Incretin Regulation of Insulin Secretion in Monogenic Diabetes

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

Detailed Description
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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: Oral Glucose Tolerance Test (OGTT): consume sugary drink and blood samples will be collected at multiple time points 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 OGTT during GLP-1 infusion IGI during Exendin-9 infusion

Official Title
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Incretin Regulation of Insulin Secretion in Monogenic Diabetes

Conditions
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Monogenic Diabetes

Intervention / Treatment
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* Drug: GLP-1
* Drug: Exendin 9-39


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 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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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Healthy controls<br>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<br>* OGTT IGI IGI with GLP-1 infusion OGTT with Exendin 9-39 infusion<br>* Other names: Glucagon-like peptide-1 (GLP-1);Drug: Exendin 9-39<br>* OGTT IGI IGI with GLP-1 infusion OGTT with Exendin 9-39 infusion<br>* Other names: Glucagon-Like Peptide 1 (GLP-1) receptor antagonist;|
| Experimental: Monogenic diabetes<br>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<br>* OGTT IGI IGI with GLP-1 infusion OGTT with Exendin 9-39 infusion<br>* Other names: Glucagon-like peptide-1 (GLP-1);Drug: Exendin 9-39<br>* OGTT IGI IGI with GLP-1 infusion OGTT with Exendin 9-39 infusion<br>* Other names: Glucagon-Like Peptide 1 (GLP-1) receptor antagonist;|

What is the study measuring?
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Primary Outcome Measures

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