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  • Preserved glucagon-like peptide-1 responses to oral glucose, but reduced incretin effect, insulin secretion and sensitivity in young Asians with type 2 diabetes mellitus

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Pathophysiology/complications
Preserved glucagon-like peptide-1 responses to oral glucose, but reduced incretin effect, insulin secretion and sensitivity in young Asians with type 2 diabetes mellitus
  1. Toh Peng Yeow1,2,
  2. Giovanni Pacini3,
  3. Andrea Tura3,
  4. Chee Peng Hor4,5,
  5. Shueh Lin Lim2,
  6. Florence Hui Sieng Tan6,
  7. Chin Voon Tong2,
  8. Janet Yeow Hua Hong7,
  9. Fuziah Md Zain7,
  10. Jens Juul Holst8,
  11. Wan Nazaimoon Wan Mohamud9
  1. 1Penang Medical College, Penang, Malaysia
  2. 2Department of Medicine, Penang General Hospital, Penang, Malaysia
  3. 3Metabolic Unit, Institute of Neuroscience, National Research Council, Padova, Italy
  4. 4Clinical Research Centre, Seberang Jaya Hospital, Penang, Malaysia
  5. 5Kepala Batas Hospital, Penang, Malaysia
  6. 6Department of Medicine, Sarawak General Hospital, Sarawak, Malaysia
  7. 7Department of Paediatrics, Hospital Putrajaya, Malaysia
  8. 8NNF Centre for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
  9. 9Department of Cardiovascular, Diabetes and Nutrition Research Centre, Institute for Medical Research, Kuala Lumpur, Malaysia
  1. Correspondence to Dr Toh Peng Yeow; tohpeng.yeow{at}pmc.edu.my

Abstract

Objective Youth onset type 2 diabetes mellitus (YT2DM) is a globally rising phenomenon with substantial Asians representation. The understanding of its pathophysiology is derived largely from studies in the obese African-American and Caucasian populations, while studies on incretin effect are scarce. We examined the insulin resistance, β-cell function (BC), glucagon-like peptide (GLP)-1 hormone and incretin effect in Asian YT2DM.

Research design and methods This case–control study recruited 25 Asian YT2DM and 15 healthy controls, matched for gender, ethnicity and body mass index. Serum glucose, insulin, C peptide and GLP-1 were sampled during 2-hour oral glucose tolerance tests (OGTTs) and 1-hour intravenous glucose tolerance tests (IVGTTs). Insulin sensitivity was derived from the Quantitative Insulin Sensitivity Check Index (QUICKI), Oral Glucose Insulin Sensitivity Index (OGIS) in OGTT and surrogate index of SI from the minimal model (calculated SI, CSI). Acute insulin response (AIR) was obtained from IVGTT. Total BC was computed as incremental area under the curve of insulin/incremental area under the curve of glucose, during OGTT (BCOG) and IVGTT (BCIV), respectively. Disposition index (DI) was calculated using the product of insulin sensitivity and insulin secretion. GLP-1 response to oral glucose was calculated as incremental area under the curve of GLP-1 (ΔAUCGLP-1). Per cent incretin effect was estimated as 100×(BCOG−BCIV)/BCOG).

Results The YT2DM had marked impairment in BC (>80% reduction in AIR and BCOG, p<0.001) and lower QUICKI (p<0.001), OGIS (p<0.001) and CSI (p=0.015) compared with controls. There was no difference in GLP-1 at all time points and ΔAUCGLP-1 but the per cent incretin effect was reduced in the YT2DM compared with controls (12.1±8.93 vs 70.0±4.03, p<0.001).

Conclusions Asian YT2DM showed similar GLP-1 response to oral glucose as controls but reduced incretin effect, BC and insulin sensitivity. The lack of compensatory mechanisms, as shown by the DI may be partly ascribed to the impaired incretin effect, similar to that of adult T2DM.

Trial registration number NMRR-12-1042-13254.

  • Youth
  • Type 2 Diabetes
  • Beta Cell Function
  • Incretin Physiology

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/bmjdrc-2016-000352

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    Footnotes

    • This study has been presented at (1) General Poster Session and Moderated Poster Discussion at the American Diabetes Association's 76th Scientific Sessions, June 10–14, 2016, in New Orleans, Louisiana, and (2) Young Investigator Award at the Diabetes Asia Conference, October 6–9, 2016 in Kuala Lumpur, Malaysia.

    • Contributors TPY conceptualized and designed the study, obtained funding and drafted the initial manuscript. GP and AT performed the modeling analyses of the OGTT, IVGTT and the incretin effect, helped in the interpretation of the results and critically reviewed and edited the manuscript. CPH maintained the database, performed statistical analyses, and critically reviewed and edited the manuscript. SLL, FHST, CVT, JYHH, FMZ collected data in each center and reviewed the manuscript. JJH and WNWM performed the laboratory measurements and reviewed and edited the manuscript. All authors approved the final version for submission. TPY is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    • Funding This work was supported by research funding from the Ministry of Health Malaysia (NMRR-12-1042-13254), the Malaysian Endocrine and Metabolic Society (MEMS) and Novartis Malaysia Sdn Bhd.

    • Competing interests None declared.

    • Ethics approval Malaysian Medical Research and Ethics Committee.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement All data are included in this manuscript. Raw data are hosted at Penang Medical College, and available for sharing on request.