Nutritional Supplementation and Insulin Sensitivity

Insulin Sensitivity Clinical Trial

Official title:

Longer-term Effects of a Novel Nutritional Combination on Muscle Insulin Sensitivity and Mitochondrial Function, and Vascular Function in Abdominally Obese Subjects

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04239482
• Other study ID #: METC 19-085
• Status: Terminated
• Phase: N/A
• Start date: September 1, 2020
• Est. completion date: October 1, 2020

Study information

• Verified date: September 2020
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: October 1, 2020
• Est. primary completion date: October 1, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypersensitivity
• Insulin Resistance
• Insulin Sensitivity
• L-arginine
• Nitrate / Nitrite
• Nitric Oxide
• Vascular Function

Intervention

Dietary Supplement:
• L-arginine + Nitrate / Nitrite
Longer-term supplementation (8 weeks)
• Placebo
Longer-term supplementation (8 weeks)

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Center	Maastricht	Limburg

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	Nutricia Research

Country where clinical trial is conducted

Netherlands, 

Outcome

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