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| Name | Class |
|---|---|
| Maastricht University Medical Center | OTHER |
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This study evaluates the existence of a day-night rhythm in skeletal muscle energy metabolism in prediabetic subjects. Subjects will stay at the research facility for 44 hours with a standardized living protocol during which several measurements of skeletal muscle and whole body energy metabolism will be performed.
Recent evidence from both observational and experimental studies indicates that disobedience of a normal day-night rhythm negatively influences metabolic and cardiovascular health, possibly leading to obesity and type 2 diabetes mellitus (T2DM). An important hallmark of obesity and T2DM is a decreased skeletal muscle mitochondrial function. Interestingly, recent research indicates that also skeletal muscle mitochondrial function is under the influence of a day-night rhythm. In this study, the presence of a day-night rhythm in skeletal muscle energy metabolism (in particular mitochondrial function) of overweight prediabetic participants will be investigated. During this study, subjects will stay at the research unit for 44 hours, with standardized meals and sleeping time. Five muscle biopsies (v. lateralis) and frequent blood draws will be taken. In addition, indirect calorimetry measurements will be performed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standardized living protocol | Other | Subjects are kept at the research facility to adhere to a standardized living protocol, mimicking a normal daily living situation. During the study, multiple tests will be performed, including muscle biopsies, blood draws, MRS measurements and indirect calorimetry. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Standardized living protocol | Other | Subjects stay at the research facility for 44 hours and adhere to a standard sleeping, eating and activity protocol. During this protocol, multiple measurements will be performed including skeletal muscle biopsies (m. vastus lateralis), blood draws, indirect calorimetry and MRS measurements. |
| Measure | Description | Time Frame |
|---|---|---|
| Day-night rhythm in skeletal muscle mitochondrial respiration | O2-flux (pmol/mg/s) measured with high resolution respirometry | measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00 |
| Measure | Description | Time Frame |
|---|---|---|
| Day-night rhythm in whole-body energy metabolism (energy expenditure) | Energy expenditure (kJ/min) measured by indirect calorimetry | measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00 |
| Day-night rhythm in whole-body energy metabolism (glucose oxidation) |
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Inclusion criteria:
Caucasian
Healthy (as determined by dependent physician)
Overweight: BMI 25 - 35 kg/m2
Prediabetic based on one or a combination of the following criteria:
Regular sleeping time (normally 7 - 9h daily)
Stable dietary habits: no weight gain or loss > 3kg in the last three months.
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Patrick Schrauwen, PhD | Maastricht University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Maastricht University | Maastricht | Limburg | 6229 ER | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38051503 | Derived | Harmsen JF, Kotte M, Habets I, Bosschee F, Frenken K, Jorgensen JA, de Kam S, Moonen-Kornips E, Cissen J, Doligkeit D, van de Weijer T, Erazo-Tapia E, Buitinga M, Hoeks J, Schrauwen P. Exercise training modifies skeletal muscle clock gene expression but not 24-hour rhythmicity in substrate metabolism of men with insulin resistance. J Physiol. 2024 Dec;602(23):6417-6433. doi: 10.1113/JP285523. Epub 2023 Dec 5. | |
| 32659272 |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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Standardized living protocol
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|
glucose oxidation (g/min) measured by indirect calorimetry |
| measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00 |
| Day-night rhythm in whole-body energy metabolism (fat oxidation) | fat oxidation (g/min) measured by indirect calorimetry | measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00 |
| Day-night rhythm in muscle protein levels of markers involved in molecular clock and mitochondrial metabolism. | Quantify protein levels by Western blots | measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00 |
| Day-night rhythm in muscle DNA of markers involved in molecular clock and mitochondrial metabolism. | Quantify DNA by qPCR | measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00 |
| Day-night rhythm in muscle DNA involved in molecular clock and mitochondrial metabolism. | Quantify DNA by micro-array | measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00 |
| Day-night rhythm in muscle mRNA markers involved in molecular clock and mitochondrial metabolism. | Quantify mRNA levels by micro array | measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00 |
| Day-night rhythm of markers of normal day-night rhythm (cortisol) | Blood cortisol levels | measured on day two, every two hours for 24 hours beginning at 08:00 |
| Day-night rhythm of in markers of normal day-night rhythm (core body temperature) | Core body temperature measured by an ingested telemetric pill. | measured continuously for 24 hours on day two |
| Day-night rhythm of in markers of normal day-night rhythm (melatonin) | Blood melatonin levels. | measured on day two, every two hours for 24 hours beginning at 08:00 |
| Day-night rhythm in serum glucose | Serum glucose levels determined from venous blood draws | measured on day two, every two hours for 24 hours beginning at 08:00 |
| Day-night rhythm in serum insulin | Serum insulin levels determined from venous blood draws | measured on day two, every two hours for 24 hours beginning at 08:00 |
| Day-night rhythm in serum free fatty acids (FFA) | Serum FFA levels determined from venous blood draws | measured on day two, every two hours for 24 hours beginning at 08:00 |
| Day-night rhythm in serum triglycerides | Serum triglyceride levels determined from venous blood draws | measured on day two, every two hours for 24 hours beginning at 08:00 |
| Day-night rhythm in serum cholesterol | Serum cholesterol levels determined from venous blood draws | measured on day two, every two hours for 24 hours beginning at 08:00 |
| Change in energy status of the heart between morning and evening | variation in phosphorus metabolites measured by Magnetic Resonance Imaging and - Spectroscopy (MRI/MRS) | Measured on first study day 5:30 PM (duration 45 minutes), second study day 7:30 AM (duration 45 minutes) |
| Derived |
| Wefers J, Connell NJ, Fealy CE, Andriessen C, de Wit V, van Moorsel D, Moonen-Kornips E, Jorgensen JA, Hesselink MKC, Havekes B, Hoeks J, Schrauwen P. Day-night rhythm of skeletal muscle metabolism is disturbed in older, metabolically compromised individuals. Mol Metab. 2020 Nov;41:101050. doi: 10.1016/j.molmet.2020.101050. Epub 2020 Jul 11. |
| D004700 | Endocrine System Diseases |
| D006946 | Hyperinsulinism |