Girl Power: Islet Transplants from Women Donors Work Better

Miriam E. Tucker

June 14, 2014

SAN FRANCISCO — Transplanted pancreatic islets from female donors outperformed those from male donors in recipients with type 1 diabetes, a new study finds.

The results were presented here at the American Diabetes Association (ADA) 2014 Scientific Sessions by Kirstie K. Danielson, PhD, assistant professor of transplant surgery and epidemiology and biostatistics at the University of Illinois at Chicago.

Among 23 consecutive adult patients with type 1 diabetes who received allogeneic pancreatic islet-cell transplants, the 11 who received islets from female donors had significantly higher C-peptide levels, greater insulin secretion, and lower average glucose levels posttransplant than did the 12 recipients of male donor islets.

"None of the outcomes were better for recipients of male islets," Dr. Danielson said.

Session moderator James A. M. Shaw, PhD, professor of regenerative medicine for diabetes at Newcastle University, United Kingdom, told Medscape Medical News, "I think it is tantalizing. It did seem real that female donors were leading to better transplant results."

The effect appeared to be related to estrogen, as other study findings included worse beta-cell function in current users of oral contraceptives (which suppress circulating estrogen) compared with nonusers; better function among premenopausal compared with postmenopausal female recipients; and better function in postmenopausal women who used hormone-replacement therapy (HRT) compared with nonusers.

Islet-Cell Transplant Success Improving

Dr. Shaw told Medscape Medical News that islet-cell transplantation is a "very safe and effective" procedure for patients with type 1 diabetes who have severe hypoglycemic unawareness. The need for immunosuppression is the primary factor preventing its wider use, he said.

"It mustn't be seen as a short-term cure. It's a real cure for people with severe hypoglycemia," he said, pointing to data from another paper presented during the same oral abstract session in which continuous glucose monitoring demonstrated significantly better glucose control and reduced glycemic variability among islet-cell recipients than among type 1 patients using the best currently available medical therapy.

"The big thing in America is [Food and Drug Administration] approval. There is no doubt success is getting better and better," he noted.

Estrogen Effects?

In Dr. Danielson's study, both the deceased islet donors and the recipients had a mean age of 46 years. Half of the donors and more than three-quarters of the recipients were female. Among the female recipients, 9 were postmenopausal (5 of whom were on HRT) and 5 were premenopausal contraceptive users.

Half of the recipients (11) achieved insulin independence at some point posttransplant, and 13 eventually required a second transplant. The current study focused on multiple measures taken during the 64 weeks following the first transplant.

After adjustment for a variety of potential confounders, including donor and recipient age and weight, cause of donor death, cold ischemia time, and number of islets received, measures of fasting C-peptide function (335 separate tests) were significantly better among the recipients of female donor islets (P = .02), as were measures of glucose-stimulated C-peptide at 0 minutes (31 measurements, P = .02) and at 6 minutes (32 measures, P = .03).

Both insulin and glucose responses to oral glucose tolerance tests were also better among the female islet recipients (P = 0.01 and P = .01, respectively).

Among postmenopausal women islet recipients, those who used HRT had significantly better insulin responses to oral glucose tolerance tests (P = .04), lower insulin dose requirements (P = .04), and higher fasting C-peptide levels (P = .006).

Dr. Shaw said: "It's very interesting to know the effect that these sex hormones have on people's diabetes and islet function, and there is other work going on about that.

"We have an opportunity with islets to really understand them before we transplant them. We need to make sure we're giving the best islets to the best patients.…Some of these factors may come into play to improve survival and function when they're transplanted," he concluded.

Dr. Danielson and Dr. Shaw have reported no relevant financial relationships .

American Diabetes Association 2014 Scientific Sessions; June 14, 2014. Abstract 83-OR

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