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.
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.


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-1but 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.


BACKGROUND
NMRR-12-1042-13254.
Penang Medical College, Penang, Malaysia; Department of Medicine, Penang General Hospital, Penang, Malaysia.
Toh Peng
TP
Yeow
Metabolic Unit , Institute of Neuroscience, National Research Council , Padova , Italy.
Giovanni
G
Pacini
Metabolic Unit , Institute of Neuroscience, National Research Council , Padova , Italy.
Andrea
A
Tura
Clinical Research Centre, Seberang Jaya Hospital, Penang, Malaysia; Kepala Batas Hospital, Penang, Malaysia.
Chee Peng
0000-0003-0119-6634
CP
Hor
Department of Medicine , Penang General Hospital , Penang , Malaysia.
Shueh Lin
SL
Lim
Department of Medicine , Sarawak General Hospital , Sarawak , Malaysia.
Florence Hui Sieng
FH
Tan
Department of Medicine , Penang General Hospital , Penang , Malaysia.
Chin Voon
CV
Tong
Department of Paediatrics , Hospital Putrajaya , Malaysia.
Janet Yeow Hua
JY
Hong
Department of Paediatrics , Hospital Putrajaya , Malaysia.
Fuziah
F
Md Zain
NNF Centre for Basic Metabolic Research, University of Copenhagen , Copenhagen , Denmark.
Jens Juul
JJ
Holst
Department of Cardiovascular , Diabetes and Nutrition Research Centre, Institute for Medical Research , Kuala Lumpur , Malaysia.
Wan Nazaimoon
WN
Wan Mohamud
Beta Cell Function; Incretin Physiology; Type 2 Diabetes; Youth