Day-night Rhythm in Muscle Metabolism of Prediabetics

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Day-night Rhythm in Muscle Metabolism of Prediabetic Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03733743
• Other study ID #: NL64753.068.18
• Status: Completed
• Phase: N/A
• Start date: July 9, 2018
• Est. completion date: March 29, 2019

Study information

• Verified date: September 2018
• Source: Maastricht University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: March 29, 2019
• Est. primary completion date: March 20, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 40 Years to 75 Years

Eligibility

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:

• Impaired Glucose Tolerance (IGT): plasma glucose values = 7.8 mmol/l and = 11.1 mmol/l 120 minutes after glucose drink consumption during OGTT in screening.

• Impaired Fasting Glucose (IFG): Fasting plasma glucose = 6.1 mmol/l and = 6.9 mmol/l.

• Insulin Resistance: glucose clearance rate = 360ml/kg/min, as determined using the OGIS120 model.

• HbA1c of 5.7-6.4%.

• Regular sleeping time (normally 7 - 9h daily)

• Stable dietary habits: no weight gain or loss > 3kg in the last three months.

Exclusion criteria:

• Use of anticoagulants

• Previously diagnosed with type 2 diabetes

• Current alcohol consumption > 20 grams alcohol/day

• Extreme early bird or extreme night person (score = 30 or = 70 on MEQ-SA questionnaire)

• Heavily varying sleep-wake rhythm

• Nightshift work during last 3 months

• Travel across > 1 time zone in the last 3 months

• Significant food allergies/intolerance (seriously hampering study meals)

• Using > 400mg caffeine daily (more than 4 coffee or energy drink)

• Smoking

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Insulin Resistance
• Prediabetic State

Intervention

Other:
• Standardized living protocol
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.

Locations

Country	Name	City	State
Netherlands	Maastricht University	Maastricht	Limburg

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University	Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	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
Secondary	Day-night rhythm in whole-body energy metabolism (glucose oxidation)	glucose oxidation (g/min) measured by indirect calorimetry	measured on day two at 8:00, 13:00, 18:00, 23:00, 04:00
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)