A Glucometabolic Evaluation of Patients With Idiopathic Ketotic Hypoglycemia

Study Overview
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Brief Summary
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The project will evaluate 1) the postprandial metabolism and 2) continuous glucose levels in subjects diagnosed with Idiopathic Ketotic Hypoglycemia (IKH)) and healthy control subjects.

Detailed Description
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IKH is a common, but not fully understood, condition in children, and in some the condition may persist in adulthood. In the present study we seek to evaluate the postprandial metabolism in adult subjects diagnosed with IKH through a clinical study including: two test days, where the subjects completes a) an oral glucose tolerance test (OGTT) and b) a miced meal test (MMT). Before, during and after ingestion of the OGTT/MMT, blood samples will be frequently drawn for the evaluation of plasma glucose, hormones, amino acids and more. During both tests, the subjects will recieve a continuous infusion of primed glucose tracer to further evaluate the glucose metabolism. a 14-day period where the subjects will lead the usual lives, wearing a continuous glucose monitor (CGM). This will enable us to evaluate long-term differences in plasma glucose levels in IKH.

Official Title
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A Glucometabolic Evaluation of Patients With Idiopathic Ketotic Hypoglycemia

Conditions
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Idiopathic Ketotic Hypoglycemia

Intervention / Treatment
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* Biological: Oral glucose tolerance test
* Biological: Mixed meal test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: IKH-participants: Verified diagnosis of IKH by health professional BMI of 18-30 kg/m2 Normal liver- and kidney function informed consent Healthy control participants Normal glucose tolerance BMI of 18-30 kg/m2 Normal liver- and kidney function informed consent Exclusion Criteria: A history of diabetes close family members with diabetes use of drugs affecting the glucose metabolism that cannot be paused anemia any condition that the study investigators deem unacceptable for participation pregnancy or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Parallel Assignment
Interventional Model Description: A case-control intervention study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects diagnosed with IKH<br>10 patients, diagnosed with IKH | Biological: Oral glucose tolerance test<br>* Consumption of 75 grams of glucose, diluted in water, added 1,5 g of acetaminophen.<br>* Other names: OGTT;Biological: Mixed meal test<br>* Consumption of a standardized liquid meal, with caloric and dietary content equal to a standard meal.<br>* Other names: MMT;|
| Experimental: Healthy control subjects<br>10 subjects, healthy, matched for gender, BMI, age | Biological: Oral glucose tolerance test<br>* Consumption of 75 grams of glucose, diluted in water, added 1,5 g of acetaminophen.<br>* Other names: OGTT;Biological: Mixed meal test<br>* Consumption of a standardized liquid meal, with caloric and dietary content equal to a standard meal.<br>* Other names: MMT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma glucose | The intergroup difference in peak to nadir difference in plasma glucose following OGTT/MMT | -120, -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 180 minutes | 
| Time in range (CGM) | The intergroup difference in time spend in glycemic range, measured by CGM | 0-14 days of CGM-period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endogenous glucose production | Rate of appearance of glucose, measured by tracer dilution technique | -120,, -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 180 minutes | 
| Glucose revomal | Rate of disappearance of glucose, measured by tracer dilution technique | -120, -60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 180 minutes | 
| Amino acids | Plasma concentrations of amino acids | -120,-60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 180 minutes | 
| Insulin | Plasma concentrations of insulin | -120,-60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 180 minutes | 
| Glucagon | Plasma concentrations of glucagon | -120,-60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 180 minutes | 
| Glucagon like peptide-1 (GLP-1) | Plasma concentrations of GLP-1 | -120,-60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 180 minutes | 
| Glucose-dependent insulinotropic polypeptide (GIP) | Plasma concentrations of GIP | -120,-60, -30, 0, 15, 30, 45, 60, 90, 120, 150, 180 minutes | 
| Coefficients of variation (CV) of plasma glucose | CV of plasma glucose measured by CGM | 0-14 days of CGM-period | 
| Mean plasma glucose | Average value of plasma glucose measured by CGM | 0-14 days of CGM-period | 
| Risk of hypoglycemia | Time spend in hypoglycemia measured by CGM | 0-14 days of CGM-period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Idiopathic ketotic hypoglycemia, Glucose metabolism, Gut homones, Amino acids, Glucagon, Insulin, Continuous glucose monitor, CGM, Oral glucose tolerance test, Mixed meal test