Clinical trial NCT02845557: Glucose Homeostasis and Incretin Effect T2DM in the Youth- a Study of the Malaysian Population
Official title: Glucose Homeostasis, Incretin Effect and Cardiovascular Risk Burden in T2DM in the Youth- a Study of the Malaysian Population
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetes Mellitus, Type 2
Keywords: Youth
Type 2 Diabetes
glucose homeostasis
incretin effect
Lead sponsor: RCSI & UCD Malaysia Campus
Sponsor class: OTHER
Collaborators: name: Sarawak General Hospital
name: Putrajaya Hospital, Malaysia
name: Penang Hospital, Malaysia
name: Institute of Neuroscience, Padova, Italy
name: University of Copenhagen
name: Institute for Medical Research, Malaysia
name: Seberang Jaya Clinical Research Centre
First posted: 2016-07-27
Enrollment: 48
Sex: ALL
Minimum age (years): 10
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 30 youths with type 2 diabetes with 18 gender- and age-matched healthy controls

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Quantitative Insulin Sensitivity Check Index (QUICKI)
timeFrame: 1 year
measure: Oral Glucose Insulin Sensitivity Index (OGIS)
timeFrame: 1 year
measure: Early phase insulin response during OGTT was calculated for the first 30 minutes
timeFrame: 1 year
measure: Area under the curve for incretin hormone
timeFrame: 1 year
Secondary outcomes:
measure: Incretin effect
timeFrame: 1 year
Other outcomes:
Locations:
city: Penang
country: Malaysia
facility: Penang Medical College
Study officials:
References:
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