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)

Study Overview
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Brief Summary
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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
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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

Official Title
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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
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Pre-diabetes, Diabetes

Intervention / Treatment
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* Procedure: Not applicable. This is an observational study.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to give informed consent At least 30 years old, and not older than 65 years Overtly healthy males or females, as determined by medical history, physical examination and laboratory results Not on any regular medications. Subjects using traditional medicine concomitantly will also be excluded in this study Exclusion Criteria: 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 Known or ongoing psychiatric disorders within 3 years Regularly use known drugs of abuse within 3 years Women who are pregnant or lactating Have donated blood of more than 500 mL within 4 weeks of study enrollment. 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) Uncontrolled hypertension (blood pressure [BP] >160/100mmHg Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1 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 Known allergy to insulin History of bleeding diathesis or coagulopathy 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 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 Significant change in weight (+/- 5%) during the past month

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| APT-2D (Normoglycemic)<br>800 Normoglycemic | Procedure: Not applicable. This is an observational study.<br>* Not applicable. This is an observational study.<br>|
| APT-2D (Pre-Diabetic)<br>1,500 Pre-Diabetic | Procedure: Not applicable. This is an observational study.<br>* Not applicable. This is an observational study.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Biomarker panel will be conducted through testing of plasma and serum samples. | 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 |