Non-Response to Exercise (NRE2)

Non-Response to Exercise - Identification of Factors Contributing to Exercise Non-response.

The purpose of this prospective intervention study is to find biomarkers and underlying pathomechanisms for non-response of improvement in glucose metabolism to exercise.

An additional goal is to identify non-responders at an early stage, where prevention strategies (pharmacologically or by specific training) will be successful.

Study Overview

• Status: Completed
• Conditions: Non-Responder
• Intervention / Treatment: Behavioral: exercise training

Detailed Description

At baseline and end of study, an intensive metabolic phenotyping including cerebral insulin sensitivity as well as tissue biopsies are performed in overweight untrained healthy participants at high risk for type 2 diabetes. During the study, an individual exercise training at 80% VO2max is performed for 9 weeks. Before and after the training intervention, acute tissue biopsies after a standardized bout of exercise are obtained.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Tübingen, Germany, 72076
    • Institute for Diabetes research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen

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:

• at least one of the following risk factors for type 2 diabetes:

  • overweight (BMI>27 kg/m2)
  • impaired fasting glucose and/ or glucose tolerance
  • former gestational diabetes
  • family history for type 2 diabetes (first-degree relative)
• sedentary participant (< 2 exercise bouts/week)

Exclusion Criteria:

• any kind of metal in or on the body
• thermosensory or heightened sensitivity to heating
• heightened sensitivity to loud noise or diseases of the ear
• claustrophobia
• Diabetes mellitus
• current pregnancy or breastfeeding
• cardiovascular diseases
• surgery, < 3 months ago
• participation in other clinical trials
• acute illness/infection, < 4 weeks ago
• severe mental illness
• hemoglobin, women < 11g/dl, men < 13g/dl
• potentially incompliant subjects and/or inability to absolve the exercise training
• glucose influencing drugs
• continuous analgetic drugs
• use of anticoagulants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
exercise response with respect to changes in insulin sensitivity from baseline to post-intervention measurement	insulin sensitivity is measured before and after the training intervention by a 5-point-75g-OGTT and calculated by ISI Matsuda	11 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
molecular mechanisms of non-response	molecular mechanisms of non-response in insulin sensitivity in peripheral insulin target tissues (skeletal muscle, adipose tissue)	11 weeks
differences in the adaptation process to exercise in responders versus non-responders	by assessing the acute inflammatory response in blood samples and tissue biopsies obtained directly after an acute bout of exercise, at the beginning, and the end of the exercise intervention	11 weeks
inflammatory response to exercise	local (muscle and fat) versus systemic (blood) inflammatory response to exercise	11 weeks
changes in brain insulin sensitivity by exercise, and brain differences in responders vs. non-responders	changes in brain insulin sensitivity, before and after the intervention	11 weeks
role of visceral fat mass in determining the non-response of insulin sensitivity to exercise	measured by MRI	11 weeks
identification of serum biomarkers of non-response		11 weeks

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Investigators: Study Director: Hans-Ulrich Häring, Prof., University Hospital Tuebingen

Publications and helpful links

General Publications

• Kullmann S, Goj T, Veit R, Fritsche L, Wagner L, Schneeweiss P, Hoene M, Hoffmann C, Machann J, Niess A, Preissl H, Birkenfeld AL, Peter A, Haring HU, Fritsche A, Moller A, Weigert C, Heni M. Exercise restores brain insulin sensitivity in sedentary adults who are overweight and obese. JCI Insight. 2022 Sep 22;7(18):e161498. doi: 10.1172/jci.insight.161498.
• Hoffmann C, Schneeweiss P, Randrianarisoa E, Schnauder G, Kappler L, Machann J, Schick F, Fritsche A, Heni M, Birkenfeld A, Niess AM, Haring HU, Weigert C, Moller A. Response of Mitochondrial Respiration in Adipose Tissue and Muscle to 8 Weeks of Endurance Exercise in Obese Subjects. J Clin Endocrinol Metab. 2020 Nov 1;105(11):dgaa571. doi: 10.1210/clinem/dgaa571.

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2017
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: May 9, 2017
• First Submitted That Met QC Criteria: May 11, 2017
• First Posted (Actual): May 12, 2017

Study Record Updates

• Last Update Posted (Actual): May 8, 2020
• Last Update Submitted That Met QC Criteria: May 6, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: 446/2016BO2

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