Adding This New Criteria Drastically Cut 72-Hour Insulinoma Fast Time

SEATTLE — Adding beta-hydroxybutyrate (BHB) stopping criteria cut down fasting time when detecting insulinomas in patients with hypoglycemia, according to late-breaking findings presented here.

By adding in a stopping point if BHB reached a level of 2.7 mmol/L or higher to the fasting protocol, fasting time was nearly 8 hours shorter on average across the board, said Michelle D. Lundholm, MD, of the Cleveland Clinic.

With this update to the protocol, the average fast duration lasted only 49.7±21.1 hours, she said during a presentation at the American Association of Clinical Endocrinology (AACE) annual meeting.

Half of the patients were able to stop because they reached this BHB elevation threshold. And those who ended because of BHB elevation only fasted an average of 44 hours, saving them an average of 25 hours fasting in the hospital.

A total of 27% fasted the full 72 hours and the remaining 23% ended the fast because they developed hypoglycemia (glucose level of 45 mg/dL or lower).

After the BHB update to the protocol, there were approximately 376 fewer cumulative hours of inpatient admissions, said Lundholm. “And for reference, it is publicly available knowledge that a day in a general medicine bed at our hospital is quoted to cost approximately $2,400,” she noted.

Importantly, Lundholm said that no cases of insulinoma were detected in any of the patients that quit the fast early due to BHB elevation.

“By adding a BHB stopping criteria to our 72-hour fast protocol, we successfully reduced inpatient hospitalization time for fasting without compromising the detection of insulinoma,” she said. “This evidence-based intervention reduces the burden on patients and more effectively utilizes hospital resources, not to mention fewer patients had to develop hypoglycemia and the symptoms associated.”

“From physiology and what has been described in the literature, this increased BHB is evidence against a hyperinsulinemic state and in fact it’s indicative of insulin suppression and it excludes insulinoma,” she added.

Lundholm said that in June 2020, her institution updated its 72-hour fast protocol — the current gold standard test for detecting insulinoma — to include a new stopping point. During the fast, BHB levels were screened every 12 hours.

Reflecting on future steps, Lundholm said there is discussion around upping the BHB testing frequency to every 6 hours, “particularly after 30 or 36 hours of fasting with the hopes of detecting that rise in BHB sooner,” although this would need to be weighed against associated costs and inconvenience of more frequent testing.

The retrospective chart review looked at all patients who completed this updated fast protocol since its implementation mid-2020. This included 30 patients from the past 2.5 years. The majority were female (87%); mean age was 45, with a BMI of 28. A fifth had diabetes and 17% had a history of bariatric surgery.

Since the original 72-hour fasting protocol was implemented in 2018 at Cleveland Clinic, insulinoma has been detected in 11% of fasted patients (n=7 of 64). Of these insulinoma cases, 57% were female with an average age of 56. About 14% had diabetes, 28% underwent bariatric surgery, and the average BMI was about 40.

All detected cases of insulinoma developed hypoglycemia at around 18.6 hours, occurred within 48 hours, and all had a BHB below 2.7 mmol/L. The median BHB was 0.15 and ranged between less than 0.01 to 1.2 — “nowhere near our cutoff of 2.7,” said Lundholm.

“So this data even additionally supports a 48-hour fast protocol,” she suggested, “and the literature reports that a 48-hour fast is effective for detecting at least 95% of insulinomas.”

She added that prior to the BHB cutoff addition, around 35% of fasts ended prematurely — but not due to one of the predefined stopping points, underscoring the difficulty in patient adherence to a fast spanning 72 hours. After the update, only 17% of fasts ended prematurely.

“This translates to fewer inconclusive fasts, fewer readmissions for fast redos, and I would argue it’s potentially a marker for improved patient experience,” she noted.

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