It's a cruel conundrum: For people with kidney disease, a transplant can be a literal lifesaver. But the medications it takes to help the body accept a new kidney can wreak havoc with the body’s insulin production, causing what amounts to diabetes in previously non-diabetic transplant recipients.
Life post-transplant is made possible by powerful drugs like prednisone and tacrolimus that suppress the immune system. Otherwise, the defenses that are supposed to fight off infections by recognizing and attacking foreign cells might attack a new kidney instead. As necessary as immunosuppressant drugs are for transplant patients, they can cause a host of side effects, including weight gain, osteoporosis, psychological problems, and high blood pressure.
Kristi Silver, MD
Associate Professor, University of Maryland School of Medicine
Clinical Translational Research Award
And in some patients, the drugs can reduce insulin secretion and increase insulin resistance. The results "look a lot like type 2 diabetes," says Kristi Silver, MD, an endocrinologist and associate professor at the University of Maryland School of Medicine. It's usually called post-transplant diabetes mellitus, or PTDM. Right now, there's no way to know whose endocrine systems will react poorly to post-transplant drugs. "Most people will return to whatever their pre-transplant glycemic state was," Silver says. "But 10 to 20 percent will develop post-transplant diabetes."
With help from ADA, Silver is looking for ways to predict before a transplant which patients are at highest risk for PTDM. The goal wouldn't be to change someone's mind about getting a transplant or to persuade a doctor not to prescribe immunosuppressants: Neither is really an option. "You'll always need to be on something; it's just a question of what combination," Silver says. "The question is: Can we look at a group beforehand to predict who's going to get [diabetes] and who isn't?"
If post-transplant diabetes could be predicted pre-transplant, it would be easier to prepare patients for what they can expect after the operation. Counseling and other measures could be put in place to help people cope with the combination of a new kidney and the stresses of dealing with what amounts to drug-induced diabetes. "It's important to mentally prepare them," Silver says. "They're so overwhelmed with everything they need to know for the transplant. Diabetes is just one thing too many. Potentially, if they know they have a chance of getting diabetes, they won't be so overwhelmed."
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To set up her study, Silver worked with a transplant surgeon to identify people who needed a kidney transplant but didn't already have diabetes, one of the two most common causes of kidney disease. (High blood pressure is the other.) In order to finish her study on time, Silver is focusing on people with less than a year to wait for a transplant. People who already have diabetes or are on immunosuppressants—because they had a transplant in the past, for example—are eliminated from the study group.
She asks potential candidates to come in for a series of exams. First, she gives them an oral glucose tolerance test, a common way to measure the body's reaction to sugar. Then she gives them a dose of prednisone, similar to what they might get after a transplant operation, and another oral glucose tolerance test. "The hypothesis is people with the highest sugars with prednisone will be the ones who are more likely to develop post-transplant diabetes," Silver says. She then follows patients for a year after their transplant, monitoring their blood test results for signs of PTDM.
She's hoping to see results that will show whether sensitivity to immunosuppressants before a transplant is an accurate way to predict who might have a diabetes-like reaction afterward. Then those patients could get good preparation for what could come next. "We would focus our energy on improving weight management, diet, and other lifestyle changes pre-transplant," Silver says, giving people at the highest risk tools to manage their post-transplant diabetes—and a better chance for good health in the years to come.