<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01698502</url>
  </required_header>
  <id_info>
    <org_study_id>EXINT2_FD</org_study_id>
    <nct_id>NCT01698502</nct_id>
  </id_info>
  <brief_title>Physical Training and the Incretin Effect</brief_title>
  <acronym>EXINT2</acronym>
  <official_title>Does Physical Training Effect the Incretin Effect</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Copenhagen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Copenhagen</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      It is well known that continuous physical exercise leads to a number of changes in the body.&#xD;
      Maximal oxygen uptake; the heart's pumping ability and muscle mass and strength increases.&#xD;
      Also the metabolism adapts: The ability to oxidize fat increase and the insulin sensitivity&#xD;
      in primarily in muscle, but also in the liver increase.&#xD;
&#xD;
      Also endocrine glands adapts according to the level of physical activity. It is known that in&#xD;
      healthy, younger people the insulin secretion from the pancreas after administration of sugar&#xD;
      consumed orally or given directly into a vein, is significantly lower in trained individuals&#xD;
      compared with untrained. This change does, however, not only apply to glucose, as also&#xD;
      stimulation by the amino acid arginine, shows the same pattern.&#xD;
&#xD;
      It seems plausible that the endocrine glands/cells adapts to the level of physical training,&#xD;
      but this has not yet been investigated.&#xD;
&#xD;
      The gastrointestinal tract is the birthplace of a variety of hormones. One group of these is&#xD;
      called incretin hormones. They stimulate the glucose dependant insulin secretion in the&#xD;
      pancreas and affect hunger/satiety. Whether the incretin production and thus their&#xD;
      concentration in the blood is regulated by physical training is unknown.&#xD;
&#xD;
      Obese and patients with type 2 diabetes, has, in contrast to well-trained, decreased insulin&#xD;
      sensitivity. As a consequence their (type 2 diabetics, at least early in their disease&#xD;
      course) meal stimulated insulin release is greater than in healthy, normal weight&#xD;
      individuals. This in spite of the fact that the incretin effect is reduced in obese people&#xD;
      and patients with type 2 diabetes compared to healthy, normal weight.&#xD;
&#xD;
      Whether physical training affects both the secretion of incretins and the incretin effect has&#xD;
      not yet been studied.&#xD;
&#xD;
      The purpose of this study is to investigate whether incretin hormones in physical&#xD;
      well-trained young men have a changed effect on insulin secretion from the pancreas compared&#xD;
      to untrained young men. A difference may indicate that the body's endocrine glands adapts to&#xD;
      training mode.&#xD;
&#xD;
      The investigators hypothesis is that incretin hormones have a decreased effect on the glucose&#xD;
      dependant insulin release in physically trained persons and thus results in a lower insulin&#xD;
      release at any given plasma glucose level.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">June 2013</completion_date>
  <primary_completion_date type="Actual">February 2013</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Crossover</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>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))</measure>
    <time_frame>Test day 1 and 2 within 7 days.</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Total Glucose-dependent Insulinotropic Peptide (GIP) Response Measured as Area Under the GIP Curve (AUC GIP).</measure>
    <time_frame>Test day 1 and 2 within 7 days.</time_frame>
    <description>Comparison of the total release of GIP during the 3 hour OGTT and IIGI.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">21</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Trained</arm_group_label>
    <description>Healthy, Endurance trained (Maximal oxygen uptake (VO2max), ml*min-1*kg-1&gt;60), 20-30 year, BMI: 18,5-25kg/m2, males.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Untrained</arm_group_label>
    <description>Healthy, sedentary (Maximal oxygen uptake (VO2max), ml*min-1*kg-1&lt;50), 20-30 year, BMI: 18,5-25kg/m2, males.</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Human plasma samples.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Danish University Students from University of Copenhagen,&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Sedentary: 50&gt;Maximal oxygen uptake (VO2max), ml*min-1*kg-1 OR endurance trained&#xD;
             VO2max, ml*min-1*kg-1&gt;60&#xD;
&#xD;
          -  20-30 years&#xD;
&#xD;
          -  BMI: 18,5-25kg/m2&#xD;
&#xD;
          -  Caucasian&#xD;
&#xD;
          -  Healthy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any kind of medication or diabetes in the family (parents, siblings),&#xD;
&#xD;
          -  Non-caucasian&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Flemming Dela, Prof. MD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Copenhagen, Dep. of Biomedical Sciences, Center of healthy Ageing, XLAB</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Copenhagen, Faculty of Health Sciences</name>
      <address>
        <city>Copenhagen</city>
        <state>North</state>
        <zip>2200</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <reference>
    <citation>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. doi: 10.1113/jphysiol.1993.sp019833.</citation>
    <PMID>8271219</PMID>
  </reference>
  <reference>
    <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):E1134-43. doi: 10.1152/ajpendo.2006.263.6.E1134.</citation>
    <PMID>1476187</PMID>
  </reference>
  <reference>
    <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. doi: 10.1152/jappl.1989.66.2.695.</citation>
    <PMID>2651385</PMID>
  </reference>
  <reference>
    <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. doi: 10.1152/ajpendo.1991.260.1.E14.</citation>
    <PMID>1987787</PMID>
  </reference>
  <reference>
    <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. doi: 10.1152/jappl.1987.63.6.2247.</citation>
    <PMID>3325486</PMID>
  </reference>
  <reference>
    <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. doi: 10.1152/ajpendo.1989.256.5.E588.</citation>
    <PMID>2655469</PMID>
  </reference>
  <reference>
    <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. doi: 10.1210/jcem-37-5-826. No abstract available.</citation>
    <PMID>4749457</PMID>
  </reference>
  <reference>
    <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. doi: 10.1016/0014-5793(87)81430-8.</citation>
    <PMID>3542566</PMID>
  </reference>
  <reference>
    <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. doi: 10.1172/JCI116186.</citation>
    <PMID>8423228</PMID>
  </reference>
  <reference>
    <citation>Knop FK, Aaboe K, Vilsboll T, Volund 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.</citation>
    <PMID>22171657</PMID>
  </reference>
  <verification_date>March 2014</verification_date>
  <study_first_submitted>September 26, 2012</study_first_submitted>
  <study_first_submitted_qc>September 28, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2012</study_first_posted>
  <results_first_submitted>December 10, 2013</results_first_submitted>
  <results_first_submitted_qc>March 24, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">April 24, 2014</results_first_posted>
  <last_update_submitted>March 24, 2014</last_update_submitted>
  <last_update_submitted_qc>March 24, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 24, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Copenhagen</investigator_affiliation>
    <investigator_full_name>Michael Taulo Lund</investigator_full_name>
    <investigator_title>MD. PhD. Student</investigator_title>
  </responsible_party>
  <keyword>Incretin</keyword>
  <keyword>Training</keyword>
  <keyword>Glucagon like peptide</keyword>
  <keyword>glucose dependent insulinotropic peptide</keyword>
  <keyword>Gut</keyword>
  <keyword>Exercise</keyword>
  <keyword>Insulin</keyword>
  <keyword>Focus:</keyword>
  <keyword>Gut hormone</keyword>
  <keyword>adaptations</keyword>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Trained</title>
          <description>Healthy, Endurance trained (VO2max, ml*min-1*kg-1&gt;60), 20-30 year, BMI: 18,5-25kg/m2, males.</description>
        </group>
        <group group_id="P2">
          <title>Untrained</title>
          <description>Healthy, sedentary (VO2max, ml*min-1*kg-1&lt;50), 20-30 year, BMI: 18,5-25kg/m2, males.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Trained</title>
          <description>Healthy, Endurance trained (Maximal oxygen uptake (VO2max), ml*min-1*kg-1&gt;60), 20-30 year, BMI: 18,5-25kg/m2, males.</description>
        </group>
        <group group_id="B2">
          <title>Untrained</title>
          <description>Healthy, sedentary (Maximal oxygen uptake (VO2max), ml*min-1*kg-1&lt;50), 20-30 year, BMI: 18,5-25kg/m2, males.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="11"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="21"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25" spread="3"/>
                    <measurement group_id="B2" value="25" spread="3"/>
                    <measurement group_id="B3" value="25" spread="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Denmark</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>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))</title>
        <description>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.</description>
        <time_frame>Test day 1 and 2 within 7 days.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Trained</title>
            <description>Healthy, Endurance trained (VO2max, ml*min-1*kg-1&gt;60), 20-30 year, BMI: 18,5-25kg/m2, males.</description>
          </group>
          <group group_id="O2">
            <title>Untrained</title>
            <description>Healthy, sedentary (VO2max, ml*min-1*kg-1&lt;50), 20-30 year, BMI: 18,5-25kg/m2, males.</description>
          </group>
        </group_list>
        <measure>
          <title>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))</title>
          <description>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.</description>
          <units>percentage</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72" spread="4"/>
                    <measurement group_id="O2" value="67" spread="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Total Glucose-dependent Insulinotropic Peptide (GIP) Response Measured as Area Under the GIP Curve (AUC GIP).</title>
        <description>Comparison of the total release of GIP during the 3 hour OGTT and IIGI.</description>
        <time_frame>Test day 1 and 2 within 7 days.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Trained</title>
            <description>Healthy, Endurance trained (VO2max, ml*min-1*kg-1&gt;60), 20-30 year, BMI: 18,5-25kg/m2, males.</description>
          </group>
          <group group_id="O2">
            <title>Untrained</title>
            <description>Healthy, sedentary (VO2max, ml*min-1*kg-1&lt;50), 20-30 year, BMI: 18,5-25kg/m2, males.</description>
          </group>
        </group_list>
        <measure>
          <title>The Total Glucose-dependent Insulinotropic Peptide (GIP) Response Measured as Area Under the GIP Curve (AUC GIP).</title>
          <description>Comparison of the total release of GIP during the 3 hour OGTT and IIGI.</description>
          <units>pmol/L * 210 min</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Post OGTT</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3978" spread="565"/>
                    <measurement group_id="O2" value="3819" spread="452"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post IIGI</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="692" spread="103"/>
                    <measurement group_id="O2" value="725" spread="202"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Trained</title>
          <description>Healthy, Endurance trained (VO2max, ml*min-1*kg-1&gt;60), 20-30 year, BMI: 18,5-25kg/m2, males.</description>
        </group>
        <group group_id="E2">
          <title>Untrained</title>
          <description>Healthy, sedentary (VO2max, ml*min-1*kg-1&lt;50), 20-30 year, BMI: 18,5-25kg/m2, males.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Michael Lund</name_or_title>
      <organization>University of Copenhagen</organization>
      <phone>+45 3532 7519</phone>
      <email>michaeltl@sund.ku.dk</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01698502
org study id: EXINT2_FD
nct id: NCT01698502
lead sponsor: 
has dmc: No
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.
observational model: Case-Crossover
time perspective: Cross-Sectional
measure: 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))
time frame: Test day 1 and 2 within 7 days.
description: 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.
measure: The Total Glucose-dependent Insulinotropic Peptide (GIP) Response Measured as Area Under the GIP Curve (AUC GIP).
time frame: Test day 1 and 2 within 7 days.
description: Comparison of the total release of GIP during the 3 hour OGTT and IIGI.
arm group label: Trained
description: Healthy, Endurance trained (Maximal oxygen uptake (VO2max), ml*min-1*kg-1>60), 20-30 year, BMI: 18,5-25kg/m2, males.
arm group label: Untrained
description: Healthy, sedentary (Maximal oxygen uptake (VO2max), ml*min-1*kg-1<50), 20-30 year, BMI: 18,5-25kg/m2, males.
Human plasma samples.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Male
minimum age: 20 Years
maximum age: 30 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Flemming Dela, Prof. MD
role: Study Chair
affiliation: University of Copenhagen, Dep. of Biomedical Sciences, Center of healthy Ageing, XLAB
facility: 
country: Denmark
citation: 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. doi: 10.1113/jphysiol.1993.sp019833.
PMID: 8271219
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):E1134-43. doi: 10.1152/ajpendo.2006.263.6.E1134.
PMID: 1476187
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. doi: 10.1152/jappl.1989.66.2.695.
PMID: 2651385
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. doi: 10.1152/ajpendo.1991.260.1.E14.
PMID: 1987787
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. doi: 10.1152/jappl.1987.63.6.2247.
PMID: 3325486
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. doi: 10.1152/ajpendo.1989.256.5.E588.
PMID: 2655469
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. doi: 10.1210/jcem-37-5-826. No abstract available.
PMID: 4749457
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. doi: 10.1016/0014-5793(87)81430-8.
PMID: 3542566
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. doi: 10.1172/JCI116186.
PMID: 8423228
citation: Knop FK, Aaboe K, Vilsboll T, Volund 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.
PMID: 22171657
responsible party type: Principal Investigator
investigator affiliation: University of Copenhagen
investigator full name: Michael Taulo Lund
investigator title: MD. PhD. Student
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 