Nutritional Supplementation and Insulin Sensitivity

Not Applicable

Terminated

• Conditions: Nitric Oxide; Insulin Sensitivity; Vascular Function; L-arginine; Nitrate / Nitrite
• Interventions: Dietary Supplement: L-arginine + Nitrate / Nitrite; Dietary Supplement: Placebo

• Registration Number: NCT04239482
• Lead Sponsor: Maastricht University Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-12-20
• Study First Submitted QC: 2020-01-20
• Study First Posted: 2020-01-27
• Status Verified: 2020-09
• Study Start: 2020-09-01
• Primary Completion: 2020-10-01
• Study Completion: 2020-10-01
• Last Update Submitted: 2021-06-08
• Last Update Posted: 2021-06-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

• 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

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
L-arginine + Nitrate/Nitrite	L-arginine + Nitrate / Nitrite	Subjects will receive 1 L-arginine tablet per day and drink 35 mL of beetroot juice for 8 weeks.
Placebo	Placebo	Subjects will receive 1 cellulose tablet per day and drink 35 mL of nitrate/nitrite depleted beetroot juice for 8 weeks.

Primary Outcome Measures

Name	Time	Method
Change in insulin sensitivity	Change between 8-week placebo and 8-week intervention period	Muscle insulin sensitivity

Secondary Outcome Measures

Name	Time	Method
Change in physical functioning (3)	Change between 8-week placebo and 8-week intervention period	Handgrip strength test
Change in physical functioning (1)	Change between 8-week placebo and 8-week intervention period	6 meter walking test
Change in vascular function (4)	Change between 8-week placebo and 8-week intervention period	Retinal microvascular calibers (Artery-to-Vein ratio)
Change in physical functioning (2)	Change between 8-week placebo and 8-week intervention period	Timed up and go test
Change in vascular function (3)	Change between 8-week placebo and 8-week intervention period	Pulse wave velocity
Change in cardiometabolic risk markers (3)	Change between 8-week placebo and 8-week intervention period	24-h Systolic and Diastolic blood pressure
Change in vascular function (2)	Change between 8-week placebo and 8-week intervention period	Pulse wave analysis
Change in cardiometabolic risk markers (2)	Change between 8-week placebo and 8-week intervention period	Plasma markers for endothelial dysfunction (NOx)
Change in vascular function (1)	Change between 8-week placebo and 8-week intervention period	Flow-mediated vasodilation of the brachial artery
Change in cardiometabolic risk markers (1)	Change between 8-week placebo and 8-week intervention period	Plasma markers for low-grade systemic inflammation (CRP)
Change in muscle metabolism	Change between 8-week placebo and 8-week intervention period	Mitochondrial activity in muscle tissue
Change in physical functioning (4)	Change between 8-week placebo and 8-week intervention period	Isokinetic muscle strength (BIODEX measurement)
Change in continuous insulin sensitivity	Change between 8-week placebo and 8-week intervention period	36-h plasma glucose values

Trial Locations

Locations (1)

Maastricht University Medical Center; 🇳🇱 Maastricht, Limburg, Netherlands