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

NCT02845557 | Completed

• 1 other identifier: NMRR-12-1042-13254
• Study Type: observational
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 2

Keywords

Youth; Type 2 Diabetes; glucose homeostasis; incretin effect

Outcome Measures

Primary Outcomes (4)

• Quantitative Insulin Sensitivity Check Index (QUICKI)

  This is a cross sectional study where the outcome was measured whenever the test was conducted.

  1 year

• Oral Glucose Insulin Sensitivity Index (OGIS)

  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

  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

  This is a cross sectional study where the outcome was measured whenever the test was conducted.

  1 year

Secondary Outcomes (1)

• Incretin effect

  1 year

Study Arms (2)

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

Interventions

OGTT and IVGTT tests OTHER

Control subjects without diabetes; Subjects with type 2 diabetes

Eligibility Criteria

• Age: 10 Years - 25 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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).

You may not qualify if:

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

Sponsors & Collaborators

• RCSI & UCD Malaysia Campus: lead
• Sarawak General Hospital: collaborator
• Putrajaya Hospital, Malaysia: collaborator
• Penang Hospital, Malaysia: collaborator
• Institute of Neuroscience, Padova, Italy: collaborator
• University of Copenhagen: collaborator
• Institute for Medical Research, Malaysia: collaborator
• Seberang Jaya Clinical Research Centre: collaborator

Study Sites (1)

Penang Medical College

George Town, 11450, Malaysia

Location

Related Publications (23)

• 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.

  PMID: 20067960 BACKGROUND

• Malloy J, Capparelli E, Gottschalk M, Guan X, Kothare P, Fineman M. Pharmacology and tolerability of a single dose of exenatide in adolescent patients with type 2 diabetes mellitus being treated with metformin: a randomized, placebo-controlled, single-blind, dose-escalation, crossover study. Clin Ther. 2009 Apr;31(4):806-15. doi: 10.1016/j.clinthera.2009.04.005.

  PMID: 19446153 BACKGROUND

• Rosenbloom AL, Silverstein JH, Amemiya S, Zeitler P, Klingensmith GJ. Type 2 diabetes in children and adolescents. Pediatr Diabetes. 2009 Sep;10 Suppl 12:17-32. doi: 10.1111/j.1399-5448.2009.00584.x. No abstract available.

  PMID: 19754615 RESULT

• D'Adamo E, Caprio S. Type 2 diabetes in youth: epidemiology and pathophysiology. Diabetes Care. 2011 May;34 Suppl 2(Suppl 2):S161-5. doi: 10.2337/dc11-s212. No abstract available.

  PMID: 21525449 RESULT

• Pinhas-Hamiel O, Zeitler P. Acute and chronic complications of type 2 diabetes mellitus in children and adolescents. Lancet. 2007 May 26;369(9575):1823-1831. doi: 10.1016/S0140-6736(07)60821-6.

  PMID: 17531891 RESULT

• Maahs DM, Snively BM, Bell RA, Dolan L, Hirsch I, Imperatore G, Linder B, Marcovina SM, Mayer-Davis EJ, Pettitt DJ, Rodriguez BL, Dabelea D. Higher prevalence of elevated albumin excretion in youth with type 2 than type 1 diabetes: the SEARCH for Diabetes in Youth study. Diabetes Care. 2007 Oct;30(10):2593-8. doi: 10.2337/dc07-0450. Epub 2007 Jul 13.

  PMID: 17630264 RESULT

• 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. doi: 10.2337/diacare.26.11.2999.

  PMID: 14578230 RESULT

• 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. doi: 10.2337/diacare.28.3.638.

  PMID: 15735201 RESULT

• Umpaichitra V, Bastian W, Taha D, Banerji MA, AvRuskin TW, Castells S. C-peptide and glucagon profiles in minority children with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2001 Apr;86(4):1605-9. doi: 10.1210/jcem.86.4.7415.

  PMID: 11297591 RESULT

• 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. doi: 10.1016/s0026-0495(00)91221-6.

  PMID: 10690942 RESULT

• 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 enteroadipocyte axis as a novel feature of fatty liver. Am J Clin Nutr. 2009 Feb;89(2):558-67. doi: 10.3945/ajcn.2008.26720. Epub 2009 Jan 13.

  PMID: 19141695 RESULT

• 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.

  PMID: 22577378 RESULT

• 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. doi: 10.2337/diacare.22.8.1325.

  PMID: 10480778 RESULT

• Kvist H, Chowdhury B, Grangard U, Tylen U, Sjostrom L. Total and visceral adipose-tissue volumes derived from measurements with computed tomography in adult men and women: predictive equations. Am J Clin Nutr. 1988 Dec;48(6):1351-61. doi: 10.1093/ajcn/48.6.1351.

  PMID: 3202084 RESULT

• 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. doi: 10.2337/diacare.28.5.1216. No abstract available.

  PMID: 15855595 RESULT

• 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):E592-9. doi: 10.1152/ajpendo.1998.274.4.E592.

  PMID: 9575818 RESULT

• Ahren B, Pacini G. Importance of quantifying insulin secretion in relation to insulin sensitivity to accurately assess beta cell function in clinical studies. Eur J Endocrinol. 2004 Feb;150(2):97-104. doi: 10.1530/eje.0.1500097.

  PMID: 14763905 RESULT

• Knop FK, Aaboe K, Vilsboll T, Volund 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. doi: 10.1111/j.1463-1326.2011.01549.x. Epub 2012 Jan 17.

  PMID: 22171657 RESULT

• 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. doi: 10.1016/s1521-690x(03)00042-3.

  PMID: 12962688 RESULT

• Bloomgarden ZT. Type 2 diabetes in the young: the evolving epidemic. Diabetes Care. 2004 Apr;27(4):998-1010. doi: 10.2337/diacare.27.4.998. No abstract available.

  PMID: 15047665 RESULT

• Svec F, Nastasi K, Hilton C, Bao W, Srinivasan SR, Berenson GS. Black-white contrasts in insulin levels during pubertal development. The Bogalusa Heart Study. Diabetes. 1992 Mar;41(3):313-7. doi: 10.2337/diab.41.3.313.

  PMID: 1551490 RESULT

• Yokoyama H, Okudaira M, Otani T, Takaike H, Miura J, Saeki A, Uchigata Y, Omori Y. Existence of early-onset NIDDM Japanese demonstrating severe diabetic complications. Diabetes Care. 1997 May;20(5):844-7. doi: 10.2337/diacare.20.5.844.

  PMID: 9135953 RESULT

• TODAY Study Group; Zeitler P, Hirst K, Pyle L, Linder B, Copeland K, Arslanian S, Cuttler L, Nathan DM, Tollefsen S, Wilfley D, Kaufman F. A clinical trial to maintain glycemic control in youth with type 2 diabetes. N Engl J Med. 2012 Jun 14;366(24):2247-56. doi: 10.1056/NEJMoa1109333. Epub 2012 Apr 29.

  PMID: 22540912 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Glucose Tolerance Test

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor Dr.

Study Record Dates

• First Submitted: July 11, 2016
• First Posted: July 27, 2016
• Study Start: February 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: July 27, 2016

Record last verified: 2016-07

Locations

MY (1)