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

Completed
Conditions
Hypoglycemia
Bariatric Surgery
Gastric Bypass
Interventions
Other: Heavy water experiment
Registration Number
NCT04332289
Lead Sponsor
Lia Bally
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
4
Inclusion Criteria

Not provided

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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Healthy controlsHeavy water experimentNon-PHH, non-surgical healthy individuals
PHH patientsHeavy water experimentPatients following Roux-en-Y gastric bypass surgery (≥1 year ago) with confirmed post-prandial hyperinsulinemic hypoglycemia
Primary Outcome Measures
NameTimeMethod
Total amount of pre-stored insulin secretedDuring the 7 days of the heavy water administration period

Measured using deuterium (2H)-labelled insulin in the plasma

Secondary Outcome Measures
NameTimeMethod
Time course of the increase in 2H-labelled insulin in urineDuring the 7 days of the heavy water administration period
Time course of the increase in 2H-labelled c-peptide in urineDuring the 7 days of the heavy water administration period
Time course of the increase in 2H-labelled insulin in plasmaDuring the 7 days of the heavy water administration period
Time course of the increase in 2H-labelled c-peptide in plasmaDuring the 7 days of the heavy water administration period

Trial Locations

Locations (1)

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

🇨🇭

Bern, Switzerland

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