Abstract

Pregnancy increases metabolic demand for insulin, which may lead to the exhaustion of intraportally transplanted islets and postgestational hyperglycemia. Here we report a successful long-term preservation of islet graft function after two subsequent pregnancies while applying preemptive insulin supplementation. 29-year-old female with T1DM achieved long-term insulin independence with HbA1c <5.8% after a single intraportal islet transplant. Before conception, mycophenolate was replaced with azathioprine and tacrolimus target trough level was decreased to 4-6ng/ml. The patient became pregnant twice, 5 years and 7.5 years after her islet transplantation. During the first and second pregnancy patient preemptively supplemented with insulin up to 35-70u/day and up to 35 units daily, respectively to target fasting blood glucose below 90mg/ml. Postpartum the patient was successfully weaned off insulin maintaining optimal blood glucose control with HbA1c below 5.7%. Islet graft function before and after the pregnancy remained optimal as reflected by BETA-2 above 17 and comparable c-peptide secretion and peak blood glucose levels below 130mg/ml during the 8.5-year follow-up in Mixed Meal Tolerance Test. Both newborns were premature and delivered at 34 weeks with emergent c-sections due to preeclampsia. Unfortunately, the first newborn died due to necrotizing enterocolitis. The second child has been developing appropriately up-to-date three months after her birth. Our report confirms that insulin supplementation during pregnancy in insulin-independent patients after islet transplantation was safe and effective in maintaining optimal blood glucose control and islet graft function in the long term. It also underscores the high-risk nature of pregnancy in islet transplant recipients and the need for close clinical monitoring. Disclosure S.Gondek: None. L.Wang: None. M.Tibudan: None. R.Barth: None. J.Fung: None. P.Witkowski: Advisory Panel; Vertex Pharmaceuticals Incorporated, Novartis. M.Ogledzinski: None. W.Lin: None. K.Milejczyk: None. B.Juengel: None. L.Potter: None. P.J.Bachul: None. L.Basto: None. L.Perea: None.

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