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

NCT01342939 | Completed

• 2 other identifiers: MODY-INKH-1-2010-130
• Study Type: observational
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Maturity-onset Diabetes of the Young

Keywords

Monogenetic diabetes; Diabetes mellitus

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Plasma GLP1 response

  Within 1 year

• Plasma GIP response

  Within 1 year

• Plasma glucagon response

  Within 1 year

Study Arms (3)

MODY2

Also called GCK (glucokinase) MODY. They have a specific mutation in the GCK gene.

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

MODY3

Also called HNF1 alfa MODY. They have a specific mutation in the HNF1 alfa gene.

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

Healthy control subjects

Other: Oral Glucose Tolerance Test (OGTT); Other: iso glycaemic intravenous (iv) glucose infusion (IIGI); Dietary Supplement: Meal test; Other: Sitagliptin

Interventions

Oral Glucose Tolerance Test (OGTT) OTHER

50g waterfree glucose dissolved in 300ml water consumed over 5 min.

Also known as: Waterfree glucose, The Pharmacy of the capital region

Healthy control subjects; MODY2; MODY3

iso glycaemic intravenous (iv) glucose infusion (IIGI) OTHER

20% glucose

Also known as: Glucose infusion, 20%

Healthy control subjects; MODY2; MODY3

Meal test DIETARY_SUPPLEMENT

Energy drink, 350ml (525 kcal: 65 g carbohydrates, 20 g fat and 21 g protein)

Also known as: Nutridrink with cocoa taste (Nutricia, Allerød, Denmark)

Healthy control subjects; MODY2; MODY3

Sitagliptin OTHER

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

Also known as: Januvia, 100mg

Healthy control subjects

Incretin effect on sulphonyl urea treatment OTHER

Subject with MODY who are treated with sulphonyl urea are investigated without medication break prior to examination.

MODY2; MODY3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Genetically well-charaterized MODY2 and MODY3 patients at Hagedorn Research Institute/Steno Diabetes Center

You may qualify if:

• Caucasians above 18 years
• BMI \> 19 kg/m2
• Negative pancreatic beta cell- and glutamate decarboxylase-65(GAD65)- autoantibodies
• Normal haemoglobin
• Normal bloodpressure
• Informed concent

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Gentofte, Copenhagen: lead
• University of Copenhagen: collaborator
• Steno Diabetes Center Copenhagen: collaborator

Study Sites (1)

Diabetes Research Division, Gentofte University Hospital, Niels Andersens vej 65, opgang 40, 2.

Hellerup, 2900, Denmark

Location

Related Publications (1)

• Ostoft SH, Bagger JI, Hansen T, Hartmann B, Pedersen O, Holst JJ, Knop FK, Vilsboll T. Postprandial incretin and islet hormone responses and dipeptidyl-peptidase 4 enzymatic activity in patients with maturity onset diabetes of the young. Eur J Endocrinol. 2015 Aug;173(2):205-15. doi: 10.1530/EJE-15-0070. Epub 2015 May 7.

  PMID: 25953829 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Buffy coat

MeSH Terms

Conditions

Mason-Type Diabetes; Diabetes Mellitus

Interventions

Glucose Tolerance Test; Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• Signe H Østoft, MD, phd stud

  Diabetes Research Division, University Hospital Gentofte, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: April 13, 2011
• First Posted: April 27, 2011
• Study Start: January 1, 2011
• Primary Completion: November 1, 2011
• Study Completion: December 1, 2011
• Last Updated: January 15, 2013

Record last verified: 2013-01

Locations

DK (1)