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Asian Indian Prediabetes Study (AIPS)

Primary Purpose

Pre Diabetes

Status
Recruiting
Phase
Not Applicable
Locations
Singapore
Study Type
Interventional
Intervention
Lifestyle (Diet and Exercise)
Sponsored by
Singapore Institute for Clinical Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Pre Diabetes focused on measuring Asian Indians, Prediabetes, Insulin Resistance, Low glycaemic diet, Ectopic Fat

Eligibility Criteria

21 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Male or female
  • Asian Indian ethnicity
  • Age between 21-50 years
  • BMI not greater than 35 or less than 25

  • Prediabetes (based on results from an OGTT conducted in the last 3 months):

    • Impaired Fasting Glucose (IFG) which is a fasting blood glucose level of between 5.6 to 6.9 mmol/l and/or
    • Impaired Glucose Tolerance (IGT) which is a blood glucose level of 7.8 to 11.0 mmol/l, 2 hours after the OGTT but below 7.0 mmol/l in the fasting state.
  • Not have type 1 or type 2 diabetes
  • Not on any diabetes medications that affect insulin sensitivity e.g. metformin, glitazones
  • No abnormality of clinical significance on medical history
  • If female, not pregnant or breast feeding
  • No history of coronary artery disease or cardiac (heart) abnormalities
  • Participants must understand the procedures involved and agree to participate in the study by giving full informed, written consent

Exclusion Criteria:

  • BMI greater than 35 or less than 25
  • Weight gain or loss of more than 5% over the past 3 months
  • Have anaemia (low haemoglobin/ red blood cell levels), a malignancy (cancer), abnormal liver function, any significant endocrinopathy (e.g. thyroid problems), or a history of metabolic disease such as liver, kidney, cardiovascular, respiratory or gastrointestinal disease.
  • Have high uncontrolled hypertension (resting seated blood pressure >160/100 mmHg)
  • Taking medications that may affect glucose metabolism e.g. steroids, thiazide diuretics at doses>25mg/day.
  • History of smoking or using nicotine products during the 6 months prior to study
  • History of heavy alcohol consumption (> 5 standard drinks/day)
  • Inability to limit alcohol consumption for study duration
  • Lactose Intolerant or have a nut allergy
  • Have depression
  • Have a musculoskeletal injury, joint or peripheral vascular disease sufficient to impede exercise (such as hip arthritis, foot, ankle problems or pain)
  • Have severe exercise-induced asthma
  • Participating in a regular aerobic or resistance exercise program
  • Currently on a weight reducing diet or have an eating disorder
  • Contraindications for MRI e.g. if you have certain metallic implants/devices such as heart valves of a cardiac pacemaker which may be affected by the magnetic field
  • Unwilling to be randomized to either diet group
  • Extended absences due to travel or other commitments
  • Unable to comprehend or cope with study requirements

Sites / Locations

  • Singapore Institute for Clinical Sciences (SICS)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Low Glycaemic Diet (LG)

Control Diet

Arm Description

Low carbohydrate, low saturated fat diet

High unrefined carbohydrate, low fat diet

Outcomes

Primary Outcome Measures

Change in β-cell Function [First-phase β-cell response (PhiD)]
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.
Change in Insulinogenic index (ΔC-peptide/∆glucose during the first 30 minutes of the OGTT)
ΔC-peptide/∆glucose during the first 30 minutes of the OGTT will be calculated as an index of early insulin secretion (Insulinogenic index).
Change in Incremental AUC
Incremental AUC over 180 minutes of the OGTT will be calculated for glucose, insulin, and C-peptide.
Change in Insulin sensitivity (Oral Minimal model)
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
Change in Matsuda index for whole body insulin sensitivity

Secondary Outcome Measures

Change in Body fat distribution
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.
Change in Weight (kg)
Change in Blood Pressure
Change in Body Composition- Total body fat
Total body fat (kg) will be assessed using DXA
Change in Body Composition- Total lean mass
Total lean mass (kg) will be assessed using DXA
Genotyping analyses
Genomic DNA isolated from blood samples will be analysed
Change in Blood Lipids (total cholesterol, HDL-C, TAG, lipoprotein subfractions)
Change in liver enzymes
Change in inflammatory markers (e.g. IL-6, TNFα and CRP)
Change in satiety hormones (e.g. leptin, ghrelin, GIP and GLP-1).
Lipidomics
Lipidomics evaluation of several lipid classes including sphingolipids (sphingomyelins, ceramides and glycosphingolipids) in plasma
Change in Plasma phospholipid fatty acid (FA) profile
Change in Gut microbiota composition
Gut microbiota composition will be assessed by 16S or shotgun metagenomic sequencing
Change in Faecal characteristics- including short chain fatty acids (SCFAs).

Full Information

First Posted
August 6, 2020
Last Updated
May 3, 2022
Sponsor
Singapore Institute for Clinical Sciences
Collaborators
National Medical Research Foundation (NMRC) Singapore, Almond Board of California
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1. Study Identification

Unique Protocol Identification Number
NCT04507685
Brief Title
Asian Indian Prediabetes Study
Acronym
AIPS
Official Title
Diet and Lifestyle Intervention Strategies to Treat β-cell Dysfunction and Insulin Resistance in Asian Indians
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 19, 2020 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Singapore Institute for Clinical Sciences
Collaborators
National Medical Research Foundation (NMRC) Singapore, Almond Board of California

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pre Diabetes
Keywords
Asian Indians, Prediabetes, Insulin Resistance, Low glycaemic diet, Ectopic Fat

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
24-week parallel arm, randomized controlled trial (RCT)
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Low Glycaemic Diet (LG)
Arm Type
Experimental
Arm Description
Low carbohydrate, low saturated fat diet
Arm Title
Control Diet
Arm Type
Active Comparator
Arm Description
High unrefined carbohydrate, low fat diet
Intervention Type
Other
Intervention Name(s)
Lifestyle (Diet and Exercise)
Intervention 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.
Primary Outcome Measure Information:
Title
Change in β-cell Function [First-phase β-cell response (PhiD)]
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.
Time Frame
Week 0, 8 and 24
Title
Change in Insulinogenic index (ΔC-peptide/∆glucose during the first 30 minutes of the OGTT)
Description
ΔC-peptide/∆glucose during the first 30 minutes of the OGTT will be calculated as an index of early insulin secretion (Insulinogenic index).
Time Frame
Week 0, 8 and 24
Title
Change in Incremental AUC
Description
Incremental AUC over 180 minutes of the OGTT will be calculated for glucose, insulin, and C-peptide.
Time Frame
Week 0, 8 and 24
Title
Change in Insulin sensitivity (Oral Minimal model)
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
Time Frame
Week 0, 8 and 24
Title
Change in Matsuda index for whole body insulin sensitivity
Time Frame
Week 0, 8 and 24
Secondary Outcome Measure Information:
Title
Change in Body fat distribution
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.
Time Frame
Week 0, 8 and 24
Title
Change in Weight (kg)
Time Frame
Week 0, 8 and 24
Title
Change in Blood Pressure
Time Frame
Week 0, 8 and 24
Title
Change in Body Composition- Total body fat
Description
Total body fat (kg) will be assessed using DXA
Time Frame
Week 0, 8 and 24
Title
Change in Body Composition- Total lean mass
Description
Total lean mass (kg) will be assessed using DXA
Time Frame
Week 0, 8 and 24
Title
Genotyping analyses
Description
Genomic DNA isolated from blood samples will be analysed
Time Frame
Week 0
Title
Change in Blood Lipids (total cholesterol, HDL-C, TAG, lipoprotein subfractions)
Time Frame
Week 0, 8 and 24
Title
Change in liver enzymes
Time Frame
Week 0, 8 and 24
Title
Change in inflammatory markers (e.g. IL-6, TNFα and CRP)
Time Frame
Week 0, 8 and 24
Title
Change in satiety hormones (e.g. leptin, ghrelin, GIP and GLP-1).
Time Frame
Week 0, 8 and 24
Title
Lipidomics
Description
Lipidomics evaluation of several lipid classes including sphingolipids (sphingomyelins, ceramides and glycosphingolipids) in plasma
Time Frame
Week 0, 8 and 24
Title
Change in Plasma phospholipid fatty acid (FA) profile
Time Frame
Week 0, 8 and 24
Title
Change in Gut microbiota composition
Description
Gut microbiota composition will be assessed by 16S or shotgun metagenomic sequencing
Time Frame
Week 0, 8 and 24
Title
Change in Faecal characteristics- including short chain fatty acids (SCFAs).
Time Frame
Week 0, 8 and 24
Other Pre-specified Outcome Measures:
Title
Change in respiratory quotient (RQ)
Description
Respiratory quotient (RQ) to assess substrate utilization by indirect calorimetry.
Time Frame
Week 0, 8 and 24
Title
Change in blood ketone (β-hydroxybutyrate, βHB) concentrations
Description
A marker of carbohydrate intake
Time Frame
Week 0, 8 and 24
Title
Change in 24-h urinary urea to creatinine ratio
Description
A marker of protein intake
Time Frame
Week 0, 8 and 24
Title
Change in Physical activity levels
Description
Assessed with 7 consecutive days of triaxial accelerometry
Time Frame
Week 0, 8 and 24
Title
Change in Exercise Classes attendance
Time Frame
24 weeks
Title
Change in dietary intake (diet checklists)
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Male or female Asian Indian ethnicity Age between 21-50 years BMI not greater than 35 or less than 25 Prediabetes (based on results from an OGTT conducted in the last 3 months): Impaired Fasting Glucose (IFG) which is a fasting blood glucose level of between 5.6 to 6.9 mmol/l and/or Impaired Glucose Tolerance (IGT) which is a blood glucose level of 7.8 to 11.0 mmol/l, 2 hours after the OGTT but below 7.0 mmol/l in the fasting state. Not have type 1 or type 2 diabetes Not on any diabetes medications that affect insulin sensitivity e.g. metformin, glitazones No abnormality of clinical significance on medical history If female, not pregnant or breast feeding No history of coronary artery disease or cardiac (heart) abnormalities Participants must understand the procedures involved and agree to participate in the study by giving full informed, written consent Exclusion Criteria: BMI greater than 35 or less than 25 Weight gain or loss of more than 5% over the past 3 months Have anaemia (low haemoglobin/ red blood cell levels), a malignancy (cancer), abnormal liver function, any significant endocrinopathy (e.g. thyroid problems), or a history of metabolic disease such as liver, kidney, cardiovascular, respiratory or gastrointestinal disease. Have high uncontrolled hypertension (resting seated blood pressure >160/100 mmHg) Taking medications that may affect glucose metabolism e.g. steroids, thiazide diuretics at doses>25mg/day. History of smoking or using nicotine products during the 6 months prior to study History of heavy alcohol consumption (> 5 standard drinks/day) Inability to limit alcohol consumption for study duration Lactose Intolerant or have a nut allergy Have depression Have a musculoskeletal injury, joint or peripheral vascular disease sufficient to impede exercise (such as hip arthritis, foot, ankle problems or pain) Have severe exercise-induced asthma Participating in a regular aerobic or resistance exercise program Currently on a weight reducing diet or have an eating disorder Contraindications for MRI e.g. if you have certain metallic implants/devices such as heart valves of a cardiac pacemaker which may be affected by the magnetic field Unwilling to be randomized to either diet group Extended absences due to travel or other commitments Unable to comprehend or cope with study requirements
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jeannie Tay, PhD
Phone
(65) 66015816
Email
jeannie_tay@sics.a-star.edu.sg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeannie Tay, PhD
Organizational Affiliation
Singapore Institute for Clinical Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Singapore Institute for Clinical Sciences (SICS)
City
Singapore
ZIP/Postal Code
117549
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jeannie Tay, PhD
Phone
(65) 66015816
Email
jeannie_Tay@sics.a-star.edu.sg

12. IPD Sharing Statement

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Asian Indian Prediabetes Study

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