Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Mar 10;5(1):e000352.
doi: 10.1136/bmjdrc-2016-000352. eCollection 2017.

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

Toh Peng Yeow  1 , Giovanni Pacini  2 , Andrea Tura  2 , Chee Peng Hor  3 , Shueh Lin Lim  4 , Florence Hui Sieng Tan  5 , Chin Voon Tong  4 , Janet Yeow Hua Hong  6 , Fuziah Md Zain  6 , Jens Juul Holst  7 , Wan Nazaimoon Wan Mohamud  8
Affiliations

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

Toh Peng Yeow et al. BMJ Open Diabetes Res Care. .

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.

Keywords: Beta Cell Function; Incretin Physiology; Type 2 Diabetes; Youth.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Plasma glucose (A), serum insulin (B), serum C peptide (C) and plasma GLP-1 level (D) during the 2-hour OGTT among subjects with normal glucose tolerance (NGT) (circles with solid line) and YT2DM (squares with dotted line). Data were presented in mean±SEM. GLP-1, glucagon-like peptide-1; OGTT, oral glucose tolerance test; YT2DM, youth onset type 2 diabetes mellitus.
Figure 2
Figure 2
OGIS (A), BC (B), DI (C) derived from OGTT parameters, and incretin effect (D) among subjects with YT2DM (bar graph with dots) and NGT (bar graph without filling pattern). Data were presented in mean±SEM. BC, β-cell function; DI, disposition index; OGIS, Oral Glucose Insulin Sensitivity Index; OGTT, oral glucose tolerance test; YT2DM, youth onset type 2 diabetes mellitus.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. D'Adamo E, Caprio S. Type 2 diabetes in youth: epidemiology and pathophysiology. Diabetes Care 2011;34(Suppl 2):S161–S65. 10.2337/dc11-s212 - DOI - PMC - PubMed
    1. Constantino MI, Molyneaux L, Limacher-Gisler F et al. . Long-term complications and mortality in young-onset diabetes: type 2 diabetes is more hazardous and lethal than type 1 diabetes. Diabetes Care 2013;36:3863–9. 10.2337/dc12-2455 - DOI - PMC - PubMed
    1. Type 2 diabetes in children and adolescents. American Diabetes Association. Diabetes Care 2000;23:381–9. 10.2337/diacare.23.3.381 - DOI - PubMed
    1. Dabelea D, Bell RA, D'Agostino RB Jr et al. . Incidence of diabetes in youth in the United States. JAMA 2007;297:2716–24. 10.1001/jama.297.24.2716 - DOI - PubMed
    1. Ehtisham S, Hattersley AT, Dunger DB et al. . First UK survey of paediatric type 2 diabetes and MODY. Arch Dis Child 2004;89:526–9. 10.1136/adc.2003.027821 - DOI - PMC - PubMed

LinkOut - more resources