<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/NCT04507685</url>
  </required_header>
  <id_info>
    <org_study_id>2019-078</org_study_id>
    <nct_id>NCT04507685</nct_id>
  </id_info>
  <brief_title>Asian Indian Prediabetes Study</brief_title>
  <acronym>AIPS</acronym>
  <official_title>Diet and Lifestyle Intervention Strategies to Treat β-cell Dysfunction and Insulin Resistance in Asian Indians</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Singapore Institute for Clinical Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Medical Research Foundation (NMRC) Singapore</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Almond Board of California</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Singapore Institute for Clinical Sciences</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Compared to other races, Indians have higher insulin resistance, poorer pancreatic function&#xD;
      and a greater risk of developing diabetes, highlighting the importance of early strategies&#xD;
      for improving insulin sensitivity and improving pancreatic function in Indians to prevent&#xD;
      diabetes and lower the risk of heart disease.&#xD;
&#xD;
      A low carbohydrate diet can deplete fat from undesirable places, such as fat around organs in&#xD;
      the abdominal cavity. In this study, we will determine if restriction of dietary&#xD;
      carbohydrates will deplete fat in the pancreas and liver, and improve insulin sensitivity and&#xD;
      early insulin secretion in Indians. These changes may prevent diabetes from developing.&#xD;
      Hepatic and pancreatic fat will be measured using magnetic resonance imaging. Insulin&#xD;
      sensitivity and secretion will be measured during an oral glucose tolerance test. In&#xD;
      addition, this study will investigate if the higher insulin resistance in Indians is due to&#xD;
      genes that cause the inability to store fat in the legs.&#xD;
&#xD;
      The results on the type of diet that is more effective for reducing pancreatic and hepatic&#xD;
      fat is important for informing dietary guidelines on the use of low carbohydrate diets for&#xD;
      diabetes prevention, particularly in Indians who have a higher risk of developing diabetes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Compared to other races, Indians have a greater risk of developing type 2 diabetes (T2D),&#xD;
      increased insulin resistance (IR) and more rapid decline in β-cell function, highlighting the&#xD;
      urgency and importance of early intervention strategies for improving insulin sensitivity and&#xD;
      preserving/improving β-cell function to prevent T2D and mitigate against the increased&#xD;
      vascular disease risk.&#xD;
&#xD;
      Preliminary findings show a reduction in glycemic load selectively depletes visceral and&#xD;
      ectopic lipid and improves insulin sensitivity and β-cell function in non-diabetic adults.&#xD;
      The proposed research will investigate if the phenotypic features increasing T2D risk in&#xD;
      individuals of Indian ancestry (IR and impaired β-cell function) can be favorably modified by&#xD;
      a low glycemic (LG) intervention, and if the increased IR is attributable to genetic factors&#xD;
      regulating adipocyte differentiation and function.&#xD;
&#xD;
      These research objectives will be achieved through a 24-week randomized controlled trial&#xD;
      (RCT) comparing isocaloric LG versus control diets in Indians with prediabetes. Compared to&#xD;
      individuals in the control group, those on the LG diet are expected to have greater ectopic&#xD;
      (pancreas, liver, visceral and intramyocellular) fat depletion assessed with MRI/MRS, and&#xD;
      improvements in first phase insulin secretion and insulin sensitivity assessed with the&#xD;
      C-peptide model and oral minimal model, respectively during an OGTT. Reductions in hepatic&#xD;
      and pancreatic lipids will be associated with improvements in first-phase β-cell response.&#xD;
      Individuals with a greater number of risk alleles from a 53-SNP IR genetic risk score will&#xD;
      have lower insulin sensitivity and leg fat, supporting the notion that impaired adipocyte&#xD;
      differentiation leading to limited peripheral adipose expansion capacity is an important&#xD;
      etiological factor underpinning IR cardiometabolic disease in Indians.&#xD;
&#xD;
      The results will broaden the evidence base for effective prevention strategies in this high&#xD;
      risk population by investigating the effect of the proposed diet intervention on underlying&#xD;
      physiological and molecular mechanisms implicated in the pathophysiology of T2D in Indians.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 19, 2020</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</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>Parallel Assignment</intervention_model>
    <intervention_model_description>24-week parallel arm, randomized controlled trial (RCT)</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in β-cell Function [First-phase β-cell response (PhiD)]</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
    <description>First-phase β-cell response (PhiD) will be calculated from blood glucose and C-peptide data during a 3h 75g oral glucose tolerance test (OGTT) using the C-peptide minimal model.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Insulinogenic index (ΔC-peptide/∆glucose during the first 30 minutes of the OGTT)</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
    <description>ΔC-peptide/∆glucose during the first 30 minutes of the OGTT will be calculated as an index of early insulin secretion (Insulinogenic index).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Incremental AUC</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
    <description>Incremental AUC over 180 minutes of the OGTT will be calculated for glucose, insulin, and C-peptide.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Insulin sensitivity (Oral Minimal model)</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
    <description>Insulin sensitivity will be calculated from blood glucose, insulin and C-peptide during a 3h 75g oral glucose tolerance test (OGTT) using both the oral minimal model</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Matsuda index for whole body insulin sensitivity</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Body fat distribution</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
    <description>Body fat distribution will be imaged and quantified using MRI and MRS. Abdominal fat will be segmented to identify and quantify subcutaneous (deep and superficial) and visceral fat compartments. Lower body gluteal fat compartment will also be imaged and quantified. Fat within liver, pancreas and skeletal muscle fibers will be determined by MRI / MRS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Weight (kg)</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Blood Pressure</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Body Composition- Total body fat</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
    <description>Total body fat (kg) will be assessed using DXA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Body Composition- Total lean mass</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
    <description>Total lean mass (kg) will be assessed using DXA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Genotyping analyses</measure>
    <time_frame>Week 0</time_frame>
    <description>Genomic DNA isolated from blood samples will be analysed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Blood Lipids (total cholesterol, HDL-C, TAG, lipoprotein subfractions)</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in liver enzymes</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in inflammatory markers (e.g. IL-6, TNFα and CRP)</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in satiety hormones (e.g. leptin, ghrelin, GIP and GLP-1).</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lipidomics</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
    <description>Lipidomics evaluation of several lipid classes including sphingolipids (sphingomyelins, ceramides and glycosphingolipids) in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Plasma phospholipid fatty acid (FA) profile</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Gut microbiota composition</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
    <description>Gut microbiota composition will be assessed by 16S or shotgun metagenomic sequencing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Faecal characteristics- including short chain fatty acids (SCFAs).</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in respiratory quotient (RQ)</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
    <description>Respiratory quotient (RQ) to assess substrate utilization by indirect calorimetry.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in blood ketone (β-hydroxybutyrate, βHB) concentrations</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
    <description>A marker of carbohydrate intake</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in 24-h urinary urea to creatinine ratio</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
    <description>A marker of protein intake</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Physical activity levels</measure>
    <time_frame>Week 0, 8 and 24</time_frame>
    <description>Assessed with 7 consecutive days of triaxial accelerometry</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Exercise Classes attendance</measure>
    <time_frame>24 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in dietary intake (diet checklists)</measure>
    <time_frame>24 weeks</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Pre Diabetes</condition>
  <arm_group>
    <arm_group_label>Low Glycaemic Diet (LG)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low carbohydrate, low saturated fat diet</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Diet</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>High unrefined carbohydrate, low fat diet</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Lifestyle (Diet and Exercise)</intervention_name>
    <description>The LG diet will comprise 20% carbohydrate, 30% protein, and 50% fat (&lt;10% saturated fat). It will have a low glycaemic load; include plant and animal protein; non-starchy vegetables and salad greens; and some low-sugar fruit. Participants will be encouraged to incorporate a variety of foods rich in monounsaturated and polyunsaturated fats in their diet.&#xD;
The control diet will comprise 50% carbohydrate, 20% protein and 30% total fat (&lt;10% saturated fat). It will reflect the Health Promotion Board's (HPB) recommendations to reduce dietary fat, emphasize wholegrains and include a variety of fruits and vegetables. In contrast to the LG diet, the control diet will have a higher glycaemic load with a greater proportion of energy derived from unrefined carbohydrate foods.&#xD;
Concurrent to the dietary intervention and consistent with physical activity guidelines, all participants will undertake a 60-min structured exercise program incorporating aerobic/ resistance exercises 3-4 days/week.</description>
    <arm_group_label>Control Diet</arm_group_label>
    <arm_group_label>Low Glycaemic Diet (LG)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female&#xD;
&#xD;
          -  Asian Indian ethnicity&#xD;
&#xD;
          -  Age between 21-50 years&#xD;
&#xD;
          -  BMI not greater than 35 or less than 25&#xD;
&#xD;
          -  Prediabetes (based on results from an OGTT conducted in the last 3 months):&#xD;
&#xD;
               -  Impaired Fasting Glucose (IFG) which is a fasting blood glucose level of between&#xD;
                  5.6 to 6.9 mmol/l and/or&#xD;
&#xD;
               -  Impaired Glucose Tolerance (IGT) which is a blood glucose level of 7.8 to 11.0&#xD;
                  mmol/l, 2 hours after the OGTT but below 7.0 mmol/l in the fasting state.&#xD;
&#xD;
          -  Not have type 1 or type 2 diabetes&#xD;
&#xD;
          -  Not on any diabetes medications that affect insulin sensitivity e.g. metformin,&#xD;
             glitazones&#xD;
&#xD;
          -  No abnormality of clinical significance on medical history&#xD;
&#xD;
          -  If female, not pregnant or breast feeding&#xD;
&#xD;
          -  No history of coronary artery disease or cardiac (heart) abnormalities&#xD;
&#xD;
          -  Participants must understand the procedures involved and agree to participate in the&#xD;
             study by giving full informed, written consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  BMI greater than 35 or less than 25&#xD;
&#xD;
          -  Weight gain or loss of more than 5% over the past 3 months&#xD;
&#xD;
          -  Have anaemia (low haemoglobin/ red blood cell levels), a malignancy (cancer), abnormal&#xD;
             liver function, any significant endocrinopathy (e.g. thyroid problems), or a history&#xD;
             of metabolic disease such as liver, kidney, cardiovascular, respiratory or&#xD;
             gastrointestinal disease.&#xD;
&#xD;
          -  Have high uncontrolled hypertension (resting seated blood pressure &gt;160/100 mmHg)&#xD;
&#xD;
          -  Taking medications that may affect glucose metabolism e.g. steroids, thiazide&#xD;
             diuretics at doses&gt;25mg/day.&#xD;
&#xD;
          -  History of smoking or using nicotine products during the 6 months prior to study&#xD;
&#xD;
          -  History of heavy alcohol consumption (&gt; 5 standard drinks/day)&#xD;
&#xD;
          -  Inability to limit alcohol consumption for study duration&#xD;
&#xD;
          -  Lactose Intolerant or have a nut allergy&#xD;
&#xD;
          -  Have depression&#xD;
&#xD;
          -  Have a musculoskeletal injury, joint or peripheral vascular disease sufficient to&#xD;
             impede exercise (such as hip arthritis, foot, ankle problems or pain)&#xD;
&#xD;
          -  Have severe exercise-induced asthma&#xD;
&#xD;
          -  Participating in a regular aerobic or resistance exercise program&#xD;
&#xD;
          -  Currently on a weight reducing diet or have an eating disorder&#xD;
&#xD;
          -  Contraindications for MRI e.g. if you have certain metallic implants/devices such as&#xD;
             heart valves of a cardiac pacemaker which may be affected by the magnetic field&#xD;
&#xD;
          -  Unwilling to be randomized to either diet group&#xD;
&#xD;
          -  Extended absences due to travel or other commitments&#xD;
&#xD;
          -  Unable to comprehend or cope with study requirements&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeannie Tay, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Singapore Institute for Clinical Sciences</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jeannie Tay, PhD</last_name>
    <phone>(65) 66015816</phone>
    <email>jeannie_tay@sics.a-star.edu.sg</email>
  </overall_contact>
  <location>
    <facility>
      <name>Singapore Institute for Clinical Sciences (SICS)</name>
      <address>
        <city>Singapore</city>
        <zip>117549</zip>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jeannie Tay, PhD</last_name>
      <phone>(65) 66015816</phone>
      <email>jeannie_Tay@sics.a-star.edu.sg</email>
    </contact>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>August 6, 2020</study_first_submitted>
  <study_first_submitted_qc>August 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2020</study_first_posted>
  <last_update_submitted>May 3, 2022</last_update_submitted>
  <last_update_submitted_qc>May 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Singapore Institute for Clinical Sciences</investigator_affiliation>
    <investigator_full_name>Jeannie Tay</investigator_full_name>
    <investigator_title>Senior Research Fellow</investigator_title>
  </responsible_party>
  <keyword>Asian Indians</keyword>
  <keyword>Prediabetes</keyword>
  <keyword>Insulin Resistance</keyword>
  <keyword>Low glycaemic diet</keyword>
  <keyword>Ectopic Fat</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prediabetic State</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/NCT04507685
org study id: 2019-078
nct id: NCT04507685
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Compared to other races, Indians have higher insulin resistance, poorer pancreatic function
      and a greater risk of developing diabetes, highlighting the importance of early strategies
      for improving insulin sensitivity and improving pancreatic function in Indians to prevent
      diabetes and lower the risk of heart disease.

      A low carbohydrate diet can deplete fat from undesirable places, such as fat around organs in
      the abdominal cavity. In this study, we will determine if restriction of dietary
      carbohydrates will deplete fat in the pancreas and liver, and improve insulin sensitivity and
      early insulin secretion in Indians. These changes may prevent diabetes from developing.
      Hepatic and pancreatic fat will be measured using magnetic resonance imaging. Insulin
      sensitivity and secretion will be measured during an oral glucose tolerance test. In
      addition, this study will investigate if the higher insulin resistance in Indians is due to
      genes that cause the inability to store fat in the legs.

      The results on the type of diet that is more effective for reducing pancreatic and hepatic
      fat is important for informing dietary guidelines on the use of low carbohydrate diets for
      diabetes prevention, particularly in Indians who have a higher risk of developing diabetes.
Compared to other races, Indians have a greater risk of developing type 2 diabetes (T2D),
      increased insulin resistance (IR) and more rapid decline in β-cell function, highlighting the
      urgency and importance of early intervention strategies for improving insulin sensitivity and
      preserving/improving β-cell function to prevent T2D and mitigate against the increased
      vascular disease risk.

      Preliminary findings show a reduction in glycemic load selectively depletes visceral and
      ectopic lipid and improves insulin sensitivity and β-cell function in non-diabetic adults.
      The proposed research will investigate if the phenotypic features increasing T2D risk in
      individuals of Indian ancestry (IR and impaired β-cell function) can be favorably modified by
      a low glycemic (LG) intervention, and if the increased IR is attributable to genetic factors
      regulating adipocyte differentiation and function.

      These research objectives will be achieved through a 24-week randomized controlled trial
      (RCT) comparing isocaloric LG versus control diets in Indians with prediabetes. Compared to
      individuals in the control group, those on the LG diet are expected to have greater ectopic
      (pancreas, liver, visceral and intramyocellular) fat depletion assessed with MRI/MRS, and
      improvements in first phase insulin secretion and insulin sensitivity assessed with the
      C-peptide model and oral minimal model, respectively during an OGTT. Reductions in hepatic
      and pancreatic lipids will be associated with improvements in first-phase β-cell response.
      Individuals with a greater number of risk alleles from a 53-SNP IR genetic risk score will
      have lower insulin sensitivity and leg fat, supporting the notion that impaired adipocyte
      differentiation leading to limited peripheral adipose expansion capacity is an important
      etiological factor underpinning IR cardiometabolic disease in Indians.

      The results will broaden the evidence base for effective prevention strategies in this high
      risk population by investigating the effect of the proposed diet intervention on underlying
      physiological and molecular mechanisms implicated in the pathophysiology of T2D in Indians.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 24-week parallel arm, randomized controlled trial (RCT)
primary purpose: Prevention
masking: Double (Investigator, Outcomes Assessor)
measure: Change in β-cell Function [First-phase β-cell response (PhiD)]
time frame: Week 0, 8 and 24
description: First-phase β-cell response (PhiD) will be calculated from blood glucose and C-peptide data during a 3h 75g oral glucose tolerance test (OGTT) using the C-peptide minimal model.
measure: Change in Insulinogenic index (ΔC-peptide/∆glucose during the first 30 minutes of the OGTT)
time frame: Week 0, 8 and 24
description: ΔC-peptide/∆glucose during the first 30 minutes of the OGTT will be calculated as an index of early insulin secretion (Insulinogenic index).
measure: Change in Incremental AUC
time frame: Week 0, 8 and 24
description: Incremental AUC over 180 minutes of the OGTT will be calculated for glucose, insulin, and C-peptide.
measure: Change in Insulin sensitivity (Oral Minimal model)
time frame: Week 0, 8 and 24
description: Insulin sensitivity will be calculated from blood glucose, insulin and C-peptide during a 3h 75g oral glucose tolerance test (OGTT) using both the oral minimal model
measure: Change in Matsuda index for whole body insulin sensitivity
time frame: Week 0, 8 and 24
measure: Change in Body fat distribution
time frame: Week 0, 8 and 24
description: Body fat distribution will be imaged and quantified using MRI and MRS. Abdominal fat will be segmented to identify and quantify subcutaneous (deep and superficial) and visceral fat compartments. Lower body gluteal fat compartment will also be imaged and quantified. Fat within liver, pancreas and skeletal muscle fibers will be determined by MRI / MRS.
measure: Change in Weight (kg)
time frame: Week 0, 8 and 24
measure: Change in Blood Pressure
time frame: Week 0, 8 and 24
measure: Change in Body Composition- Total body fat
time frame: Week 0, 8 and 24
description: Total body fat (kg) will be assessed using DXA
measure: Change in Body Composition- Total lean mass
time frame: Week 0, 8 and 24
description: Total lean mass (kg) will be assessed using DXA
measure: Genotyping analyses
time frame: Week 0
description: Genomic DNA isolated from blood samples will be analysed
measure: Change in Blood Lipids (total cholesterol, HDL-C, TAG, lipoprotein subfractions)
time frame: Week 0, 8 and 24
measure: Change in liver enzymes
time frame: Week 0, 8 and 24
measure: Change in inflammatory markers (e.g. IL-6, TNFα and CRP)
time frame: Week 0, 8 and 24
measure: Change in satiety hormones (e.g. leptin, ghrelin, GIP and GLP-1).
time frame: Week 0, 8 and 24
measure: Lipidomics
time frame: Week 0, 8 and 24
description: Lipidomics evaluation of several lipid classes including sphingolipids (sphingomyelins, ceramides and glycosphingolipids) in plasma
measure: Change in Plasma phospholipid fatty acid (FA) profile
time frame: Week 0, 8 and 24
measure: Change in Gut microbiota composition
time frame: Week 0, 8 and 24
description: Gut microbiota composition will be assessed by 16S or shotgun metagenomic sequencing
measure: Change in Faecal characteristics- including short chain fatty acids (SCFAs).
time frame: Week 0, 8 and 24
measure: Change in respiratory quotient (RQ)
time frame: Week 0, 8 and 24
description: Respiratory quotient (RQ) to assess substrate utilization by indirect calorimetry.
measure: Change in blood ketone (β-hydroxybutyrate, βHB) concentrations
time frame: Week 0, 8 and 24
description: A marker of carbohydrate intake
measure: Change in 24-h urinary urea to creatinine ratio
time frame: Week 0, 8 and 24
description: A marker of protein intake
measure: Change in Physical activity levels
time frame: Week 0, 8 and 24
description: Assessed with 7 consecutive days of triaxial accelerometry
measure: Change in Exercise Classes attendance
time frame: 24 weeks
measure: Change in dietary intake (diet checklists)
time frame: 24 weeks
arm group label: Low Glycaemic Diet (LG)
arm group type: Experimental
description: Low carbohydrate, low saturated fat diet
arm group label: Control Diet
arm group type: Active Comparator
description: High unrefined carbohydrate, low fat diet
intervention type: Other
intervention name: Lifestyle (Diet and Exercise)
description: The LG diet will comprise 20% carbohydrate, 30% protein, and 50% fat (<10% saturated fat). It will have a low glycaemic load; include plant and animal protein; non-starchy vegetables and salad greens; and some low-sugar fruit. Participants will be encouraged to incorporate a variety of foods rich in monounsaturated and polyunsaturated fats in their diet.
The control diet will comprise 50% carbohydrate, 20% protein and 30% total fat (<10% saturated fat). It will reflect the Health Promotion Board's (HPB) recommendations to reduce dietary fat, emphasize wholegrains and include a variety of fruits and vegetables. In contrast to the LG diet, the control diet will have a higher glycaemic load with a greater proportion of energy derived from unrefined carbohydrate foods.
Concurrent to the dietary intervention and consistent with physical activity guidelines, all participants will undertake a 60-min structured exercise program incorporating aerobic/ resistance exercises 3-4 days/week.
arm group label: Control Diet
arm group label: Low Glycaemic Diet (LG)
criteria: 
gender: All
minimum age: 21 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jeannie Tay, PhD
role: Principal Investigator
affiliation: Singapore Institute for Clinical Sciences
last name: Jeannie Tay, PhD
phone: (65) 66015816
email: jeannie_tay@sics.a-star.edu.sg
facility: 
status: Recruiting
contact: 
country: Singapore
responsible party type: Principal Investigator
investigator affiliation: Singapore Institute for Clinical Sciences
investigator full name: Jeannie Tay
investigator title: Senior Research Fellow
mesh term: Prediabetic State