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Islet transplantation restored glucose counter-regulation in patients with type 1 diabetes
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Pancreatic islet cell transplantation can help patients with type 1 diabetes regain normal internal recognition of hypoglycemia, following the loss of awareness that occurs with insulin treatments over time, according to research published in Diabetes.
“The results of this study suggest that islet cell transplantation may be an effective treatment for patients with type 1 diabetes who are experiencing significant hypoglycemic events because their body isn’t able to recognize their low blood sugar levels,” Michael R. Rickels, MD, director of the Pancreatic Islet Cell Transplant Program at University of Pennsylvania, Philadelphia.
“Currently, islet cell transplantation is considered investigational for type 1 diabetes patients, but this study shows that it has the potential to dramatically improve a patient’s ability to defend against and recognize symptoms of hypoglycemia and eliminate severe hypoglycemic episodes,” he said.
Rickels, with colleagues from the Perelman School of Medicine at the institution and the Monell Chemical Senses Center, also in Philadelphia, longitudinally studied 12 patients with hypoglycemia unawareness and frequent severe hypoglycemia who were assigned to one or two islet infusions to achieve insulin-independence; disease duration was approximately 30 years.
Prior to and 6 months after intrahepatic islet transplantation, the investigators assessed hypoglycemia recognition capability using stepped hyperinsulinemic-hypoglycemic and paired hyperinsulinemic-euglycemic clamps with infusion of 6,6-2H2-glucose, then compared results with those from a control group of 8 participants without diabetes.
HbA1c was normalized following islet transplantation. Further, time spent in hypoglycemia (<70
mg/dL) was nearly eliminated, based on continuous glucose monitoring.
In response to insulin-induced hypoglycemia, C-peptide, absent prior to transplant, was aptly suppressed, glucagon secretion recovered and epinephrine secretion improved following transplantation.
Consistent with hormonal changes, endogenous glucose production response to insulin-induced hypoglycemia, also absent prior to transplant, was normalized following; a similar effect was seen for autonomic symptoms.
“Now that we’ve seen improvement in the protection against hypoglycemia as a result of islet cell transplantation, we’re evaluating the longer-term durability of these restored defense mechanisms,” Rickels said in the release.
Fellow investigator Ali Naji, MD, PhD, also at Penn, aims to develop new immunosuppression medication approaches to reduce the risk for adverse side effects through work now being conducted in his laboratory.
Disclosure: This work was a project of the Clinical Islet Transplantation Consortium clinical research collaboration, headquartered at the NIDDKD and the NIAID, and supported by Public Health Services Research Grants.
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