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Research explores link between stem cell transplant, diabetes

Jan. 17, 2019, 10:01 AM

Dae Kwang Jung, left, Brian Engelhardt, MD, MSCI, and colleagues are studying why stem cell transplant patients are at risk of developing diabetes.
Dae Kwang Jung, left, Brian Engelhardt, MD, MSCI, and colleagues are studying why stem cell transplant patients are at risk of developing diabetes. (photo by Anne Rayner)

by Amanda Johnson

About a decade ago, at the beginning of his career in academic medicine, Brian Engelhardt, MD, MSCI, noticed that many of his patients receiving a stem cell transplant for their blood cancer ended up with diabetes.

A little digging revealed that his observations accurately represented reality.

Current studies estimate that as many as 50 percent of stem cell transplant recipients develop diabetes. Further, diabetes also dramatically increases the risk of death for these patients, although not via the cardiovascular and kidney complications normally associated with uncontrolled blood sugar.

“When you really look at the incidence of the disease and its effect on transplant outcomes, it’s actually a very big problem,” said Engelhardt, associate professor of Medicine in Vanderbilt’s Division of Hematology and Oncology.

Engelhardt also found this problem has very few accepted answers. No one knows how stem cell transplantation leads to diabetes or why diabetes has such a negative outcome in many stem cell transplant patients.

Engelhardt was determined to answer these questions. He realized, however, that his knowledge of hematology, oncology and stem cell transplantation gave him insight into only part of the problem.

Fortunately, he found access at Vanderbilt to all the expertise he needed. An interdisciplinary team consisting of experts in diabetes, immunology, endocrine surgery and transplantation is empowering Engelhardt’s research to fully investigate the transplant-diabetes link.

Colleagues at Vanderbilt University Medical Center and the School of Medicine include:

  • General surgeon and metabolism expert Naji Abumrad, MD, the John L. Sawyers Professor of Surgical Sciences;
  • James Crowe Jr., MD, the Ann Scott Carell Professor in the Departments of Pediatrics and Pathology, Microbiology and Immunology;
  • Diabetes researcher Maureen Gannon, PhD, professor of Medicine, Molecular Physiology and Biophysics, and Cell and Developmental Biology;
  • Madan Jagasia, MBBS, MSCI, MMHC, chief medical officer and director of the stem cell transplant program in the Vanderbilt-Ingram Cancer Center (VICC); and
  • Alvin Powers, MD, the Joe C. Davis Professor of Biomedical Science, director of the Division of Diabetes, Endocrinology and Metabolism in the Department of Medicine and director of the Vanderbilt Diabetes Research and Training Center.

“Engelhardt has done a cool thing,” said Crowe, who directs the Vanderbilt Vaccine Center and who serves as one of Engelhardt’s mentors. “He has leveraged the expertise of the Diabetes Center, the Vaccine Center (and) VICC to put together an interdisciplinary project on diabetes and transplant. This is a translational research project that is really unusual and could only be done at VUMC.”

Last spring the National Institutes of Health (NIH) also recognized the power of this approach, awarding Engelhardt his first R01 (research project grant), a five-year, $2 million award to determine why patients undergoing stem cell transplantation are at risk of developing diabetes.

To date, Engelhardt and his colleagues have found that transplant patients who develop diabetes show slightly elevated blood sugar levels and evidence of decreased sensitivity to the blood-sugar lowering hormone insulin even before they undergo transplantation.

This condition, known as prediabetes or insulin resistance, precedes outright diabetes by years to decades in the general population. In transplant patients, however, the rise in blood sugar levels from prediabetic to diabetic levels occurs over a span of mere days to months.

The researchers are testing the hypothesis that increases in inflammation caused by transplantation correlate with abnormal insulin production and the rapid development of diabetes in this patient population.

Engelhardt hopes findings from his research will provide insights into diabetes and cancer in the general population, as these disorders also involve abnormal inflammation.

Engelhardt credited the cross-collaboration between VICC and the Division of Diabetes, Endocrinology and Metabolism “and all these great investigators” for making his study possible. “Vanderbilt is a great place to do this type of research,” he said.

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