Reaven, Gerald , MD
Addition of the long-acting glucagon-like peptide-1, liraglutide, to a calorie-restricted diet augments weight loss, and decreases risk of type 2 diabetes and cardiovascular disease in older, overweight/obese, prediabetic individuals.
General Research Subject: Insulin Resistance Pre Diabetes
Type of Grant: Novo Nordisk Clinical Research
Project Start Date: September 1, 2009
Project End Date: August 31, 2012
Funded by Novo Nordisk
The population in the United States is getting older, heavier, and less physically active; characteristics that greatly increase the likelihood of developing type 2 diabetes and/or heart attack. Current medical advice to such individuals is to lose weight and become more physically active. Although this is good advice, it is not so easy to follow. The last few years have seen the introduction of a new class of drugs to treat type 2 diabetes that work by increasing the plasma concentration of glucagon-like peptide-1 (GLP-1). In contrast to other drugs to treat type 2 diabetes, improvement in diabetic control with drugs that increase GLP-1 levels is often associated with weight loss. Liraglutide is a member of this class of drugs, and has been shown to effectively lower glucose in patients with type 2 diabetes. However, there is little information concerning the possibility that use of drugs like liraglutide could be beneficial before diabetes develops in those at greatest risk.
The goal of this research proposal is to evaluate this possibility by seeing if the addition of liraglutide to a weight loss diet is more effective in achieving weight loss and decreasing risk factors for type 2 diabetes and heart attack than weight loss alone. If this pilot study finds that this is the case, it could serve as the scientific basis for a much larger study to identify a more effective clinical approach to decrease type 2 diabetes and heart attack in our older, heavier, and more sedentary population.
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 efforts are focused on a group of individuals at greatly increased risk to develop type 2 diabetes, and its associated risk factors for cardiovascular disease - older, heavier, and prediabetic individuals.
The conventional approach attempting to prevent these adverse outcomes is to urge these individuals to lose weight and increase their level of physical activity. As appropriate as these suggestions are, they are not always easy to follow. Our project is based on the hypothesis that the addition of a glucagon-like peptide-1 to a calorie-restricted diet will significantly decrease the risk of developing diabetes and cardiovascular disease than will diet alone. If our hypothesis can be validated, it will provide an effective pharmacological alternative to complement currently therapeutic approaches to the high risk subjects displaying the features of the volunteers enrolled in our project.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
At this time we know that older and heavier individuals are more likely to develop type 2 diabetes, and the higher their blood glucose level within the nondiabetic range, the more likely that this will occur. Furthermore, we know that weight loss and increased physical activity will help mitigate the risks of developing diabetes in these individuals. Unfortunately, we also know that it is difficult, for a variety of reasons, for many high-risk individuals to succeed in accomplishing these goals. Our project is aimed at testing the likelihood that a new class of drugs that are useful in treating type 2 diabetes, glucagon-like peptide-1(GLP-1), may be also be useful in helping to prevent diabetes and cardiovascular disease in older, heavier and prediabetic persons.
Indeed, we believe that the combination of a low-calorie diet and a GLP-1 drug will provide more weight loss, and greater benefit in preventing type 2 diabetes and cardiovascular dieses in these high-risk individuals than only a calorie-restricted diet. Thus, our research efforts are not aimed at individuals who already have diabetes, but helping to prevent the development of diabetes and cardiovascular disease in the much larger population of those at high-risk to develop these diseases.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
My interest in diabetes research began as a young physician-scientist when I became aware of the clinical importance of what was once-called 'maturity-onset diabetes'. At that time I felt that the seriousness of this clinical problem was not appreciated, and that the views of its pathogenesis were over-simplistic. This situation has clearly changed over the period in which I have been able to be engaged in diabetes research; the clinical importance of type 2 diabetes is clearly recognized, and there is considerable concern over how best to address what is now understood to be an epidemic of this syndrome.
It sees reasonable to suggest that an exceedingly useful approach at this point would be to improve our ability to prevent the development of type 2 diabetes in individuals that can be well-characterized as being at great risk. This award provides me the opportunity to address this crucial question by evaluating a combined nutritional /pharmacological approach to evaluate what I believe could become a very useful intervention to prevent diabetes and its associated risk of cardiovascular disease in older, heavier, prediabetic individuals - a numerically common group at greatly increased risk to develop these adverse outcomes.
In what direction do you see the future of diabetes research going?
Speaking only of type 2 diabetes, I believe there will be two major thrusts. One aimed at understanding the genetics of type 2 diabetes in order to best identify those at increased risk to develop the clinical syndrome. Secondly, I think it will become clear that our current knowledge is substantial, and greater research efforts must be made to evaluate the best way to: 1) initiate interventions aimed at preventing the development of the full-blown clinical syndrome; and 2) more effectively address and treat all of all of the abnormalities associated with type 2 diabetes that contribute to its morbidity and mortality.
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