Clinical trial NCT02006459: Involvement of Extrapancreatic Factors on Gastrointestinal-mediated Glucose Disposal
Official title: Involvement of Extrapancreatic Factors on Gastrointestinal-mediated Glucose Disposal
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetes
Keywords: Gastrointestinal-mediated glucose disposal
Total pancreatectomy
Incretin hormones
Glucagon
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
name: European Foundation for the Study of Diabetes
First posted: 2013-12-10
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients operated at/or cared for at the endocrinology out-patient-clinic, Rigshospitalet, University of Copenhagen, Copenhagen Denmark

Brief summary: We want to investigate the mechanisms of extrapancreatic effects on gastrointestinal-mediated glucose disposal. In order to do so we will perform oral glucose tolerance tests and isoglycemic intravenous glucose infusions in total pancreatectomised patients and in healthy controls.

Detailed description: In the current project we wish to identify the possible contribution of extrapancreatic effects on gastrointestinal-mediated glucose disposal (GIGD). GIGD reflects the percentage of an individual's glucose disposal following oral glucose tolerance test (OGTT) which is caused by the oral route of glucose administration. In healthy subjects GIGD amounts to \~60%. GIGD describes not only the impact of the incretin effect (insulinotropic substances released upon intestinal stimulation) but includes all factors affecting glucose disposal differently during oral vs. iv administration of glucose (including neural reflexes, activation of afferent nerves in the intestinal mucosa, differences in glucagon secretion, hepatic glucose production and first-pass hepatic uptake of glucose, differences in portal and venous blood glucose concentrations and/or at the present unknown factors. It is likely that the incretin effect (pancreatic effect) constitutes a major contributor to GIGD, but so far it has been impossible to discriminate between pancreatic and extrapancreatic mechanisms underlying GIGD

Eligibility criteria: Inclusion Criteria:

* Pancreatectomized patients

  * Caucasians above 18 years of age who have undergone total pancreatectomy
  * Normal haemoglobin
  * Informed consent Healthy Subjects
  * Normal fasting plasma glucose (FPG) and normal HbA1C (according to the World Health Organization (WHO) criteria)
  * Normal haemoglobin
  * Age above 18 years
  * Informed consent

Exclusion Criteria:

* Pancreatectomized patients

  * Inflammatory bowel disease
  * Operation within the last 3 months
  * Ongoing chemotherapy or chemotherapy within the last 3 months
  * Ostomy
  * Nephropathy (serum creatinine \>150 µM and/or albuminuria)
  * Severe liver disease (serum alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) \>3×normal values)
  * Pregnancy and/or breastfeeding
  * Age above 80 years
  * Any condition that the investigator feels would interfere with trial participation Healthy Subjects
  * Diabetes mellitus (DM)
  * Prediabetes (impaired glucose tolerance and/or impaired FPG)
  * First degree relatives with DM
  * Inflammatory bowel disease
  * Intestinal resection and/or ostomy
  * Nephropathy (serum creatinine \>150 µM and/or albuminuria
  * Liver disease (ALAT and/or serum ASAT \>2×normal values)
  * Pregnancy and/or breastfeeding
  * Age above 80 years
  * Any condition that the investigator feels would interfere with trial participation

Primary outcomes:
measure: Gastrointestinal-mediated glucose disposal (GIGD)
timeFrame: Calculated when the study days are all complete. approximately in 6month
measure: plasma Glucagon
timeFrame: Glucagon will be measured at time points: -30,-15,0,10,20,30,50,70,90,120,150,180 min on all days.
Secondary outcomes:
measure: endogenous glucose production
timeFrame: Endogenous glucose production will be calculated based on blood samples at time points: -30,-15,0,10,20,30,50,70,90,120,150,180 min on all days.
measure: Incretin Hormones
timeFrame: incretin hormone levels will be measured at time points: -30,-15,0,10,20,30,50,70,90,120,150,180 min on all days.
measure: Satiety, hunger, appetite
timeFrame: Satiety, hunger and appetite will be measured at time points:0,30,60,90,120,150,180 min during each day.
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: Diabetes Research Division, University Hospital Gentofte
Study officials:
References:
citation: Lund A, Bagger JI, Wewer Albrechtsen NJ, Christensen M, Grondahl M, Hartmann B, Mathiesen ER, Hansen CP, Storkholm JH, van Hall G, Rehfeld JF, Hornburg D, Meissner F, Mann M, Larsen S, Holst JJ, Vilsboll T, Knop FK. Evidence of Extrapancreatic Glucagon Secretion in Man. Diabetes. 2016 Mar;65(3):585-97. doi: 10.2337/db15-1541. Epub 2015 Dec 15.