Physical Training and the Incretin Effect

Healthy Clinical Trial

— EXINT2  

Official title:

Does Physical Training Effect the Incretin Effect

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01698502
• Other study ID #: EXINT2_FD
• Status: Completed
• Phase: N/A
• First received: September 26, 2012
• Last updated: March 24, 2014
• Start date: August 2012
• Est. completion date: June 2013

Study information

• Verified date: March 2014
• Source: University of Copenhagen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: The Regional Committee on Biomedical Research Ethics
• Study type: Observational

Clinical Trial Summary

It is well known that continuous physical exercise leads to a number of changes in the body. Maximal oxygen uptake; the heart's pumping ability and muscle mass and strength increases. Also the metabolism adapts: The ability to oxidize fat increase and the insulin sensitivity in primarily in muscle, but also in the liver increase.

Also endocrine glands adapts according to the level of physical activity. It is known that in healthy, younger people the insulin secretion from the pancreas after administration of sugar consumed orally or given directly into a vein, is significantly lower in trained individuals compared with untrained. This change does, however, not only apply to glucose, as also stimulation by the amino acid arginine, shows the same pattern.

It seems plausible that the endocrine glands/cells adapts to the level of physical training, but this has not yet been investigated.

The gastrointestinal tract is the birthplace of a variety of hormones. One group of these is called incretin hormones. They stimulate the glucose dependant insulin secretion in the pancreas and affect hunger/satiety. Whether the incretin production and thus their concentration in the blood is regulated by physical training is unknown.

Obese and patients with type 2 diabetes, has, in contrast to well-trained, decreased insulin sensitivity. As a consequence their (type 2 diabetics, at least early in their disease course) meal stimulated insulin release is greater than in healthy, normal weight individuals. This in spite of the fact that the incretin effect is reduced in obese people and patients with type 2 diabetes compared to healthy, normal weight.

Whether physical training affects both the secretion of incretins and the incretin effect has not yet been studied.

The purpose of this study is to investigate whether incretin hormones in physical well-trained young men have a changed effect on insulin secretion from the pancreas compared to untrained young men. A difference may indicate that the body's endocrine glands adapts to training mode.

The investigators hypothesis is that incretin hormones have a decreased effect on the glucose dependant insulin release in physically trained persons and thus results in a lower insulin release at any given plasma glucose level.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: June 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 30 Years

Eligibility

Inclusion Criteria:

• Sedentary: 50>Maximal oxygen uptake (VO2max), ml*min-1*kg-1 OR endurance trained VO2max, ml*min-1*kg-1>60

• 20-30 years

• BMI: 18,5-25kg/m2

• Caucasian

• Healthy

Exclusion Criteria:

• Any kind of medication or diabetes in the family (parents, siblings),

• Non-caucasian

Study Design

Observational Model: Case-Crossover, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Healthy

Locations

Country	Name	City	State
Denmark	University of Copenhagen, Faculty of Health Sciences	Copenhagen	North

Sponsors (1)

Lead Sponsor	Collaborator
University of Copenhagen

Country where clinical trial is conducted

Denmark, 

References & Publications (10)

Dela F, Handberg A, Mikines KJ, Vinten J, Galbo H. GLUT 4 and insulin receptor binding and kinase activity in trained human muscle. J Physiol. 1993 Sep;469:615-24. — View Citation

Dela F, Mikines KJ, Von Linstow M, Galbo H. Effect of training on response to a glucose load adjusted for daily carbohydrate intake. Am J Physiol. 1991 Jan;260(1 Pt 1):E14-20. — View Citation

Dela F, Mikines KJ, von Linstow M, Secher NH, Galbo H. Effect of training on insulin-mediated glucose uptake in human muscle. Am J Physiol. 1992 Dec;263(6 Pt 1):E1134-43. — View Citation

Dupre J, Ross SA, Watson D, Brown JC. Stimulation of insulin secretion by gastric inhibitory polypeptide in man. J Clin Endocrinol Metab. 1973 Nov;37(5):826-8. — View Citation

Holst JJ, Orskov C, Nielsen OV, Schwartz TW. Truncated glucagon-like peptide I, an insulin-releasing hormone from the distal gut. FEBS Lett. 1987 Jan 26;211(2):169-74. — View Citation

King DS, Dalsky GP, Staten MA, Clutter WE, Van Houten DR, Holloszy JO. Insulin action and secretion in endurance-trained and untrained humans. J Appl Physiol (1985). 1987 Dec;63(6):2247-52. — View Citation

Knop FK, Aaboe K, Vilsbøll T, Vølund A, Holst JJ, Krarup T, Madsbad S. Impaired incretin effect and fasting hyperglucagonaemia characterizing type 2 diabetic subjects are early signs of dysmetabolism in obesity. Diabetes Obes Metab. 2012 Jun;14(6):500-10. doi: 10.1111/j.1463-1326.2011.01549.x. Epub 2012 Jan 17. — View Citation

Mikines KJ, Sonne B, Farrell PA, Tronier B, Galbo H. Effect of training on the dose-response relationship for insulin action in men. J Appl Physiol (1985). 1989 Feb;66(2):695-703. — View Citation

Mikines KJ, Sonne B, Tronier B, Galbo H. Effects of training and detraining on dose-response relationship between glucose and insulin secretion. Am J Physiol. 1989 May;256(5 Pt 1):E588-96. — View Citation

Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W. Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest. 1993 Jan;91(1):301-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incretin Effect (the % of Insulin Secreted Due to the Release of the Intestinal Hormones Glucagon Like Peptide-1 (GLP-1 and Glucose-dependent Insulinotropic Peptide (GIP))	The Incretin effect (the % of insulin secreted due to the release of the intestinal hormones GLP-1 and GIP) is calculated as the difference between the insulin concentration during a 3 hour oral glucose tolerance test (OGTT) (day 1) compared to a 3 hour isoglycemic intravenous glucose infusion (IIGI) (day 2) that has similar glucose excursions.	Test day 1 and 2 within 7 days.	No
Secondary	The Total Glucose-dependent Insulinotropic Peptide (GIP) Response Measured as Area Under the GIP Curve (AUC GIP).	Comparison of the total release of GIP during the 3 hour OGTT and IIGI.	Test day 1 and 2 within 7 days.	No