News & Research

    Albert Einstein College of Medicine, Bronx, New York

Effect of vitamin D repletion on insulin resistance and systemic inflammation

General Research Subject: Type 2 Diabetes

Focus: Clinical Therapeutics/New Technology

Type of Grant: Merck

Project Start Date: July 1, 2009

Project End Date: June 30, 2013

Research Description

Obesity is increasingly recognized to be risk factor for many diseases, including diabetes mellitus and heart disease. Proteins secreted from various tissues including from fat tissue are suggested to be the link between obesity, type 2 diabetes and heart disease. Over the last several years, studies have shown that low vitamin D levels may increase the risk of development of type 2 diabetes. Low vitamin D concentrations have been shown to be associated with high glucose and insulin levels when subjects are given standard amounts of glucose by mouth. A large national health and nutrition survey which studied a multi-ethnic sample of more than 6000 adults reported an inverse association between vitamin D status and diabetes. Another recent study has also showed that low vitamin D levels are associated with increased risk of heart disease. In this proposal, we will administer vitamin D to non diabetic, obese subjects with vitamin D deficiency to increase the levels to normal range. We will examine whether restoring Vitamin D levels to the normal range will allow the body to better utilize insulin and improve blood glucose levels. We will also examine if normalizing Vitamin D levels will change the amount of proteins secreted from fat tissue

This study will help to establish the clinical relevance of vitamin D deficiency to type 2 diabetes. Demonstrating the ability of vitamin D to reverse these effects related to obesity would be of tremendous therapeutic importance, and can be used in ameliorating many of the conditions associated with the obesity such as heart disease and type 2 diabetes.

Reseacher Profile

Mentor: Meredith Hawkins, MD   Postdoctoral Fellow: Sudha Koppaka, MD

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

The proposed research project covers the areas of type 2 diabetes, pre-diabetes and insulin resistance. Obesity is increasingly recognized to be a risk factor for many diseases, including diabetes mellitus and heart disease. Proteins secreted from various tissues including from fat tissue are suggested to be the link between obesity, type 2 diabetes and heart disease. Over the last several years, studies have shown that low vitamin D levels may increase the risk of development of type 2 diabetes. Low vitamin D concentrations have been shown to be associated with high glucose and insulin levels when subjects are given standard amounts of glucose by mouth.

A large national health and nutrition survey which studied a multi-ethnic sample of more than 6000 adults reported an inverse association between vitamin D status and diabetes. Another recent study has also showed that low vitamin D levels are associated with increased risk of heart disease. In this proposal, we will administer vitamin D to non diabetic, obese subjects with vitamin D deficiency to increase the levels to normal range. We will examine whether restoring Vitamin D levels to the normal range will result in better insulin response and improve blood glucose levels. Demonstrating the ability of vitamin D to reverse these effects related to obesity would be of tremendous therapeutic importance, and can be used in ameliorating many of the conditions associated with the obesity, including 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? 

Type 2 diabetes is associated with a defect in body's ability to respond to insulin, and many proteins secreted from fat tissue are known to worsen this defect. A causal link between vitamin D deficiency and its effect on the body's ability to respond to insulin, and changes in amounts of 'bad' proteins secreted from fat tissue has not yet been established in humans. This research study is indispensable to establishing the clinical relevance of Vitamin D deficiency to defective insulin response.

If restoring vitamin D is proven to be associated with improvement in insulin response and better glucose control, it would be of tremendous therapeutic importance in type 2 diabetes and in the pre-diabetic state, particularly in light of the feasibility and safety of vitamin D repletion.

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

My passion for diabetes research actually began at the age of twelve, when I read the story of how Banting and Best discovered insulin in Toronto (my hometown!) in 1921. I decided that diabetes was the most interesting disease I had ever heard of, and resolved to pursue diabetes research when I grew up. Diabetes indeed remained my passion through medical school and internal medicine residency, and I did indeed become an Endocrinologist and a diabetes researcher. My interest in diabetes continues to be fueled by my experiences in the developing world, in my capacity as Director of the Global Diabetes Initiative. Witnessing, first-hand, the scourges of diabetes among the world's poorest and most vulnerable populations has done much to motivate me to advance our understanding of the mechanisms that contribute to the development of diabetes.

The ADA-Merck Clinical/Translational Science Postdoctoral Fellowship award will support the annual stipend of research fellow Dr. Koppaka who is working with me in this project. The project will give opportunities to the fellow to learn state of the art technologies like performing insulin clamps and a wide array of other research methodologies in addition to encouraging critical and independent thinking. This would provide the fellow with an invaluable experience to master many skills necessary to ultimately become a successful independent clinical diabetes investigator. 

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

In my view, future directions of diabetes research will include: 1. Restoration of beta cell function, including stem cell approaches2. Delineating the role of central nervous system in regulating insulin signaling3. Determining the effects of inflammatory factors from adipose tissue on insulin action and glucose production4. Exploring the role of gut flora in the etiology of diabetes and obesity5. Exploring the genetic basis of defects in insulin secretion and action.