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ORLANDO -- Use of a continuous glucose monitor (CGM) accurately predicted and prevented severe post-bariatric hypoglycemia, according to a small proof-of-concept study.
Christopher Mulla, MD, of Beth Israel Deaconess Medical Center in Boston, reported that two of five participants avoided severe hypoglycemia (<60 mg/dL) following a mini-dose of an investigational, stable liquid glucagon, which was administered through an event-based patch pump.
"We report the first use of an event-based glucagon rescue system, which successfully predicted and helped prevent severe hypoglycemic episodes," Mulla said in his presentation at ENDO 2017 here.
Action Points
- Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
"Patients with post-bariatric hypoglycemia (PBH) experience severe hypoglycemia and neuroglycopenia. Current nutritional and medication therapies are incompletely effective for hypoglycemia prevention. However, severe hypoglycemia in PBH can be treated successfully with rescue glucagon. Due to difficulties in implementation, it has not had wide implementation; the aim of our study was to create a novel approach to treat and prevent hypoglycemia."
Mulla's group developed a novel, CGM-driven hypoglycemia prediction algorithm for PBH. They hypothesized that small doses of an investigational stable liquid glucagon delivered via subcutaneous infusion pump, guided by alerts from a CGM-triggered low glucose prediction algorithm, could prevent severe hypoglycemia without rebound hyperglycemia.
The team studied four females and one male with PBH and neuroglycopenia. Mean age was 47, mean body mass index was 32, and the patients were 100 months post-surgery. None of the patients had a history of diabetes, and their A1C levels were normal.
After screening, all patients received two sensors and then returned 1-2 days later after an overnight fast. The sensor most concordant with plasma glucose was utilized to guide the system, explained Mulla.
Participants consumed a liquid mixed meal (Ensure Compact, 236 ml size, which had 64 g of carbohydrates and 18 g protein); and sensor and plasma glucose (YSI), insulin, and glucagon were then measured. The low glucose prediction algorithm used CGM data to estimate trends and time to impending hypoglycemia.
Two distinct alarms were used in parallel to ensure reliable detection:
- A post-bariatric hypoglycemia (PBH) postprandial alarm, issued after a meal when sensor glucose was rapidly dropping
- A hypoglycemia proximity alarm, issued when sensor glucose was close to the hypoglycemia threshold
Glucagon (Xeris, 150 μg) was administered in response to the predicted hypoglycemia alert, and blood sampling was continued for 2 hours.
Mean peak post-meal glucose was 205 mg/dl, occurring at 38 minutes, with plasma insulin at 234 µU/ml. Glucose fell rapidly thereafter, with the maximum rate of change -8 mg/dl/min, Mulla reported.
Predictive hypoglycemia alerts were triggered at 105 minutes after the liquid mixed meal, prompting physician glucagon delivery via pump 6 minutes later. The mean CGM and YSI glucose at alert were 92 and 78 mg/dl, respectively, with insulin 31 µU/ml, he added.
Glucagon levels were undetectable at alert, but peaked at 387 pg/ml 20 minutes after bolus, Mulla said. Minimum glucose during the study was 59 mg/dl. Two patients required oral glucose following glucagon. No rebound hyperglycemia was observed.
When a meeting attendee pointed out that the presentation did not include data on symptoms, Mulla noted that symptoms were measured with the Edinburgh hypoglycemia scale: "We did note that at baseline, patients' levels were low or normal, but after that, some did report some symptoms, even before the patients were hypoglycemic. At the time of hypoglycemia they did repeat some symptoms. We measured symptoms at 15, 30, and 60 minutes after the glucagon application, and levels increased after 15 minutes."
Mulla added that higher doses of glucagon may be required to fully reverse rapid postprandial falls in glucose in the setting of very high, peak postprandial insulin levels in patients with PBH.
The next step, he told 鶹ý, is development of a modified dosing system that will use this algorithm with a modified dosing regimen in a closed loop system.
Disclosures
Mulla and co-authors disclosed relevant relationships with Xeris Pharmaceuticals, and some of the co-authors are company employees.
Primary Source
ENDO 2017
Mulla C, et al "Automated event-based system for the prevention of post-bariatric hypoglycemia using a mini-dose of a stable glucagon formulation" ENDO 2017; Abstract OR 14-5.