Impact of Nitrate Ingestion on Protein Synthesis

Study Overview
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Brief Summary
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A diet rich in leafy green vegetables has been shown to reduce the risk of developing chronic metabolic disease. The health benefits from these particular vegetables may be attributed to their high nitrate content. Recent work suggests that dietary nitrate triggers endogenous nitric oxide release, thereby stimulating vasodilation and improving muscle perfusion in an insulin-independent manner. We hypothesize that in an insulin-resistant state, nitrate co-ingestion will increase muscle perfusion, thereby improving post-prandial delivery of nutrients to skeletal muscle tissue. Specifically, a more efficient delivery of food derived amino acids will stimulate post-prandial muscle protein synthesis and, as such, compensate for a blunted muscle protein synthetic response to food intake in the elderly. This proposal will investigate the efficacy of nitrate co-ingestion as a means to augment muscle protein synthesis in elderly, type 2 diabetes patients and may lead to a novel therapy in the clinical care of type 2 diabetes patients.

Official Title
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The Impact of Dietary Nitrate Ingestion on Muscle Protein Synthesis in Elderly Type II Diabetics

Conditions
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Muscle Protein Synthesis

Intervention / Treatment
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* Dietary Supplement: Nitrate
* Dietary Supplement: Sodium chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male Aged between 70-85 years BMI < 30 kg/m2 Non insulin-dependent diabetes mellitus type 2 patients (T2DM) ( >1 y since diagnoses) Exclusion Criteria: Smoking Hypertension (according to WHO criteria)[29] and/or cardiovascular disease treated with medication containing nitrates and/or having vasodilatory effects Use of medication, except for oral blood glucose lowering medication Use of insulin All co-morbidities interacting with mobility and muscle metabolism of the lower limbs (e.g. arthritis, spasticity/rigidity, all neurological disorders and paralysis). HbA1c > 10.0% (86 mmol/mol) Donated blood in last 3 months Diagnosed impaired renal or liver function Myocardial infarction within the last 3 years Gastric acid inhibitors Use of anti-coagulants

Ages Eligible for Study
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Minimum Age: 70 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nitrate<br>Sodium nitrate ingestion prior to ingesting intrinsically labeled protein | Dietary Supplement: Nitrate<br>* 0.15 mmol/kg body weight sodium nitrate (dissolved in 250 mL water)<br>|
| Placebo Comparator: Sodium chloride<br>Sodium chloride placebo group | Dietary Supplement: Sodium chloride<br>* 0.15 mmol sodium chloride dissolved in 250 mL water.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle protein fractional synthetic rate | Muscle protein fractional synthetic rate assessed using the muscle biopsy technique. | -2, 0, +2, +5 h during the trial | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma amino acids | Blood sampling will occur through a catheter placed in an anticubital vein every 30 minutes throughout the test day. We will be using this plasma to measure plasma amino acids to determine the enrichment of labeled amino acids from both the IV tracer and the intrinsically-labeled casein protein. We wish to track the changes in amino acids from the intrinsically-labeled casein protein. | every 30 min (from -2 h to + 5 h during the test day) | 
| Plasma nitrate | Plasma nitrate will be measured every 30 minutes during the test day through blood sampling from the catheter inserted into an antecubital vein. We want to measure the changes in plasma nitrate after consuming the nitrate or placebo beverage. | every 30 min (from -2 h to + 5 h during the test day) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type II diabetes, protein synthesis, nitrate, elderly