Pathophysiological Implications of the Incretin Hormones in Maturity Onset of Diabetes of the Young (MODY)

Study Overview
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Brief Summary
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The purpose of this study is to describe the incretin effect and postprandial incretin response in patients with MODY2 and MODY3 and a group of matched healthy subjects. In sulphonyl urea treated subjects the purpose is also to compare the incretin effect with and without treatment. In healthy subjects the purpose is also to investigate the incretin effect under increased levels of endogen incretin hormones.

Detailed Description
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Comparison of of insulin secretion (AUC) during the experimental days. Furthermore a comparison of GIP, GLP1 and glucagon responses as well as plasma glucose levels.

Official Title
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Postprandial Secretion of of Incretin Hormones and Incretin Effect in Patients With Maturity-onset Diabetes of the Young (MODY)

Conditions
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Maturity-onset Diabetes of the Young

Intervention / Treatment
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* Other: Oral Glucose Tolerance Test (OGTT)
* Other: iso glycaemic intravenous (iv) glucose infusion (IIGI)
* Dietary Supplement: Meal test
* Other: Sitagliptin
* Other: Incretin effect on sulphonyl urea treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Caucasians above 18 years BMI > 19 kg/m2 Negative pancreatic beta cell- and glutamate decarboxylase-65(GAD65)- autoantibodies Normal haemoglobin Normal bloodpressure Informed concent Exclusion Criteria: Known liver disease or affected liver enzymes (ALAT/ASAT >2 x upper normal limit) Nephropathy (see creatinine> 130 μM and / or albuminuria) Treatment with medications that cannot be discontinued for 12 hours Any condition that the investigators feel would interfere with trial participation Pregnancy or lactation

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MODY2<br>Also called GCK (glucokinase) MODY. They have a specific mutation in the GCK gene. | Other: Oral Glucose Tolerance Test (OGTT)<br>* 50g waterfree glucose dissolved in 300ml water consumed over 5 min.<br>* Other names: Waterfree glucose, The Pharmacy of the capital region;Other: iso glycaemic intravenous (iv) glucose infusion (IIGI)<br>* 20% glucose<br>* Other names: Glucose infusion, 20%;Dietary Supplement: Meal test<br>* Energy drink, 350ml (525 kcal: 65 g carbohydrates, 20 g fat and 21 g protein)<br>* Other names: Nutridrink with cocoa taste (Nutricia, Allerød, Denmark);Other: Incretin effect on sulphonyl urea treatment<br>* Subject with MODY who are treated with sulphonyl urea are investigated without medication break prior to examination.<br>|
| MODY3<br>Also called HNF1 alfa MODY. They have a specific mutation in the HNF1 alfa gene. | Other: Oral Glucose Tolerance Test (OGTT)<br>* 50g waterfree glucose dissolved in 300ml water consumed over 5 min.<br>* Other names: Waterfree glucose, The Pharmacy of the capital region;Other: iso glycaemic intravenous (iv) glucose infusion (IIGI)<br>* 20% glucose<br>* Other names: Glucose infusion, 20%;Dietary Supplement: Meal test<br>* Energy drink, 350ml (525 kcal: 65 g carbohydrates, 20 g fat and 21 g protein)<br>* Other names: Nutridrink with cocoa taste (Nutricia, Allerød, Denmark);Other: Incretin effect on sulphonyl urea treatment<br>* Subject with MODY who are treated with sulphonyl urea are investigated without medication break prior to examination.<br>|
| Healthy control subjects<br> | Other: Oral Glucose Tolerance Test (OGTT)<br>* 50g waterfree glucose dissolved in 300ml water consumed over 5 min.<br>* Other names: Waterfree glucose, The Pharmacy of the capital region;Other: iso glycaemic intravenous (iv) glucose infusion (IIGI)<br>* 20% glucose<br>* Other names: Glucose infusion, 20%;Dietary Supplement: Meal test<br>* Energy drink, 350ml (525 kcal: 65 g carbohydrates, 20 g fat and 21 g protein)<br>* Other names: Nutridrink with cocoa taste (Nutricia, Allerød, Denmark);Other: Sitagliptin<br>* Healthy control subject are given an acute dosage of 100mg the evening before the experimental day, and the same morning in order to increase levels of endogen incretin hormones<br>* Other names: Januvia, 100mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incretin effect | The difference in insulin responses, as assessed by the area under curve (AUC) for plasma insulin and C-peptide concentrations, during the two different glucose stimuli: OGTT and isoglycemic iv glucose infusion aswell as after a test meal in MODY-patients compared to healthy control subjects. | Within 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma GLP1 response | Comparing GLP1 responses of the different experimental days, compared to healthy control subjects. | Within 1 year | 
| Plasma GIP response | Comparing GIP responses of the different experimental days, compared to healthy control subjects. | Within 1 year | 
| Plasma glucagon response | Comparing glucagon responses of the different experimental days, compared to healthy control subjects. | Within 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Monogenetic diabetes, Diabetes mellitus