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

Completed

• Conditions: Maturity-onset Diabetes of the Young
• Interventions: 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

• Registration Number: NCT01342939
• Lead Sponsor: University Hospital, Gentofte, Copenhagen

Brief Summary

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

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.

Study Timeline

• Study Start: 2011-01
• Study First Submitted: 2011-04-13
• Study First Submitted QC: 2011-04-26
• Study First Posted: 2011-04-27
• Primary Completion: 2011-11
• Study Completion: 2011-12
• Status Verified: 2013-01
• Last Update Submitted: 2013-01-14
• Last Update Posted: 2013-01-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 31

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
MODY2	Meal test	Also called GCK (glucokinase) MODY. They have a specific mutation in the GCK gene.
MODY3	Meal test	Also called HNF1 alfa MODY. They have a specific mutation in the HNF1 alfa gene.
MODY2	Oral Glucose Tolerance Test (OGTT)	Also called GCK (glucokinase) MODY. They have a specific mutation in the GCK gene.
MODY2	iso glycaemic intravenous (iv) glucose infusion (IIGI)	Also called GCK (glucokinase) MODY. They have a specific mutation in the GCK gene.
Healthy control subjects	Meal test	-
Healthy control subjects	Sitagliptin	-
MODY3	iso glycaemic intravenous (iv) glucose infusion (IIGI)	Also called HNF1 alfa MODY. They have a specific mutation in the HNF1 alfa gene.
MODY2	Incretin effect on sulphonyl urea treatment	Also called GCK (glucokinase) MODY. They have a specific mutation in the GCK gene.
MODY3	Incretin effect on sulphonyl urea treatment	Also called HNF1 alfa MODY. They have a specific mutation in the HNF1 alfa gene.
MODY3	Oral Glucose Tolerance Test (OGTT)	Also called HNF1 alfa MODY. They have a specific mutation in the HNF1 alfa gene.
Healthy control subjects	Oral Glucose Tolerance Test (OGTT)	-
Healthy control subjects	iso glycaemic intravenous (iv) glucose infusion (IIGI)	-

Primary Outcome Measures

Name	Time	Method
Incretin effect	Within 1 year	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.

Secondary Outcome Measures

Name	Time	Method
Plasma GLP1 response	Within 1 year	Comparing GLP1 responses of the different experimental days, compared to healthy control subjects.
Plasma GIP response	Within 1 year	Comparing GIP responses of the different experimental days, compared to healthy control subjects.
Plasma glucagon response	Within 1 year	Comparing glucagon responses of the different experimental days, compared to healthy control subjects.

Trial Locations

Locations (1)

Diabetes Research Division, Gentofte University Hospital, Niels Andersens vej 65, opgang 40, 2.; 🇩🇰 Hellerup, Denmark