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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02845557
• Other study ID #: NMRR-12-1042-13254
• Status: Completed
• Phase: N/A
• First received: July 11, 2016
• Last updated: July 23, 2016
• Start date: February 2013
• Est. completion date: December 2014

Study information

• Verified date: July 2016
• Source: Penang Medical College
• Contact: n/a
• Is FDA regulated: No
• Health authority: Malaysia: Medical Research and Ethics Committee
• Study type: Observational

Clinical Trial 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.

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of diabetes clinic in Penang General Hospital in 2012, 56.7% of patients under age of 20 have clinical T2DM (data yet unpublished).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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 10 Years to 25 Years

Eligibility

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 Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Other:
• OGTT and IVGTT tests

Locations

Country	Name	City	State
Malaysia	Penang Medical College	Penang

Sponsors (8)

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

Country where clinical trial is conducted

Malaysia, 

References & Publications (23)

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D'Adamo E, Caprio S. Type 2 diabetes in youth: epidemiology and pathophysiology. Diabetes Care. 2011 May;34 Suppl 2:S161-5. doi: 10.2337/dc11-s212. Review. — View Citation

Danadian K, Balasekaran G, Lewy V, Meza MP, Robertson R, Arslanian SA. Insulin sensitivity in African-American children with and without family history of type 2 diabetes. Diabetes Care. 1999 Aug;22(8):1325-9. — View Citation

Gungor N, Bacha F, Saad R, Janosky J, Arslanian S. Youth type 2 diabetes: insulin resistance, beta-cell failure, or both? Diabetes Care. 2005 Mar;28(3):638-44. — View Citation

Hillier TA, Pedula KL. Complications in young adults with early-onset type 2 diabetes: losing the relative protection of youth. Diabetes Care. 2003 Nov;26(11):2999-3005. — View Citation

Knop FK, Aaboe K, Vilsbøll T, Vølund A, Holst JJ, Krarup T, Madsbad S. Impaired incretin effect and fasting hyperglucagonaemia characterizing type 2 diabetic subjects are early signs of dysmetabolism in obesity. Diabetes Obes Metab. 2012 Jun;14(6):500-10. — View Citation

Kobayashi K, Amemiya S, Higashida K, Ishihara T, Sawanobori E, Kobayashi K, Mochizuki M, Kikuchi N, Tokuyama K, Nakazawa S. Pathogenic factors of glucose intolerance in obese Japanese adolescents with type 2 diabetes. Metabolism. 2000 Feb;49(2):186-91. — View Citation

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McQuaid S, O'Gorman DJ, Yousif O, Yeow TP, Rahman Y, Gasparro D, Pacini G, Nolan JJ. Early-onset insulin-resistant diabetes in obese Caucasians has features of typical type 2 diabetes, but 3 decades earlier. Diabetes Care. 2005 May;28(5):1216-8. — View Citation

Musso G, Gambino R, Pacini G, De Michieli F, Cassader M. Prolonged saturated fat-induced, glucose-dependent insulinotropic polypeptide elevation is associated with adipokine imbalance and liver injury in nonalcoholic steatohepatitis: dysregulated enteroad — View Citation

Pacini G, Mari A. Methods for clinical assessment of insulin sensitivity and beta-cell function. Best Pract Res Clin Endocrinol Metab. 2003 Sep;17(3):305-22. Review. — View Citation

Pacini G, Tonolo G, Sambataro M, Maioli M, Ciccarese M, Brocco E, Avogaro A, Nosadini R. Insulin sensitivity and glucose effectiveness: minimal model analysis of regular and insulin-modified FSIGT. Am J Physiol. 1998 Apr;274(4 Pt 1):E592-9. — View Citation

Pacini G, Tura A, Winhofer Y, Kautzky-Willer A. Incretin Effect in Women with Former Gestational Diabetes within a Short Period after Delivery. Int J Endocrinol. 2012;2012:247392. doi: 10.1155/2012/247392. Epub 2012 Apr 19. — View Citation

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Wadwa RP, Urbina EM, Anderson AM, Hamman RF, Dolan LM, Rodriguez BL, Daniels SR, Dabelea D; SEARCH Study Group. Measures of arterial stiffness in youth with type 1 and type 2 diabetes: the SEARCH for diabetes in youth study. Diabetes Care. 2010 Apr;33(4):881-6. doi: 10.2337/dc09-0747. Epub 2010 Jan 12. — View Citation

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* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quantitative Insulin Sensitivity Check Index (QUICKI)	This is a cross sectional study where the outcome was measured whenever the test was conducted.	1 year	No
Primary	Oral Glucose Insulin Sensitivity Index (OGIS)	This is a cross sectional study where the outcome was measured whenever the test was conducted.	1 year	No
Primary	Early phase insulin response during OGTT was calculated for the first 30 minutes	This is a cross sectional study where the outcome was measured whenever the test was conducted.	1 year	No
Primary	Area under the curve for incretin hormone	This is a cross sectional study where the outcome was measured whenever the test was conducted.	1 year	No
Secondary	Incretin effect	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	No