Duality of Lipids: the Athlete's Paradox

NCT03314714 | Completed

• 1 other identifier: DDZ-LIDDIA01
• Study Type: interventional
• Target: 100
• Locations: 2 countries
• Sites: 2

Brief Summary

Accumulation of intramyocellular lipids (IMCLs) due to increased supply of fatty acids can induce defects in the insulin signaling cascade, causing skeletal muscle insulin resistance. However, the causes for muscle insulin resistance are not well understood. The association of elevated IMCLs and insulin resistance has been shown in obese humans and individuals with type 2 diabetes as well as several animal models of insulin resistance. Despite the strong relationship between IMCLs and insulin resistance, this suggested relationship disappears when well-trained endurance athletes are included into this consideration as this group is highly insulin sensitive. This metabolic enigma has been termed the 'athlete's paradox'. The aim of this project is to resolve the mechanisms contributing to the athlete's paradox.

Conditions

Insulin Resistance, Diabetes; Lipid Metabolism Disorders

Outcome Measures

Primary Outcomes (2)

• Assessment of intramyocellular lipid content via magnetic resonance spectroscopy

  Intramyocellular lipid content assessed via magnetic resonance spectroscopy (%lipid) in endurance-trained athletes and sedentary individuals

  2 years

• Assessment of intramyocellular lipid composition via mass spectrometry

  Detailed composition of intramyocellular lipids assessed via mass spectrometry (concentration of bioactive lipids) in endurance-trained athletes and sedentary individuals

  2 years

Study Arms (1)

Acute bout of endurance exercise

EXPERIMENTAL

Intramyocellular lipid metabolism will be assessed in insulin resistant and healthy, sedentary individuals after an acute bout of endurance exercise.

Procedure: Acute bout of endurance exercise

Interventions

Acute bout of endurance exercise PROCEDURE

Individuals will undergo an acute bout of endurance exercise for 90 min at 75% of maximal oxygen uptake.

Acute bout of endurance exercise

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Insulin-resistant, non-athletic persons with a comparable content of IMCLs as the athletes
• Healthy, insulin-sensitive, normal-weight, non-athletic (BMI 18-25 kg / m2) individuals
• Endurance trained individuals (VO2max≥60 mL / kg / min ♂ and 45 mL / kg / min ♀)
• Male and female, age between ≥ 18 and ≤ 69 years

You may not qualify if:

• Acute infections / fever
• Immunosuppressive therapy
• Serious heart, kidney or liver disease: - New York Heart Association-Classification (NYHA) stage ≥ II - creatinine ≥ 1.6 mg / dl - Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) ≥ two-fold upper reference value - severe peripheral artery disease (PAD) (stage IV)
• autoimmune diseases
• Anemia (Hb \<12g / l)
• Severe psychiatric illness or addiction
• Malignant cancer
• Participation in another intervention study
• Blood clotting disorders or increased risk of thrombosis
• Pregnancy, lactation
• Cigarettes (or non-smokers \<1 year)
• alcohol consumption (men\> 30g / d, women\> 20g / d)
• ECG changes (ST reductions or - elevations, high-grade rhythm disorders (salvage or polytope extrasystoles, ventricular tachycardia)
• Heart diseases (angina pectoris at rest or under light load, myocardial infarction, thromboembolic processes / pulmonary embolism or severe arteriosclerosis, acute myocarditis or pericarditis, cardiac wall aneurysms, cor pulmonale, aortic stenosis)
• Hypertension (\> 220/120 mmHg)

Sponsors & Collaborators

• German Diabetes Center: lead
• Maastricht University: collaborator

Study Sites (2)

German Diabetes Center

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Maastricht University

Maastricht, 6200, Netherlands

Location

Related Publications (4)

• Goodpaster BH, He J, Watkins S, Kelley DE. Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J Clin Endocrinol Metab. 2001 Dec;86(12):5755-61. doi: 10.1210/jcem.86.12.8075.

  PMID: 11739435 BACKGROUND

• Roden M, Price TB, Perseghin G, Petersen KF, Rothman DL, Cline GW, Shulman GI. Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest. 1996 Jun 15;97(12):2859-65. doi: 10.1172/JCI118742.

  PMID: 8675698 BACKGROUND

• Szendroedi J, Yoshimura T, Phielix E, Koliaki C, Marcucci M, Zhang D, Jelenik T, Muller J, Herder C, Nowotny P, Shulman GI, Roden M. Role of diacylglycerol activation of PKCtheta in lipid-induced muscle insulin resistance in humans. Proc Natl Acad Sci U S A. 2014 Jul 1;111(26):9597-602. doi: 10.1073/pnas.1409229111. Epub 2014 Jun 16.

  PMID: 24979806 BACKGROUND

• Pesta D, Anadol-Schmitz E, Sarabhai T, Op den Kamp Y, Gancheva S, Trinks N, Zaharia OP, Mastrototaro L, Lyu K, Habets I, Op den Kamp-Bruls YMH, Dewidar B, Weiss J, Schrauwen-Hinderling V, Zhang D, Gaspar RC, Strassburger K, Kupriyanova Y, Al-Hasani H, Szendroedi J, Schrauwen P, Phielix E, Shulman GI, Roden M. Determinants of increased muscle insulin sensitivity of exercise-trained versus sedentary normal weight and overweight individuals. Sci Adv. 2025 Jan 3;11(1):eadr8849. doi: 10.1126/sciadv.adr8849. Epub 2025 Jan 1.

  PMID: 39742483 DERIVED

MeSH Terms

Conditions

Insulin Resistance; Diabetes Mellitus; Lipid Metabolism Disorders

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Michael Roden, Prof., MD

  German Diabetes Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2017
• First Posted: October 19, 2017
• Study Start: April 3, 2017
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2023
• Last Updated: June 13, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); NL (1)