Personalized Glucose Optimization Through Nutritional Intervention

NCT03708419 | Completed DMC

• 1 other identifier: NL63768.068.17
• Study Type: interventional
• Target: 242
• Locations: 1 country
• Sites: 2

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.

Conditions

Obesity; Pre-diabetic; Type 2 Diabetes Mellitus

Keywords

Insulin resistance; Personalized nutrition

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (40)

• Mean 24h glucose concentrations

  Change from baseline at week 12 dietary intervention

• Glucose incremental area under the curve (iAUC)

  Change from baseline at week 12 dietary intervention

• The frequency and duration of hypo- and hyperglycemia

  Change from baseline at week 12 dietary intervention

• Glucose tolerance

  Change from baseline at week 12 dietary intervention

• Muscle insulin sensitivity

  Change from baseline at week 12 dietary intervention

Study Arms (2)

Optimal diet

EXPERIMENTAL

Participants will follow a diet for a total duration of 12 weeks, optimal for their metabolic phenotype. For participants with muscle insulin resistance (MIR) this will be a diet high in monounsaturated fatty acids, for participants with liver insulin resistance (LIR) this will be a diet high in protein and fiber and low in fat.

Other: Optimal diet

Suboptimal diet

EXPERIMENTAL

Participants will follow a diet for a total duration of 12 weeks, suboptimal for their metabolic phenotype. For participants with liver insulin resistance (LIR) this will be a diet high in monounsaturated fatty acids, for participants with muscle insulin resistance (MIR) this will be a diet high in protein and fiber and low in fat.

Other: Suboptimal diet

Interventions

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.

Optimal diet

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.

Suboptimal diet

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Wageningen University and Research: collaborator
• Top Institute Food and Nutrition: collaborator
• Netherlands Organisation for Scientific Research: collaborator

Study Sites (2)

Department of Human Biology, Maastricht University Medical Centre

Maastricht, 6200MD, Netherlands

Location

Wageningen University and Research

Wageningen, 6700AA, Netherlands

Location

Related Publications (5)

• Jardon KM, Umanets A, Gijbels A, Trouwborst I, Hul GB, Siebelink E, Vliex LMM, Bastings JJAJ, Argamasilla R, Chenal E, Venema K, Afman LA, Goossens GH, Blaak EE. Distinct gut microbiota and metabolome features of tissue-specific insulin resistance in overweight and obesity. Gut Microbes. 2025 Dec;17(1):2501185. doi: 10.1080/19490976.2025.2501185. Epub 2025 May 7.

  PMID: 40336254 DERIVED

• Gijbels A, Jardon KM, Trouwborst I, Manusama KC, Goossens GH, Blaak EE, Feskens EJ, Afman LA. Fasting and postprandial plasma metabolite responses to a 12-wk dietary intervention in tissue-specific insulin resistance: a secondary analysis of the PERSonalized glucose Optimization through Nutritional intervention (PERSON) randomized trial. Am J Clin Nutr. 2024 Aug;120(2):347-359. doi: 10.1016/j.ajcnut.2024.05.027. Epub 2024 Jun 6.

  PMID: 38851634 DERIVED

• Trouwborst I, Jardon KM, Gijbels A, Hul G, Feskens EJM, Afman LA, Linge J, Goossens GH, Blaak EE. Body composition and body fat distribution in tissue-specific insulin resistance and in response to a 12-week isocaloric dietary macronutrient intervention. Nutr Metab (Lond). 2024 Apr 9;21(1):20. doi: 10.1186/s12986-024-00795-y.

  PMID: 38594756 DERIVED

• Trouwborst I, Gijbels A, Jardon KM, Siebelink E, Hul GB, Wanders L, Erdos B, Peter S, Singh-Povel CM, de Vogel-van den Bosch J, Adriaens ME, Arts ICW, Thijssen DHJ, Feskens EJM, Goossens GH, Afman LA, Blaak EE. Cardiometabolic health improvements upon dietary intervention are driven by tissue-specific insulin resistance phenotype: A precision nutrition trial. Cell Metab. 2023 Jan 3;35(1):71-83.e5. doi: 10.1016/j.cmet.2022.12.002.

  PMID: 36599304 DERIVED

• 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.

  PMID: 34277687 DERIVED

MeSH Terms

Conditions

Obesity; Glucose Intolerance; Diabetes Mellitus, Type 2; Insulin Resistance

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Diabetes Mellitus; Endocrine System Diseases; Hyperinsulinism

Study Officials

• Ellen E Blaak, Prof.

  Maastricht University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2018
• First Posted: October 17, 2018
• Study Start: June 4, 2018
• Primary Completion: November 29, 2021
• Study Completion: November 29, 2021
• Last Updated: February 14, 2022

Record last verified: 2022-02

Locations

NL (2)