News & Research

    Thomas Jefferson University, Philadelphia, Pennsylvania

Adipose tissue inflammation, kidney disease and transplant associated hyperglycemia

General Research Subject: Type 2 Diabetes

Focus: Adipocytes, Signal Transduction (Non-Insulin Action), Signal Transduction (Non-Insulin Action)\Hormones, Transplantation

Type of Grant: Junior Faculty

Project Start Date: July 1, 2012

Project End Date: June 30, 2015

Research Description

Glucose abnormalities after renal transplantation occur frequently and increase the risk of losing the transplanted organ, developing heart problems and death. Some of the most important hormones that regulate glucose levels are called adipokines or hormones produced by fat tissue, and among them one of the most important is adiponectin. The effect of adipokines in patients with kidney disease and after recovery of kidney function post-transplant is unknown. A study is proposed to investigate the role of adipokines in the development of glucose abnormalities after organ transplantation and to investigate the function of these hormones in patients with kidney disease.

It is hypothesized that patients with kidney disease are resistant to adipokines and this resistance makes them more prone to developing glucose abnormalities after a kidney transplant. To study this hypothesis, fat and muscle tissue from kidney disease patients and healthy controls will be utilized to measure adipokines levels and transplant patients will be monitored for the development of glucose abnormalities. The intracellular pathway that follows the binding of adiponectin to their cell surface receptor in tissues of subjects with kidney dysfunction and normal kidneys will be characterized. If glucose abnormalities are due to resistance to adipokines they will likely be able to predict which patients are at higher risk for developing glucose abnormalities after transplantation so that preventive measurements could be adopted.

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 an area of diabetes that is poorly understood and not well characterized. Transplant associated hyperglycemia is the term that describes abnormalities in glucose metabolism that appear after a solid organ transplantation. Glucose abnormalities after a kidney transplant are extremely common. Diabetes after kidney transplant occurs in 15 to 20% of patients and the development of diabetes is associated with an increased risk of death and losing the transplant. My research project will study the role of adipokines or hormones produced by fat tissue in the development of glucose abnormalities after a kidney transplant.  By better understanding the role of adipokines in glucose sensitivity after kidney transplant we can better predict who are more likely to develop diabetes and in the future allow us to develop drugs that modulate adipokine levels in order to treat or prevent diabetes after kidney transplant.

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

The ability to identify kidney transplant recipients at high risk for developing glucose abnormalities would help us build preventive strategies to decrease the risk of becoming diabetic in this subgroup of patients. Also understanding the role that the fat tissue hormones play regulating glucose levels after transplant may also help to develop new treatments targeting these hormones. Control and prevention of glucose abnormalities after a renal transplant is of great importance for maintain the health and longevity of the patients and the transplanted organ.

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

Diabetes after transplant is one of the most severe complications that our patients suffer which commonly leads to death, disability and organ failure. In fact, although outcomes at one year post-transplant have constantly improved over the last 20 years we have not been able to improve long-term outcomes. As a transplant nephrologist, my principal goal is to contribute to the development of novel findings that lead to improved outcomes in renal transplantation. In order to achieve my career goal, the proposed project is designed to gain broader knowledge of glucose abnormalities after kidney transplantation.  I am hopeful that my research efforts will contribute to novel therapeutic approaches that can improve kidney and patient survival. This award will allow me to continue to spend time in the laboratory to better understand the role of fat tissue in this type of diabetes occurs and how to possibly prevent it.

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

I see the future of diabetes research having two main avenues. One is to continue to improve current treatment strategies and develop new therapeutics using novel targets that could include adipokines or inflammation. Another area of diabetic research will include prevention strategies that will help reduce the  incidence of diabetes across all the ages.