L-arginine and Asymmetric Dimethylarginine (ADMA) and Lifestyle Protocols

The Effects of Different Acute Nutritional Protocols and Lifestyle Modification on Circulating L-arginine and Asymmetric Dimethylarginine (ADMA) in Obese and Type 2 Diabetic Subjects

Low serum L-arginine (Arg) and high asymmetric dimethylarginine (ADMA) can predict microvascular complications in type 2 diabetes (T2DM). The investigators examined whether or not Arg and ADMA are affected by dietary factors or lifestyle modification in overweight/ obese and T2DM subjects.

Study Overview

• Status: Completed
• Conditions: Obesity; Diabetes Mellitus, Type 2; Arginine; Asymmetric Dimethylarginine
• Intervention / Treatment: Behavioral: Acute dietary protocols and lifestyle modification

Detailed Description

The investigators tested the effects on serum Arg and ADMA of a) a single load of ingested dextrose, protein, fat or alcohol, each consumed within 10 minutes; b) a single episode of physical exercise; c) a 12 weeks lifestyle modification program comprised of a standard dietary and physical activity counseling in obese or T2DM subjects on circulating Arg and ADMA (n=43)

• Study Type: Interventional
• Enrollment (Actual): 243
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Holon, Israel, 5822012
    • Diabetes Unit, E. Wolfson Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• obese and/ or T2DM subjects

Exclusion Criteria:

• type 1 diabetes
• insulin-treated T2DM
• active coronary disease (recent [≤ 6months] myocardial infarction, unstable angina, recent coronary catheterization, or coronary bypass grafting
• individuals with significant impairment in liver enzymes (≥ 2.5 the upper limit of the normal range)
• serum creatinine higher than 1.5mg%
• known malabsorption, alcoholism or illicit use of drugs
• abnormal thyroid function tests
• concomitant or recent use of glucocorticoids
• uncertain mental state (to avoid invalid informed consent or lack of compliance).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acute glucose tolerance test; A standard oral glucose tolerance test (75 grams of dextrose in 180 cc of water)	Behavioral: Acute dietary protocols and lifestyle modification; The investigators tested the effects on serum Arg and ADMA of a) a single load of ingested dextrose, protein, fat or alcohol, each consumed within 10 minutes; b) a single episode of physical exercise; c) a 12 weeks lifestyle modification program comprised of a standard dietary and physical activity counseling in obese or T2DM subjects on circulating Arg and ADMA (n=43).
Experimental: Acute protein load test; A protein-rich, vanilla-flavored powder (Pro-gym, Telpharma, Is	Behavioral: Acute dietary protocols and lifestyle modification; The investigators tested the effects on serum Arg and ADMA of a) a single load of ingested dextrose, protein, fat or alcohol, each consumed within 10 minutes; b) a single episode of physical exercise; c) a 12 weeks lifestyle modification program comprised of a standard dietary and physical activity counseling in obese or T2DM subjects on circulating Arg and ADMA (n=43).
Experimental: Acute fat load test; a 100-gram portion of sweet cream containing 300 Kacls, of which 94% of the ingested calories were fat	Behavioral: Acute dietary protocols and lifestyle modification; The investigators tested the effects on serum Arg and ADMA of a) a single load of ingested dextrose, protein, fat or alcohol, each consumed within 10 minutes; b) a single episode of physical exercise; c) a 12 weeks lifestyle modification program comprised of a standard dietary and physical activity counseling in obese or T2DM subjects on circulating Arg and ADMA (n=43).
Experimental: Acute alcohol load test; Vodka (100 cc, 40% alcohol)	Behavioral: Acute dietary protocols and lifestyle modification; The investigators tested the effects on serum Arg and ADMA of a) a single load of ingested dextrose, protein, fat or alcohol, each consumed within 10 minutes; b) a single episode of physical exercise; c) a 12 weeks lifestyle modification program comprised of a standard dietary and physical activity counseling in obese or T2DM subjects on circulating Arg and ADMA (n=43).
Experimental: Acute exercise; 30 minutes of supervised graded walking on a treadmill according to each subject's individual ability. A goal heart rate was calculated as 70% of the age-adjusted maximal allowable heart rate.	Behavioral: Acute dietary protocols and lifestyle modification; The investigators tested the effects on serum Arg and ADMA of a) a single load of ingested dextrose, protein, fat or alcohol, each consumed within 10 minutes; b) a single episode of physical exercise; c) a 12 weeks lifestyle modification program comprised of a standard dietary and physical activity counseling in obese or T2DM subjects on circulating Arg and ADMA (n=43).
Experimental: Lifestyle modification program - 12 weeks; 12 weeks of weight-loss dietary program constructed according to the guidelines of the American Diabetes Association. Based on weight, gender, and age, daily dietary allowance varied at 1200-1800 Kcal, 50% carbohydrates, 20% protein, and 30% fat. Participants were also asked to engage in moderate physical activity comprised of a 40-minute walk three times a week. A weekly clinic visit alternating with a weekly telephone contact was also required.	Behavioral: Acute dietary protocols and lifestyle modification; The investigators tested the effects on serum Arg and ADMA of a) a single load of ingested dextrose, protein, fat or alcohol, each consumed within 10 minutes; b) a single episode of physical exercise; c) a 12 weeks lifestyle modification program comprised of a standard dietary and physical activity counseling in obese or T2DM subjects on circulating Arg and ADMA (n=43).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum L-arginine change	Change in arginine levels (absolute and relative) (µmol/l)	For acute phase: before the nutritional/exercise load (time 0), as well as 30, 60, 90, 120 and 150 minutes after the challenge test. And from baseline to 12 weeks for lifestyle modification phase
High asymmetric dimethylarginine (ADMA) change	Change in ADMA levels (absolute and relative) (µmol/l)	For acute phase: before the nutritional/exercise load (time 0), as well as 30, 60, 90, 120 and 150 minutes after the challenge test. And from baseline to 12 weeks for lifestyle modification phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body mass index (BMI) change	Change in BMI levels (Kg/m2)	From baseline to 12 weeks for lifestyle modification phase
Glycated hemoglobin (HbA1c) change	Change in HbA1c levels (%)	From baseline to 12 weeks for lifestyle modification phase

Collaborators and Investigators

• Sponsor: Tel-Aviv Sourasky Medical Center
• Collaborators: Wolfson Medical Center
• Investigators: Principal Investigator: Naftali Stern, MD, Tel-Aviv Sourasky Medical Center

Publications and helpful links

General Publications

• Buch A, Ganz T, Wainstein J, Gilad S, Limor R, Shefer G, Boaz M, Stern N. Alcohol Drinks Induce Acute Lowering in Circulating l-Arginine in Obese and Type 2 Diabetic Subjects. J Med Food. 2022 Jun;25(6):675-682. doi: 10.1089/jmf.2021.0045.

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2006
• Primary Completion (Actual): April 4, 2008
• Study Completion (Actual): December 10, 2008

Study Registration Dates

• First Submitted: May 25, 2020
• First Submitted That Met QC Criteria: May 25, 2020
• First Posted (Actual): May 28, 2020

Study Record Updates

• Last Update Posted (Actual): June 2, 2020
• Last Update Submitted That Met QC Criteria: May 30, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No