The Effect of 4 Weeks of L-Citrulline Supplementation on Macro- and Microvascular Function in Type 2 Diabetes

Texas Tech University36 enrolled

Overview

The purpose of this study is to examine the effect of 4 weeks of Citrulline supplementation on macro- and microvascular function during acute hyperglycemia in middle-aged and older adults with type 2 diabetes.

Using a double-blind, randomized, placebo-controlled, and cross-over design, middle-aged and older adults with type 2 diabetes will be randomized to receive either CIT supplementation (6g/day) or placebo (Microcrystalline Cellulose, 6g/day) for 4 weeks. There will be a total of 5 laboratory visits. Visit 1 (screening visit) will take approximately 1 hour and 30 minutes, visit 2 will take approximately 2 hours and 30 minutes, and visits 3-5 will be approximately 3 hours each. Visit 1 will measure blood pressure, blood glucose and lipid levels, anthropometry, body composition, and muscle strengths. Visits 2-5 will assess vascular function and glucose control during fasted and acute hyperglycemia conditions induced by 75g of glucose ingestion.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Type 2 Diabetes

Interventions

L-citrullineDIETARY_SUPPLEMENT

4 weeks of L-citrulline (6 g/day) in 8 capsules. Supplementation will be ingested daily, half of the doses in the morning and half at night.

PlaceboDIETARY_SUPPLEMENT

4 weeks of microcrystalline cellulose in 8 capsules. Supplementation will be ingested daily, half of the doses in the morning and half at night.

Eligibility

Sex: ALLMin age: 40 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Middle-aged and older women and men between 40-75 years old * A physician diagnosed type 2 diabetes at least 3 months ago * Treated with an oral hypoglycemic medication * Body mass index \< 40 kg/m2 * Systolic blood pressure \< 160 mmHg * Sedentary (defined as \< 120 min/week of exercise) * Not currently participating in exercise or dietary interventions for at least 2 months prior the present study and willing to abstain from participating in those strategies during the duration of this study. Exclusion Criteria: * \< 40 years of age and \> 65 years of age * Use of medications and/or any supplements that may affect outcome variables (such as arginine- or citrulline-containing supplements, nitrates, and nitroglycerin) * Body mass index ≥ 40 kg/m2 * Systolic blood pressure ≥ 160 mmHg * Recent changes in medications within 3 months * Current smoking any tobacco use * Type 1 diabetes, severe cardiovascular/renal/pulmonary diseases * More than 7 alcoholic drinks/week of consumption * Premenopausal women with an irregular menstrual cycle (oligomenorrhea) or pregnancy

Locations (1)

TTU Kinesiology and Sport Management Building

Lubbock, Texas, United States

Outcomes

Primary Outcomes

Change in macrovascular endothelial function in the fasted condition

Macrovascular endothelial function will be measured using brachial artery flow mediated dilation (ultrasonography) during reactive hyperemia at baseline and after 4 weeks of supplementation.

Time frame: 4 weeks

Change in macrovascular endothelial function during acute hyperglycemia

Macrovascular endothelial function will be measured using brachial artery flow mediated dilation (ultrasonography) during reactive hyperemia at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.

Time frame: 4 weeks

Change in microvascular endothelial function in the fasted condition

Microvascular endothelial function will be assessed using peripheral arterial tonometry (EndoPAT device) during reactive hyperemia at baseline and after 4 weeks of supplementation.

Time frame: 4 weeks

Change in microvascular endothelial function in the fasted condition

Microvascular endothelial function will be assessed using forearm muscle oxygenation (near-infrared spectroscopy) during reactive hyperemia at baseline and after 4 weeks of supplementation.

Time frame: 4 weeks

Change in microvascular endothelial function during acute hyperglycemia

Microvascular endothelial function will be assessed using forearm muscle oxygenation (near-infrared spectroscopy) during reactive hyperemia at 60 minutes after oral glucose ingestion at baseline and after 4 weeks of supplementation.

Time frame: 4 weeks

Change in blood glucose levels in the fasted condition

Blood glucose levels will be measured by finger prick at baseline and after 4 weeks of supplementation.

Time frame: 4 weeks

Data from ClinicalTrials.gov

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Secondary Outcomes

Change in body composition

Body composition (fat and lean mass) will be measured at baseline and after 4 weeks of supplementation.

Time frame: 4 weeks

Change in muscle strength

Maximal handgrip strength will be measured using handgrip dynamometer. Leg extension and plantar flexion strength will be measured using the 10RM test at baseline and after 4 weeks of supplementation.

Time frame: 4 weeks

Change in insulin levels

Serum insulin levels will be tested at baseline and after 4 weeks of supplementation.

Time frame: 4 weeks

Change in serum arginine levels

Serum arginine levels will tested at baseline and after 4 weeks of supplementation.

Time frame: 4 weeks

Change in serum arginase activity levels

Serum arginase activity levels will tested at baseline and after 4 weeks of supplementation.

Time frame: 4 weeks

Change in 24-hour ambulatory blood pressure monitoring

Ambulatory blood pressure will be obtained using a monitor during daytime and nighttime on two separate days at baseline and after 4 weeks of supplementation.

Time frame: 4 weeks