High Intensity Interval Training in Prediabetes

Impact of High Intensity Interval Training vs. Continuous Aerobic Training on Platelet Insulin Resistance, Platelet Function and Hepatic Steatosis in Patients With Prediabetes

This trial investigates if high intensity interval training is more effective than moderate intensity continuous training in suppressing platelet reactivity and hepatic fat content in prediabetic individuals.

Study Overview

• Status: Unknown
• Conditions: Prediabetic State
• Intervention / Treatment: Behavioral: High intensity interval training (HIIT); Behavioral: Moderate intensity continuous training (MICT)

Detailed Description

Background:

The prevalence of type 2 diabetes mellitus (T2DM) is rising dramatically. T2DM represents a major cause for cardiovascular disease -related mortality and morbidity and increasingly burdens healthcare systems. While the fundamental pathomechanism of T2DM is insulin resistance of muscle and adipose tissue, recent studies demonstrate that insulin resistance in T2DM also occurs in platelets. As insulin directly inhibits platelet function, this mechanism might contribute to platelet activation and platelet hyperreactivity, which were in fact detected in diabetic patients. Since (inadvertent) platelet activation is causally linked to the development of atherosclerosis and atherothrombosis, regulation of platelet function is of utmost importance. Exercise training, performed on a regular basis has been shown to reduce morbidity and mortality in sedentary and diseased populations. Furthermore, exercise training improves whole body insulin sensitivity - however, it is currently unclear, if exercise training also affects insulin sensitivity of platelets. Recently, a time-saving interval training protocol has been adapted for T2DM-patients. Since this adapted high intensity interval training (HIIT) needs a fractional time commitment of exercise training according to current guidelines, HIIT possibly represents a promising instrument to increase adherence to exercise and thereby reduce T2DM morbidity.

Aims:

The primary aim of this study is to investigate the effect of 12 weeks of HIIT vs. continuous training (CT) on platelet insulin sensitivity and platelet (hyper)reactivity in prediabetic patients.

Secondary aims are to assess the effect of HIIT and CT on whole body insulin sensitivity and fitness in prediabetic patients as well as on various parameters of platelet function and on the hepatic fat content.

Hypotheses:

Our main hypothesis is that HIIT increases platelet insulin sensitivity and thereby decreases platelet activation/reactivity in patients with prediabetes. Methods: 44 prediabetic (see inclusion criteria) patients will be enrolled in this study. Patients will randomly be assigned to a HIIT group (committed to a supervised training program) or a CT group. After initial examinations (supervised graded exercise test, platelet function tests, oral glucose tolerance test, measurement of the hepatic fat content via FibroScan®), supervised training will be performed over a period of 12 weeks. Tests performed at the beginning of the study will be repeated after the training period.

• Study Type: Interventional
• Enrollment (Anticipated): 44
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ivo Volf, PhD; Phone Number: 31421 +43 40160; Email: ivo.volf@meduniwien.ac.at
• Study Contact Backup: Name: Rochus Pokan, MD; Phone Number: +43 4277 4887225; Email: rochus.pokan@univie.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • MUVienna
    • Contact: Stefan Heber, MD, PhD; Phone Number: 31425 0043 1 40160; Email: stefan.heber@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• prediabetic (insulin-insensitive) patients
• either fasting plasma glucose 100- 125 mg/dl or HbA1c 5.7 - 6.4
• < 3kg bodyweight change within the last 6 months

Exclusion Criteria:

• Any contraindications for exercise
• resulting from anamnesis ( e.g. history of angina pectoris, peripheral arterial disease), ECG at rest or during graded exercise test, echocardiogram, echocardiography or lung function test
• chronical joint pain that makes exercise training on bicycle ergometers impossible
• any conditions that make the successful participation in the study unlikely
• islet cell autoantibodies
• Medication: insulin, thiazolidindiones, statins, antidepressants
• Secondary diseases: History of end-stage liver or kidney disease; pronounced neuropathy or retinopathy
• drug or alcohol abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: High intensity interval training; 3x/week the following 45 min training protocol on bicycle ergometer for 12 weeks: 5 minutes warm-up phase with a power output of 40% of the maximal power output achieved in an incremental exercise test; 30 minutes: intensive cycling bouts of 60s interspersed with 60s of recovery intervals. Power output will be 90% (week 1-6) or 95% (week 7-12) of the maximal power output of the exercise test during the intensive cycling bouts. During recovery intervals, subjects will pedal with a power output of 30% (week 1-6) or 35% (week 7-12) of the maximal power output of the exercise test.; 10 minutes with 30% of maximal power output.	Behavioral: High intensity interval training (HIIT); Exercise training on bicycle ergometer with high intensity bouts of 1 min interspersed by low intensity recovery intervals
ACTIVE_COMPARATOR: Moderate intensity continuous training; 3x/week the following 45 min training protocol on bicycle ergometer for 12 weeks: 5 minutes warm-up phase with a power output of 40% of the maximal power output achieved in an incremental exercise test; 30 minutes: Continuous training with 60% (week 1-6) or 65% (week 7-12) of maximal power output; 10 minutes with 30% of maximal power output.	Behavioral: Moderate intensity continuous training (MICT); Exercise training on bicycle ergometer with moderate intensity (60 - 65 % of individual maximal power output)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
EC50 (half-maximal effective concentration) of TRAP-6 (thrombin-receptor activating peptide) in terms of surface CD62P (=platelet selectin, P-selectin) expression: group differences after 12 weeks of training	12 weeks
EC50 of insulin in terms of intraplatelet VASP (vasodilator-stimulated phosphoprotein)-phosphorylation: group differences after 12 weeks of training	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
whole body insulin sensitivity		12 weeks
Maximal oxygen consumption	Unit: ml/min/kg bodymass	12 weeks
EC50 of other platelet agonists in terms of various platelet activation markers		12 weeks
EC50 of prostacyclin in terms of intraplatelet VASP-phosphorylation		12 weeks
Transient elastography (FibroScan®) controlled attenuation parameter (CAP)	The controlled attenuation parameter (CAP) has demonstrated good accuracy in quantifying the levels of liver steatosis and fibrosis in patients with NAFLD	12 weeks
Fatty Liver Index (FLI)		12 weeks

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Collaborators: University of Vienna, Institute for Sport Science; Sanatorium Hera Vienna

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 4, 2019
• Primary Completion (ANTICIPATED): December 1, 2020
• Study Completion (ANTICIPATED): February 1, 2021

Study Registration Dates

• First Submitted: December 10, 2018
• First Submitted That Met QC Criteria: December 11, 2018
• First Posted (ACTUAL): December 12, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 9, 2019
• Last Update Submitted That Met QC Criteria: January 7, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Prediabetic State
• Other Study ID Numbers: Exercise_platelet_insulin

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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