colesevelam hypoglycemia bile acid binding in rygb : a meal test study

Rationale:
Postprandial hyperinsulinemic hypoglycaemia often occurs after bariatric surgery and is called PBH.
We previously found that 48% of patients after RYGB developed a hypoglycemic event in a mixed meal test (MMT). In these patients bile acid (BA) concentrations were much higher compared to those without hypoglycemia. Furthermore, more patients with hypoglycemia had undergone a cholecystectomy (CCx). The role of postprandial bile acids in PBH has up till now not been elucidated
Objective:
Primary : To investigate the effects of BA binding on the occurrence of hypoglycemia (glucose < 3.0 mmol/L) during a mixed meal test (MMT) in those patients after RYGB and cholecystectomy who develop a hypoglycemic event (glucose < 3.0 mmol/L) during a MMT.
Study design: prospective, non-blinded, pre- and posttreatment.
Study population:
Patients between 20 and 60 years who underwent RYGB surgery 2 years or more before and have a history of CCx
Intervention : only for those who develop a hypoglycemic event during the first MMT: colesevelam tablets 625mg , 6 tablets dissolved in water ingested just before the meal.
Main study parameters/endpoints:
Glucose nadir during the MMT
Number of patients developing hypoglycemia during the MMT
Glucose disposal rate and endogenous glucose production during the MMT measured with stable isotope dilution
Changes in bile acids and subclasses during the MMT
Changes in insulin, GLP-1, PYY, FGF19 during the MMT
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
Patients have to visit the outpatient clinic 1-2 times in fasting condition.
Via an indwelling catheter blood samples will be drawn 11 times to a total amount of 264 mL
The meal can induce dumping complaints and can induce a low blood sugar, which will be monitored and treated if necessary.

Bile acids play a role in stimulating GI-hormone release after RYGB leading to an increased secretion of insulin causing postprandial hypoglycemia (PBH). Bile acid sequestrants could decrease the binding of BA with the TGR-5 receptor on L-cells. This would result in less GLP-1 release causing a lower insulin response to glucose leading to amelioration of postprandial hyperinsulinemic hypoglycemia.

20 patients will start the first MMT f Those who developed a hypoglycemia (glucose < 3.0 mmol/L) will enter the second part of the study. The MMT will be repeated preceded by colesevelam 3750 mg dissolved in water ingested just before the start of the MMT.

colesevelam 625mg tablets, 6 tablets dissolved in water ingested together