Pancreatectomy; Hyperglycemia
Conditions
Brief summary
The two gut-derived hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are secreted from intestinal cells in relation to a meal and increase insulin secretion from the pancreas. The hormones also exert effects outside the pancreas, but especially for GIP, these are poorly investigated. Because of this, only GLP-1 based drugs (GLP-1 receptor agonists) are on the market for the treatment of type 2 diabetes and obesity. Nonetheless, a new drug is in clinical development: a combined GIP-GLP-1-receptor agonist (tirzepatide), which has shown better results than GLP-1 alone. The mechanism behind these impressive effects are unknown and in this study, the investigators will look into the exptrapancreatic effects of GIP and GLP-1, separate and combined and thus elucidate the mechanisms of action of this new drug class.
Interventions
OTHERIntravenous Infusion
Glucose-dependent Insulinotropic Polypeptide
Sponsors
University Hospital, Gentofte, Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Total pancreatectomy * Caucasians between 30-75 years of age * Blood haemoglobin \>7.0 mmol/l for males and \>6.5 mmol/l for females
Exclusion criteria
* Pancreatectomy within the last 3 months * Ongoing chemotherapy or chemotherapy within the last 3 months * Treatment with GLP-1 receptor agonists within the last 3 months * Renal impairment (estimated by estimated glomerular filtration rate (eGFR) \<60 ml/min/1.73 m2) and/or albuminuria * Calcium related disease, hypo-/hyperthyroidism * Known significant liver disease, plasma alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 × normal value or INR (The international normalised ratio based on prothrombin time) outside the normal range * Severe arteriosclerotic heart disease or heart failure (New York Heart Association (NYHA) group III or IV) * Pregnancy and/or breastfeeding * Use of more than 14 units of alcohol per week or abuse of narcotics * Any condition that the investigator feels would interfere with trial participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma glucose | Up to two months | Changes in plasma levels of glucose between interventions assessed through frequently blood sampling during the experimental days |
| Plasma glucagon | Up to two months | Changes in plasma levels of glucagon (gut-derived) between interventions assessed through frequently blood sampling during the experimental days |
| Plasma Insulin/C-peptide | Up to two months | Changes in plasma levels of insulin/C-peptide between interventions assessed through frequently blood sampling during the experimental days |
| Plasma triglycerides | Up to two months | Changes in plasma triglycerides between interventions assessed through frequently blood sampling during the experimental days |
| Plasma CTX | Up to two months | Changes in CTX between interventions assessed through frequently blood sampling during the experimental days |
| Plasma PINP | Up to two months | Changes in plasma PINP between interventions assessed through frequently blood sampling during the experimental days |
Countries
Denmark
Outcome results
None listed