Pancreatectomy; Hyperglycemia
Conditions
Brief summary
The two gut-derived hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) is 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
GIP receptor antagonist (GIP(3-30)NH2)
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 70 Years
Healthy volunteers
No
Inclusion criteria
* Total pancreatectomy * Caucasians * Blood haemoglobin \>7 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-1R agonists within the last 3 months * Renal impairment (estimated by eGFR \<60 ml/min/1.73 m2) and/or albuminuria * Calcium related disease, hypo-/hyperthyroidism * Known significant liver disease, ALT or AST \>3 times normal value or INR outside normal range * Severe arteriosclerotic heart disease or heart failure (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 |
|---|---|---|
| Changes in brown adipose tissue activity between interventions, assessed by thermographic camera | Up to two months | — |
| Changes in plasma levels of glucose between interventions assessed through frequently blood sampling during the experimental days | Up to two months | mmol/l |
| Changes in plasma levels of glucagon (gut-derived) between interventions assessed through frequently blood sampling during the experimental days | Up to two months | pmol/l |
| Changes in plasma levels of insulin/C-peptide between interventions assessed through frequently blood sampling during the experimental days | Up to two months | pmol/l |
| Changes in plasma triglycerides between interventions assessed through frequently blood sampling during the experimental days. | Up to two months | mmol/l lipoproteins, neutral and complex lipids. |
| Changes in plasma lipoproteins between interventions assessed through frequently blood sampling during the experimental days. | Up to two months | mg/dl |
| Changes in adiponectin in plasma between interventions, assessed through frequently blood sampling during the experimental days. | Up to two months | μg/mL |
| Changes in CTX between interventions assessed through frequently blood sampling during the experimental days | Up to two months | ng/ml |
| Changes in plasma P1NP between interventions assessed through frequently blood sampling during the experimental days | Up to two months | ng/ml |
Countries
Denmark
Outcome results
None listed