The Effect of Insulin-induced Hypoglycaemia on Gut-derived Glucagon Secretion (Px-Hypo)

Diabetes After Total Pancreatectomy Clinical Trial

Official title:

The Effect of Insulin-induced Hypoglycaemia on Gut-derived Glucagon Secretion

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04064203
• Other study ID #: H-17014216
• Status: Completed
• Phase: N/A
• Start date: July 5, 2017
• Est. completion date: September 20, 2018

Study information

• Verified date: August 2019
• Source: University Hospital, Gentofte, Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: September 20, 2018
• Est. primary completion date: September 20, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes After Total Pancreatectomy
• Hypoglycemia

Intervention

Other:
• Oral glucose tolerance test
50 grams OGTT
• Clamp experiment
insulin-induced hypoglycaemic clamp followed by an 50 grams OGTT

Locations

Country	Name	City	State
Denmark	Center for Clinical Metabolic Research	Hellerup	Capital Region

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Gentofte, Copenhagen	University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	p-glucagon	Plasma glucagon excursions measured as incremental area under the curve (iAUC)	-30, -15, 0, 15, 40, 50, 60, 70, 80, 90, 105, 120, 135, 150, 165, 180, 210, 240 minutes
Secondary	p-glucose	plasma glucose excursions measured as incremental area under the curve (iAUC)	-30, -15, 0, 15, 40, 50, 60, 70, 80, 90, 105, 120, 135, 150, 165, 180, 210, 240 minutes
Secondary	GIP, GLP-1, GLP-2, GIP, oxyntomodulin, ghrelin, peptide YY, gastrin	excursions in Gut hormones measured as incremental area under the curve (iAUC)	-30, -15, 0, 15, 40, 50, 60, 70, 80, 90, 105, 120, 135, 150, 165, 180, 210, 240 minutes
Secondary	catecholamines	p-adrenaline and p-noradrenaline, excursions measured as incremental area under the curve (iAUC)	-30, -15, 0, 15, 40, 50, 60, 70, 80, 90 minutes
Secondary	cortisol	p-cortisol excursions measured as incremental area under the curve (iAUC)	-30, -15, 0, 15, 40, 50, 60, 70, 80, 90 minutes
Secondary	growth hormone	p-growth hormone excursions measured as incremental area under the curve (iAUC)	-30, -15, 0, 15, 40, 50, 60, 70, 80, 90 minutes