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)

Medicine

Status: Unknown

Conditions: Diabetes; Pre-diabetes

Treatments: Procedure: Not applicable. This is an observational study.

Study type: Observational

Funder types: Other; Industry

Identifiers

NCT02838693

28431754DIA4019

Details and patient eligibility

About

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.

Full 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

Enrollment: 2,300 estimated patients

Sex: All

Ages: 30 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

2,300 participants in 2 patient groups

APT-2D (Normoglycemic)

Description:

800 Normoglycemic

Treatment:

Procedure: Not applicable. This is an observational study.

APT-2D (Pre-Diabetic)

Description:

1,500 Pre-Diabetic

Treatment:

Procedure: Not applicable. This is an observational study.