Assessing Progression to Type-2 Diabetes (APT-2D): A Prospective Cohort Study Expanded From BRITE-SPOT (Bio-bank and Registry for StratIfication and Targeted intErventions in the Spectrum Of Type 2 Diabetes)

• Conditions: Diabetes; Pre-diabetes
• Interventions: Procedure: Not applicable. This is an observational study.

• Registration Number: NCT02838693
• Lead Sponsor: Medicine

Brief Summary

The Bio-bank and Registry for StratIfication and Targeted intErventions in the Spectrum Of Type 2 Diabetes (BRITE-SPOT) has been set up to prospectively collect clinical data and biologically relevant samples from individuals with, and at risk for type 2 diabetes (T2D), with the aim of delineating factors related to susceptibility, progression, complications and response to treatment. Expanded from BRITE-SPOT, Assessing the Progression to Type - 2 Diabetes (APT-2D) is a prospective cohort with a focus on non-diabetics (normoglycemic or prediabetic), to expand the sample size and depth of metabolic phenotyping in these upstream groups, with the more targeted aim of delineating factors related to insulin sensitivity versus secretion, that relate to progression to T2D.

Detailed Description

This is a prospective open cohort study.

The study will comprise the following periods:

Screening

• Complete screening checklist and informed consent form

Procedures.

* Following the screening visit, subjects are required to return to undergo the following:

* Oral Glucose Tolerance Test (OGTT) to assess glucose tolerance and beta cell function

* Frequently-Sampled Intravenous Glucose Tolerance test (FSIVGTT) to assess acute insulin response to glucose

* Euglycemic Hyperinsulinemic Clamp (EHC) to obtain the insulin sensitivity index and assess insulin action

* The Disposition index (DI) that quantifies the relationship between insulin sensitivity and insulin secretion, will be determined through the results obtained during FSIVGTT and EHC to determine subject's risk for Type 2 diabetes.

* OGTT will be repeated every 6 months to assess for conversion to Type 2 Diabetes. Plasma C-peptide, and glucose will be measured at 7 time points during the OGTT for minimal model assessment of beta cell function

* FSIVGTT and EHC will be repeated within 3 months of conversion to Type 2 Diabetes, or at 3 years from recruitment, whichever comes sooner.

Normoglycemic Subjects: 800 Pre-Diabetic Subjects: 1500

Study Timeline

• Study Start: 2016-03
• Study First Submitted: 2016-06-21
• Status Verified: 2016-07
• Study First Submitted QC: 2016-07-17
• Study First Posted: 2016-07-20
• Last Update Submitted: 2016-07-21
• Last Update Posted: 2016-07-22
• Primary Completion: 2021-09
• Study Completion: 2021-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 2300

Inclusion Criteria

1. Ability to give informed consent
2. At least 30 years old, and not older than 65 years
3. Overtly healthy males or females, as determined by medical history, physical examination and laboratory results
4. Not on any regular medications. Subjects using traditional medicine concomitantly will also be excluded in this study

Exclusion Criteria

1. History or presence of current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, malignancy or neurological disorders capable of significantly altering the performance of the biomarker panel; or of interfering with the interpretation of data

2. Known or ongoing psychiatric disorders within 3 years

3. Regularly use known drugs of abuse within 3 years

4. Women who are pregnant or lactating

5. Have donated blood of more than 500 mL within 4 weeks of study enrollment.

6. Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females) (1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits)

7. Uncontrolled hypertension (blood pressure [BP] >160/100mmHg

8. Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1

9. Treatment with any investigational drug, or biological agent within one (1) month of screening or plans to enter into an investigational drug/ biological agent study during the duration of this study

10. Known allergy to insulin

11. History of bleeding diathesis or coagulopathy

12. Any of the following laboratory values at screening:

    • LDL > 190mg/dL (>4.9mmol/L)
    • TG > 500mg/dL (>5.6mmol/L)
    • Hba1C >= 6.5%
    • Fasting glucose >=126mg/dL(>=7mmol/L) or 2 hour post-prandial glucose >=200mg/dL (>=11.1mmol/L)
    • ALT > 3.0 x upper limit of normal
    • Estimated creatinine clearance <60 mL/min

13. Have any other conditions, which, in the opinion of the Investigator would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the study

14. Significant change in weight (+/- 5%) during the past month

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
APT-2D (Normoglycemic)	Not applicable. This is an observational study.	800 Normoglycemic
APT-2D (Pre-Diabetic)	Not applicable. This is an observational study.	1,500 Pre-Diabetic

Primary Outcome Measures

Name	Time	Method
Changes in insulin sensitivity in Asian populations with normal glucose tolerance and prediabetes over 3 years. Data will be presented at the end of 5.5years.	Data for each participant will be analysed upon completion of both of the FSIVGTT and EHC visits	Disposition index assessed via glucose and insulin results from FSIVGTT and EHC.
Changes in beta-cell function in Asian populations with normal glucose tolerance and prediabetes over 3 years.	Data for each participant will be analysed upon completion all their OGTT visits	Glucose \& c-peptide laboratory results, from OGTT, will be used to assess glucose tolerance and beta cell function

Secondary Outcome Measures

Name	Time	Method
To discover and/or validate biomarkers that predict which subjects will progress from NGT to prediabetes and/or from prediabetes to diabetes. Data will be presented at the end of 5.5years.	All samples collected during the study will be consolidated at the end of 5.5years or upon study completion, whichever that comes first, and analysed in one single batch to ensure consistency of the data	Biomarker panel will be conducted through testing of plasma and serum samples.

Trial Locations

Locations (1)

National University Hospital; 🇸🇬 Singapore, Singapore