Clinical trial NCT04064203: The Effect of Insulin-induced Hypoglycaemia on Gut-derived Glucagon Secretion (Px-Hypo)
Official title: The Effect of Insulin-induced Hypoglycaemia on Gut-derived Glucagon Secretion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes After Total Pancreatectomy
Keywords: glucagon
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
First posted: 2019-08-21
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 12 totally pancreatectomized patients and 12 healthy control subjects
Primary purpose: BASIC_SCIENCE

Brief summary: The overall objective of this study is to investigate whether hypoglycaemia (the most potent stimulus of pancreatic glucagon secretion) affects the secretion of gut-derived glucagon in totally pancreatectomized patients.

Detailed description: The investigators want to assess the plasma glucagon response to insulin-induced hypoglycaemia in totally pancreatectomised patients and at the same time evaluate whether hypoglycaemia affects a range of other products from endocrine cells in the gastrointestinal tract including ghrelin, gastrin, cholecystokinin (CCK), glucose-dependent insulinotropic polypeptide (GIP), GLP-1, glucagon-like peptide-2 (GLP-2), oxyntomodulin and peptide YY (PYY). Furthermore the investigators will evaluate how hypoglycaemia in these patients affects other counter-regulatory mechanisms including plasma responses of the hormones adrenaline, noradrenaline, growth hormone and cortisol as well as the rate of gastric emptying rate (which under normal circumstances accelerates during hypoglycaemia) during an oral glucose tolerance test (OGTT).

Eligibility criteria: Inclusion Criteria:

Pancreatectomised patients

* Caucasian above 30 years of age who have undergone total pancreatectomy
* Blood haemoglobin \>7.0 mmol/l for males and \>6.5 mmol/l for females Non-diabetic control subjects
* Normal fasting plasma glucose and normal HbA1c (according to the World Health Organization (WHO) criteria)
* Normal blood haemoglobin
* Caucasian above 30 years of age
* BMI (body mass index) 17-30
* Informed consent

Exclusion Criteria:

Pancreatectomised patients

* Pancreatectomy within the last 3 months
* Ongoing chemotherapy or chemotherapy within the last 3 months
* Previous or ongoing treatment with GLP-1 receptor agonists or dipeptidyl peptidase 4 (DPP-4) inhibitors
* Inflammatory bowel disease
* Gastrointestinal resection (other than the gastro-duodenectomy performed in connection with total pancreatectomy) and/or ostomy
* Nephropathy (eGFR\<60 and/or albuminuria)
* Known liver disease (excluding non-alcoholic fatty liver disease) and/or serum alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) \>3 × normal values)
* Severe lung disease
* Pregnancy and/or breastfeeding
* Age above 85 years
* Uncontrolled hypertension and/or significant cardiovascular disease
* Any condition that the investigator feels would interfere with trial participation Non-diabetic control subjects
* Diabetes or prediabetes (according to WHO criteria)
* First-degree relatives with diabetes
* Inflammatory bowel disease
* Gastrointestinal resection and/or ostomy
* Nephropathy (serum creatinine \>150 µmol/l and/or albuminuria)
* Known liver disease (excluding non-alcoholic fatty liver disease) and/or serum ALAT and/or serum ASAT \>3 × normal values)
* Severe lung disease
* Pregnancy and/or breastfeeding
* Age above 85 years
* Uncontrolled hypertension and/or significant cardiovascular disease
* Any condition that the investigator feels would interfere with trial participation

Primary outcomes:
measure: p-glucagon
timeFrame: -30, -15, 0, 15, 40, 50, 60, 70, 80, 90, 105, 120, 135, 150, 165, 180, 210, 240 minutes
Secondary outcomes:
measure: p-glucose
timeFrame: -30, -15, 0, 15, 40, 50, 60, 70, 80, 90, 105, 120, 135, 150, 165, 180, 210, 240 minutes
measure: GIP, GLP-1, GLP-2, GIP, oxyntomodulin, ghrelin, peptide YY, gastrin
timeFrame: -30, -15, 0, 15, 40, 50, 60, 70, 80, 90, 105, 120, 135, 150, 165, 180, 210, 240 minutes
measure: catecholamines
timeFrame: -30, -15, 0, 15, 40, 50, 60, 70, 80, 90 minutes
measure: cortisol
timeFrame: -30, -15, 0, 15, 40, 50, 60, 70, 80, 90 minutes
measure: growth hormone
timeFrame: -30, -15, 0, 15, 40, 50, 60, 70, 80, 90 minutes
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: Center for Clinical Metabolic Research
state: Capital Region
Study officials:
References: