Delineation of the Role of Glucagon-like Peptide-1 Signalling in Relation to Increased Carbohydrate Content in the Distal Small Intestines

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Role of Glucagon-like Peptide-1 Receptor Signalling in the Glucose-lowering Effect of Increased Carbohydrate Content in the Distal Small Intestines After Meal Ingestion in Patients With Type 2 Diabetes

Conditions
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Glucose Metabolism Disorders

Intervention / Treatment
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* Drug: Acarbose
* Drug: Placebo Oral Tablet
* Drug: Exendin (9-39)
* Drug: Placebo Saline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acarbose<br>50 mg and 100 mg glucobay tablets. 2 weeks. Other name: Precose | Drug: Acarbose<br>* Glucobay tablets on experimental day.<br>* Other names: Glucobay, Precose;|
| Placebo Comparator: Placebo Oral tablets<br>180 mg. 2 weeks. | Drug: Placebo Oral Tablet<br>* Placebo tablets on experimental day.<br>|
| Experimental: Exendin (9-39)<br>Infusion of GLP-1 receptor antagonist as a study tool to block GLP-1 activity on experimental day. | Drug: Exendin (9-39)<br>* Infusion of GLP-1 receptor antagonist as a study tool to block GLP-1 activity on experimental day.<br>* Other names: Ex(9-39);|
| Placebo Comparator: Placbo Saline<br>9 mg/ml placebo saline infusion on experimental day. | Drug: Placebo Saline<br>* 9 mg/ml placebo saline infusion on experimental day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma glucose | 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). | 240 min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glp-1, alpha-glucosidase inhibitor, acarbose