby certain lipids drive beta cell loss and, therefore, diabetes, several clinical trials are underway targeting triglyceride-rich lipoprotein metabolism, making this line of research clearly translational. We thus hope that in the near future, there will be additional therapies (beyond statins) that target the dyslipidemia often present in people with diabetes. And these therapies might have the added benefit of reducing people’s risk of diabetes.
Why important for you, personally, to become involved in diabetes research? What role will this award play?Diabetes can be a debilitating disease, with an increased risk of complications resulting from long-term diabetes, something I have spent most of my career trying to understand. This award allows me to take a step back, learn more, and explore what we think are important parameters for complications in the onset and development of diabetes.
In what direction do you see the future of diabetes research going?In the future, diabetes research, I think, will be focused on precision medicine. That is individualized approaches that will benefit each person’s needs. This will require research to understand better why specific lipids are evaluated in one person but not the next and why statins result in an increased risk of diabetes in some but not all.