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NCT Number: NCT03708419

Personalized Glucose Optimization Through Nutritional Intervention

Maintaining well-controlled blood glucose concentrations is essential in the prevention of chronic cardiometabolic diseases. The blood glucose response to dietary and/or lifestyle patterns may vary between individuals. Insulin resistance in specific metabolic organs such as skeletal muscle, adipose tissue or the liver may underlie differential blood glucose responses.

This dietary intervention study aims to obtain insight into the metabolic and lifestyle determinants of postprandial blood glucose responses, and to establish the effect of macronutrient manipulation of a 12-week dietary intervention on blood glucose homeostasis in metabolically different subgroups an its relationship to physical and mental performance and well-being.

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Key information

Conditions

Obesity Body Weight Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Intolerance Glucose Metabolism Disorders Hyperglycemia Hyperinsulinism Insulin Resistance Metabolic Diseases Nutrition Disorders Nutritional and Metabolic Diseases Overnutrition Overweight Pathological Conditions, Signs and Symptoms Pre-diabetic Signs and Symptoms Type 2 Diabetes Mellitus

Age range

40 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Department of Human Biology, Maastricht University Medical Centre, Maastricht, Netherlands

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About this study

Study design: this study is a double-blinded, randomised, controlled, parallel design dietary intervention study. The study will be conducted at Maastricht University and Wageningen University and Research, the Netherlands.

Study population: the study population will consist of 240 men and women between 40-75 years old, with a BMI 25-40 kg/m2. Participants will be either muscle insulin resistant (MIR) or liver insulin resistant (LIR), as classified by an oral glucose tolerance test (OGTT) during the screening procedure. A subgroup of 80 participants will be selected for detailed metabolic phenotyping.

Intervention: for 12 weeks, participants will receive either a diet optimal for MIR (high in mono-unsaturated fatty acids) or a diet optimal for LIR (high in protein and fiber, low in fat) with respect to changes in disposition index. Participants will be randomly allocated to one of the two diets. Detailed laboratory and daily life phenotyping will be done pre- and post intervention.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • BMI 25 to <40 kg/m2
  • Predominantly muscle (MIR) or liver (LIR) insulin resistant
  • Weight stability for at least 3 months (+/- 3 kg)

Exclusion criteria

Diseases

  • Pre-diagnosis of type 1 or type 2 diabetes mellitus
  • Renal or hepatic malfunctioning (pre-diagnosis or determined based on alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) and creatinine values)
  • Gastrointestinal diseases or abdominal surgery (allowed i.e.: appendectomy, cholecystectomy)
  • Food allergies, intolerances (including gluten/lactose intolerance) and/or dietary restrictions interfering with the study (including special diets, vegetarians and eating disorders)
  • Cardiovascular diseases (e.g. heart failure) or cancer (e.g. non-invasive skin cancer allowed)
  • High blood pressure (untreated >160/100 mmHg, drug-regulated >140/90 mmHg)
  • Diseases affecting glucose and/or lipid metabolism (e.g. pheochromocytoma, Cushing's syndrome, acromegaly)
  • Anemia defined as hemoglobin (Hb) men <8.5 and women <7.5 mmol/l
  • Diseases with a life expectation shorter than 5 years
  • Major mental disorders
  • Drug treated thyroid diseases (well substituted hypothyroidism is allowed inclusion)
  • Other physical/mental conditions that could interfere with study outcomes

Medication

  • Medication known to interfere with study outcomes (e.g. peroxisome proliferator-activated receptor-α (PPAR-α) or PPAR-γ agonists (fibrates), sulfonylureas, biguanides, α-glucosidase inhibitors, thiazolidinediones, repaglinide, nateglinide and insulin, chronic use of NSAIDs)
  • Use of anticoagulants
  • Use of antidepressants (stable use ≥ 3 months prior to and during the study is allowed)
  • Use of statins (stable use ≥ months prior to and during study allowed)
  • Use of β-blockers (only for the extensive phenotyping participants)
  • Chronic corticosteroids treatment (>7 consecutive days of treatment)
  • Use of antibiotics within 3 months prior to the study

Lifestyle

  • Participation in regular sports activities (>4 hours per week)
  • Having a restricted dietary pattern interfering with the study diets (e.g. vegan or Atkins diet)
  • Plans to lose weight
  • Abuse of alcohol (alcohol consumption >14 units/week) and/or drugs (cannabis included)
  • Not willing to limit alcohol consumption to 7 drinks per week
  • Regular smoking (including use of e-cigarettes)
  • Use of strong vitamins or dietary supplements (e.g. pre- or probiotics) expected to interfere with the study outcomes

Other

  • Pregnant or lactating women who are planning to become pregnant
  • Inability to comply with the study diet
  • Blood donation within the last 3 months
  • Participation in possibly interfering studies within the last 3 months
  • Inability to understand study information and/or communicate with staff
  • Unwillingness to be randomized or sign informed consent
  • Unwillingness to save data for 15 years

Treatment and study plan

Optimal diet

Other

Based on a 7-points OGTT, participants will be classified as MIR or LIR. The hypothesized optimal diet for MIR has a moderate fat content which is high in mono- unsaturated fatty acids (HMUFA) with a macronutrient breakdown of 38 E% from fat (20% MUFA, 10% polyunsaturated fatty acids (PUFA), 8% saturated fatty acids (SFA)), 48 E% from carbohydrates (CHO, 35% complex), and 14 E% from protein (35-40% plant protein). The hypothesized optimal diet for LIR is low in fat, high in protein (LFHP) and increased fiber with a macronutrient breakdown of <28 E% from fat (10% MUFA, 10% PUFA, 8% SFA), 48 E% from CHO (35% complex), and 24 E% from protein (35-40% plant protein), and an additional supplement of 6g of soluble fiber per day. Participants wil be randomly allocated to one of the two diets.

Suboptimal diet

Other

The optimal diet for the other metabolic phenotype will be considered as "suboptimal"/ control diet. For the MIR phenotype this is the high protein, high fiber, low fat diet; for the LIR phenotype this is the high monounsaturated fatty acid diet. See the description above.

Primary outcomes

  1. Disposition index

    Time frame: Change from baseline at week 12 dietary intervention

    The primary objective of this study is to establish the effect of a metabolically targeted, optimal versus suboptimal macronutrient manipulated 12-week dietary intervention on the change in disposition index, a composite marker of first phase insulin secretion and insulin sensitivity during a 2-hour 7-points oral glucose tolerance test (OGTT). Disposition index will be calculated as follows: [Insulin sensitivity index (ISI) * (AUC30 min insulin / AUC30 min glucose)], where AUC30 min is the area under the curve between 0 and 30 minutes of the OGTT for insulin (pmol/l) and glucose (mmol/l), respectively, and ISI is defined as: [10,000 ÷ square root of (fasting plasma glucose (mmol/l) x fasting insulin (pmol/l)) x (mean glucose (mmol/l) x mean insulin (pmol/l))]. Higher values represent a higher insulin sensitivity.

Secondary outcomes

  1. Mean 24h glucose concentrations

    Time frame: Change from baseline at week 12 dietary intervention

    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.

  2. Glucose incremental area under the curve (iAUC)

    Time frame: Change from baseline at week 12 dietary intervention

    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.

  3. The frequency and duration of hypo- and hyperglycemia

    Time frame: Change from baseline at week 12 dietary intervention

    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.

  4. Glucose tolerance

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Determined by 2-hour glucose values (mmol/L) during an oral glucose tolerance test.

  5. Muscle insulin sensitivity

    Time frame: Change from baseline at week 12 dietary intervention

    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.

  6. Hepatic insulin sensitivity

    Time frame: Change from baseline at week 12 dietary intervention

    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.

  7. Insulin sensitivity

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Glucose infusion rate (mg/kg/min) during a 2-step hyper-insulinemic euglycemic clamp as golden standard method.

  8. Body composition

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Body composition will be determined by using a dual-energy X-ray absorptiometry scan (DXA).

  9. Waist circumference

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Waist circumferences in centimeters.

  10. Hip circumferences

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Hip circumferences in centimeters.

  11. Body fat distribution

    Time frame: Change from baseline at week 12 dietary intervention

    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).

  12. Blood pressure

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Systolic and diastolic blood pressure in mmHg.

  13. Fasting circulating metabolic markers

    Time frame: Change from baseline at week 12 dietary intervention

    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).

  14. Fasting blood lipid spectrum

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Metabolomics will be used to determine the fasting blood lipid spectrum.

  15. Postprandial circulating metabolic markers

    Time frame: Change from baseline at week 12 dietary intervention

    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).

  16. Energy expenditure

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Fasting and insulin-stimulated energy expenditure will be determined by indirect calorimetry during a 2-step hyperinsulinemic-euglycemic clamp.

  17. Substrate oxidation

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Fasting and insulin-stimulated substrate oxidation will be determined by indirect calorimetry during a 2-step hyperinsulinemic-euglycemic clamp.

  18. Fecal microbiota composition

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Fecal samples to be used for analysing microbiota composition will be collected.

  19. Oral microbiota composition

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Saliva samples to be used for analysing microbiota composition will be collected.

  20. Self-reported perceived stress

    Time frame: Change from baseline at week 12 dietary intervention

    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.

  21. Self-reported self efficacy in physical activity

    Time frame: Change from baseline at week 12 dietary intervention

    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.

  22. Self-reported sleep behaviour

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Sleep behaviour will be assessed using the Munich Chronotype Questionnaire (MCTQ).

  23. Self-reported sleep quality over a 1 month period

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Sleeping quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI).

  24. Self-reported daytime sleepiness

    Time frame: Change from baseline at week 12 dietary intervention

    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.

  25. Self-reported fatigue

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Self-reported fatigue will be assessed using the Chalder Fatigue Scale.

  26. Self-reported sedentary behaviour

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Sedentary behaviour will be assessed using the sedentary behaviour questionnaire (AQUAA).

  27. Self-reported physical activity

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Self-reported physical activity will be assessed using the physical activity questionnaire (Baecke).

  28. Self-reported eating rate

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Self-reported eating rate will be assessed using the eating rate index.

  29. Self-reported intestinal health

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Self-reported intestinal health will be assessed using an intestinal health questionnaire and the Bristol Stool Chart.

  30. Self-reported quality of life

    Time frame: Change from baseline at week 12 dietary intervention

    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.

  31. Physical activity patterns

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Physical activity patterns will be monitored continuously with the ActivPAL3 device.

  32. Cognitive performance

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Cognitive function will be assessed using the Cambridge Neuropsychological Test Automated Battery.

  33. Subcutaneous adipose tissue biopsy

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Subcutaneous adipose tissue biopsies will be taken for histology and gene and protein expression analysis.

  34. Skeletal muscle biopsy

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Skeletal muscle biopsies will be taken for histology and gene and protein expression analysis.

  35. Advanced glycation end-product (AGE) accumulation

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. AGE accumulation will be measured by skin autofluorescence using an AGE reader (Diagnoptics)

  36. Fasting immune metabolism (PBMCs)

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Assessment of PBMCs as measure of fasting immune metabolism

  37. Carotid artery reactivity

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Assessment of (peripheral) vascular function by carotid artery reactivity (CAR) in response to a cold pressor test.

  38. Food preferences

    Time frame: Change from baseline at week 12 dietary intervention

    Optimal versus suboptimal diet. Food preferences will be assessed by using the computer-based Macronutrient and Taste Preference Ranking Task (MTPRT).

  39. Intervention effects on all above outcomes within the LIR and MIR group.

    Time frame: Change from baseline at week 12 dietary intervention

    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.

  40. DNA analysis

    Time frame: Baseline

    Buffy coats will be collected for DNA analysis, pre-intervention only.

Sponsors and collaborators

Lead sponsor

Maastricht University Medical Center

Other

Collaborators

  • Netherlands Organisation for Scientific Research
  • Top Institute Food and Nutrition
  • Wageningen University and Research

Registry information

Acronym: PERSON

Important dates

Study start
2018
Primary completion
2021
Study completion
2021
First posted
Oct 17, 2018
Registry last updated
Feb 14, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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