<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/NCT03022344</url>
  </required_header>
  <id_info>
    <org_study_id>44110</org_study_id>
    <nct_id>NCT03022344</nct_id>
  </id_info>
  <brief_title>DD2-Coronary Plaque Morphology and Plaque Progression</brief_title>
  <acronym>DD2plaque</acronym>
  <official_title>Coronary Plaque Morphology and Plaque Progression in Patients With Newly Diagnosed Type-2 Diabetes Mellitus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital of South West Jutland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Danish Diabetes Academy supported by the Novo Nordisk Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Southern Denmark</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Department of Regional Health Research - Center Southwest</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Edith and Vagn Hedegaard Jensens Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Karola Jørgensens Foundation and Foundation for Cardiology in Southwest Denmark.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospital of South West Jutland</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      However, there is only very sparse information regarding the atherosclerotic burden and&#xD;
      cardiovascular biomarkers in the early stages of type-2 diabetes, as the vast majority of&#xD;
      studies have concerned diabetes populations with more than 5 years average diabetes age or&#xD;
      high-risk subgroups, who at inclusion already had atherosclerotic disease manifestations.&#xD;
&#xD;
      Consequently, this study aims on evaluating the occurrence of early-stage subclinical&#xD;
      atherosclerosis in newly diagnosed type-2 diabetes with special emphasis on coronary plaque&#xD;
      characteristics by modern imaging techniques. These findings will be compared to the&#xD;
      functional status of various peripheral arterial segments and biomarkers in the&#xD;
      cross-sectional part of this study. The 5-year follow-up study intends to describe&#xD;
      relationships between these selected measures for general atherosclerotic involvement and the&#xD;
      progression of the coronary atherosclerotic burden by contemporary techniques.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      THE AIM&#xD;
&#xD;
      The objective of this study is to:&#xD;
&#xD;
      Study I: Compare the prevalence and complexity of coronary plaques in patients with newly&#xD;
      discovered type-2 diabetes with a healthy control group matched for age and gender, as&#xD;
      evaluated by coronary computed tomography angiography.&#xD;
&#xD;
      Study II: Describe the relationship between morphological, functional and biochemical&#xD;
      estimates of arteriosclerosis in newly diagnosed type-2 diabetes.&#xD;
&#xD;
      Study III: Characterize the progression of coronary plaques in patients with newly discovered&#xD;
      type-2 diabetes in a 5-year follow-up study.&#xD;
&#xD;
      DESIGN&#xD;
&#xD;
      &quot;Coronary plaque morphology and plaque progression in patients with newly diagnosed type-2&#xD;
      diabetes mellitus&quot; (DD2-plaque study) is a prospective cohort follow up study.&#xD;
&#xD;
      The inclusion phase will run for 2 years. The follow-up phase is 5 years from inclusion.&#xD;
&#xD;
      The DD2-plaque study (diabetic patient's cohort):&#xD;
&#xD;
      Recruitment in this cohort will take place in three ways:&#xD;
&#xD;
        1. From the &quot;Danish centers for strategic research in type 2 diabetes&quot; (DD2) - patients who&#xD;
           agreed to be contacted for participation in a future study.&#xD;
&#xD;
        2. Direct from outpatient clinics in The Region of Southern. Patients will either be&#xD;
           recruited through general practitioners or from outpatient clinics in The Region of&#xD;
           Southern Denmark. The investigators expect to be able to include 100 asymptomatic&#xD;
           patients with newly diagnosed type-2 diabetes.&#xD;
&#xD;
      Inclusion criteria&#xD;
&#xD;
        1. Newly diagnosed (&lt; 1 year) diabetes patients clinically classified as type-2 diabetes&#xD;
           patients of both sex.&#xD;
&#xD;
        2. Age 18 +.&#xD;
&#xD;
      Exclusion criteria&#xD;
&#xD;
        1. Type 1 diabetes (or have age&lt;30 years and C-peptid&lt;300pmol/l and GAD-ab titer&gt; 20&#xD;
           IU/ml).&#xD;
&#xD;
        2. Renal insufficiency (GFR &lt; 45 or se-creatinine &gt;140 micromol/l).&#xD;
&#xD;
        3. BMI &gt; 35 kg/m2&#xD;
&#xD;
        4. Atrial fibrillation.&#xD;
&#xD;
        5. Life expectancy below 2 years.&#xD;
&#xD;
        6. Mental disease and/or misuse of alcohol or drugs that affects patient's ability to give&#xD;
           informed consent.&#xD;
&#xD;
        7. Pregnancy at time of or planned at inclusion.&#xD;
&#xD;
        8. Patients with a history of prior atherothrombotic disease (including acute coronary&#xD;
           syndromes, prior revascularization, ischemic stroke or peripheral arterial disease).&#xD;
&#xD;
      The DD2-plaque study (control patients cohort):&#xD;
&#xD;
      100 controls will be recruited from the general population by advertisement in the local&#xD;
      press. Controls with cardiovascular disease (criteria consistent with those described for&#xD;
      patients with type-2 diabetes) and type-2 diabetes (undiagnosed type-2 diabetes in this group&#xD;
      was excluded by fasting plasma glucose and by an oral glucose tolerance test) will be&#xD;
      excluded. In addition, exclusion criteria are also consistent with those described for&#xD;
      patients with type-2 diabetes.&#xD;
&#xD;
      Longitudinal measurements will be done at the screening visit and after 5 years.&#xD;
&#xD;
        1. The proxy statement.&#xD;
&#xD;
        2. Participants will fill in a questionnaire concerning:&#xD;
&#xD;
             -  Cardiovascular and diabetes hereditary&#xD;
&#xD;
             -  Medication&#xD;
&#xD;
             -  Alcohol and drugs consumption&#xD;
&#xD;
             -  Smoking habits (current, prior and never smokers)&#xD;
&#xD;
             -  Family history (cardiac events or strokes for women &lt; 65 years of age and men &lt; 55&#xD;
                years of age in first generation relatives)&#xD;
&#xD;
             -  Medical history&#xD;
&#xD;
        3. Physical examination will include measurement of:&#xD;
&#xD;
             -  Height, weight, BMI.&#xD;
&#xD;
             -  Waist/hip ratio&#xD;
&#xD;
             -  ECG&#xD;
&#xD;
        4. Brachial blood pressure will be measured by oscillometric technics during 24 hours using&#xD;
           TM-2430 (A&amp;D CO., LTD, Saitama, Japan) or BDM Mobil-O-Graph® NG Classic (IEM GmbH,&#xD;
           Stolberg, Germany).&#xD;
&#xD;
        5. Blood samples: Procedures for handling and shipping samples is available in the trial&#xD;
           master and at www.DD2.nu under &quot;blodprøvetagning&quot;.&#xD;
&#xD;
           An exception to these procedures are that the blood samples will be frozen at site and&#xD;
           send on ice to the biobank.&#xD;
&#xD;
           2 x 9 ml. containers with green lid (Li-hep) 2 x 2.7 ml. containers with blue lid&#xD;
           (Na-citrat) 2 x 9 ml. containers with purple lid (EDTA) 2 x 4 ml. containers with&#xD;
           purple/dark purple lid (EDTA) 2 x 3 ml. containers with pink lid (Fluoridcitrat) 2 x 9&#xD;
           ml. containers with brown lid (Serum)&#xD;
&#xD;
           1 container for urine with yellow lid 10 ml of morning midstream urine will be sampled.&#xD;
           Urine sticks will be used to rule out urinary tract infection. If this is present the&#xD;
           urine should be resembled. A total of 73.4 ml + 10 ml of blood will be drawn.&#xD;
&#xD;
           For a subset of patients the DD2 cohort registration and the baseline visit will take&#xD;
           place in the same day. These patients will have 146.8 ml of blood drawn on the same day.&#xD;
           Containers will be sent to the patients.&#xD;
&#xD;
        6. Biochemical analysis: total cholesterol, S-LDL-cholesterol, S-HDL-cholesterol and&#xD;
           S-triglycerides, HbA1c, glucose, C-reactive protein, D-dimer, creatinin and fibrinogen.&#xD;
           All analyses are performed at our local Dept. of Clinical Biochemistry.&#xD;
&#xD;
        7. All patients will undergone:&#xD;
&#xD;
           Carotid intima media thickness (IMT) will be measured by B-mode ultrasound (Model IE33,&#xD;
           Koninklijke Philips Electronics N.V, Eindhoven, The Netherlands) using a linear array&#xD;
           transducer, L11-3 with a frequency up to 11 MHz.&#xD;
&#xD;
        8. Pulse wave velocity: Using sphygmocor (ArtCor, Sydney, Australia).&#xD;
&#xD;
        9. Ankle brachial index.&#xD;
&#xD;
       10. Albumin creatinine ratio&#xD;
&#xD;
       11. Coronary atherosclerosis is evaluated by measurement of calcium in the coronary arteries&#xD;
           and by evaluation of coronary plaques using contrast enhanced cardiac CT. Coronary&#xD;
           artery calcifications will be estimated by the Agatston score while the evaluation of&#xD;
           coronary plaques will be performed by a dedicated plaque-analysis tool, Auto-Plaque.&#xD;
&#xD;
      STATISTICS&#xD;
&#xD;
      Sample size estimations are performed for comparison of calcium scoring between patients with&#xD;
      type-2 diabetes and normal controls (Un-paired evaluation) and comparison of calcium scoring&#xD;
      between type-2 diabetes patients at inclusion and at follow-up (Paired). From previous&#xD;
      studies on calcium scoring in the Danish Risk Score Study cohort, the standard deviation, SD,&#xD;
      on coronary calcification is known to be 32.7 UE (Agatston Score). It is supposed that SD in&#xD;
      the diabetic patients is equal to the figure in controls. Under the assumptions that 15% will&#xD;
      drop-out, a MIREDIF of 20 (twice the threshold for registering the occurrence of coronary&#xD;
      calcification in the central West Danish Heart Registry, VDH), beta= 0, 1 and alfa= 0.02&#xD;
      (Planned comparative analysis of 2-3 plaque-components) it is calculated, that it is needed&#xD;
      to include 41 patients in each group for the un-paired analyses and to follow 41 diabetic&#xD;
      patients for 5 years (Paired analysis). It is supposed, that app. 40% of type-2 diabetes&#xD;
      patients meet the age criteria (55+/-5 years or 65+/-5 years) for comparison with the&#xD;
      background population, which means that app. 100 type-2 diabetes patients should be included&#xD;
      in the DD2 plaque study.&#xD;
&#xD;
      Students T-test will be used for comparison of normally distributed continuous variables and&#xD;
      the Mann-Whitney test will be used for comparison of continuous variables that are not&#xD;
      normally distributed. The χ2- test is performed for comparison of dichotomous variables.&#xD;
      Continuous variables are presented as either mean or standard deviation or median and&#xD;
      interquartile range. P-values &lt;0.05 will be considered statistically significant. Stepwise&#xD;
      multivariate logistic regression will be performed for analysis of which factors are&#xD;
      associated with coronary atherosclerosis using either presence coronary artery calcification&#xD;
      or other plaque variables as dependant variables.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>November 2014</start_date>
  <completion_date type="Anticipated">October 2021</completion_date>
  <primary_completion_date type="Anticipated">June 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression of contrast enhanced cardiac CT in relation to baseline and follow-up cardiovascular risk factors and biomarkers.</measure>
    <time_frame>5 years</time_frame>
    <description>Coronary artery calcification were quantified by non-contrast cardiac CT and were assessed by summing up the scores from all foci in the coronary arteries, expressed in Agatston units (U), using dedicated software (Syngo Calcium scoring, (Siemens Healthcare).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Biochemical analysis in relation to contrast enhanced cardiac CT</measure>
    <time_frame>1 year</time_frame>
    <description>no. of participants with abnormal laboratory values compared to abnormal/normal enhanced cardiac CT</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Body mass index (kg/m2)</measure>
    <time_frame>1 year</time_frame>
    <description>Cardiovascular risk factors. No of participants with body mass index &gt; 30 kg/m2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Carotid intima media thickness</measure>
    <time_frame>1 year</time_frame>
    <description>A measure of the combined thickness of intima and media layers of carotid artery, assessed by B-mode ultrasound.values between 0.6 and 0.7 mm have been considered normal. Values &gt; 1 mm or more has been associated with significant increased absolute risk of atherosclerosis. No of participants with values &gt; 1 mm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ankle brachial index</measure>
    <time_frame>1year</time_frame>
    <description>An ankle brachial index between and including 0.9 and 1.2 considered normal (free from significant peripheral artery disease), while a lesser than 0.9 indicates arterial disease. No of participants with value &lt; 0.9.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>waist hip ratio (m)</measure>
    <time_frame>1 year</time_frame>
    <description>Abdominal obesity was defined as a waist-hip ratioabove 0.90 for males and above 0.85 for females,or a body mass index above 30.0 kg/m2. No of participants with abdominal obesity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure (mmHg)</measure>
    <time_frame>1 year</time_frame>
    <description>Hypertension was defined as blood pressures ≥ 140/90. No of participants with hypertension</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Diabetes</condition>
  <condition>Plaque</condition>
  <condition>Atherosclerosis</condition>
  <arm_group>
    <arm_group_label>Healthy</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Patients in this cohort consist of 100 healthy patients</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diabetes mellitus</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Newly diagnosed (&lt; 1 year) diabetes patients clinically classified as type-2 diabetes patients of both sex</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Cardiac CT</intervention_name>
    <arm_group_label>Diabetes mellitus</arm_group_label>
    <arm_group_label>Healthy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Newly diagnosed (&lt; 1 year) diabetes patients clinically classified as type-2 diabetes&#xD;
             patients of both sex.&#xD;
&#xD;
          -  Age 18 +.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Type 1 diabetes (or have age&lt;30 years and C-peptid&lt;300pmol/l and GAD-ab titer&gt; 20&#xD;
             IU/ml).&#xD;
&#xD;
          -  Renal insufficiency (GFR &lt; 45 or se-creatinine &gt;140 micromol/l).&#xD;
&#xD;
          -  BMI &gt; 35.&#xD;
&#xD;
          -  Atrial fibrillation.&#xD;
&#xD;
          -  Life expectancy below 2 years.&#xD;
&#xD;
          -  Mental disease and/or misuse of alcohol or drugs that affects patient's ability to&#xD;
             give informed consent.&#xD;
&#xD;
          -  Pregnancy at time of or planned at inclusion.&#xD;
&#xD;
          -  Patients with a history of prior atherothrombotic disease (including acute coronary&#xD;
             syndromes, prior revascularization, ischemic stroke or peripheral arterial disease).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Sydvestjysk sygehus</name>
      <address>
        <city>Esbjerg</city>
        <zip>DK-6700</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>January 9, 2017</study_first_submitted>
  <study_first_submitted_qc>January 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 16, 2017</study_first_posted>
  <last_update_submitted>May 6, 2018</last_update_submitted>
  <last_update_submitted_qc>May 6, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 8, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital of South West Jutland</investigator_affiliation>
    <investigator_full_name>Monija Mrgan</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>DD2 plaque study</keyword>
  <keyword>Coronary plaque</keyword>
  <keyword>Type-2 diabetes mellitus</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atherosclerosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03022344
org study id: 44110
nct id: NCT03022344
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
However, there is only very sparse information regarding the atherosclerotic burden and
      cardiovascular biomarkers in the early stages of type-2 diabetes, as the vast majority of
      studies have concerned diabetes populations with more than 5 years average diabetes age or
      high-risk subgroups, who at inclusion already had atherosclerotic disease manifestations.

      Consequently, this study aims on evaluating the occurrence of early-stage subclinical
      atherosclerosis in newly diagnosed type-2 diabetes with special emphasis on coronary plaque
      characteristics by modern imaging techniques. These findings will be compared to the
      functional status of various peripheral arterial segments and biomarkers in the
      cross-sectional part of this study. The 5-year follow-up study intends to describe
      relationships between these selected measures for general atherosclerotic involvement and the
      progression of the coronary atherosclerotic burden by contemporary techniques.
THE AIM

      The objective of this study is to:

      Study I: Compare the prevalence and complexity of coronary plaques in patients with newly
      discovered type-2 diabetes with a healthy control group matched for age and gender, as
      evaluated by coronary computed tomography angiography.

      Study II: Describe the relationship between morphological, functional and biochemical
      estimates of arteriosclerosis in newly diagnosed type-2 diabetes.

      Study III: Characterize the progression of coronary plaques in patients with newly discovered
      type-2 diabetes in a 5-year follow-up study.

      DESIGN

      "Coronary plaque morphology and plaque progression in patients with newly diagnosed type-2
      diabetes mellitus" (DD2-plaque study) is a prospective cohort follow up study.

      The inclusion phase will run for 2 years. The follow-up phase is 5 years from inclusion.

      The DD2-plaque study (diabetic patient's cohort):

      Recruitment in this cohort will take place in three ways:

        1. From the "Danish centers for strategic research in type 2 diabetes" (DD2) - patients who
           agreed to be contacted for participation in a future study.

        2. Direct from outpatient clinics in The Region of Southern. Patients will either be
           recruited through general practitioners or from outpatient clinics in The Region of
           Southern Denmark. The investigators expect to be able to include 100 asymptomatic
           patients with newly diagnosed type-2 diabetes.

      Inclusion criteria

        1. Newly diagnosed (< 1 year) diabetes patients clinically classified as type-2 diabetes
           patients of both sex.

        2. Age 18 +.

      Exclusion criteria

        1. Type 1 diabetes (or have age<30 years and C-peptid<300pmol/l and GAD-ab titer> 20
           IU/ml).

        2. Renal insufficiency (GFR < 45 or se-creatinine >140 micromol/l).

        3. BMI > 35 kg/m2

        4. Atrial fibrillation.

        5. Life expectancy below 2 years.

        6. Mental disease and/or misuse of alcohol or drugs that affects patient's ability to give
           informed consent.

        7. Pregnancy at time of or planned at inclusion.

        8. Patients with a history of prior atherothrombotic disease (including acute coronary
           syndromes, prior revascularization, ischemic stroke or peripheral arterial disease).

      The DD2-plaque study (control patients cohort):

      100 controls will be recruited from the general population by advertisement in the local
      press. Controls with cardiovascular disease (criteria consistent with those described for
      patients with type-2 diabetes) and type-2 diabetes (undiagnosed type-2 diabetes in this group
      was excluded by fasting plasma glucose and by an oral glucose tolerance test) will be
      excluded. In addition, exclusion criteria are also consistent with those described for
      patients with type-2 diabetes.

      Longitudinal measurements will be done at the screening visit and after 5 years.

        1. The proxy statement.

        2. Participants will fill in a questionnaire concerning:

             -  Cardiovascular and diabetes hereditary

             -  Medication

             -  Alcohol and drugs consumption

             -  Smoking habits (current, prior and never smokers)

             -  Family history (cardiac events or strokes for women < 65 years of age and men < 55
                years of age in first generation relatives)

             -  Medical history

        3. Physical examination will include measurement of:

             -  Height, weight, BMI.

             -  Waist/hip ratio

             -  ECG

        4. Brachial blood pressure will be measured by oscillometric technics during 24 hours using
           TM-2430 (A&D CO., LTD, Saitama, Japan) or BDM Mobil-O-Graph® NG Classic (IEM GmbH,
           Stolberg, Germany).

        5. Blood samples: Procedures for handling and shipping samples is available in the trial
           master and at www.DD2.nu under "blodprøvetagning".

           An exception to these procedures are that the blood samples will be frozen at site and
           send on ice to the biobank.

           2 x 9 ml. containers with green lid (Li-hep) 2 x 2.7 ml. containers with blue lid
           (Na-citrat) 2 x 9 ml. containers with purple lid (EDTA) 2 x 4 ml. containers with
           purple/dark purple lid (EDTA) 2 x 3 ml. containers with pink lid (Fluoridcitrat) 2 x 9
           ml. containers with brown lid (Serum)

           1 container for urine with yellow lid 10 ml of morning midstream urine will be sampled.
           Urine sticks will be used to rule out urinary tract infection. If this is present the
           urine should be resembled. A total of 73.4 ml + 10 ml of blood will be drawn.

           For a subset of patients the DD2 cohort registration and the baseline visit will take
           place in the same day. These patients will have 146.8 ml of blood drawn on the same day.
           Containers will be sent to the patients.

        6. Biochemical analysis: total cholesterol, S-LDL-cholesterol, S-HDL-cholesterol and
           S-triglycerides, HbA1c, glucose, C-reactive protein, D-dimer, creatinin and fibrinogen.
           All analyses are performed at our local Dept. of Clinical Biochemistry.

        7. All patients will undergone:

           Carotid intima media thickness (IMT) will be measured by B-mode ultrasound (Model IE33,
           Koninklijke Philips Electronics N.V, Eindhoven, The Netherlands) using a linear array
           transducer, L11-3 with a frequency up to 11 MHz.

        8. Pulse wave velocity: Using sphygmocor (ArtCor, Sydney, Australia).

        9. Ankle brachial index.

       10. Albumin creatinine ratio

       11. Coronary atherosclerosis is evaluated by measurement of calcium in the coronary arteries
           and by evaluation of coronary plaques using contrast enhanced cardiac CT. Coronary
           artery calcifications will be estimated by the Agatston score while the evaluation of
           coronary plaques will be performed by a dedicated plaque-analysis tool, Auto-Plaque.

      STATISTICS

      Sample size estimations are performed for comparison of calcium scoring between patients with
      type-2 diabetes and normal controls (Un-paired evaluation) and comparison of calcium scoring
      between type-2 diabetes patients at inclusion and at follow-up (Paired). From previous
      studies on calcium scoring in the Danish Risk Score Study cohort, the standard deviation, SD,
      on coronary calcification is known to be 32.7 UE (Agatston Score). It is supposed that SD in
      the diabetic patients is equal to the figure in controls. Under the assumptions that 15% will
      drop-out, a MIREDIF of 20 (twice the threshold for registering the occurrence of coronary
      calcification in the central West Danish Heart Registry, VDH), beta= 0, 1 and alfa= 0.02
      (Planned comparative analysis of 2-3 plaque-components) it is calculated, that it is needed
      to include 41 patients in each group for the un-paired analyses and to follow 41 diabetic
      patients for 5 years (Paired analysis). It is supposed, that app. 40% of type-2 diabetes
      patients meet the age criteria (55+/-5 years or 65+/-5 years) for comparison with the
      background population, which means that app. 100 type-2 diabetes patients should be included
      in the DD2 plaque study.

      Students T-test will be used for comparison of normally distributed continuous variables and
      the Mann-Whitney test will be used for comparison of continuous variables that are not
      normally distributed. The χ2- test is performed for comparison of dichotomous variables.
      Continuous variables are presented as either mean or standard deviation or median and
      interquartile range. P-values <0.05 will be considered statistically significant. Stepwise
      multivariate logistic regression will be performed for analysis of which factors are
      associated with coronary atherosclerosis using either presence coronary artery calcification
      or other plaque variables as dependant variables.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Screening
masking: None (Open Label)
measure: Progression of contrast enhanced cardiac CT in relation to baseline and follow-up cardiovascular risk factors and biomarkers.
time frame: 5 years
description: Coronary artery calcification were quantified by non-contrast cardiac CT and were assessed by summing up the scores from all foci in the coronary arteries, expressed in Agatston units (U), using dedicated software (Syngo Calcium scoring, (Siemens Healthcare).
measure: Biochemical analysis in relation to contrast enhanced cardiac CT
time frame: 1 year
description: no. of participants with abnormal laboratory values compared to abnormal/normal enhanced cardiac CT
measure: Body mass index (kg/m2)
time frame: 1 year
description: Cardiovascular risk factors. No of participants with body mass index > 30 kg/m2
measure: Carotid intima media thickness
time frame: 1 year
description: A measure of the combined thickness of intima and media layers of carotid artery, assessed by B-mode ultrasound.values between 0.6 and 0.7 mm have been considered normal. Values > 1 mm or more has been associated with significant increased absolute risk of atherosclerosis. No of participants with values > 1 mm.
measure: Ankle brachial index
time frame: 1year
description: An ankle brachial index between and including 0.9 and 1.2 considered normal (free from significant peripheral artery disease), while a lesser than 0.9 indicates arterial disease. No of participants with value < 0.9.
measure: waist hip ratio (m)
time frame: 1 year
description: Abdominal obesity was defined as a waist-hip ratioabove 0.90 for males and above 0.85 for females,or a body mass index above 30.0 kg/m2. No of participants with abdominal obesity
measure: Blood pressure (mmHg)
time frame: 1 year
description: Hypertension was defined as blood pressures ≥ 140/90. No of participants with hypertension
arm group label: Healthy
arm group type: Sham Comparator
description: Patients in this cohort consist of 100 healthy patients
arm group label: Diabetes mellitus
arm group type: Sham Comparator
description: Newly diagnosed (< 1 year) diabetes patients clinically classified as type-2 diabetes patients of both sex
intervention type: Radiation
intervention name: Cardiac CT
arm group label: Diabetes mellitus
arm group label: Healthy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Hospital of South West Jutland
investigator full name: Monija Mrgan
investigator title: MD
mesh term: Atherosclerosis
sharing ipd: No