News & Research

    University of Colorado Denver, Denver, Colorado

The role of lipotoxicity in insulin resistance and cardiovascular and mitochondrial dysfunction in type 1 diabetes

General Research Subject: Type 1 Diabetes

Focus: Complications\ Macrovascular-Atherosclerotic CVD and Human Diabetes, Integrated Physiology\Insulin Resistance

Type of Grant: Junior Faculty

Project Start Date: July 1, 2011

Project End Date: June 30, 2014

Research Description

The management of type 1 diabetes has made huge advances over the last decades. With improvements in blood sugar control, microvascular complication rates have fallen dramatically. In contrast, advances in cardiovascular disease have been limited and cardiovascular disease remains the primary cause of early mortality in this population. Our study of a large group of type 1 diabetic subjects and similar controls has demonstrated that insulin resistance in the type 1 diabetic subjects correlates with coronary artery calcification, a marker of cardiovascular disease. Neither insulin resistance nor coronary artery calcification are correlated with blood sugar control. Our hypothesis is that non-glycemic metabolic changes, changes that are currently not addressed by any available treatment or dietary recommendation, contribute to the increased risk of cardiovascular disease in type 1 diabetes. The proposed study uses two interventions, an acute fatty acid-targeted intervention with acipimox, a form of niacin, and a dietary intervention with a high carbohydrate diet and increased insulin dosing, to determine whether elevated fatty acid levels are an important mediator of cardiovascular and mitochondrial dysfunction in type 1 diabetes. The results will determine whether durable fatty acid lowering is a valid target for new drug development and will inform dietary recommendations for optimal management of cardiovascular disease risk in type 1 diabetes.

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?

My research project covers the area of prevention and treatment of cardiovascular disease in type 1 diabetes. Current treatment of type 1 diabetes is focused entirely on glucose control. However, my research and the research of others have shown that individuals with type 1 diabetes are also resistant to insulin. In other groups of people, including those with type 2 diabetes, obesity, and metabolic syndrome, insulin resistance is strongly associated with the risk of heart disease. My research is directed at understanding why people with type 1 diabetes are insulin resistance and whether this insulin resistance is also associated with damage to the heart and blood vessels. If so, treatment of type 1 diabetes should include medications or lifestyle changes that improve insulin sensitivity. My research will also address what these medications and lifestyle changes should be to optimally improve cardiovascular disease risk in type 1 diabetes.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

This research project could change the way we treat type 1 diabetes in a way that would better protect the heart and blood vessels from the damage that occurs in diabetes. This would improve life expectancy and quality of life in people with type 1 diabetes.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?

As a practicing Endocrinologist, I see people with type 1 diabetes regularly in clinic. The toll this disease takes on the vascular system and the fact that current treatment options are inadequate to prevent this is apparent with so many of these patients. This award will allow me to explore a new target for prevention of cardiovascular disease in type 1 diabetes.

In what direction do you see the future of diabetes research going?

I believe that efforts to cure diabetes, including type 1 diabetes, will continue, and will eventually succeed. In the meantime, however, millions of people are living with the consequences of their diabetes and more are diagnosed every day. Until we have a cure, further research into prevention and treatment of the severe sequelae of diabetes is essential.