Clinical trial NCT03708419: Personalized Glucose Optimization Through Nutritional Intervention
Official title: Personalized Glucose Optimization Through Nutritional Intervention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Pre-diabetic
Type 2 Diabetes Mellitus
Keywords: Insulin resistance
Personalized nutrition
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Wageningen University and Research
name: Top Institute Food and Nutrition
name: Netherlands Organisation for Scientific Research
First posted: 2018-10-17
Enrollment: 242
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Disposition index
timeFrame: Change from baseline at week 12 dietary intervention
Secondary outcomes:
measure: Mean 24h glucose concentrations
timeFrame: Change from baseline at week 12 dietary intervention
measure: Glucose incremental area under the curve (iAUC)
timeFrame: Change from baseline at week 12 dietary intervention
measure: The frequency and duration of hypo- and hyperglycemia
timeFrame: Change from baseline at week 12 dietary intervention
measure: Glucose tolerance
timeFrame: Change from baseline at week 12 dietary intervention
measure: Muscle insulin sensitivity
timeFrame: Change from baseline at week 12 dietary intervention
measure: Hepatic insulin sensitivity
timeFrame: Change from baseline at week 12 dietary intervention
measure: Insulin sensitivity
timeFrame: Change from baseline at week 12 dietary intervention
measure: Body composition
timeFrame: Change from baseline at week 12 dietary intervention
measure: Waist circumference
timeFrame: Change from baseline at week 12 dietary intervention
measure: Hip circumferences
timeFrame: Change from baseline at week 12 dietary intervention
measure: Body fat distribution
timeFrame: Change from baseline at week 12 dietary intervention
measure: Blood pressure
timeFrame: Change from baseline at week 12 dietary intervention
measure: Fasting circulating metabolic markers
timeFrame: Change from baseline at week 12 dietary intervention
measure: Fasting blood lipid spectrum
timeFrame: Change from baseline at week 12 dietary intervention
measure: Postprandial circulating metabolic markers
timeFrame: Change from baseline at week 12 dietary intervention
measure: Energy expenditure
timeFrame: Change from baseline at week 12 dietary intervention
measure: Substrate oxidation
timeFrame: Change from baseline at week 12 dietary intervention
measure: Fecal microbiota composition
timeFrame: Change from baseline at week 12 dietary intervention
measure: Oral microbiota composition
timeFrame: Change from baseline at week 12 dietary intervention
measure: Self-reported perceived stress
timeFrame: Change from baseline at week 12 dietary intervention
measure: Self-reported self efficacy in physical activity
timeFrame: Change from baseline at week 12 dietary intervention
measure: Self-reported sleep behaviour
timeFrame: Change from baseline at week 12 dietary intervention
measure: Self-reported sleep quality over a 1 month period
timeFrame: Change from baseline at week 12 dietary intervention
measure: Self-reported daytime sleepiness
timeFrame: Change from baseline at week 12 dietary intervention
measure: Self-reported fatigue
timeFrame: Change from baseline at week 12 dietary intervention
measure: Self-reported sedentary behaviour
timeFrame: Change from baseline at week 12 dietary intervention
measure: Self-reported physical activity
timeFrame: Change from baseline at week 12 dietary intervention
measure: Self-reported eating rate
timeFrame: Change from baseline at week 12 dietary intervention
measure: Self-reported intestinal health
timeFrame: Change from baseline at week 12 dietary intervention
measure: Self-reported quality of life
timeFrame: Change from baseline at week 12 dietary intervention
measure: Physical activity patterns
timeFrame: Change from baseline at week 12 dietary intervention
measure: Cognitive performance
timeFrame: Change from baseline at week 12 dietary intervention
measure: Subcutaneous adipose tissue biopsy
timeFrame: Change from baseline at week 12 dietary intervention
measure: Skeletal muscle biopsy
timeFrame: Change from baseline at week 12 dietary intervention
measure: Advanced glycation end-product (AGE) accumulation
timeFrame: Change from baseline at week 12 dietary intervention
measure: Fasting immune metabolism (PBMCs)
timeFrame: Change from baseline at week 12 dietary intervention
measure: Carotid artery reactivity
timeFrame: Change from baseline at week 12 dietary intervention
measure: Food preferences
timeFrame: Change from baseline at week 12 dietary intervention
measure: Intervention effects on all above outcomes within the LIR and MIR group.
timeFrame: Change from baseline at week 12 dietary intervention
measure: DNA analysis
timeFrame: Baseline
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Department of Human Biology, Maastricht University Medical Centre
city: Wageningen
country: Netherlands
facility: Wageningen University and Research
Study officials:
affiliation: Maastricht University
name: Ellen E Blaak, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gijbels A, Trouwborst I, Jardon KM, Hul GB, Siebelink E, Bowser SM, Yildiz D, Wanders L, Erdos B, Thijssen DHJ, Feskens EJM, Goossens GH, Afman LA, Blaak EE. The PERSonalized Glucose Optimization Through Nutritional Intervention (PERSON) Study: Rationale, Design and Preliminary Screening Results. Front Nutr. 2021 Jun 30;8:694568. doi: 10.3389/fnut.2021.694568. eCollection 2021.