Glucose Homeostasis and Incretin Effect T2DM in the Youth- a Study of the Malaysian Population

July 23, 2016 updated by: Toh-Peng Yeow, RCSI & UCD Malaysia Campus

Glucose Homeostasis, Incretin Effect and Cardiovascular Risk Burden in T2DM in the Youth- a Study of the Malaysian Population

Early onset type 2 diabetes mellitus among adolescents/youth (YT2DM) is a rising phenomenon. The pathophysiology has been studied primarily on non-Asian populations while literature on incretin effect is scarce. The investigators evaluated insulin sensitivity, beta-cell function, incretin hormones and their effect in YT2DM from a multiethnic Malaysian population. The characterization of this population may enable us to better tailor their antidiabetic care.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

  • The prevalence of Type 2 Diabetes Mellitus (T2DM) in the youth is increasing. Until 10 years ago in USA, T2DM accounted for less than 3% of all cases of new onset diabetes in adolescents. More recent data suggest up to 45% of cases are attributed to it.
  • The prevalence of Diabetes Mellitus in Malaysia has risen from 11.6% to 15.2% over the last 5 years according to the National Health and Morbidity Survey in 2011. Among the population age 20-24 years old, the prevalence of diabetes has risen also from 2.0% to 4.9%. Of greater concern still is 90% of these young diabetes were previously undiagnosed, thus raising the possibility that these were predominantly T2DM. The report from the Malaysian DiCare registry (2006-2007) shows that T2DM accounted for 17.6% of diabetes in adolescents. In a more recent audit of diabetes clinic in Penang General Hospital in 2012, 56.7% of patients under age of 20 have clinical T2DM (data yet unpublished). The marked difference in proportion of young T2DM in both audits may be contributed by possible under-reporting in the first audit but raise the possibility also of rising incidence of young T2DM in Malaysia.
  • This rising prevalence of T2DM in the youth has significant public health challenge. Studies in young adults have suggested that the development and progression of clinical complications might be especially rapid when the onset of T2DM is early. This, coupled with longer lifetime exposure to diabetes, raises the possibility of a serious public health challenge in the next few decades. Detailed understanding of the pathophysiology and complications burden among this population is therefore crucial to the development of appropriate management plan.
  • Studies of youth onset T2DM suggest that it is driven by a combination of insulin resistance and beta cell dysfunction, and hyperglycemia does not develop until the beta cell fails to compensate appropriately to the peripheral insulin resistance state. However, these studies are predominantly done among the western populations and mainly in the Black and Hispanic ethnic groups. There are reasons to believe that pathophysiology may be different in different populations. The ability of the beta cell to secrete sufficient insulin to adequately respond to the peripheral insulin resistance state is influenced by genetic and environmental factors. Degree of insulin resistance appears to vary among different population studies. There is currently a paucity of literature with regards to pathophysiology underpinning T2DM among the Malaysian youth.
  • The knowledge that incretin effect is severely reduced in patients with adult onset T2DM has been used to good pharmacotherapeutic effect in the patients. However, the incretin effect is less well studied among T2DM in the youth and understanding in this area will be helpful in guiding the use of incretin hormone for treatment of youth onset T2DM.

Study Type

Observational

Enrollment (Actual)

48

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Malaysia
      • Penang, Malaysia, 11450
        • Penang Medical College

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years to 25 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

30 youths with type 2 diabetes with 18 gender- and age-matched healthy controls

Description

Inclusion Criteria:

  • Youth with T2DM diagnosed at less than 25 years old
  • The diagnosis of T2DM established based on the American Diabetes Association criteria for diabetes and absence of GAD antibodies and islet cell antibodies (ICAs).

Exclusion Criteria:

  • Subjects with Type 1 Diabetes or secondary Diabetes
  • Patients on medication that may impair glucose metabolism (e.g., steroids)
  • Pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Control subjects without diabetes

(i) 2-hour 75g OGTT with sampling of glucose, insulin, C-peptide and GLP-1 hormone, with sampling at fasting (time zero) and 30, 60, 90, 120 min after the glucose load.

(ii) 1-hour IVGTT, with sampling at time 10 and 1 min, after which glucose (300 mg/kg body weight) infused in a contralateral vein within 30 s, starting at time zero. Blood further sampled for glucose, insulin and C-Peptide with sampling schedule: 3, 5, 6, 8, 10, 15, 20, 25,30 ,40 ,50 ,60 min;

(iii) computed tomography scan, (CT) for abdominal subcutaneous and visceral fat quantification.
Other: OGTT and IVGTT tests
Subjects with type 2 diabetes

(i) 2-hour 75g OGTT with sampling of glucose, insulin, C-peptide and GLP-1 hormone, with sampling at fasting (time zero) and 30, 60, 90, 120 min after the glucose load.

(ii) 1-hour IVGTT, with sampling at time 10 and 1 min, after which glucose (300 mg/kg body weight) infused in a contralateral vein within 30 s, starting at time zero. Blood further sampled for glucose, insulin and C-Peptide with sampling schedule: 3, 5, 6, 8, 10, 15, 20, 25,30 ,40 ,50 ,60 min;

(iii) computed tomography scan, (CT) for abdominal subcutaneous and visceral fat quantification.
Other: OGTT and IVGTT tests

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quantitative Insulin Sensitivity Check Index (QUICKI)
Time Frame: 1 year
This is a cross sectional study where the outcome was measured whenever the test was conducted.
1 year
Oral Glucose Insulin Sensitivity Index (OGIS)
Time Frame: 1 year
This is a cross sectional study where the outcome was measured whenever the test was conducted.
1 year
Early phase insulin response during OGTT was calculated for the first 30 minutes
Time Frame: 1 year
This is a cross sectional study where the outcome was measured whenever the test was conducted.
1 year
Area under the curve for incretin hormone
Time Frame: 1 year
This is a cross sectional study where the outcome was measured whenever the test was conducted.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incretin effect
Time Frame: 1 year
It is estimated by relating the differences in beta cell responses from C peptide between stimulation with oral and intravenous glucose. The incretin effect is estimated by the formula 100 ×(BCOG BCIV)/BCOG).
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

RCSI & UCD Malaysia Campus

Collaborators

University of Copenhagen
Sarawak General Hospital
Penang Hospital, Malaysia
Seberang Jaya Clinical Research Centre
Putrajaya Hospital, Malaysia
Institute of Neuroscience, Padova, Italy
Institute for Medical Research, Malaysia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2013

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

July 11, 2016

First Submitted That Met QC Criteria

July 23, 2016

First Posted (Estimate)

July 27, 2016

Study Record Updates

Last Update Posted (Estimate)

July 27, 2016

Last Update Submitted That Met QC Criteria

July 23, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NMRR-12-1042-13254

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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