Exercise as a Tool for Studying the Mechanisms and Applicability of Glycemic Variability (ETSMAGV)

Exercise as a Tool for Studying the Mechanisms and Applicability of Glycemic Variability in Individuals With and Without Type 2 Diabetes Mellitus

The aim this study is characterize glycemic variability using linear and nonlinear mathematical tools, under basal conditions and in response to specific protocols acute exercise that evoke oxidative stress and inflammation in healthy subjects and type 2 diabetes patients. For this purpose, the sample size will consist of 37 individuals healthy and 32 without type 2 diabetes mellitus wore a CGMS during 3 days. Participants randomly performed aerobic and eccentric sessions, both in the morning (24h after CGMS placement), and at least 7 days apart. Glucose variability was evaluated by glucose standard deviation, glucose variance, mean amplitude of glycemic excursions (MAGE), and glucose coefficient of variation (conventional methods) as well as by spectral and symbolic analysis (non-conventional methods). Physiological mechanisms altered by exercise protocols (Human Soluble Interleukin-6 and Glutathione), will be measured in blood samples.

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Other: Aerobic Exercises; Other: Eccentric Exercise; Device: Continuous glucose monitoring system (Guardian, Medtronic, Northridge, USA)

Detailed Description

The aim this study is characterize glycemic variability using linear and nonlinear mathematical tools, under basal conditions and in response to specific protocols acute exercise that evoke oxidative stress and inflammation in healthy subjects and type 2 diabetes patients. For this purpose, the sample size will consist of 37 individuals healthy and 32 without type 2 diabetes mellitus, which will undertake the two types of exercise, randomly distributed. The maximal incremental exercise test will be performed in electrically braked cycle ergometer (ER-900, Jaeger, Wu¨ rzburg, Germany) in order to assess possible contraindications to the proposed protocol as well functional capacity, which will be used in prescription of the aerobic exercise session and a testing strength maximal will be conducted and used in the prescription of the eccentric exercise session.

The glucose variability will be assessed by continuous glucose monitoring system (CGMS) during 72h. Glucose variability will be evaluated by glucose standard deviation, glucose variance, mean amplitude of glycemic excursions (MAGE), and glucose coefficient of variation (conventional methods) as well as by spectral and symbolic analysis (non-conventional methods). Physiological mechanisms altered by exercise protocols will be measured in blood samples., Human Soluble Interleukin-6 ( HU IL 6 ELISA KIT - BIOSOURCE) and Glutathione (GSH) indicator of oxidative stress (GSH assay in: Rahman I, Kode A, Biswas SK. Nat Protoc. 2006;1(6):3159-65). The aerobic session will consist of 40 min of lower limb bicycle at 70% of the peak heart rate, as determined in the incremental exercise test and eccentric session will consist of 40 min of one lower -limb exercises (leg press) with 6 sets of 10 repetitions at 120% of 1-RM. The protocol was approved by the Ethics in Research Committee at Hospital de Clínicas de Porto Alegre and all patients will provide their written informed consent before the participation.The research will be performed at the Exercise Pathophysiology Research laboratory of the Hospital de Clínicas de Porto Alegre. We believe that signs of glycemic variability has characteristics detectable by alternative, related to hysiological processes such as oxidative stress and inflammation, evoked by aerobic and eccentric exercise protocols mathematical methods, may help explain the acute response of healthy individuals and patients with type 2 diabetes.

• Study Type: Interventional
• Enrollment (Anticipated): 69
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 90035-003
      • Recruiting
      • Hospital De Clinicas De Porto Alegre
      • Contact: Marcia Raymundo, PhD; Phone Number: +55 51 21 01 8304; Email: mraymundo@hcpa.ufrgs.br
      • Principal Investigator: Beatriz Schaan, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Type 2 diabetes Male and female 18-65 years old

Exclusion Criteria:

Chronic kidney failure; Limb amputation Diabetic proliferative retinopathy; Regular physical training; Severe autonomic neuropathy; Diabetic nephropathy established; Coronary artery disease; Heart failure; Uncontrolled hypertension Treatment of insulin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patients with type 2 diabetes	Other: Aerobic Exercises; Exercise intensity for each individual by a heart rate monitor (Polar F1 TM, Polar Electro Oy, Helsinki, Finland), and a Borg 0-10 scale used to register individuals' perceived exertion every 5 minutes throughout the experimental sessions. Aerobic session will consist of 40 min of lower limb bicycle at 70% of the peak heart rate, as determined in the incremental exercise test.; Other: Eccentric Exercise; Eccentric session will consist of 40 min of one lower -limb exercises (leg press) with 6 sets of 10 repetitions at 120% of 1-RM.; Device: Continuous glucose monitoring system (Guardian, Medtronic, Northridge, USA); Subjects will be admitted to the laboratory in the morning at approximately 9:00 a.m., 24 h before the exercise session, when the glucose sensor (Sof-SensorTM, Medtronic Mini-Med, Northridge, USA) will be inserted subcutaneously. The sensor is a glucose oxidase based platinum electrode that is inserted through a needle into the subcutaneous tissue of the anterior abdominal wall, using a spring-loaded device (Senserter, Medtronic, Northridge, USA). Glucose profiles will be collected the day before (day 1), the day of (day 2), and the day following (day 3) and 40 min of exercise. Each sensor will be used continuously for up to 72 h.
Other: Healthy	Other: Aerobic Exercises; Exercise intensity for each individual by a heart rate monitor (Polar F1 TM, Polar Electro Oy, Helsinki, Finland), and a Borg 0-10 scale used to register individuals' perceived exertion every 5 minutes throughout the experimental sessions. Aerobic session will consist of 40 min of lower limb bicycle at 70% of the peak heart rate, as determined in the incremental exercise test.; Other: Eccentric Exercise; Eccentric session will consist of 40 min of one lower -limb exercises (leg press) with 6 sets of 10 repetitions at 120% of 1-RM.; Device: Continuous glucose monitoring system (Guardian, Medtronic, Northridge, USA); Subjects will be admitted to the laboratory in the morning at approximately 9:00 a.m., 24 h before the exercise session, when the glucose sensor (Sof-SensorTM, Medtronic Mini-Med, Northridge, USA) will be inserted subcutaneously. The sensor is a glucose oxidase based platinum electrode that is inserted through a needle into the subcutaneous tissue of the anterior abdominal wall, using a spring-loaded device (Senserter, Medtronic, Northridge, USA). Glucose profiles will be collected the day before (day 1), the day of (day 2), and the day following (day 3) and 40 min of exercise. Each sensor will be used continuously for up to 72 h.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic variability by continuous glucose monitoring system	Will be assessed conventional and non-conventional methods to analyze glucose variability derived from multiple measurements performed with continuous glucose monitoring system (CGMS).Subjects will be admitted to the laboratory in the morning at approximately 9:00 a.m., 24 h before the exercise session, when the glucose sensor (Sof-SensorTM, Medtronic Mini-Med, Northridge, USA) will be inserted subcutaneously. The sensor is a glucose oxidase based platinum electrode that is inserted through a needle into the subcutaneous tissue of the anterior abdominal wall, using a spring-loaded device (Senserter, Medtronic, Northridge, USA). Glucose profiles will be collected the day before (day 1), the day of (day 2), and the day following (day 3) and 40 min of exercise. Each sensor will be used continuously for up to 72 h.	The monitor that analyzes the data every 10s and reports average values every 5 min, totalizing 288 readings per day. Glucose profiles will be collected the day before (day 1), the day of (day 2), and the day following (day 3) of 40 min of both exercise.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxidative stress	Will be assessed by Glutathione (GSH) indicator of oxidative stress (GSH assay in: Rahman I, Kode A, Biswas SK Nat PROTOC 2006, 1 (6): 3159-65.	10 minutes before the exercise sessions and 10 minutes after the exercise sessions.

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre

Publications and helpful links

General Publications

• Rahman I, Kode A, Biswas SK. Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method. Nat Protoc. 2006;1(6):3159-65. doi: 10.1038/nprot.2006.378.
• Figueira FR, Umpierre D, Bock PM, Waclawovsky G, Guerra AP, Donelli A, Andrades M, Casali KR, Schaan BD. Effect of exercise on glucose variability in healthy subjects: randomized crossover trial. Biol Sport. 2019 Jun;36(2):141-148. doi: 10.5114/biolsport.2019.83006. Epub 2019 Feb 22.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Anticipated): July 1, 2015
• Study Completion (Anticipated): August 1, 2015

Study Registration Dates

• First Submitted: September 23, 2014
• First Submitted That Met QC Criteria: October 7, 2014
• First Posted (Estimate): October 13, 2014

Study Record Updates

• Last Update Posted (Estimate): October 15, 2014
• Last Update Submitted That Met QC Criteria: October 13, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Glycemic variability, exercise, diabetes
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 120148