Assessing Insulin Turnover Using an In-vivo Deuterated Water Experiment. (DEEP1A)

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.

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.

Study Overview

• Status: Completed
• Conditions: Hypoglycemia; Gastric Bypass; Bariatric Surgery
• Intervention / Treatment: Other: Heavy water experiment

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.

• Study Type: Observational
• Enrollment (Actual): 4

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Department of Diabetes, Endocrinology, Clinical Nutrition and Metabolism, Inselspital, Bern University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PHH patients; Patients following Roux-en-Y gastric bypass surgery (≥1 year ago) with confirmed post-prandial hyperinsulinemic hypoglycemia	Other: Heavy water experiment; 3 times daily heavy water (deuterated-water) and mixed meal administration for one week
Healthy controls; Non-PHH, non-surgical healthy individuals	Other: Heavy water experiment; 3 times daily heavy water (deuterated-water) and mixed meal administration for one week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total amount of pre-stored insulin secreted	Measured using deuterium (2H)-labelled insulin in the plasma	During the 7 days of the heavy water administration period

Secondary Outcome Measures

Outcome Measure	Time Frame
Time course of the increase in 2H-labelled insulin in plasma	During the 7 days of the heavy water administration period
Time course of the increase in 2H-labelled insulin in urine	During the 7 days of the heavy water administration period
Time course of the increase in 2H-labelled c-peptide in plasma	During the 7 days of the heavy water administration period
Time course of the increase in 2H-labelled c-peptide in urine	During the 7 days of the heavy water administration period

Collaborators and Investigators

• Sponsor: Lia Bally
• Investigators: Principal Investigator: Lia Bally, MD, PhD, Bern University Hospital, University of Bern

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2020
• Primary Completion (Actual): August 13, 2020
• Study Completion (Actual): August 20, 2020

Study Registration Dates

• First Submitted: March 30, 2020
• First Submitted That Met QC Criteria: March 31, 2020
• First Posted (Actual): April 2, 2020

Study Record Updates

• Last Update Posted (Actual): October 1, 2020
• Last Update Submitted That Met QC Criteria: September 29, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Insulin secretion; Insulin turnover; Deuterated Water; De-novo insulin synthesis
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hypoglycemia; Physiological Effects of Drugs; Antineoplastic Agents; Protective Agents; Radiation-Protective Agents; Deuterium Oxide
• Other Study ID Numbers: DEEP1A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No