<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/NCT01713023</url>
  </required_header>
  <id_info>
    <org_study_id>Debora-TAS1R2</org_study_id>
    <secondary_id>CEP-151/2011</secondary_id>
    <nct_id>NCT01713023</nct_id>
  </id_info>
  <brief_title>Fructose and Glucose and TAS1R2 in Type 1 Diabetes</brief_title>
  <acronym>TAS1R2</acronym>
  <official_title>Effect of Fructose and Glucose and TAS1R2 in Glucose, Triglycerides, Uremia, Oxidative Stress, Feelings Related to Food Intake of Individuals With Type 1 Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidade Federal do Rio de Janeiro</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Rio de Janeiro State Research Supporting Foundation (FAPERJ)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universidade Federal do Rio de Janeiro</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      -  BACKGROUND: Individuals with diabetes report innate preference for sweet foods, possibly&#xD;
           due to genetic variants. In addition, studies have shown that ingestion of fructose&#xD;
           promotes lower postprandial blood glucose, compared to glucose. However, excessive&#xD;
           intake may increase triglycerides, uric acid and oxidative stress, due to oxidative&#xD;
           priority.&#xD;
&#xD;
        -  AIMS: To investigate the influence of fructose and glucose and taste receptor, type 1,&#xD;
           member 2 (TAS1R2) in glucose, triglycerides, uremia, oxidative stress, feelings related&#xD;
           to food intake and palatability of individuals with type 1 diabetes.&#xD;
&#xD;
        -  METHODS: The trial is a single-blind, two-way crossover (1-week washout) study in 30&#xD;
           subjects with type 1 diabetes. Blood samples were collected before and 2-hours after the&#xD;
           participants receive 75g of fructose or 75g of glucose dissolved in 200 ml water.&#xD;
           Capillary blood glucose were assessed at 30, 90, 120, and 180 minutes to determine&#xD;
           glucose, and visual analogue scales for measurement of appetite sensation were assessed&#xD;
           at 70, 120, and 190 minutes.&#xD;
&#xD;
        -  PURPOSE: The research proposal adds knowledge about the TAS1R2 (Ile191Val) polymorphism&#xD;
           and around the most suitable monosaccharide for individuals with diabetes type 1.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      INTRODUCTION:&#xD;
&#xD;
      Fructose is transported via the portal vein to the liver, where is rapidly taken up by&#xD;
      hepatocytes and phosphorylated to fructose-1-phosphate independent of insulin action by the&#xD;
      enzyme fructokinase. Thus, under normal conditions, fructose is converted mainly to glucose,&#xD;
      glycogen, and lactate, and to a small extent also to triglycerides. However a&#xD;
      hypertriglyceridemia has been occur during high intakes of fructose.&#xD;
&#xD;
      Large amounts of fructose, unlike glucose, may result in increased lactate, pyruvate, and&#xD;
      uric acid level in healthy subjects and patients with uncontrolled diabetes. However, uric&#xD;
      acid also has pro-oxidative properties. Possibly, the uric acid neutralizes oxidative damage.&#xD;
&#xD;
      Sweetness is very attractive to patients with diabetes possibly due to genetic variants. The&#xD;
      sweet taste receptor is a heterodimer of 2 protein subunits, T1R2 (taste receptor, type 1,&#xD;
      member 2) and taste receptor, type 1, member 3, located on human chromosome 1. T1R2 is the&#xD;
      component specific to sweet taste perception because taste receptor, type 1, member 3 is also&#xD;
      involved in the detection of umami when it dimerizes with taste receptor, type 1, member 1.&#xD;
&#xD;
      At moment, none study assessed TAS1R variants in individuals with type 1 diabetes.&#xD;
&#xD;
      EXPERIMENTAL DESIGN:&#xD;
&#xD;
      This is a randomized, single-blind, two-way, crossover study conducted at the Research Centre&#xD;
      (Clementino Fraga Filho University Hospital) including 30 adults with type 1 diabetes.&#xD;
&#xD;
      All volunteers will be instruct to complete the usual dietary record, register their&#xD;
      capillary blood glucose and to abstain from vigorous physical activity, alcohol, high-fat&#xD;
      foods and excess caffeine for 24 days before each study day.&#xD;
&#xD;
      One day before each study day, we will call to volunteer to ask about possible events that&#xD;
      may influence the biochemical results (such as: infections, flu, fever). If we detect some,&#xD;
      the test will be rescheduled.&#xD;
&#xD;
      Basal insulin doses will be retained, and no bolus insulin will be allowed in the morning of&#xD;
      the day study. The study day will be performed if the blood glucose target level is between&#xD;
      70 and 200 mg/dL in the morning.&#xD;
&#xD;
      All volunteers will be assessed two-way crossover in a single blind, randomized fashion, with&#xD;
      the two studies in the same subject, 1 week apart. The study was divided into two-days (the&#xD;
      order of which was randomized): one-day with a solution containing glucose and the other with&#xD;
      a solution containing glucose.&#xD;
&#xD;
      The subjects were admitted to the Research Centre (Nutritional Laboratory) at approximately&#xD;
      7-h on the day of study to test capillary blood glucose, collect arterial venous blood&#xD;
      sample, assessed appetite sensations. After these measurements, they will rapidly drink the&#xD;
      test solution.&#xD;
&#xD;
      Palatability ratings of the solution will assessed immediately after. Appetite sensations and&#xD;
      will be tested using VAS scores immediately before and 70, 130, and 180 minutes after&#xD;
      solution.&#xD;
&#xD;
      The second arterial venous blood sample will be collected 185 minutes after solution and test&#xD;
      capillary blood glucose before and 30, 90, 120, and 180 minutes after solution.&#xD;
&#xD;
      We excluded volunteers who not complete both tests.&#xD;
&#xD;
      TEST SOLUTION Solution will be containing 75g of glucose or the same amount of fructose&#xD;
      diluted in 200 mL of water.These amounts were calculated considering the usual oral glucose&#xD;
      tolerance test. In addition, at moment, no studies indicate the ability capacity of fructose&#xD;
      in patients with type 1 diabetes, however, it has been suggested that the absorption capacity&#xD;
      of fructose in healthy adults varies from 30g to 40g.&#xD;
&#xD;
      USUAL DIETARY ASSESSMENT Usual dietary intake will be evaluated from 3-day diet records, and&#xD;
      24-hour recalls will be performed in the day study. All dietary records will be analyzed&#xD;
      using a local nutritional software.&#xD;
&#xD;
      ANTHROPOMETRIC ASSESSMENT BMI will be calculated as body weight in kilograms divided by the&#xD;
      square of height in meters.&#xD;
&#xD;
      Waist circumference will be determined as the average of two measurements calculated to the&#xD;
      nearest 0.1cm midway between the lower rib margin and the ilial crest after a normal&#xD;
      expiration.&#xD;
&#xD;
      Body composition will be measured by tetrapolar bioelectrical impedance(Biodynamic Model&#xD;
      450).&#xD;
&#xD;
      BIOCHEMICAL ASSESSMENT All arterial venous blood sample will be collected by trained&#xD;
      healthcare professionals with disposable materials in the Research Centre (Nutritional&#xD;
      Laboratory) and analyzed at Clinical Analysis Laboratory (located on Federal University).&#xD;
&#xD;
      Glycosylated hemoglobin, total cholesterol, HDL, creatinine, aspartate aminotransferase,&#xD;
      alanine aminotransferase, and creatinine will be assessed to characterize the study&#xD;
      population. Glucose, triglycerides, uric acid, pyruvic acid, lactate, and malonaldehyde will&#xD;
      be measured before and 180 min after ingestion of solution&#xD;
&#xD;
      Glycosylated hemoglobin will be performed by high-performance liquid chromatography. Glucose,&#xD;
      total cholesterol, HDL and triglycerides will be measured by enzymatic colorimetric method.&#xD;
      LDL cholesterol will be calculated by Friedewald equation. Creatinine will be assessed by&#xD;
      kinetic colorimetric method to calculates the creatinine clearance using the Cockcroft-Gault.&#xD;
      Pyruvic acid, aspartate aminotransferase and alanine aminotransferase will be determined by&#xD;
      ultraviolet kinetic method. Uric acid and lactate assessed by enzyme kinetic method.&#xD;
      Malonaldehyde wil be detected by enzyme-linked immunosorbent assay.&#xD;
&#xD;
      GENOTYPING Deoxyribonucleic acid (DNA) will be isolated from whole blood using the DNA&#xD;
      Multi-Sample Kit (Applied Biosystems®) and samples were stored at -20 degree Celsius until&#xD;
      amplification assays in a Research Laboratory (Laboratory of Molecular Biology, Federal&#xD;
      University).&#xD;
&#xD;
      The Ile191Val (rs35874116) polymorphism in TAS1R2 gene will be detected by using a TaqMan&#xD;
      allelic discrimination assay (ABI number C_55646_20; Applied Biosystems, Foster City, CA)&#xD;
      with real-time polymerase chain reaction on an ABI 7000 Sequence Detection System (Applied&#xD;
      Biosystems). Conditions of the polymerase chain reaction is 95 degree Celsius for 10 min and&#xD;
      40 cycles of 95 degree Celsius for 15 s and 60 degree Celsius for 1 min. Genotyping will be&#xD;
      verified by using positive control subjects in each 30-well plate as well as rerunning ≥ 5%&#xD;
      of the samples, which were 100% concordant.&#xD;
&#xD;
      APPETITE AND PALATABILITY ASSESSMENT Visual analogue scales will be used to assess hunger,&#xD;
      satiety, fullness, prospective food consumption, and palatability of the test solution, and&#xD;
      appetite sensations will be evaluated palatability, taste, aftertaste, smell, and visual&#xD;
      appeal of the solutions.&#xD;
&#xD;
      Both ratings consists of a visual analogue scale is a premeasured 100-mm scale that can be&#xD;
      used to represent symptom intensity visually. Each scale is anchored at its ends by opposing&#xD;
      feelings descriptors. Volunteers will be asked to describe their feelings by placing a&#xD;
      vertical mark along the line that best represents the intensity of a given feelings about the&#xD;
      solution. The distance of this mark from the appropriate anchor is measured and then&#xD;
      translated into a score, ranging from 0 (none or best possible) to 10 (worst possible).&#xD;
&#xD;
      DIABETES TYPE 1 MANAGEMENT The investigators only included volunteers in a basal-bolus&#xD;
      regimen with insulin infusion pump or insulin analogs (basal: detemir or glargine; bolus:&#xD;
      lispro, glulisine or aspart) to avoid glucose oscillations during the experiment.&#xD;
&#xD;
      All volunteers will be instructed to not modify basal insulin doses and not take the morning&#xD;
      bolus insulin. The subjects will be admitted in the Research Centre at approximately 7-h and&#xD;
      will be test theirs capillary blood glucose, and if the blood glucose target level is between&#xD;
      70 and 200 mg/dL the experiment will be performed.&#xD;
&#xD;
      Before and during the experiment, we will test the capillary blood glucose levels 5-times&#xD;
      using Accu-Check® Active, Roche, and will be canceled in glucose ≥350 mg/dL. In this case, we&#xD;
      will take a bolus correction insulin dosage.&#xD;
&#xD;
      STATISTICAL Statistical analyzes will be performed with statistical software and significance&#xD;
      level of 5%.&#xD;
&#xD;
      Quantitative variables will be described as the mean and standard deviation. Mann-Whitney&#xD;
      test will be used for between-group comparison and Wilcoxon test to compare the effects of&#xD;
      solution in each group. Spearman's correlation coefficient and regression will also be used.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2013</start_date>
  <completion_date type="Actual">January 2016</completion_date>
  <primary_completion_date type="Actual">December 2014</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Compare the effects of fructose and glucose and TAS1R2 in postprandial metabolism of individuals with type 1 diabetes</measure>
    <time_frame>baseline up to 3 hours each day study. Total study: 2 years</time_frame>
    <description>Determine the blood glucose, triglycerides, oxidation of substrates, uremia, oxidative stress, feelings related to food intake of individuals with type 1 diabetes, before and 3-hours after ingestion of 75g of fructose or 75g of glucose.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effect of fructose or glucose on blood glucose</measure>
    <time_frame>Baseline, and up to 3-hours after solutions</time_frame>
    <description>Determine the peak plasma blood glucose before and 3-hours after ingestion of 75g of fructose or 75g of glucose.&#xD;
We also test capillary blood glucose before and 30, 90, 120, and 180 minutes after solutions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of fructose or glucose on triglycerides levels</measure>
    <time_frame>Baseline, and up to 3-hours after solutions</time_frame>
    <description>Determine the triglycerides levels before and 3-hours after ingestion of 75g of fructose or 75g of glucose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of fructose or glucose on uric acid, pyruvic acid, and lactate</measure>
    <time_frame>Baseline, and up to 3-hours after solutions</time_frame>
    <description>Determine the uric acid, pyruvic acid, and lactate levels before and 3-hours after ingestion of 75g of fructose or 75g of glucose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of fructose or glucose on oxidative stress</measure>
    <time_frame>Baseline, and up to 3-hours after solutions</time_frame>
    <description>Determine the malondialdehyde level before and 3-hours after ingestion of 75g of fructose or 75g of glucose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of two polymorphisms in the gene TAS1R2 in the sweet taste perception</measure>
    <time_frame>only at baseline</time_frame>
    <description>TAS1R2 (taste receptor, type 1, member 2 T1R2) is the component specific to sweet taste perception, and does not change during the life.&#xD;
We will determine whether Ser9Cys (dbSNP: rs9701796) and Ile191Val (dbSNP: rs35874116)variations in TAS1R2 were associated with differences the sweet taste perceptions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of fructose or glucose on blood glucose</measure>
    <time_frame>Baseline, and up to 3-hours after solutions</time_frame>
    <description>Determine the peak plasma blood glucose before and 3-hours after ingestion of 75g of fructose or 75g of glucose.&#xD;
We also test capillary blood glucose before and 30, 90, 120 and 180 minutes after solutions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of fructose or glucose on appetite and palatability</measure>
    <time_frame>Baseline, and up 120 minutes</time_frame>
    <description>Two different visual analogue scales will be used to assess hunger, satiety, fullness, prospective food consumption, palatability, taste, aftertaste, smell, and visual appeal of the solutions.&#xD;
The scales will be performed at 7, 35, 95 and 120 minutes after solutions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of fructose or glucose on glucagon levels</measure>
    <time_frame>Baseline, and up to 3-hours after solutions</time_frame>
    <description>Determine the glucagon levels before and 3-hours after ingestion of 75g of fructose or 75g of glucose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effect of fructose or glucose on leptin levels</measure>
    <time_frame>Baseline, and up to 3-hours after solutions</time_frame>
    <description>Determine the leptin levels before and 3-hours after ingestion of 75g of fructose or 75g of glucose</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Type 1 Diabetes</condition>
  <arm_group>
    <arm_group_label>Glucose solution</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Solution containing 75g of glucose diluted in 200 mL of water</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fructose solution</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Solution containing 75g of fructose diluted in 200 mL of water</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Glucose</intervention_name>
    <description>The same described in Arm description</description>
    <arm_group_label>Fructose solution</arm_group_label>
    <arm_group_label>Glucose solution</arm_group_label>
    <other_name>75g of glucose diluted in 200 mL of water</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Fructose</intervention_name>
    <description>The same described in Arm description</description>
    <arm_group_label>Fructose solution</arm_group_label>
    <arm_group_label>Glucose solution</arm_group_label>
    <other_name>75g of fructose diluted in 200 mL of water</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type 1 diabetes ( ≥ three years after diagnosis)&#xD;
&#xD;
          -  Adults&#xD;
&#xD;
          -  Normal-weight (BMI between 18.5 e 25.0 kg/m2)&#xD;
&#xD;
          -  Using basal-bolus regimen with insulin infusion pump or insulin analogs (basal:&#xD;
             detemir or glargine; bolus: lispro, glulisine or aspart).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Smokers;&#xD;
&#xD;
          -  Drinkers;&#xD;
&#xD;
          -  Use of exogenous hormone (with the exception of insulin);&#xD;
&#xD;
          -  Use of antibiotics, anti-inflammatories or oral antidiabetics pharmacotherapy;&#xD;
&#xD;
          -  Diagnosis of nephropathy;&#xD;
&#xD;
          -  Diagnosis of liver diseases;&#xD;
&#xD;
          -  With other types of diabetes family history;&#xD;
&#xD;
          -  Visual disturbances.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Débora L Souto</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ph. D. student in Nutrition Sciences at the Federal University of Rio de Janeiro, Brazil</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital of Rio de Janeiro, Federal University of Rio de Janeiro</name>
      <address>
        <city>Rio de Janeiro</city>
        <zip>21941-590</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <link>
    <url>http://www.hucff.ufrj.br/</url>
    <description>Federal University</description>
  </link>
  <verification_date>April 2016</verification_date>
  <study_first_submitted>October 19, 2012</study_first_submitted>
  <study_first_submitted_qc>October 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 24, 2012</study_first_posted>
  <last_update_submitted>April 14, 2016</last_update_submitted>
  <last_update_submitted_qc>April 14, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 15, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universidade Federal do Rio de Janeiro</investigator_affiliation>
    <investigator_full_name>Débora Lopes Souto</investigator_full_name>
    <investigator_title>Ph. D. student in Nutrition Sciences at the Federal University of Rio de Janeiro</investigator_title>
  </responsible_party>
  <keyword>type 1 diabetes</keyword>
  <keyword>fructose</keyword>
  <keyword>glucose</keyword>
  <keyword>TAS1R2</keyword>
  <keyword>oxidative stress</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_browse>
  <!-- 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/NCT01713023
org study id: Debora-TAS1R2
secondary id: CEP-151/2011
nct id: NCT01713023
lead sponsor: 
collaborator: 
has dmc: Yes
-  BACKGROUND: Individuals with diabetes report innate preference for sweet foods, possibly
           due to genetic variants. In addition, studies have shown that ingestion of fructose
           promotes lower postprandial blood glucose, compared to glucose. However, excessive
           intake may increase triglycerides, uric acid and oxidative stress, due to oxidative
           priority.

        -  AIMS: To investigate the influence of fructose and glucose and taste receptor, type 1,
           member 2 (TAS1R2) in glucose, triglycerides, uremia, oxidative stress, feelings related
           to food intake and palatability of individuals with type 1 diabetes.

        -  METHODS: The trial is a single-blind, two-way crossover (1-week washout) study in 30
           subjects with type 1 diabetes. Blood samples were collected before and 2-hours after the
           participants receive 75g of fructose or 75g of glucose dissolved in 200 ml water.
           Capillary blood glucose were assessed at 30, 90, 120, and 180 minutes to determine
           glucose, and visual analogue scales for measurement of appetite sensation were assessed
           at 70, 120, and 190 minutes.

        -  PURPOSE: The research proposal adds knowledge about the TAS1R2 (Ile191Val) polymorphism
           and around the most suitable monosaccharide for individuals with diabetes type 1.
INTRODUCTION:

      Fructose is transported via the portal vein to the liver, where is rapidly taken up by
      hepatocytes and phosphorylated to fructose-1-phosphate independent of insulin action by the
      enzyme fructokinase. Thus, under normal conditions, fructose is converted mainly to glucose,
      glycogen, and lactate, and to a small extent also to triglycerides. However a
      hypertriglyceridemia has been occur during high intakes of fructose.

      Large amounts of fructose, unlike glucose, may result in increased lactate, pyruvate, and
      uric acid level in healthy subjects and patients with uncontrolled diabetes. However, uric
      acid also has pro-oxidative properties. Possibly, the uric acid neutralizes oxidative damage.

      Sweetness is very attractive to patients with diabetes possibly due to genetic variants. The
      sweet taste receptor is a heterodimer of 2 protein subunits, T1R2 (taste receptor, type 1,
      member 2) and taste receptor, type 1, member 3, located on human chromosome 1. T1R2 is the
      component specific to sweet taste perception because taste receptor, type 1, member 3 is also
      involved in the detection of umami when it dimerizes with taste receptor, type 1, member 1.

      At moment, none study assessed TAS1R variants in individuals with type 1 diabetes.

      EXPERIMENTAL DESIGN:

      This is a randomized, single-blind, two-way, crossover study conducted at the Research Centre
      (Clementino Fraga Filho University Hospital) including 30 adults with type 1 diabetes.

      All volunteers will be instruct to complete the usual dietary record, register their
      capillary blood glucose and to abstain from vigorous physical activity, alcohol, high-fat
      foods and excess caffeine for 24 days before each study day.

      One day before each study day, we will call to volunteer to ask about possible events that
      may influence the biochemical results (such as: infections, flu, fever). If we detect some,
      the test will be rescheduled.

      Basal insulin doses will be retained, and no bolus insulin will be allowed in the morning of
      the day study. The study day will be performed if the blood glucose target level is between
      70 and 200 mg/dL in the morning.

      All volunteers will be assessed two-way crossover in a single blind, randomized fashion, with
      the two studies in the same subject, 1 week apart. The study was divided into two-days (the
      order of which was randomized): one-day with a solution containing glucose and the other with
      a solution containing glucose.

      The subjects were admitted to the Research Centre (Nutritional Laboratory) at approximately
      7-h on the day of study to test capillary blood glucose, collect arterial venous blood
      sample, assessed appetite sensations. After these measurements, they will rapidly drink the
      test solution.

      Palatability ratings of the solution will assessed immediately after. Appetite sensations and
      will be tested using VAS scores immediately before and 70, 130, and 180 minutes after
      solution.

      The second arterial venous blood sample will be collected 185 minutes after solution and test
      capillary blood glucose before and 30, 90, 120, and 180 minutes after solution.

      We excluded volunteers who not complete both tests.

      TEST SOLUTION Solution will be containing 75g of glucose or the same amount of fructose
      diluted in 200 mL of water.These amounts were calculated considering the usual oral glucose
      tolerance test. In addition, at moment, no studies indicate the ability capacity of fructose
      in patients with type 1 diabetes, however, it has been suggested that the absorption capacity
      of fructose in healthy adults varies from 30g to 40g.

      USUAL DIETARY ASSESSMENT Usual dietary intake will be evaluated from 3-day diet records, and
      24-hour recalls will be performed in the day study. All dietary records will be analyzed
      using a local nutritional software.

      ANTHROPOMETRIC ASSESSMENT BMI will be calculated as body weight in kilograms divided by the
      square of height in meters.

      Waist circumference will be determined as the average of two measurements calculated to the
      nearest 0.1cm midway between the lower rib margin and the ilial crest after a normal
      expiration.

      Body composition will be measured by tetrapolar bioelectrical impedance(Biodynamic Model
      450).

      BIOCHEMICAL ASSESSMENT All arterial venous blood sample will be collected by trained
      healthcare professionals with disposable materials in the Research Centre (Nutritional
      Laboratory) and analyzed at Clinical Analysis Laboratory (located on Federal University).

      Glycosylated hemoglobin, total cholesterol, HDL, creatinine, aspartate aminotransferase,
      alanine aminotransferase, and creatinine will be assessed to characterize the study
      population. Glucose, triglycerides, uric acid, pyruvic acid, lactate, and malonaldehyde will
      be measured before and 180 min after ingestion of solution

      Glycosylated hemoglobin will be performed by high-performance liquid chromatography. Glucose,
      total cholesterol, HDL and triglycerides will be measured by enzymatic colorimetric method.
      LDL cholesterol will be calculated by Friedewald equation. Creatinine will be assessed by
      kinetic colorimetric method to calculates the creatinine clearance using the Cockcroft-Gault.
      Pyruvic acid, aspartate aminotransferase and alanine aminotransferase will be determined by
      ultraviolet kinetic method. Uric acid and lactate assessed by enzyme kinetic method.
      Malonaldehyde wil be detected by enzyme-linked immunosorbent assay.

      GENOTYPING Deoxyribonucleic acid (DNA) will be isolated from whole blood using the DNA
      Multi-Sample Kit (Applied Biosystems®) and samples were stored at -20 degree Celsius until
      amplification assays in a Research Laboratory (Laboratory of Molecular Biology, Federal
      University).

      The Ile191Val (rs35874116) polymorphism in TAS1R2 gene will be detected by using a TaqMan
      allelic discrimination assay (ABI number C_55646_20; Applied Biosystems, Foster City, CA)
      with real-time polymerase chain reaction on an ABI 7000 Sequence Detection System (Applied
      Biosystems). Conditions of the polymerase chain reaction is 95 degree Celsius for 10 min and
      40 cycles of 95 degree Celsius for 15 s and 60 degree Celsius for 1 min. Genotyping will be
      verified by using positive control subjects in each 30-well plate as well as rerunning ≥ 5%
      of the samples, which were 100% concordant.

      APPETITE AND PALATABILITY ASSESSMENT Visual analogue scales will be used to assess hunger,
      satiety, fullness, prospective food consumption, and palatability of the test solution, and
      appetite sensations will be evaluated palatability, taste, aftertaste, smell, and visual
      appeal of the solutions.

      Both ratings consists of a visual analogue scale is a premeasured 100-mm scale that can be
      used to represent symptom intensity visually. Each scale is anchored at its ends by opposing
      feelings descriptors. Volunteers will be asked to describe their feelings by placing a
      vertical mark along the line that best represents the intensity of a given feelings about the
      solution. The distance of this mark from the appropriate anchor is measured and then
      translated into a score, ranging from 0 (none or best possible) to 10 (worst possible).

      DIABETES TYPE 1 MANAGEMENT The investigators only included volunteers in a basal-bolus
      regimen with insulin infusion pump or insulin analogs (basal: detemir or glargine; bolus:
      lispro, glulisine or aspart) to avoid glucose oscillations during the experiment.

      All volunteers will be instructed to not modify basal insulin doses and not take the morning
      bolus insulin. The subjects will be admitted in the Research Centre at approximately 7-h and
      will be test theirs capillary blood glucose, and if the blood glucose target level is between
      70 and 200 mg/dL the experiment will be performed.

      Before and during the experiment, we will test the capillary blood glucose levels 5-times
      using Accu-Check® Active, Roche, and will be canceled in glucose ≥350 mg/dL. In this case, we
      will take a bolus correction insulin dosage.

      STATISTICAL Statistical analyzes will be performed with statistical software and significance
      level of 5%.

      Quantitative variables will be described as the mean and standard deviation. Mann-Whitney
      test will be used for between-group comparison and Wilcoxon test to compare the effects of
      solution in each group. Spearman's correlation coefficient and regression will also be used.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Health Services Research
masking: Single (Participant)
measure: Compare the effects of fructose and glucose and TAS1R2 in postprandial metabolism of individuals with type 1 diabetes
time frame: baseline up to 3 hours each day study. Total study: 2 years
description: Determine the blood glucose, triglycerides, oxidation of substrates, uremia, oxidative stress, feelings related to food intake of individuals with type 1 diabetes, before and 3-hours after ingestion of 75g of fructose or 75g of glucose.
measure: Effect of fructose or glucose on blood glucose
time frame: Baseline, and up to 3-hours after solutions
description: Determine the peak plasma blood glucose before and 3-hours after ingestion of 75g of fructose or 75g of glucose.
We also test capillary blood glucose before and 30, 90, 120, and 180 minutes after solutions.
measure: Effect of fructose or glucose on triglycerides levels
time frame: Baseline, and up to 3-hours after solutions
description: Determine the triglycerides levels before and 3-hours after ingestion of 75g of fructose or 75g of glucose.
measure: Effect of fructose or glucose on uric acid, pyruvic acid, and lactate
time frame: Baseline, and up to 3-hours after solutions
description: Determine the uric acid, pyruvic acid, and lactate levels before and 3-hours after ingestion of 75g of fructose or 75g of glucose.
measure: Effect of fructose or glucose on oxidative stress
time frame: Baseline, and up to 3-hours after solutions
description: Determine the malondialdehyde level before and 3-hours after ingestion of 75g of fructose or 75g of glucose.
measure: Effect of two polymorphisms in the gene TAS1R2 in the sweet taste perception
time frame: only at baseline
description: TAS1R2 (taste receptor, type 1, member 2 T1R2) is the component specific to sweet taste perception, and does not change during the life.
We will determine whether Ser9Cys (dbSNP: rs9701796) and Ile191Val (dbSNP: rs35874116)variations in TAS1R2 were associated with differences the sweet taste perceptions.
measure: Effect of fructose or glucose on blood glucose
time frame: Baseline, and up to 3-hours after solutions
description: Determine the peak plasma blood glucose before and 3-hours after ingestion of 75g of fructose or 75g of glucose.
We also test capillary blood glucose before and 30, 90, 120 and 180 minutes after solutions.
measure: Effect of fructose or glucose on appetite and palatability
time frame: Baseline, and up 120 minutes
description: Two different visual analogue scales will be used to assess hunger, satiety, fullness, prospective food consumption, palatability, taste, aftertaste, smell, and visual appeal of the solutions.
The scales will be performed at 7, 35, 95 and 120 minutes after solutions.
measure: Effect of fructose or glucose on glucagon levels
time frame: Baseline, and up to 3-hours after solutions
description: Determine the glucagon levels before and 3-hours after ingestion of 75g of fructose or 75g of glucose
measure: Effect of fructose or glucose on leptin levels
time frame: Baseline, and up to 3-hours after solutions
description: Determine the leptin levels before and 3-hours after ingestion of 75g of fructose or 75g of glucose
arm group label: Glucose solution
arm group type: Experimental
description: Solution containing 75g of glucose diluted in 200 mL of water
arm group label: Fructose solution
arm group type: Experimental
description: Solution containing 75g of fructose diluted in 200 mL of water
intervention type: Dietary Supplement
intervention name: Glucose
description: The same described in Arm description
arm group label: Fructose solution
arm group label: Glucose solution
other name: 75g of glucose diluted in 200 mL of water
intervention type: Dietary Supplement
intervention name: Fructose
description: The same described in Arm description
arm group label: Fructose solution
arm group label: Glucose solution
other name: 75g of fructose diluted in 200 mL of water
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: Débora L Souto
role: Principal Investigator
affiliation: Ph. D. student in Nutrition Sciences at the Federal University of Rio de Janeiro, Brazil
facility: 
country: Brazil
url: http://www.hucff.ufrj.br/
description: Federal University
responsible party type: Principal Investigator
investigator affiliation: Universidade Federal do Rio de Janeiro
investigator full name: Débora Lopes Souto
investigator title: Ph. D. student in Nutrition Sciences at the Federal University of Rio de Janeiro
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1