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

Abstract

ObjectiveYouth 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 methodsThis 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).ResultsThe 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).ConclusionsAsian 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 numberNMRR-12-1042-13254.

Challenges in the classification and management of Asian youth-onset diabetes mellitus- lessons learned from a single centre study

“…Further studies are needed to understand if there were subtypes of T2D with different pathophysiology necessitating different treatment approach. Asian youths with T2D have preserved glucagon-like peptide-1 response to oral glucose, but decreased incretin effect, beta-cell function and insulin sensitivity [25]. Further studies are needed to elucidate the possibility of GLP-1 resistance in youth with T2D and role of incretin-based therapy.…”

Intestinal Fructose and Glucose Metabolism in Health and Disease

“…However, it is necessary to be cautious with this upregulation of incretins in response to high-sugar diets, because it has been described that in diabetic patients, who have increased levels of incretins, a reduced incretin effect is observed, which suggest the development of an "incretin resistance" process [280][281][282][283].…”

The Pattern of Fasting and Post 75 G Glucose Loading of Glucagon-Like Peptide 1 Levels in Obese and Non-Obese Subjects

“…A study from Malaysia in subjects with young-onset T2DM and healthy control showed that Asian young-onset T2DM showed similar GLP-1 response to oral glucose as a control but reduced incretin effects, beta cell functions, and insulin sensitivity. The peak GLP-1 levels were observed at 15 minutes in both groups [13]. Study on GLP-1 levels during 75 g glucose loading in a Japanese population with normal glucose tolerance showed that GLP-1 levels increased post glucose loading from fasting state and the peaked levels was observed at 60 minutes and declined until the end of observation at 180 minutes [14].…”