Glucose Metabolism Disorders
Conditions
Keywords
Glp-1, alpha-glucosidase inhibitor, acarbose
Brief summary
Investigation of GLP-1 signalling in the glucose-lowering effect of increased carbohydrate content in the distal small intestines induced by alpha-glucosidase inhibition during meal ingestion in patients with type 2 diabetes
Detailed description
The primary aim of the study is to investigate whether GLP-1 released as a result of increased carbohydrate content in the distal and L cell-rich part of the small intestine after a meal affects postprandial plasma glucose levels in patients with type 2 diabetes. This will be done by applying an alpha-glucosidase inhibitor (to increase the postprandial carbohydrate content in the distal small intestine) and the specific GLP-1 receptor antagonist exendin(9-39) (to isolate any GLP-1-mediated effects) during meal tests in patients with type 2 diabetes.
Interventions
DRUGAcarbose
Glucobay tablets on experimental day.
DRUGPlacebo Oral Tablet
Placebo tablets on experimental day.
DRUGExendin (9-39)
Infusion of GLP-1 receptor antagonist as a study tool to block GLP-1 activity on experimental day.
DRUGPlacebo Saline
9 mg/ml placebo saline infusion on experimental day.
Sponsors
University of Copenhagen
University Hospital, Gentofte, Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes for at least three months (diagnosed according to the criteria of the World Health Organization (WHO)) treated with metformin monotherapy * Caucasian ethnicity * Normal haemoglobin * Age \>18 years * BMI \>23 kg/m2 and \<35 kg/m2 * Informed and written consent
Exclusion criteria
* Liver disease (alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) \>2 times normal values) or history of hepatobiliary disorder * Gastrointestinal disease, previous intestinal resection, cholecystectomy or any major intra-abdominal surgery * Reduced kidney function or nephropathy (estimated glomerular filtration rate (eGFR) \<60 ml/min/1.73 m2 (based on serum creatinine) and/or albuminuria * Treatment with medicine that cannot be paused for 12 hours * Intake of antibiotics two months prior to study * Treatment with glucose-lowering drugs other than metformin * Hypo- and hyperthyroidism * Treatment with oral anticoagulants * Active or recent malignant disease * Any treatment or condition requiring acute or sub-acute medical or surgical intervention * Lack of effective birth control in premenopausal women * Positive pregnancy test on study days in premenopausal women * Pregnancy * Women who are breastfeeding * Any condition considered incompatible with participation by the investigators * If the subjects receive any antibiotic treatment while included in the study they will be excluded
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma glucose | 240 min | The primary outcome is the difference between the effect of increased carbohydrate content in the distal part of the small intestine (obtained by inhibiting alpha-glucosidase with acarbose) on postprandial glucose tolerance (as assessed by area under curve (AUC) for plasma glucose during a standardised liquid mixed meal test) with and without blockade of GLP-1 signalling by exendin(9-39). |
Countries
Denmark
Outcome results
None listed