Clinical trial NCT04332289: Assessing Insulin Turnover Using an In-vivo Deuterated Water Experiment.
Official title: Deciphering the Enigma of Postprandial Hyperinsulinaemic Hypoglycaemia After Bariatric Surgery, Part 1 A: Assessing Insulin Turnover Using an In-vivo Deuterated Water Experiment. A Proof-of-concept Study.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Bariatric Surgery
Hypoglycemia
Gastric Bypass
Keywords: Insulin turnover
Insulin secretion
Deuterated Water
De-novo insulin synthesis
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2020-04-02
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will be recruited by referral from our outpatient endocrine clinic and collaborating Centres of Excellence for Metabolic Surgery. Non-surgical controls will be recruited through advertisement according to guidelines from swissethics.

Brief summary: The primary objective of this study is to observe the kinetics of pre-stored and de-novo synthesized insulin that is secreted into the circulation using an in-vivo heavy water (D2O) labelling experiment in patients with postprandial hyperinsulinaemic hypoglycaemia (PHH) and non-surgical non-PHH controls.

Detailed description: Despite an increased prevalence, the underlying pathophysiology of PHH remains incompletely understood. It is generally assumed that PHH is caused by excess insulin secretion, either due to an intrinsic beta-cell abnormality (histology showing increased beta-cell mass or signs of hyperfunction) and/or increased postprandial insulinotropic signals (also known as the incretin-effect) as a consequence of the re-arranged gastrointestinal tract and accelerated nutrient transit and absorption. Either of the two explanations would imply an altered insulin turnover in these patients with higher amounts of pre-stored insulin and/or accelerated de-novo insulin synthesis in response to stimulus-depletion of the available insulin pool. A non-invasive in vivo technique to study insulin turnover has not been established yet and data related to PHH are consequently lacking.

The primary objective of this study is to observe the kinetics of pre-stored and de-novo synthesized insulin that is secreted into the circulation using an in-vivo heavy water (D2O) labelling experiment in patients with postprandial hyperinsulinaemic hypoglycaemia (PHH) and non-surgical non-PHH controls. The investigators hypothesize that the suggested methodological approach is feasible to assess insulin turnover and provides the foundation for further studies in different target groups.

Eligibility criteria: Inclusion criteria for PHH patients:

* Aged ≥18 years
* Roux-en-Y gastric bypass ≥1 year ago
* PHH defined as postprandial plasma or sensor glucose\<3.0mmol/l according to the International Hypoglycaemia Study Group and exclusion of other causes of hypoglycaemia

Inclusion criteria for non-PHH non-surgical controls:

* Aged ≥18 years
* Absence of any condition or previous surgery known to affect gastro-intestinal integrity and food absorption

Exclusion Criteria:

* Clinically relevant weight changes (≥5%) within the past 3 months
* Incapacity to give informant consent
* Historical or current diabetes based on HbA1c ≥6.5% without glucose-lowering treatment
* Haemoglobin level below 13.5 g/l
* Ongoing treatment with glucose-lowering drugs, anorectic drugs, steroids or any medications known to affect gastric motility
* Active heart, lung, liver, gastrointestinal, renal or neurological disease
* Inability to follow study procedures
* Pregnancy or breast-feeding

Primary outcomes:
measure: Total amount of pre-stored insulin secreted
timeFrame: During the 7 days of the heavy water administration period
Secondary outcomes:
measure: Time course of the increase in 2H-labelled insulin in plasma
timeFrame: During the 7 days of the heavy water administration period
measure: Time course of the increase in 2H-labelled insulin in urine
timeFrame: During the 7 days of the heavy water administration period
measure: Time course of the increase in 2H-labelled c-peptide in plasma
timeFrame: During the 7 days of the heavy water administration period
measure: Time course of the increase in 2H-labelled c-peptide in urine
timeFrame: During the 7 days of the heavy water administration period
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Department of Diabetes, Endocrinology, Clinical Nutrition and Metabolism, Inselspital, Bern University Hospital
Study officials:
affiliation: Bern University Hospital, University of Bern
name: Lia Bally, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: