Bariatric Surgery, Gastric Bypass, Hypoglycemia
Conditions
Keywords
Insulin turnover, Insulin secretion, Deuterated Water, De-novo insulin synthesis
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.
Interventions
OTHERHeavy water experiment
3 times daily heavy water (deuterated-water) and mixed meal administration for one week
Sponsors
Lia Bally
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total amount of pre-stored insulin secreted | During the 7 days of the heavy water administration period | Measured using deuterium (2H)-labelled insulin in the plasma |
Secondary
| 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 |
Countries
Switzerland
Outcome results
None listed