News & Research

    Stanford University, Stanford, California

Role of insulin resistance and insulin secretion in states of abnormal carbohydrate metabolism in human disease

General Research Subject: Insulin Resistance Pre Diabetes

Focus: Insulin Action, Insulin Action\Insulin Resistance, Integrated Physiology, Integrated Physiology\Insulin Secretion and Islet Hormones

Type of Grant: Mentor Based Postdoctoral Fellowship

Project Start Date: July 1, 2012

Project End Date: June 30, 2016

Research Description

The increased prevalence of obesity and decreased physical activity has an adverse effect on insulin action, increasing the risk of type 2 diabetes and thereby threatening health, well-being, and economic welfare worldwide. As these problems increase, the world's population is at increased risk of developing other life-threatening diseases such as heart attack and stroke. Our ongoing research program is focused on pre-diabetes and insulin resistance, a state where the body is resistant to the action of insulin. We strive to better understand the roles of insulin action, insulin secretion, and related metabolic abnormalities in human physiology and disease.

Our current studies evaluate the relationships among overweight/obesity, insulin resistance/insulin secretion, and cardiovascular disease in insulin resistant and/or prediabetic individuals. These studies share a common rationale that insulin resistance and its associated abnormalities play a central role in the development of diabetes and cardiovascular disease. Through our work we have the potential to better understand how type 2 diabetes can be prevented in people at risk. We believe the results of our studies will provide new insights into the interplay among obesity, insulin resistance, insulin secretion, and type 2 diabetes; knowledge that has the potential to lead to novel preventative and/or therapeutic interventions. With our ongoing projects and the support of the ADA we will have the opportunity to provide our postdoctoral fellow with the training essential for a successful academic career as a clinical-scientist, with a focus on carbohydrate metabolism.

Research Profile

Mentor: Gerald M. Reaven, MD
Postdoctoral Fellow: Danit Ariel, MD

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?

Type 2 diabetes occurs when insulin resistant individuals can no longer secrete enough insulin to maintain the plasma glucose concentration within the normal range. Once frank hyperglycemia develops, the high plasma glucose concentration, per se, has an adverse effect on both insulin resistance and insulin secretion. Under these circumstances, it is extremely difficult to differentiate between the defects in insulin resistance and insulin secretion that led to the development of diabetes from those abnormalities that are secondary to the diabetic state. Consequently, our clinical research studies consist of attempts to increase understanding of factors modulating insulin resistance and insulin secretion in the prediabetic state.

It is generally accepted that there is an epidemic of type 2 diabetes. Although several new pharmacological approaches to treat type 2 diabetes have emerged, there is every reason to believe that the ultimate goal should be to prevent the development of type 2 diabetes in those identified as being at increased risk. It seems self-evident that the more we understand factors regulating insulin resistance and insulin secretion, and how these variables interact to maintain normal glucose concentrations, the more able we will be to develop new strategies to prevent the prediabetic individual from developing type 2 diabetes.

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

First-degree relatives of patients with type 2 diabetes are at a significantly greater risk of developing type 2 diabetes. Thus, the results of our clinical studies have the potential of yielding information leading to interventions that would decrease the likelihood of their children and/or siblings of developing type 2 diabetes.

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

I became interested in research on type 2 diabetes as a consequence of two, somewhat conflicting issues. On the one hand, there was substantial understanding of the enormous degree of morbidity and mortality associated with type 2 diabetes. On the other hand, understanding of the metabolic changes that conspired to lead to type 2 diabetes had not attained the same level of certainty. Thus, it seemed important to try my best to initiate clinical studies aimed at understanding of how defects in insulin action and secretion lead to the development of type 2 diabetes.

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

I believe that in the future major efforts will be aimed at more precise identification of individuals at high-risk for type 2 diabetes. With this knowledge we will be able to target and tailor new interventions aimed at preventing the development of type 2 diabetes.