Glucose and Glycogen Dynamics in Prediabetes
- Registration Number
- NCT06317142
- Lead Sponsor
- Maastricht University Medical Center
- Brief Summary
The goal of this observational study is to investigate changes in nocturnal and postprandial glucose and glycogen metabolism in individuals with impaired fasting glucose and impaired glucose tolerance compared to healthy, non-diabetic, overweight participants (15 per group). In addition, it will be investigated if reducing gluconeogenesis, by using the challenge agent Acipimox, in people with prediabetes can increase glucose tolerance and fat oxidation by increased reliance on hepatic glycogen. The main questions this project aims to answer are:
* whether there are differences in nocturnal glucose/glycogen metabolism in individuals with impaired fasting glucose, impaired glucose tolerance and healthy overweight controls.
* whether there are differences in postprandial glucose/glycogen metabolism in individuals with impaired fasting glucose, impaired glucose tolerance and healthy overweight controls.
Participants will visit the university for a screening visit and a visit with overnight stay for measurements of gluconeogenesis, glycogen, and substrate oxidation. A subgroup will receive \[18F\]-FDG to assess tissue-specific postprandial glucose uptake. Thereafter, 20 prediabetic individuals will follow a 4-day treatment with acipimox to decrease gluconeogenesis, followed by a second overnight visit with similar measurements as mentioned for the first visit.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 45
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Prediabetes volunteers-IGT Acipimox 250 mg Oral Capsule This group will include 15 subjects with impaired glucose tolerance (IGT). These participants will undergo two test days with one overnight stay. During these days several tests will be conducted including measurements such as muscle and liver glycogen, whole-body gluconeogenesis, substrate oxidation and postprandial hepatic and muscle glucose uptake will be assessed by 18F-FDG PET combined with an oral glucose tolerance test. A subset of IGT prediabetes individuals with impaired fasting glucose (first 10 subjects enrolled) will receive a 4-day Acipimox treatment (3x 250mg capsules for three days (one with breakfast, one with lunch and one with snack) and 1x 250mg in the morning of day 4. After the intervention the participants will come to the university for two days with an overnight stay for tests (muscle and liver glycogen, whole-body gluconeogenesis, substrate oxidation, oral glucose tolerance test). Prediabetes volunteers-IFG Acipimox 250 mg Oral Capsule This group will include 15 subjects with impaired fasting glucose (IFG). These participants will undergo two test days with one overnight stay. During these days several tests will be conducted including measurements such as muscle and liver glycogen, whole-body gluconeogenesis, substrate oxidation and postprandial hepatic and muscle glucose uptake will be assessed by 18F-FDG PET combined with an oral glucose tolerance test. A subset of IFG prediabetes individuals with impaired fasting glucose (first 10 subjects enrolled) will receive a 4-day Acipimox treatment (3x 250mg capsules for three days (one with breakfast, one with lunch and one with snack) and 1x 250mg in the morning of day 4. After the intervention the participants will come to the university for two days with an overnight stay for tests (muscle and liver glycogen, whole-body gluconeogenesis, substrate oxidation, oral glucose tolerance test).
- Primary Outcome Measures
Name Time Method Whole body gluconeogenesis determined by deuterated water During day 1 and day 2 Difference in whole-body gluconeogenesis between healthy overweight volunteers and IFG and IGT volunteers
Hepatic and muscle glycogen measured by 13Carbon-Magnetic resonance spectroscopy (13C-MRS) During day 1 and day 2 Difference in overnight and postprandial change of hepatic and muscle glycogen measured by 13C-MRS between healthy overweight volunteers and volunteers with IFG and IGT
Postprandial hepatic and muscle glucose uptake determined by Fluorodeoxyglucose-Positron emission tomography ([18F]-FDG-PET) combined with oral glucose tolerance test (OGTT) During day 2 Difference in glucose uptake between healthy overweight volunteers and IFG and IGT volunteers
- Secondary Outcome Measures
Name Time Method Oral glucose tolerance after acipimox treatment measured by OGTT During day 2 and day 6 Difference in glucose tolerance measured by OGTT before and after 4 days of acipimox treatment in prediabetic volunteers (intra- and inter-group comparisons)
Whole body gluconeogenesis after acipimox treatment determined by deuterated water During day 1,2, 5 and 6 Difference in whole body gluconeogenesis before and after 4 days of acipimox treatment in prediabetic volunteers (intra- and inter-group comparisons)
Hepatic glycogen after acipimox treatment measured by 13C-MRS During day 1,2, 5 and 6 Difference in overnight change of hepatic glycogen before and after 4 days of acipimox treatment in prediabetic volunteers (intra- and inter-group comparisons)
Trial Locations
- Locations (1)
Maastricht University
🇳🇱Maastricht, Limburg, Netherlands