New Protocol Cuts Fasting Time to Rule Out Insulinoma

SEATTLE — Use of a new protocol — sequential beta-hydroxybutyrate testing with a cut-off for ruling out insulinoma in patients with hypoglycemia — may allow for a shortening of the gold-standard 72-hour fasting time normally required for this diagnosis, therefore yielding significant hospital cost savings, new data suggest.

Insulinomas are small, rare types of pancreatic tumors that are benign but secrete excess insulin, leading to hypoglycemia. More than 99% of people with insulinoma develop hypoglycemia within 72 hours, hence, the use of a 72-hour fast to detect these tumors.

But most people who are evaluated for hypoglycemia do not have an insulinoma and fasting in hospital for 3 days is burdensome and costly.

As part of a quality improvement project, Cleveland Clinic endocrinology fellow Michelle D. Lundholm, MD, and colleagues modified their hospital's protocol to include measurement of beta-hydroxybutyrate (BHB), a marker of insulin suppression, every 12 hours with a cutoff of ≥ 2.7mmol/L for stopping the fast if hypoglycemia (venous glucose ≤ 45mg/dL) hasn't occurred. This intervention cut in half the number of patients who needed to fast for the full 72 hours, without missing any insulinomas.

"We are excited to share how a relatively simple adjustment to our protocol allowed us to successfully reduce the burden of fasting on patients and more effectively utilize hospital resources. We hope that this encourages other centers to consider doing the same," Lundholm told Medscape Medical News.

"These data support a 48-hour fast. The literature supports that's sufficient to detect 95% of insulinomas...But, given our small insulinoma cohort, we are looking forward to learning from other studies," she added.

Lundholm presented the late-breaking oral abstract on May 5 at the American Association of Clinical Endocrinology Annual Meeting.

Asked to comment, session moderator Jenna Sarvaideo, MD, told Medscape Medical News: "We're often steeped in tradition. That's why this abstract and this quality improvement project is so exciting to me because it challenges the history…and I think it's ultimately helping patients."

Sarvaideo, of Clement J. Zablocki VA Medical Center, Milwaukee, Wisconsin, noted that, typically, although the fast will be stopped before 72 hours if the patient develops hypoglycemia, "often they don't, so we keep going on and on. If we just paid more attention to the beta-hydroxybutyrate, I think that would be practice-changing."

She added that more data would be optimal, given that there were under 100 patients in the study, "but I do think that devising protocols is...very much still at the hands of the endocrinologists. I think that this work could make groups re-evaluate their protocol and change it, maybe even with a small dataset and then move on from there and see what they see."

Indeed, Lundholm pointed out that some institutions, such as the Mayo Clinic, already include 6-hour BHB measurements (along with glucose and insulin) in their protocols.

"For any institution that already draws regular BHB levels like this, it would be very easy to implement a new stopping criterion without adding any additional costs," she told Medscape Medical News.

All Insulinomas Became Apparent in Less Than 48 Hours

The first report to look at the value of testing BHB at regular intervals was published by the Mayo Clinic in 2005 after they noticed patients without insulinoma were complaining of ketosis symptoms such as foul breath and digestive problems toward the end of the fast.

However, although BHB testing is used today as part of the evaluation, it's typically only drawn at the start of the protocol and again at the time of hypoglycemia or at the end of 72 hours because more frequent values hadn't been thought to be useful for guiding clinical management, Lundholm explained.

Between January 2018 and June 2020, Lundholm and colleagues followed 34 Cleveland Clinic patients who completed the usual 72-hour fast protocol. Overall, 71% were female and 26% had undergone prior bariatric surgery procedures. Eleven (32%) developed hypoglycemia and stopped fasting. The other 23 (68%) fasted for the full 72 hours.

Lundholm and colleagues determined that the fast could have ended earlier in 35% of patients based on an elevated BHB without missing any insulinomas.

And so, in June 2020 the group revised their protocol to include the BHB ≥ 2.7mmol/L stopping criteria. Of the 30 patients evaluated from June 2020 to January 2023, 87% were female and 17% had undergone a bariatric procedure.

Here, 15 (50%) reached a BHB ≥ 2.7mmol/L and ended their fast at an average of 43.8 hours. Another seven (23%) ended the fast after developing hypoglycemia. Just eight patients (27%) fasted for the full 72 hours.

Overall, this resulted in approximately 376 fewer cumulative hours of inpatient admission than if patients had fasted for the full time.

Of the 64 patients who have completed the fasting protocol since 2018, seven (11%) who did have an insulinoma developed hypoglycemia within 48 hours and with a BHB < 2.7 mmol/L (median, 0.15).

Advantages: Cost, Adherence

A day in a general medicine bed at Cleveland Clinic was quoted as costing $2,420, based on publicly available information as of January 1, 2023. "If half of patients leave one day earlier, this equates to about $1,210 per patient in savings from bed costs alone," Lundholm told Medscape Medical News.

The revised protocol required an additional two to four blood draws, depending on the length of the fast. "The cost of these extra blood tests varies by lab and by count, but even at its highest does not exceed the amount of savings from bed costs," she noted.

Patient adherence is another potential benefit of the revised protocol.

"Any study that requires 72 hours of patient cooperation is a challenge, particularly in an uncomfortable position like fasting. When we looked at these adherence numbers, we found that the percentage of patients who prematurely ended their fast decreased from 35% to 17% with the updated protocol," Lundholm continued.

"This translates to fewer inconclusive results and fewer readmissions for repeat 72-hour fasting. While this was not our primary outcome, it was another noted benefit of our change," she said.

Lundholm and Sarvaideo have reported no relevant financial relationships.

American Association of Clinical Endocrinology (AACE) Annual Meeting 2023. Abstract #1494000. Presented May 5, 2023.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR's Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.

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