Pre Diabetes
Conditions
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.
Interventions
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.
Sponsors
Maastricht University Medical Center
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
for all groups: * 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) Inclusion Criteria for Prediabetic groups specifically: 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
for all groups: * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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) |
| 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) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Dynamic water relaxation measurements with 1H-MRS (surrogate glycogen) | During day 1,2, 5 and 6 | Difference in water relaxation measures between healthy overweight volunteers and IFG and IGT volunteers. |
| Substrate oxidation (fat and carbohydrate oxidation) determined by indirect calorimetry | During day 1,2, 5 and 6 | Difference in substrate oxidation (fat and carbohydrate oxidation) between healthy overweight volunteers and IFG and IGT volunteers and the difference in substrate oxidation before and after 4 days of acipimox treatment in IFG and IGT volunteers (intra- and inter-group comparisons). |
| Anthropometric measurements | During the screening day | weight and height will be combined to report BMI in kg/m\^2 (to characterize participants) |
| Body composition determined by Bodpod | During day 1 | fat mass and fat free mass as % (to characterize participants) |
| Hepatic acetylcarnitine as a measure for hepatic gluconeogenesis determined by H-MRS | During day 1,2, 5 and 6 | Difference in hepatic acetylcarnitine between healthy overweight volunteers and individuals with IGT and IFG and the difference in hepatic acetylcarnitine before and after 4 days of acipimox treatment in prediabetic volunteers (intra- and inter-group comparisons). |
Countries
Netherlands
Contacts
Primary ContactKay Roumans, PhD
Backup ContactMijke Buitinga, PhD
Outcome results
None listed