Separate and Combined Extrapancreatic Effects of the Incretin Hormones

University Hospital, Gentofte, Copenhagen13 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Pancreatectomy; Hyperglycemia

Interventions

Eligibility

Sex: ALLMin age: 30 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Changes in plasma levels of glucose between interventions assessed through frequently blood sampling during the experimental days

mmol/l

Time frame: Up to two months

Changes in plasma levels of glucagon (gut-derived) between interventions assessed through frequently blood sampling during the experimental days

pmol/l

Time frame: Up to two months

Changes in plasma levels of insulin/C-peptide between interventions assessed through frequently blood sampling during the experimental days

pmol/l

Time frame: Up to two months

Changes in plasma triglycerides between interventions assessed through frequently blood sampling during the experimental days.

mmol/l lipoproteins, neutral and complex lipids.

Time frame: Up to two months

Changes in plasma lipoproteins between interventions assessed through frequently blood sampling during the experimental days.

mg/dl

Time frame: Up to two months

Changes in brown adipose tissue activity between interventions, assessed by thermographic camera

Time frame: Up to two months

Changes in adiponectin in plasma between interventions, assessed through frequently blood sampling during the experimental days.

μg/mL

Time frame: Up to two months

Changes in CTX between interventions assessed through frequently blood sampling during the experimental days

ng/ml

Time frame: Up to two months

Changes in plasma P1NP between interventions assessed through frequently blood sampling during the experimental days

ng/ml

Time frame: Up to two months

Separate and Combined Extrapancreatic Effects of the Incretin Hormones

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes