Clinical trial NCT03773731: High Intensity Interval Training in Prediabetes
Official title: Impact of High Intensity Interval Training vs. Continuous Aerobic Training on Platelet Insulin Resistance, Platelet Function and Hepatic Steatosis in Patients With Prediabetes
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Prediabetic State
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
Collaborators: name: University of Vienna, Institute for Sport Science
name: Sanatorium Hera Vienna
First posted: 2018-12-12
Enrollment: 44
Sex: MALE
Minimum age (years): 19
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 12 weeks
measure: EC50 of insulin in terms of intraplatelet VASP (vasodilator-stimulated phosphoprotein)-phosphorylation: group differences after 12 weeks of training
timeFrame: 12 weeks
Secondary outcomes:
measure: whole body insulin sensitivity
timeFrame: 12 weeks
measure: Maximal oxygen consumption
timeFrame: 12 weeks
measure: EC50 of other platelet agonists in terms of various platelet activation markers
timeFrame: 12 weeks
measure: EC50 of prostacyclin in terms of intraplatelet VASP-phosphorylation
timeFrame: 12 weeks
measure: Transient elastography (FibroScan®) controlled attenuation parameter (CAP)
timeFrame: 12 weeks
measure: Fatty Liver Index (FLI)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: MUVienna
Study officials:
References: