One to two years after receiving experimental islet-cell transplants, 48 adults with tough-to-control type 1 diabetes were enjoying major health benefits according to a recent, headline-grabbing study funded by the National Institutes of Health, published online March 21 in the journal Diabetes Care. For 88%, severe hypoglycemia—episodes of unpredictable, life-threatening low blood sugar—stopped. Fifty-two percent no longer needed insulin injections and others required lower doses. Their blood sugar levels improved, too.
The study volunteers reported that their everyday lives were better. They felt more energetic and less stressed-out about their diabetes. Most dramatically, their nagging fears about low blood sugar—which can occur without warning or during sleep in some people with Type 1 diabetes— eased, too. The islet-cell recipients also said their overall health was better, even though they needed lifelong treatment with immune-suppressing drugs to prevent transplant rejection.
The study involved 48 women and men, average age 48, who’d had type 1 diabetes for an average of 28 years. All had “brittle” diabetes that’s difficult to control despite careful management and expert care from a diabetes specialist. And they all had hypoglycemia unawareness. At any time, their blood sugar could drop to dangerous lows without detectable warning signs, a potentially fatal problem for 10-15% of people with type 1.
“Hypoglycemic unawareness is prevalent among people with Type 1 diabetes, and presents a considerable burden both to them as well as to their families and loved ones,” Andrew Stewart, MD, director of the Diabetes, Obesity and Metabolic Institute, Icahn School of Medicine at Mount Sinai, who was not involved with the study, told OnTrack Diabetes. “This is an interesting study that shows that these considerable and very realistic worries and fears are lessened over the course of the first year following pancreatic islet transplantation…In addition, it underscores the point that it is not necessary to become insulin-free to achieve these quality-of-life improvements.”
Transplants of insulin-producing islet cells for people with diabetes are still experimental in the U.S. While people with type 1 and type 2 can receive a whole pancreas transplant, these are rare and are usually done in people who are receiving a kidney transplant. In this NIH study, participants received injections of insulin-producing islet cells into the portal vein, which carries blood from the intestines to the liver. The cells settle in the liver. There, they sense glucose levels in the bloodstream and release insulin as needed to tell the body to absorb the blood sugar. Most study volunteers needed one injection, but several required two shots.
Due to the need for a lifetime of anti-rejection drugs—which raise risk for infections—transplant studies in the US focus on type 1s with hypoglycemia unawareness. The reason: Experts think the benefits outweigh risks posed by the drugs. “If, in the future, research leads to better immunosuppressive drugs with fewer side effects, or to a way to give islets without the need for immunosuppression, then islet transplantation might become an appropriate treatment for more people with T1D,” study co-author Nancy D. Bridges, MD, chief of the Transplantation Branch of the National Institute of Allergy and Infectious Diseases, told OnTrack Diabetes.
Transplants for people with Type 2 diabetes could happen even farther in the future. “Some diabetes researchers think that islet transplantation might be appropriate for some patients with T2D,” says Thomas L. Eggerman, MD, PhD, program director of the Division of Diabetes, Endocrinology, and Metabolic Diseases at the National Institute of Diabetes and Digestive and Kidney Diseases. “However, there have been no clinical trials to study the use of islet transplantation to treat T2D.”
This study could move islet-cell transplants closer to FDA approval, Dr. Bridges notes, because it used a standardized manufacturing protocol to prepare purified islets for transplant. The cells come from the pancreases of deceased human donors. The National Institute of Allergy and Infectious Diseases has submitted final reports and clinical trial data to FDA, laying the groundwork for universities and companies to apply for licenses to manufacture the cells for transplants.
“If an islet product is licensed, then islet transplantation can become a “standard of care” procedure that can be paid for in the same way as other medical treatments, that is, by medical insurance (including Medicare),” she says. “This will make the procedure available to more people and make it easier for researchers to continue to improve islet transplantation. In addition, FDA licensure of a product helps to ensure the quality of the product, so that if a patient receives a licensed product called “Purified Human Pancreatic Islets (PHPI)”, they know precisely what they are getting.”
It’s not clear when that would happen. “The data are currently being evaluated at the FDA. We don’t know what, or when, the next step will be,” Bridges says.