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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes After Total Pancreatectomy
• Intervention / Treatment: Other: Oral glucose tolerance test; Other: Clamp experiment

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).

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Capital Region
    • Hellerup, Capital Region, Denmark, 2900
      • Center for Clinical Metabolic Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Totally pancreatectomized patients; Oral glucose tolerance test + insulin-induced hypoglycaemic clamp followed by an oral glucose tolerance test	Other: Oral glucose tolerance test; 50 grams OGTT; Other: Clamp experiment; insulin-induced hypoglycaemic clamp followed by an 50 grams OGTT
Experimental: Healthy controls; Oral glucose tolerance test + insulin-induced hypoglycaemic clamp followed by an oral glucose tolerance test	Other: Oral glucose tolerance test; 50 grams OGTT; Other: Clamp experiment; insulin-induced hypoglycaemic clamp followed by an 50 grams OGTT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
cortisol	p-cortisol excursions measured as incremental area under the curve (iAUC)	-30, -15, 0, 15, 40, 50, 60, 70, 80, 90 minutes
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

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Collaborators: University of Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2017
• Primary Completion (Actual): September 20, 2018
• Study Completion (Actual): September 20, 2018

Study Registration Dates

• First Submitted: August 16, 2019
• First Submitted That Met QC Criteria: August 19, 2019
• First Posted (Actual): August 21, 2019

Study Record Updates

• Last Update Posted (Actual): August 21, 2019
• Last Update Submitted That Met QC Criteria: August 19, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: glucagon
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hypoglycemia
• Other Study ID Numbers: H-17014216

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No