The purpose of this study is to investigate the effect of 2 weeks dapagliflozin treatment in individuals with a disrupted glucose homeostasis on the switch between carbohydrate and lipid oxidation during the night
To investigate if dapagliflozin improves nocturnal substrate oxidation expressed as respiration quotient (RQ) during the sleeping period in comparison with placebo after 2-weeks double blind treatment in subjects with a disrupted glucose homeostasis.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
16
The study consist of 2 weeks treatment period 1, 6-8 weeks wash-out period and 2 weeks treatment period 2. The subject may be administered dapagliflozin 10 mg during Period 1 or Period 2.
The study consist of 2 weeks treatment period 1, 6-8 weeks wash-out period and 2 weeks treatment period 2. The subject may be administered placebo during Period 1 or Period 2.
Maastricht University and Medical Centre
Maastricht, Limburg, Netherlands
Change in nightly substrate oxidation measured as respiration quotient (RQ) during the sleeping period
Comparison of dapagliflozin versus placebo after 14 days of treatment on nightly substrate oxidation as measured by respiratory quotient (VCO2/VO2) during the sleeping period.
Time frame: From screening to day 14
Change in morning and late afternoon hepatic glycogen content
Comparison of dapagliflozin versus placebo after 14 days of treatment on hepatic glycogen content determined by non-invasive 13C-MRS (magnetic resonance spectroscopy) in the morning and evening
Time frame: 1 hour
Change in 24h substrate oxidation as determined by indirect calorimetry in a whole-body respiratory chamber and based on urinary nitrogen excretion
Comparison of dapagliflozin versus placebo after 14 days of treatment on 24h substrate oxidation as determined by indirect calorimetry in a whole-body respiratory chamber and based on urinary nitrogen excretion
Time frame: 24 hours
Change in 24h plasma markers
Comparison of dapagliflozin versus placebo after 14 days of treatment on 24h plasma markers including plasma glucose, NEFA, total amino acid levels incl BCAA levels, insulin and glucagon
Time frame: 24 hours
Change in muscle mitochondrial function
Comparison of dapagliflozin versus placebo after 14 days of treatment on muscle mitochondrial function as determined by high resolution respirometry
Time frame: 60 minutes
Change in intrahepatic lipid content and composition
Comparison of dapagliflozin versus placebo after 14 days of treatment on intrahepatic lipid content and composition as determined by non-invasive 1H-MRS (magnetic resonance spectroscopy )
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: 45 minutes
Change in intramyocellular lipid content and composition - including acylcarnitine levels
Comparison of dapagliflozin versus placebo after 14 days of treatment on intramyocellular lipid content and composition-including acylcarnitine levels as determined in muscle biopsies
Time frame: 45 minutes
Change in muscle glycogen content
Comparison of dapagliflozin versus placebo after 14 days of treatment on muscle glycogen content as determined biochemically in muscle biopsies
Time frame: 45 minutes
Change in systolic and diastolic blood pressure
Comparison of dapagliflozin versus placebo after 14 days of treatment on systolic and diastolic blood pressure
Time frame: 45 minutes