Type 2 Diabetes
Conditions
Brief summary
The investigators aim to investigate the physiological importance of LEAP-2 in healthy volunteers focusing on its potential insulinotropic effects.
Detailed description
The dramatic and almost immediate effects of Roux-en-Y gastric bypass (RYGB) surgery on type 2 diabetes (T2D) can only in part be explained by alterations in the plasma concentrations of known peptides. Thus, other - yet unknown - signals or hormones elicited from the endocrine cells of the small intestine may play an important role for the remission of T2D observed following RYGB. In a recent study, a predicted sequence of liver-enriched antimicrobial peptide 2 (LEAP-2) was shown to induce a glucose-stimulated insulin secretion in isolated human pancreatic islets. The fragment was subsequently identified to be circulating in human plasma in concentrations comparable to the circulating levels of other known gut secreted hormones, hereby validating that LEAP-2 is an endogenous circulating peptide. The investigators hypothesise that LEAP-2 increases insulin secretion during a graded glucose infusion as assessed by plasma insulin and C-peptide compared with saline (placebo) in healthy subjects. The study is designed as a clinical, placebo-controlled, double-blinded cross-over study involving two experimental study days and ten young healthy male participants. The co-primary endpoints are the difference in plasma insulin levels during a graded glucose infusion and beta-cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration between the two study days with either saline (placebo) or LEAP-2 infusion.
Interventions
BIOLOGICALLiver-enriched antimicrobial peptide 2
Infusion of LEAP-2 during a 180 min grated glucose infusion.
OTHERPlacebo
Saline
Sponsors
Gubra ApS
University Hospital, Gentofte, Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Day A and B will be conducted in a randomised, double-blinded order (blinded for the participant and the investigator) and noted by a third person not participating in the collection or analyses of data. The infusion order will be opened after the primary data analyses.
Intervention model description
The study is designed as a clinical, placebo-controlled, double-blinded cross-over study involving two experimental study days.
Eligibility
Sex/Gender
MALE
Age
18 Years to 25 Years
Healthy volunteers
Yes
Inclusion criteria
* Caucasian men * Age between 18 and 25 years * Body mass index between 20-25 kg/m2 * Informed consent
Exclusion criteria
* Anaemia (haemoglobin below normal range) * ALAT and/or ASAT \>2 times normal values or history of hepatobiliary and/or gastrointestinal disorder(s) * Nephropathy (serum creatinine above normal range and/or albuminuria) * Any physical or psychological condition that the investigator evaluates would interfere with trial participation including any acute or chronic illnesses * Any ongoing medication that the investigator evaluates would interfere with trial participation. * First- and second-degree relatives with diabetes * Regular tobacco smoking
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma insulin | -45 to 180 minutes | Difference in plasma insulin levels |
| Beta-cell secretion | -45 to 180 minutes | Beta-cell secretion assessed by plasma C-peptide concentration relative to plasma glucose concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LEAP-2 | -45 to 210 minutes | Plasma concentrations of LEAP-2 |
| Resting energy expenditure | -20 to 160 minutes | Changes in resting energy expenditure using indirect calorimetry |
| Appetite, satiety, and general well-being | -45 to 210 minutes | Appetite, satiety, and general well-being assessed by visual analogue scale (VAS) |
Countries
Denmark
Outcome results
None listed