Metabolic Effects of Natural Office Light in Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Natural Daylight to Improve 24h Metabolism and Glucose Control in Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05263232
• Other study ID #: NL77984.068.21
• Status: Completed
• Phase: N/A
• Start date: March 16, 2022
• Est. completion date: April 18, 2023

Study information

• Verified date: August 2023
• Source: Maastricht University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will investigate the potential benefit of scheduled natural daylight exposure to improve glucose control in type 2 diabetes (T2D) patients and to unravel molecular mechanisms underlying the effects of natural daylight on circadian clocks and (glucose) metabolism in human skeletal muscle from T2D patients. Participants will stay at our research facilities and will be exposed to natural daylight or artificial light during the daytime over 4.5 days in a randomized cross-over design. For both conditions, the evening and night will be spent under standardized dim and dark conditions.

Description:

Obesity and type 2 diabetes (T2D) are both strongly associated with a westernized lifestyle of low physical activity levels and high caloric intake. However, recently it has been recognized that also our 24-hour culture, characterized by working and eating late, reduced sleep (quantity and quality), and excessive light exposure in the evening and at night, should be considered as lifestyle factors that may negatively impact metabolic health. In this context, a factor that is often overlooked and underestimated is the lack of natural daylight since most people spend almost their entire work time in indoor office environments with limited access to natural daylight through windows. Therefore, this study investigates the potential benefit of scheduled natural daylight exposure to improve glucose control in T2D individuals and to unravel molecular mechanisms underlying effects of natural daylight on circadian clocks and (glucose) metabolism in human skeletal muscle from T2D patients. For this purpose, overweight to obese T2D patients (male and female) will undergo a randomized cross-over trial in which each subject serves as its own control. Participants will stay at our research facilities and will be exposed to natural daylight or artificial light during the daytime over 4.5 days. For both conditions, the evening and night will be spent under standardized dim and dark conditions, respectively. Over these two 4.5 days intervention periods, extensive 24h metabolic profiling will be conducted, including 24h continuous glucose monitoring, 24h blood and saliva sampling, 24h blood pressure and heart rate assessments, 24h core and skin temperature assessments, 24h energy expenditure and whole-body substrate metabolism, and a skeletal muscle biopsy and a mixed meal tolerance test with indirect calorimetry will be performed on the respectively last test day.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: April 18, 2023
• Est. primary completion date: November 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

• Participants are able to provide signed and dates written consent prior to any study specific procedures
• Male + females (postmenopausal defined as at least 1 year post cessation of menses)
• T2DM duration at least 1 year
• BMI: = 25 kg/m²
• Age: 40-75
• Well-controlled diabetes with respect to glycemic control and on stable anti-diabetes medication regimes
• Habitual bedtime of 23:00 ± 2h
• Regular sleep duration (7-9 h/night)
• Stable dietary habits: no weight gain or loss > 5 kg in the last three months

Exclusion Criteria:

• Insulin treatment
• Uncontrolled hypertension
• Signs of active diabetes-related co-morbidities like active cardiovascular diseases, active diabetic foot, polyneuropathy or retinopathy
• Signs of active liver or kidney malfunction
• Use of SGLT2 inhibitors
• Using > 400mg caffeine daily (more than 4 coffee or energy drink)
• Extreme early bird or extreme night person (score =30 or =70 on MEQ-SA questionnaire)
• shift work or travel across more than one time zone in the 3 months before the study
• Heavily varying sleep-wake rhythm
• Frequent engagement in programmed exercise as judged by the investigator
• Any medication that will interfere with the study outcomes or hamper the safety of the participant
• Alcohol consumption of >2 servings per day for men and >1 serving per day for woman
• Significant food allergies/intolerance (seriously hampering study meals)
• Subjects who do not want to be informed about unexpected medical findings during the screening /study, or do not wish that their physician is informed
• Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the Investigator
• Smoking in the past 6 months

Related Conditions & MeSH terms

• Chronobiology Disorders
• Circadian Dysregulation
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Other:
• Natural or artificial office light exposure
Over 4.5 days, participants will stay at our research facilities under different light conditions. Over these days different measurements will take place, including 24h continuous glucose monitoring, 24h blood and saliva sampling, 24h blood pressure and heart rate assessments, 24h core and skin temperature assessments, 24h energy expenditure and whole-body substrate metabolism, and a skeletal muscle biopsy and a mixed meal tolerance test with indirect calorimetry will be performed on the respectively last test day.

Locations

Country	Name	City	State
Netherlands	Maastricht University	Maastricht

Sponsors (3)

Lead Sponsor	Collaborator
Maastricht University	University of Geneva, Switzerland, Velux Fonden

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	24 hour energy expenditure	Energy expenditure (kJ/min)	measured at 8:00, 13:00, 18:00 and 22:30 on Day 4
Other	24h whole-body energy metabolism (cabrohydrate oxidation)	Carbohydrate oxidation (µmol/kg x min) measured by indirect calorimetry	measured at 8:00, 13:00, 18:00 and 22:30 on Day 4
Other	24h whole-body energy metabolism (fatty acid oxidation)	Fatty acid oxidation (µmol/kg x min) measured by indirect calorimetry	measured at 8:00, 13:00, 18:00 and 22:30 on Day 4
Other	24h profiles of plasma metabolites (i.e. free fatty acids, triglycerides, insulin)	Plasma levels determined from venous blood draws	measured on Day 4 at 8:00, 10:00, 12:00, 13:00, 14:00, 16:00, 18:00, 20:00, 22:00, 23:00, and on Day 5 at 00:00, 02:00, 04:00 and 06:00h
Other	Mass spectrometry-based 24h serum lipidomics	analysis of all lipid species evident in serum	measured on Day 4 at 8:00, 12:00, 16:00, 20:00, and on Day 5 at 00:00, 04:00 and 8:00
Other	Sleep quality questionnaire (Leeds Sleep Evaluations Questionnaire - LSEQ)	LSEQ scores	after each of the 4 nights
Other	Sleep quality questionnaire (Pittsburgh Sleep Quality Index - PSQI)	PSQI scores	after each of the 4 nights
Other	24h blood pressure	blood pressure (mmHg)	measured hourly from 7:00 to 23:00h on Day 4, and every second hour from 0:00 to 6:00 on Day 5
Other	24h heart rate	heart rate (bpm) assesses through chest-worn heart rate monitor	measured continously over 4.5 days
Other	24h skin temperature	skin temperature (°C) assessed via wireless temperature sensors (iButtons)	measured continously on Day 3
Other	24h core body temperature	Core body temperature measured by an ingested telemetric pill (°C)	measured continously on Day 3
Other	mRNA in peripheral blood mononuclear cells (PBMC) of markers involved in the molecular clock	Quantify mRNA levels by micro array	blood samples taken on Day 4 at 8:00, 13:00, 18:00, 23:00, and on Day 5 at 4:00 and 9:00
Primary	average 24h blood glucose levels	Interstistial glucose levels determined by continuous glucose monitoring	continously over 4.5 days
Secondary	Postprandial metabolism upon a mixed-meal tolerance test (energy expenditure)	Energy expenditure (kJ/min) measured by indirect calorimetry	measured at 9:00, 9:30, 10:00, 11:00, 12:00 and 13:00 on Day 5
Secondary	Postprandial metabolism upon a mixed-meal tolerance test (carbohydrate oxidation)	Carbohydrate oxidation (µmol/kg x min) measured by indirect calorimetry	measured at 9:00, 9:30, 10:00, 11:00, 12:00 and 13:00 on Day 5
Secondary	Postprandial metabolism upon a mixed-meal tolerance test (fatty acid oxidation)	Fatty acid oxidation (µmol/kg x min) measured by indirect calorimetry	measured at 9:00, 9:30, 10:00, 11:00, 12:00 and 13:00 on Day 5
Secondary	Postprandial plasma metabolites upon a mixed-meal tolerance test (glucose)	Plasma glucose levels determined from venous blood draws	measured at 9:00, 9:15, 9:30, 9:45, 10:00, 10:30, 11:00, 11:30, 12:00, 13:00 on Day 5
Secondary	Postprandial plasma metabolites upon a mixed-meal tolerance test (insulin)	Plasma insulin levels determined from venous blood draws	measured at 9:00, 9:15, 9:30, 9:45, 10:00, 10:30, 11:00, 11:30, 12:00, 13:00 on Day 5
Secondary	Postprandial plasma metabolites upon a mixed-meal tolerance test (free fatty acids)	Plasma FFA levels determined from venous blood draws	measured at 9:00, 9:15, 9:30, 9:45, 10:00, 10:30, 11:00, 11:30, 12:00, 13:00 on Day 5
Secondary	Postprandial plasma metabolites upon a mixed-meal tolerance test (triglycerides)	Plasma triglyceride levels determined from venous blood draws	measured at 9:00, 9:15, 9:30, 9:45, 10:00, 10:30, 11:00, 11:30, 12:00, 13:00 on Day 5
Secondary	Skeletal muscle biopsy outcomes (Circadian transciptome)	Quantify DNA by micro-array	muscle tissue taken at 7:30h on Day 5
Secondary	Culturing human primary myotubes to assess circadian reporter characteristics	in vivo culturing of primary myotubes	muscle tissue taken at 7:30h on Day 5