Glucose and Glycogen Dynamics in Prediabetes

NCT ID: NCT06317142

Last Updated: 2024-04-09

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 45 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-02-20
• Study Completion Date: 2025-07-31

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.

Conditions

Pre Diabetes

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Healthy overweight volunteers

This group includes 15 healthy overweight volunteers. 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.

No interventions assigned to this group

Prediabetes volunteers-IFG

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).

Acipimox 250 mg Oral Capsule

Intervention Type: DRUG

A subset of prediabetes individuals (first 10 IFG and 10 IGT 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.

Prediabetes volunteers-IGT

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).

Acipimox 250 mg Oral Capsule

Intervention Type: DRUG

A subset of prediabetes individuals (first 10 IFG and 10 IGT 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.

Interventions

Acipimox 250 mg Oral Capsule

A subset of prediabetes individuals (first 10 IFG and 10 IGT 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.

Intervention Type: DRUG

Other Intervention Names

Olbetam 250 mg oral capsule

Eligibility Criteria

Inclusion Criteria

• Participants are able to provide signed and dated written informed consent prior to any study specific procedures
• Participants should have suitable veins for cannulation or repeated venipuncture
• Women are post-menopausal (defined as at least 1 year post cessation of menses)
• Aged ≥ 45 and ≤ 75 years
• Body mass index (BMI) 27 - 38 kg/m2
• Stable dietary habits (no weight loss or gain >5kg in the past 3 months)
• Sedentary lifestyle (not more than 2 hours of sports per week)

Impaired Fasting Glucose: fasting blood glucose between 6.1 and 6.9 mmol/L and 2-h plasma glucose after ingestion of 75g oral glucose load below 7.8 mmol/L Impaired Glucose Tolerance: fasting blood glucose below 6.1 mmol/L and 2-h plasma glucose after ingestion of 75g oral glucose load between 7.8 and 11.1 mmol/L

Exclusion Criteria

• Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the Investigator
• Previously diagnosed with type 2 diabetes
• Patients with congestive heart failure and/or severe renal (eGFR <50mL/min) and or liver insufficiency or another condition that may interfere with outcomes measured in this study.
• Any contra-indication MRI scanning
• Alcohol consumption of >2 servings per day for men and >1 servings per day for woman
• Smoking in the past 6 months
• Medication use that may influence main outcome parameters, specifically the following types of medication: Type 2 diabetes medication, corticosteroids, thyroid medication.
• Participation in research or medical examination that included PET scanning in the last 3 months

• Any of the criteria mentioned above to define prediabetes

• Gout
• Hypersensitivity to acipimox or to any of the excipients in the tablet
• Peptic ulcer/dyspepsia
• Medication that interferes with Acipimox (statins, fibrates).

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vera Schrauwen, PhD

Role: PRINCIPAL_INVESTIGATOR

Maastricht University Medical Center

Locations

Maastricht University

Maastricht, Limburg, Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Kay Roumans, PhD

Role: CONTACT

k.roumans@maastrichtuniversity.nl

+31433882124

Mijke Buitinga, PhD

Role: CONTACT

m.buitinga@maastrichtuniversity.nl

+31883887286

Facility Contacts

Kay Roumans, PhD

Role: primary

k.roumans@maastrichtuniversity.nl

433882124 ext. 31

Other Identifiers

NL84574.068.23

Identifier Type: -

Identifier Source: org_study_id