Pediatric endocrinologist Deborah Elder, MD, usually takes new clinical practice recommendations from the American Diabetes Association (ADA) in stride. But this one was different.

Elder is endocrine director at the Pancreas Care Center at Cincinnati Children’s, whose team has successfully performed more than 100 total pancreatectomy with islet autotransplantations (TPIATs). She is responsible for helping patients maintain tight glycemic control after TPIAT. In 2021, she and other researchers at Cincinnati Children’s published a study demonstrating that the drug hydroxyurea, used to prevent postoperative reactive thrombocytosis, resulted in false elevations of glucose sensor readings when using Dexcom continuous glucose monitor (CGM) devices. Which brings us to the ADA clinical practice recommendations.

Like thousands of other endocrinologists, Elder attended the 83rd annual ADA Scientific Sessions in San Diego, CA, in June 2023. During the Updates in Standards Symposium, she realized the presenters were recommending a change in practice guidelines based on her team’s research. The recommendation was to counsel patients and families about the “hydroxyurea effect” and advise reliance on glucometer testing rather than the Dexcom sensor for six to nine hours after hydroxyurea administration.

“The announcement and recognition took me by surprise and made me so happy,” Elder says. “Especially because a parent helped our team make the connection between hydroxyurea and the false elevation sensor glucose readings. The new guideline will help care teams everywhere avoid potentially life-threatening hypoglycemic events after TPIAT and in other populations that use this medication.”

Recognizing the “Hydroxyurea Effect”

TPIAT can alleviate severe pain caused by acute recurrent and chronic pancreatitis but can lead to fully insulin-dependent, post-pancreatectomy diabetes. A glucotoxic environment can escalate the risk of beta cell failure and apoptosis of the transplanted islet cells, which is why the TPIAT team prioritizes tight glycemic control.

Once the pancreas is removed, patients receive intravenous insulin with the goal of achieving a blood glycemic range of 80–120 mg/dL. When stable post-operatively, the patients are transferred from the ICU to a specialized endocrine/surgical floor for insulin pump therapy and continuous glucose monitoring. Certified diabetes educators at Cincinnati Children’s provide extensive diabetes management education before, during and after the hospital stay.

Patients rely on a glucometer to test their blood glucose before bolusing, especially six to nine hours after hydroxyurea administration. “Before we recognized the hydroxyurea effect, we saw large discrepancies in device readings—the CGM might say 300, but the glucometer would say 96,” Elder says. “It was frustrating for parents, and started to erode their trust in the technology. Of course, it was also a safety concern. If parents were to go home from the hospital and rely on CGM readings when bolusing, it could cause a severe hypoglycemic event.”

Parent Input Led to the Discovery

Elder was talking with a mom during a clinic encounter when she wondered aloud whether a medication was causing the false readings. “The mom noted that the spike always occurred after her child received their daily dosing of hydroxyurea and aspirin for reactive thrombocytosis prevention,” she says. “That’s what prompted our investigation.”

Elder pulled data from inpatient documentation of medication administration, glucometer readings and Dexcom sensor reports from 46 patients post-TPIAT. The discrepancy correlated to hydroxyurea administration (not aspirin) and was dose-dependent. Elder says the drug’s chemical structure penetrates the Dexcom sensor, causing abnormal values. The results led to changes in the TPIAT education process at Cincinnati Children’s, and Dexcom added the discovery to their package insert.

“We are grateful we recognized the hydroxyurea issue before the widespread use of automated insulin delivery systems at our center.” Elder notes. “We now program each child’s insulin pump to ‘manual mode’ and use established pre-programmed basal rates.”

Tight Glycemic Control Correlates to Favorable Outcomes

Efforts to maintain tight glycemic control are leading to favorable outcomes in children post-TPIAT at Cincinnati Children’s. Elder and her colleagues published a paper in the Journal of Clinical Medicine in May 2023 demonstrating that during the first 10 post-op days, early insulin pump therapy initiation led to less blood glucose variability, more time in range and fewer incidences of hyper- and hypoglycemia.

The hydroxyurea study was published in Diabetes Technology & Therapeutics in June 2021. To learn more, contact Deborah.Elder@cchmc.org.