Mean 24h glucose concentrations
Optimal versus suboptimal diet. The mean 24h glucose concentrations will be measured continuously with the iPro2 device and Enlite Glucose Sensor (Medtronic) and expressed as mmol/L.
Glucose incremental area under the curve (iAUC)
Optimal versus suboptimal diet. The iAUC will be calculated using the trapezoid rule from data obtained from the iPro2 device and Enlite Glucose Sensor (Medtronic). The iAUC provides a summary measure of the net increase in glucose levels above the fasting level during a 24-hour period and is expressed as mmol/min/L.
The frequency and duration of hypo- and hyperglycemia
Optimal versus suboptimal diet. The frequency and duration of hypo- and hyperinsulinemia will be monitored using the iPro2 device and Enlite Glucose Sensor (Medtronic) and is defined as a glucose level of ≥10.0 mmol/l for hyperglycemia, whilst hypoglycemia will be defined as a glucose concentration ≤3.9 mmol/l.
Glucose tolerance
Optimal versus suboptimal diet. Determined by 2-hour glucose values (mmol/L) during an oral glucose tolerance test.
Muscle insulin sensitivity
Optimal versus suboptimal diet. Determined during a 2-hour, 7-points oral glucose tolerance test. The muscle insulin sensitivity index (MISI) will be calculated as follows: MISI (mmol/l/min/pmol/l) = (dG/dt) / mean plasma insulin concentration (pmol/l) during OGTT. Here, dG/dt is the rate of decay of plasma glucose concentration (mmol/L) during the OGTT, calculated as the slope of the least square fit to the decline in plasma glucose concentration from peak to nadir. Higher values represent higher muscle insulin sensitivity.
Hepatic insulin sensitivity
Optimal versus suboptimal diet. Determined during a 2-hour, 7-points oral glucose tolerance test. The hepatic insulin resistance index (HIRI) will be calculated using the square root of the product of the area under curves (AUCs) for glucose and insulin during the first 30 min of the OGTT - i.e., square root (glucose0-30 [AUC in mmol/l·h] · insulin 0-30 [AUC in pmol/l·h). Higher IR values represent lower hepatic insulin sensitivity.
Insulin sensitivity
Optimal versus suboptimal diet. Glucose infusion rate (mg/kg/min) during a 2-step hyper-insulinemic euglycemic clamp as golden standard method.
Body composition
Optimal versus suboptimal diet. Body composition will be determined by using a dual-energy X-ray absorptiometry scan (DXA).
Waist circumference
Optimal versus suboptimal diet. Waist circumferences in centimeters.
Hip circumferences
Optimal versus suboptimal diet. Hip circumferences in centimeters.
Body fat distribution
Optimal versus suboptimal diet. Magnetic Resonance Imaging (MRI)(UM) and Magnetic resonance spectroscopy (1H-MRS)(WUR) measurements will be included to quantify both subcutaneous and visceral fat depots, and ectopic fat deposition (e.g. in liver and muscle).
Blood pressure
Optimal versus suboptimal diet. Systolic and diastolic blood pressure in mmHg.
Fasting circulating metabolic markers
Optimal versus suboptimal diet. Fasting circulating metabolic markers include: glucose, insulin, hemoglobin A1c (HbA1c), triacylglycerol, free glycerol, free fatty acids (FFA), lactate, high density lipoprotein (HDL), total cholesterol, short chain fatty acids (SCFA), bile acids, glucagon-like peptide-1 (GLP-1), peptide YY (PYY).
Fasting blood lipid spectrum
Optimal versus suboptimal diet. Metabolomics will be used to determine the fasting blood lipid spectrum.
Postprandial circulating metabolic markers
Optimal versus suboptimal diet. Postprandial circulating metabolic markers will be determined during a high-fat mixed-meal test and include: glucose, insulin, triacylglycerol, free glycerol, free fatty acids (FFA), lactate, high density lipoprotein (HDL), total cholesterol, short chain fatty acids (SCFA), bile acids, glucagon-like peptide-1 (GLP-1), peptide YY (PYY).
Energy expenditure
Optimal versus suboptimal diet. Fasting and insulin-stimulated energy expenditure will be determined by indirect calorimetry during a 2-step hyperinsulinemic-euglycemic clamp.
Substrate oxidation
Optimal versus suboptimal diet. Fasting and insulin-stimulated substrate oxidation will be determined by indirect calorimetry during a 2-step hyperinsulinemic-euglycemic clamp.
Fecal microbiota composition
Optimal versus suboptimal diet. Fecal samples to be used for analysing microbiota composition will be collected.
Oral microbiota composition
Optimal versus suboptimal diet. Saliva samples to be used for analysing microbiota composition will be collected.
Self-reported perceived stress
Optimal versus suboptimal diet. Perceived stress will be assessed using a 10-item perceived stress scale (PSS-10). Items will be scored based on a 5-point Likert scale, with higher scores representing higher perceived stress levels.
Self-reported self efficacy in physical activity
Optimal versus suboptimal diet. Self efficacy in physical activity will be assessed using Likert scales, determining an individual's ability to achieve performing physical activity.
Self-reported sleep behaviour
Optimal versus suboptimal diet. Sleep behaviour will be assessed using the Munich Chronotype Questionnaire (MCTQ).
Self-reported sleep quality over a 1 month period
Optimal versus suboptimal diet. Sleeping quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI).
Self-reported daytime sleepiness
Optimal versus suboptimal diet. Daytime sleepiness is assessed using the 8-item Epworth Sleepiness Scale (ESS). Items will be scored on a scale of 0-3, with a higher score representing a higher probability of falling asleep.
Self-reported fatigue
Optimal versus suboptimal diet. Self-reported fatigue will be assessed using the Chalder Fatigue Scale.
Self-reported sedentary behaviour
Optimal versus suboptimal diet. Sedentary behaviour will be assessed using the sedentary behaviour questionnaire (AQUAA).
Self-reported physical activity
Optimal versus suboptimal diet. Self-reported physical activity will be assessed using the physical activity questionnaire (Baecke).
Self-reported eating rate
Optimal versus suboptimal diet. Self-reported eating rate will be assessed using the eating rate index.
Self-reported intestinal health
Optimal versus suboptimal diet. Self-reported intestinal health will be assessed using an intestinal health questionnaire and the Bristol Stool Chart.
Self-reported quality of life
Optimal versus suboptimal diet. Self-reported quality of life will be assessed using the 36-Item Short Form Health Survey (SF-36). Higher scores represent less disability.
Physical activity patterns
Optimal versus suboptimal diet. Physical activity patterns will be monitored continuously with the ActivPAL3 device.
Cognitive performance
Optimal versus suboptimal diet. Cognitive function will be assessed using the Cambridge Neuropsychological Test Automated Battery.
Subcutaneous adipose tissue biopsy
Optimal versus suboptimal diet. Subcutaneous adipose tissue biopsies will be taken for histology and gene and protein expression analysis.
Skeletal muscle biopsy
Optimal versus suboptimal diet. Skeletal muscle biopsies will be taken for histology and gene and protein expression analysis.
Advanced glycation end-product (AGE) accumulation
Optimal versus suboptimal diet. AGE accumulation will be measured by skin autofluorescence using an AGE reader (Diagnoptics)
Fasting immune metabolism (PBMCs)
Optimal versus suboptimal diet. Assessment of PBMCs as measure of fasting immune metabolism
Carotid artery reactivity
Optimal versus suboptimal diet. Assessment of (peripheral) vascular function by carotid artery reactivity (CAR) in response to a cold pressor test.
Food preferences
Optimal versus suboptimal diet. Food preferences will be assessed by using the computer-based Macronutrient and Taste Preference Ranking Task (MTPRT).
Intervention effects on all above outcomes within the LIR and MIR group.
In contrast to the other outcomes, the intervention effect within the MIR and LIR group will be analysed for all above mentioned outcomes (as compared to an analysis of optimal versus the suboptimal diet). MIR and LIR are two measures of insulin resistance, in primarily the muscle and liver, respectively. MIR and LIR can be modelled from an OGTT, as described above. Thus, for each of the outcomes described above, their change following 12 weeks of dietary intervention will be compared between the two metabolic phenotypes, MIR and LIR.
DNA analysis
Buffy coats will be collected for DNA analysis, pre-intervention only.