Personalized Glucose Optimization Through Nutritional Intervention

Obesity Clinical Trial

— PERSON  

Official title:

Personalized Glucose Optimization Through Nutritional Intervention

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03708419
• Other study ID #: NL63768.068.17
• Status: Completed
• Phase: N/A
• Start date: June 4, 2018
• Est. completion date: November 29, 2021

Study information

• Verified date: February 2022
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 242
• Est. completion date: November 29, 2021
• Est. primary completion date: November 29, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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-a (PPAR-a) or PPAR-? agonists (fibrates), sulfonylureas, biguanides, a-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 ß-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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Obesity
• Pre-diabetic
• Prediabetic State
• Type 2 Diabetes Mellitus

Intervention

Other:
• Optimal diet
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
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.

Locations

Country	Name	City	State
Netherlands	Department of Human Biology, Maastricht University Medical Centre	Maastricht
Netherlands	Wageningen University and Research	Wageningen

Sponsors (4)

Lead Sponsor	Collaborator
Maastricht University Medical Center	Netherlands Organisation for Scientific Research, Top Institute Food and Nutrition, Wageningen University and Research

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disposition index	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.	Change from baseline at week 12 dietary intervention
Secondary	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.	Change from baseline at week 12 dietary intervention
Secondary	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.	Change from baseline at week 12 dietary intervention
Secondary	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.	Change from baseline at week 12 dietary intervention
Secondary	Glucose tolerance	Optimal versus suboptimal diet. Determined by 2-hour glucose values (mmol/L) during an oral glucose tolerance test.	Change from baseline at week 12 dietary intervention
Secondary	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.	Change from baseline at week 12 dietary intervention
Secondary	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.	Change from baseline at week 12 dietary intervention
Secondary	Insulin sensitivity	Optimal versus suboptimal diet. Glucose infusion rate (mg/kg/min) during a 2-step hyper-insulinemic euglycemic clamp as golden standard method.	Change from baseline at week 12 dietary intervention
Secondary	Body composition	Optimal versus suboptimal diet. Body composition will be determined by using a dual-energy X-ray absorptiometry scan (DXA).	Change from baseline at week 12 dietary intervention
Secondary	Waist circumference	Optimal versus suboptimal diet. Waist circumferences in centimeters.	Change from baseline at week 12 dietary intervention
Secondary	Hip circumferences	Optimal versus suboptimal diet. Hip circumferences in centimeters.	Change from baseline at week 12 dietary intervention
Secondary	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).	Change from baseline at week 12 dietary intervention
Secondary	Blood pressure	Optimal versus suboptimal diet. Systolic and diastolic blood pressure in mmHg.	Change from baseline at week 12 dietary intervention
Secondary	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).	Change from baseline at week 12 dietary intervention
Secondary	Fasting blood lipid spectrum	Optimal versus suboptimal diet. Metabolomics will be used to determine the fasting blood lipid spectrum.	Change from baseline at week 12 dietary intervention
Secondary	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).	Change from baseline at week 12 dietary intervention
Secondary	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.	Change from baseline at week 12 dietary intervention
Secondary	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.	Change from baseline at week 12 dietary intervention
Secondary	Fecal microbiota composition	Optimal versus suboptimal diet. Fecal samples to be used for analysing microbiota composition will be collected.	Change from baseline at week 12 dietary intervention
Secondary	Oral microbiota composition	Optimal versus suboptimal diet. Saliva samples to be used for analysing microbiota composition will be collected.	Change from baseline at week 12 dietary intervention
Secondary	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.	Change from baseline at week 12 dietary intervention
Secondary	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.	Change from baseline at week 12 dietary intervention
Secondary	Self-reported sleep behaviour	Optimal versus suboptimal diet. Sleep behaviour will be assessed using the Munich Chronotype Questionnaire (MCTQ).	Change from baseline at week 12 dietary intervention
Secondary	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).	Change from baseline at week 12 dietary intervention
Secondary	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.	Change from baseline at week 12 dietary intervention
Secondary	Self-reported fatigue	Optimal versus suboptimal diet. Self-reported fatigue will be assessed using the Chalder Fatigue Scale.	Change from baseline at week 12 dietary intervention
Secondary	Self-reported sedentary behaviour	Optimal versus suboptimal diet. Sedentary behaviour will be assessed using the sedentary behaviour questionnaire (AQUAA).	Change from baseline at week 12 dietary intervention
Secondary	Self-reported physical activity	Optimal versus suboptimal diet. Self-reported physical activity will be assessed using the physical activity questionnaire (Baecke).	Change from baseline at week 12 dietary intervention
Secondary	Self-reported eating rate	Optimal versus suboptimal diet. Self-reported eating rate will be assessed using the eating rate index.	Change from baseline at week 12 dietary intervention
Secondary	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.	Change from baseline at week 12 dietary intervention
Secondary	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.	Change from baseline at week 12 dietary intervention
Secondary	Physical activity patterns	Optimal versus suboptimal diet. Physical activity patterns will be monitored continuously with the ActivPAL3 device.	Change from baseline at week 12 dietary intervention
Secondary	Cognitive performance	Optimal versus suboptimal diet. Cognitive function will be assessed using the Cambridge Neuropsychological Test Automated Battery.	Change from baseline at week 12 dietary intervention
Secondary	Subcutaneous adipose tissue biopsy	Optimal versus suboptimal diet. Subcutaneous adipose tissue biopsies will be taken for histology and gene and protein expression analysis.	Change from baseline at week 12 dietary intervention
Secondary	Skeletal muscle biopsy	Optimal versus suboptimal diet. Skeletal muscle biopsies will be taken for histology and gene and protein expression analysis.	Change from baseline at week 12 dietary intervention
Secondary	Advanced glycation end-product (AGE) accumulation	Optimal versus suboptimal diet. AGE accumulation will be measured by skin autofluorescence using an AGE reader (Diagnoptics)	Change from baseline at week 12 dietary intervention
Secondary	Fasting immune metabolism (PBMCs)	Optimal versus suboptimal diet. Assessment of PBMCs as measure of fasting immune metabolism	Change from baseline at week 12 dietary intervention
Secondary	Carotid artery reactivity	Optimal versus suboptimal diet. Assessment of (peripheral) vascular function by carotid artery reactivity (CAR) in response to a cold pressor test.	Change from baseline at week 12 dietary intervention
Secondary	Food preferences	Optimal versus suboptimal diet. Food preferences will be assessed by using the computer-based Macronutrient and Taste Preference Ranking Task (MTPRT).	Change from baseline at week 12 dietary intervention
Secondary	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.	Change from baseline at week 12 dietary intervention
Secondary	DNA analysis	Buffy coats will be collected for DNA analysis, pre-intervention only.	Baseline