Visualizing beta cells in patients with (postprandial) hyperinsulinemic hypoglycemia after bariatric surgery

Hyperinsulinemic hypoglycemia (HH) is a rare complication that occurs 1 to 5
year after gastric bypass surgery. The underlying mechanism of this
complication is not yet completely understood. Changes in hormone levels, such
as GLP1, after RYGB, nesidioblastosis or an increase in the number of beta
cells may be one of the underlying causes. However, several study results are
conflicting and it is hypothesized that the patient population with HH after
RYGB is heterogeneous and several underlying causes may be present. In order
to differentiate between hyperfunction with normal B-cell mass and a general
or localized increase in beta cell mass we aim to compare quantitative
68Ga-exendin-4 PET imaging of the pancreas between patients with and without HH
after RYGB. Thereby, we aim to increase the insight in the underlying mechanism
of HH after RYGB. If different underlying causes can be diagnosed, treatment
for HH can be optimized for patients.

The main objective is to examine if 68Ga-exendin tracer accumulation (i.e. beta
cell mass) differs in patients with persisting HH after RYGB compared to
matched patients without HH after RYGB.

The secondary objectives are:
- compare GLP1 and GIP responses after MMT in post-RYGB patients with and
without HH
- determine the correlation between measured exendin accumulation and beta cell
function and
- evaluate the distribution of 68Ga-exendin over the pancreas and compare
between both groups

For recruiting control individuals, hypoglycemia is excluded using a 14-day
continuous glucose monitoring. After recruitment of the participating
individuals, all patients will undergo an enrollment check at Rijnstate
hospital consisting of a medical interview and a physical examination performed
by a qualified physician. Recent blood samples for standard laboratory checks
(blood counts, electrolytes, liver enzymes, creatinine, inflammation
parameters) will be analyzed. Another visit is needed for an mixed meal test
and a glucose-dependent arginine-stimulation test to investigate meal responses
and the beta-cell function. At the third visit, a PET/CT scan will be performed
at the Radboudumc. 68Ga-NODAGA-exendin-4 will be administered to all patients
and the PET/CT scan will be performed 1 hour after injection of the
radiopharmaceutical.

All individuals will undergo physical examination and blood sampling for
standard laboratory parameters. In addition, all patients will undergo amixed
meal test and an arginine stimulation test. At the third visit,
68Ga-NODAGA-exendin-4 will be administered intravenously and PET/CT scanning
will be performed 1 hour after injection of the tracer. After injection of the
radiopharmaceutical, blood samples will be drawn from an intravenous catheter
for determination of blood glucose levels and blood pressure will be measured.
Injection of the radiopharmaceutical may theoretically result in nausea and
headache as has been reported for (much higher doses) Byetta® in therapy
studies. In addition, single cases of low blood pressure and low blood glucose
levels have been described. Although low blood glucose levels only occurred
after accidental heavy overdosing of Byetta®, patients will be closely
monitored. Furthermore, in a previous study (CPOP-EX), we did not observe any
side or adverse effects after 111In-DTPA-[K40]-exendin-4 injection for all 20
patients included.
The expected radiation exposure will not exceed 5 mSv per PET/CT scan and is
therefore considered minimal to little. However, if the technique would indeed
allow sensitive and specific visualization and quantification of beta cell mass
in patients with hyperinsulinemic hypoglycemia, this would make further
diagnosis and patient specific treatment possible in the future.