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| Name | Class |
|---|---|
| Nutricia Research | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| L-arginine + Nitrate/Nitrite | Experimental | Subjects will receive 1 L-arginine tablet per day and drink 35 mL of beetroot juice for 8 weeks. |
|
| Placebo | Placebo Comparator | Subjects will receive 1 cellulose tablet per day and drink 35 mL of nitrate/nitrite depleted beetroot juice for 8 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| L-arginine + Nitrate / Nitrite | Dietary Supplement | Longer-term supplementation (8 weeks) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in insulin sensitivity | Muscle insulin sensitivity | Change between 8-week placebo and 8-week intervention period |
| Measure | Description | Time Frame |
|---|---|---|
| Change in muscle metabolism | Mitochondrial activity in muscle tissue | Change between 8-week placebo and 8-week intervention period |
| Change in physical functioning (1) | 6 meter walking test |
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Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Peter J Joris, PhD | Maastricht University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Maastricht University Medical Center | Maastricht | Limburg | 6229 ER | Netherlands |
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| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D001120 | Arginine |
| D009566 | Nitrates |
| D009573 | Nitrites |
| ID | Term |
|---|---|
| D024361 | Amino Acids, Basic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000599 | Amino Acids, Diamino |
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| Placebo | Dietary Supplement | Longer-term supplementation (8 weeks) |
|
| Change between 8-week placebo and 8-week intervention period |
| Change in physical functioning (2) | Timed up and go test | Change between 8-week placebo and 8-week intervention period |
| Change in physical functioning (3) | Handgrip strength test | Change between 8-week placebo and 8-week intervention period |
| Change in physical functioning (4) | Isokinetic muscle strength (BIODEX measurement) | Change between 8-week placebo and 8-week intervention period |
| Change in vascular function (1) | Flow-mediated vasodilation of the brachial artery | Change between 8-week placebo and 8-week intervention period |
| Change in vascular function (2) | Pulse wave analysis | Change between 8-week placebo and 8-week intervention period |
| Change in vascular function (3) | Pulse wave velocity | Change between 8-week placebo and 8-week intervention period |
| Change in vascular function (4) | Retinal microvascular calibers (Artery-to-Vein ratio) | Change between 8-week placebo and 8-week intervention period |
| Change in cardiometabolic risk markers (1) | Plasma markers for low-grade systemic inflammation (CRP) | Change between 8-week placebo and 8-week intervention period |
| Change in cardiometabolic risk markers (2) | Plasma markers for endothelial dysfunction (NOx) | Change between 8-week placebo and 8-week intervention period |
| Change in cardiometabolic risk markers (3) | 24-h Systolic and Diastolic blood pressure | Change between 8-week placebo and 8-week intervention period |
| Change in continuous insulin sensitivity | 36-h plasma glucose values | Change between 8-week placebo and 8-week intervention period |
| D000601 | Amino Acids, Essential |
| D000838 | Anions |
| D007477 | Ions |
| D004573 | Electrolytes |
| D007287 | Inorganic Chemicals |
| D017942 | Nitric Acid |
| D017672 | Nitrogen Compounds |
| D009930 | Organic Chemicals |
| D009608 | Nitrous Acid |