Incretin Regulation of Insulin Secretion in Monogenic Diabetes

The purpose of this study is to explore the mechanisms of metabolic control in monogenic diabetes patients treated with sulfonylurea medications.

Study Overview

• Status: Completed
• Conditions: Monogenic Diabetes
• Intervention / Treatment: Drug: GLP-1; Drug: Exendin 9-39

Detailed Description

Monogenic diabetes patients and healthy matched controls will be admitted to the University of Chicago Clinical Resource Center for a total of 4 nights. The following will take place on separate days:

1. Oral Glucose Tolerance Test (OGTT): consume sugary drink and blood samples will be collected at multiple time points
2. Isoglycemic glucose infusion (IGI) test: glucose will be infused via a vein in the arm and and blood samples will be collected at multiple time points
3. OGTT during GLP-1 infusion
4. IGI during Exendin-9 infusion

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 87 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Monogenic Diabetes Subjects:

Inclusion Criteria:

• Diagnosis of monogenic diabetes
• Previously participated in US Neonatal Diabetes Registry (IRB 15617B) or Genetics of diabetes mellitus (IRB 6858)
• Age: 18 years +

Exclusion Criteria:

• Pregnancy
• Acute medical illness or chronic conditions including: cardiac failure, renal insufficiency (estimated glomerular filtration rate <50 ml/min), hepatic insufficiency (known cirrhosis or hepatitis), chronic obstructive pulmonary disease, gastrointestinal disorders causing malabsorption, anemia (Hct < 36%), or uncontrolled hypertension

Healthy Controls:

Inclusion Criteria:

• Good general health
• Stable weight for 6 months
• Age: 18 years +

Exclusion Criteria:

• Pregnancy
• Acute medical illness or chronic conditions including: cardiac failure, renal insufficiency (estimated glomerular filtration rate <50 ml/min), hepatic insufficiency (known cirrhosis or hepatitis), chronic obstructive pulmonary disease, gastrointestinal disorders causing malabsorption, anemia (Hct < 36%), or uncontrolled hypertension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Healthy controls; Healthy controls will be matched (age, gender, BMI) to monogenic diabetes subjects. Healthy controls will participate in the following: OGTT; IGI; IGI with GLP-1 infusion; OGTT with Exendin 9-39 infusion	Drug: GLP-1; OGTT IGI IGI with GLP-1 infusion OGTT with Exendin 9-39 infusion; Other Names: Glucagon-like peptide-1 (GLP-1); Drug: Exendin 9-39; OGTT IGI IGI with GLP-1 infusion OGTT with Exendin 9-39 infusion; Other Names: Glucagon-Like Peptide 1 (GLP-1) receptor antagonist
Experimental: Monogenic diabetes; Monogenic diabetes subjects will be matched (age, gender, BMI) to healthy controls. Monogenic diabetes subjects will participate in the following: OGTT; IGI; IGI with GLP-1 infusion; OGTT with Exendin 9-39 infusion	Drug: GLP-1; OGTT IGI IGI with GLP-1 infusion OGTT with Exendin 9-39 infusion; Other Names: Glucagon-like peptide-1 (GLP-1); Drug: Exendin 9-39; OGTT IGI IGI with GLP-1 infusion OGTT with Exendin 9-39 infusion; Other Names: Glucagon-Like Peptide 1 (GLP-1) receptor antagonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incretin Effect	Directly calculated from the difference between oral and IV stimulated insulin secretion	Baseline

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Siri Atma W Greeley, MD, PhD, University of Chicago

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: February 15, 2013
• First Submitted That Met QC Criteria: February 19, 2013
• First Posted (Estimate): February 20, 2013

Study Record Updates

• Last Update Posted (Actual): April 10, 2017
• Last Update Submitted That Met QC Criteria: April 6, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Glucagon; Glucagon-Like Peptide 1
• Other Study ID Numbers: 12-1517

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: We do not plan to share data with other researchers.