Nutritional Supplementation and Insulin Sensitivity

NCT04239482 | Terminated

• 1 other identifier: METC 19-085
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Type 2 diabetes mellitus (T2DM) is a progressive disease and early intervention and prevention strategies are therefore very important. An important early hallmark in the development of T2DM is insulin resistance. Since the majority of postprandial glucose disposal occurs in skeletal muscle, improving muscle insulin sensitivity will thus have a major impact on disease prevention. Abdominally obese men and women have an increased risk to develop T2DM, and are also characterized by an impaired vascular function. This may hamper proper delivery of insulin, glucose and oxygen to muscles, thereby contributing to - and possibly causing - muscle insulin resistance. Earlier it has been shown that supplementation with L- arginine improves vascular function by improving nitric oxide (NO) bioavailability. These NO- mediated beneficial effects on vascular function may improve delivery of insulin, glucose and oxygen to the muscle tissue, thereby improving muscle insulin sensitivity and mitochondrial function. However, the doses needed of this amino acid cannot be provided by regular diets or supplements, also due to the bitter taste of L-arginine. Alternatively, smaller amounts of L- arginine with a specific combination of other nutritional components (i.e. nitrate and nitrite), which are already part of the regular diet and support alternative pathways to improve NO- mediated vascular function, may also induce beneficial effects. The investigators now hypothesize that in abdominally obese adults with impaired fasting glucose concentrations L-arginine combined with nitrate/nitrite increases muscle insulin sensitivity.

Conditions

Nitric Oxide; Insulin Sensitivity; Vascular Function; L-arginine; Nitrate / Nitrite

Outcome Measures

Primary Outcomes (1)

• Change in insulin sensitivity

  Muscle insulin sensitivity

  Change between 8-week placebo and 8-week intervention period

Secondary Outcomes (13)

• Change in muscle metabolism

  Change between 8-week placebo and 8-week intervention period

• Change in physical functioning (1)

  Change between 8-week placebo and 8-week intervention period

• Change in physical functioning (2)

  Change between 8-week placebo and 8-week intervention period

• Change in physical functioning (3)

  Change between 8-week placebo and 8-week intervention period

• Change in physical functioning (4)

  Change between 8-week placebo and 8-week intervention period

Study Arms (2)

L-arginine + Nitrate/Nitrite

EXPERIMENTAL

Subjects will receive 1 L-arginine tablet per day and drink 35 mL of beetroot juice for 8 weeks.

Dietary Supplement: L-arginine + Nitrate / Nitrite

Placebo

PLACEBO COMPARATOR

Subjects will receive 1 cellulose tablet per day and drink 35 mL of nitrate/nitrite depleted beetroot juice for 8 weeks.

Dietary Supplement: Placebo

Interventions

L-arginine + Nitrate / Nitrite DIETARY_SUPPLEMENT

Longer-term supplementation (8 weeks)

L-arginine + Nitrate/Nitrite

Placebo DIETARY_SUPPLEMENT

Longer-term supplementation (8 weeks)

Placebo

Eligibility Criteria

• Age: 50 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged between 50-70 years
• Men and postmenopausal (two or more years after last menstruation) women
• Waist circumference for men 3 102 cm and for women 3 88 cm (abdominally obese)
• Impaired fasting glucose concentrations (between 5.6 - 7.0 mmol/L in accordance with the American Diabetes Association guidelines for prediabetes) at two screening visits
• Fasting serum total cholesterol \< 8.0 mmol/L
• Stable body weight (weight gain or loss \< 3 kg in the past three months)
• Willingness to give up being a blood donor from 8 weeks before the start of the study, during the study and for 4 weeks after completion of the study
• No difficult venipuncture as evidenced during the screening visit
• Willingness to give up the use of antibacterial mouth wash or antibacterial toothpaste, chewing-gum and tongue-scraping during the study

You may not qualify if:

• Current smoker, or smoking cessation \< 12 months
• Diabetic patients
• Familial hypercholesterolemia
• Abuse of drugs
• More than 3 alcoholic consumptions per day
• Use of dietary supplements known to interfere with the main study outcomes as judged by the principal investigators
• Use of anticoagulant drugs or drugs to treat blood pressure, lipid/glucose metabolism
• Use of an investigational product within another biomedical intervention trial within the previous 1-month
• Intolerance or allergy to the ingredients of the intervention products
• Severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease (COPD), inflammatory bowel diseases, auto inflammatory diseases and rheumatoid arthritis
• Active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Nutricia Research: collaborator

Study Sites (1)

Maastricht University Medical Center

Maastricht, Limburg, 6229 ER, Netherlands

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

Arginine; Nitrates; Nitrites

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential; Anions; Ions; Electrolytes; Inorganic Chemicals; Nitric Acid; Nitrogen Compounds; Organic Chemicals; Nitrous Acid

Study Officials

• Peter J Joris, PhD

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2019
• First Posted: January 27, 2020
• Study Start: September 1, 2020
• Primary Completion: October 1, 2020
• Study Completion: October 1, 2020
• Last Updated: June 11, 2021

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)