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

Hypoglycemia Clinical Trial

— DEEP1A  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04332289
• Other study ID #: DEEP1A
• Status: Completed
• Start date: July 9, 2020
• Est. completion date: August 20, 2020

Study information

• Verified date: September 2020
• Source: University Hospital Inselspital, Berne
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: August 20, 2020
• Est. primary completion date: August 13, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bariatric Surgery
• Gastric Bypass
• Hypoglycemia

Intervention

Other:
• Heavy water experiment
3 times daily heavy water (deuterated-water) and mixed meal administration for one week

Locations

Country	Name	City	State
Switzerland	Department of Diabetes, Endocrinology, Clinical Nutrition and Metabolism, Inselspital, Bern University Hospital	Bern

Sponsors (1)

Lead Sponsor	Collaborator
Lia Bally

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Time course of the increase in 2H-labelled insulin in plasma		During the 7 days of the heavy water administration period
Secondary	Time course of the increase in 2H-labelled insulin in urine		During the 7 days of the heavy water administration period
Secondary	Time course of the increase in 2H-labelled c-peptide in plasma		During the 7 days of the heavy water administration period
Secondary	Time course of the increase in 2H-labelled c-peptide in urine		During the 7 days of the heavy water administration period