{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T17:34:34Z","timestamp":1770917674247,"version":"3.50.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Impaired secretion of glucagon-like peptide-1 (GLP-1) among Caucasians contributes to reduced incretin effect in type 2 diabetes mellitus (T2DM) patients. However, studies emanating from East Asia suggested preserved GLP-1 levels in pre-diabetes (pre-DM) and T2DM. We aimed to resolve these conflicting findings by investigating GLP-1 levels during oral glucose tolerance test (OGTT) among Malay, Chinese, and Indian ethnicities with normal glucose tolerance (NGT), pre-DM, and T2DM. The association between total GLP-1 levels, insulin resistance, and insulin sensitivity, and GLP-1 predictors were also analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 174 subjects were divided into NGT (n=58), pre-DM (n=54), and T2DM (n=62). Plasma total GLP-1 concentrations were measured at 0, 30, and 120\u00a0min during a 75-g OGTT. Homeostasis model assessment of insulin resistance (HOMA-IR), HOMA of insulin sensitivity (HOMA-IS), and triglyceride\u2013glucose index (TyG) were calculated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Total GLP-1 levels at fasting and 30\u00a0min were significantly higher in T2DM compared with pre-DM and NGT (27.18 \u00b1 11.56 pmol\/L vs. 21.99 \u00b1 10.16 pmol\/L vs. 16.24 \u00b1 7.79 pmol\/L, p=0.001; and 50.22 \u00b1 18.03 pmol\/L vs. 41.05 \u00b1 17.68 pmol\/L vs. 31.44 \u00b1 22.59 pmol\/L, p&amp;lt;0.001; respectively). Ethnicity was a significant determinant of AUC<jats:sub>GLP-1<\/jats:sub>, with the Indians exhibiting higher GLP-1 responses than Chinese and Malays. Indians were the most insulin resistant, whereas Chinese were the most insulin sensitive. The GLP-1 levels were positively correlated with HOMA-IR and TyG but negatively correlated with HOMA-IS. This relationship was evident among Indians who exhibited augmented GLP-1 responses proportionately to their high insulin-resistant states.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the first study that showed GLP-1 responses are augmented as IR states increase. Fasting and post-OGTT GLP-1 levels are raised in T2DM and pre-DM compared to that in NGT. This raises a possibility of an adaptive compensatory response that has not been reported before. Among the three ethnic groups, the Indians has the highest IR and GLP-1 levels supporting the notion of an adaptive compensatory secretion of GLP-1.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.961432","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T17:41:32Z","timestamp":1662745292000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Fasting and stimulated glucagon-like peptide-1 exhibit a compensatory adaptive response in diabetes and pre-diabetes states: A multi-ethnic comparative study"],"prefix":"10.3389","volume":"13","author":[{"given":"Shiau Chin","family":"Chong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norlela","family":"Sukor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah Anne","family":"Robert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim Fong","family":"Ng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nor Azmi","family":"Kamaruddin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"key":"B1","unstructured":"Brussels, BelgiumIdf diabetes atlas2021"},{"key":"B2","unstructured":"MalaysiaMinistry of HealthVol. II: Non-communicable diseases, risk factors & other health problems2019"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00260","article-title":"From the incretin concept and the discovery of glp-1 to today's diabetes therapy","volume":"10","author":"Holst","year":"2019","journal-title":"Front Endocrinol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1007\/s11892-015-0602-9","article-title":"\u03b2 cell dysfunction versus insulin resistance in the pathogenesis of type 2 diabetes in East asians","volume":"15","author":"Yabe","year":"2015","journal-title":"Curr Diabetes Rep"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2013.10.008","article-title":"Higher insulin and glucagon-like peptide-1 (Glp-1) levels in healthy, young south asians as compared to caucasians during an oral glucose tolerance test","volume":"63","author":"Sleddering","year":"2014","journal-title":"Metabolism"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/j.2040-1124.2010.00010.x","article-title":"Little enhancement of meal-induced glucagon-like peptide 1 secretion in Japanese: Comparison of type 2 diabetes patients and healthy controls","volume":"1","author":"Yabe","year":"2010","journal-title":"J Diabetes Investig"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.K09E-269","article-title":"Intact glucagon-like peptide-1 levels are not decreased in Japanese patients with type 2 diabetes","volume":"57","author":"Lee","year":"2010","journal-title":"Endocr J"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12167","article-title":"The incretin effect in Korean subjects with normal glucose tolerance or type 2 diabetes","volume":"80","author":"Oh","year":"2014","journal-title":"Clin Endocrinol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2010.06.004","article-title":"Incretin secretion and serum dpp-iv activity in Korean patients with type 2 diabetes","volume":"89","author":"Han","year":"2010","journal-title":"Diabetes Res Clin Pract"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2010.01350.x","article-title":"Effect of linagliptin monotherapy on glycaemic control and markers of \u03b2-cell function in patients with inadequately controlled type 2 diabetes: A randomized controlled trial","volume":"13","author":"Del Prato","year":"2011","journal-title":"Diabetes Obes Metab"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2337\/dc20-S002","article-title":"Standards of medical care in diabetes\u20132020","volume":"43","year":"2019","journal-title":"Diabetes Care"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2018.09.010","article-title":"Triglycerides and glucose index as an insulin resistance marker in a sample of healthy adults","volume":"13","author":"Toro-Huamanchumo","year":"2019","journal-title":"Diabetes Metab Syndr"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031374","article-title":"Quantitative insulin sensitivity check index and the reciprocal index of homeostasis model assessment are useful indexes of insulin resistance in type 2 diabetic patients with wide range of fasting plasma glucose","volume":"89","author":"Yokoyama","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"B15","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1093\/clinchem\/18.6.499","article-title":"Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge","volume":"18","author":"Friedewald","year":"1972","journal-title":"Clin Chem"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12352","article-title":"Specificity and sensitivity of commercially available assays for glucagon-like peptide-1 (Glp-1): Implications for GLP-1 measurements in clinical studies","volume":"16","author":"Bak","year":"2014","journal-title":"Diabetes Obes Metab"},{"key":"B17","article-title":"Multi species GLP-1 total ELISA","volume-title":"EZGLP1T-36k","year":""},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-010-1896-4","article-title":"Secretion of glucagon-like peptide-1 (Glp-1) in type 2 diabetes: What is up, what is down","volume":"54","author":"Nauck","year":"2011","journal-title":"Diabetologia"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/7583506","article-title":"Glucagon-like peptide 1: A predictor of type 2 diabetes","volume":"2017","author":"Larsen","year":"2017","journal-title":"J Diabetes Res"},{"key":"B20","doi-asserted-by":"publisher","first-page":"48","DOI":"10.15537\/smj.2016.1.12035","article-title":"Impaired secretion of glucagon-like peptide 1 during oral glucose tolerance test in patients with newly diagnosed type 2 diabetes mellitus","volume":"37","author":"Wang","year":"2016","journal-title":"Saudi Med J"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.4128","article-title":"Impaired secretion of total glucagon-like peptide-1 in people with impaired fasting glucose combined impaired glucose tolerance","volume":"9","author":"Zhang","year":"2012","journal-title":"Int J Med Sci"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.8.7750","article-title":"Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients","volume":"86","author":"Toft-Nielsen","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.3.609","article-title":"Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients","volume":"50","author":"Vilsb\u00f8ll","year":"2001","journal-title":"Diabetes"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.2337\/db14-1751","article-title":"Glp-1 response to oral glucose is reduced in prediabetes, screen-detected type 2 diabetes, and obesity and influenced by sex: The addition-pro study","volume":"64","author":"F\u00e6rch","year":"2015","journal-title":"Diabetes"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0191114","article-title":"Incretin responses to oral glucose and mixed meal tests and changes in fasting glucose levels during 7 years of follow-up: The hoorn meal study","volume":"13","author":"Koopman","year":"2018","journal-title":"PloS One"},{"key":"B26","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1111\/jdi.12305","article-title":"Incretin physiology and pathophysiology from an Asian perspective","volume":"6","author":"Cho","year":"2015","journal-title":"J Diabetes Investig"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2010.01.134","article-title":"Similar incretin secretion in obese and non-obese Japanese subjects with type 2 diabetes","volume":"393","author":"Kozawa","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-013-2841-0","article-title":"Secretion of glucagon-like peptide-1 in patients with type 2 diabetes mellitus: Systematic review and meta-analyses of clinical studies","volume":"56","author":"Calanna","year":"2013","journal-title":"Diabetologia"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.4103\/2230-8210.146861","article-title":"Incretin response in Asian type 2 diabetes: Are indians different","volume":"19","author":"Singh","year":"2015","journal-title":"Indian J Endocrinol Metab"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00326.2004","article-title":"Human duodenal enteroendocrine cells: Source of both incretin peptides, glp-1 and gip","volume":"290","author":"Theodorakis","year":"2006","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-13-0487","article-title":"Preserved glp-1 and exaggerated gip secretion in type 2 diabetes and relationships with triglycerides and alt","volume":"169","author":"Alssema","year":"2013","journal-title":"Eur J Endocrinol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.diabet.2013.03.001","article-title":"Incretin dysfunction in type 2 diabetes: Clinical impact and future perspectives","volume":"39","author":"Ahren","year":"2013","journal-title":"Diabetes Metab"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0140618","article-title":"Serum levels of soluble Cd26\/Dipeptidyl peptidase-iv in type 2 diabetes mellitus and its association with metabolic syndrome and therapy with antidiabetic agents in Malaysian subjects","volume":"10","author":"Ahmed","year":"2015","journal-title":"PloS One"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/651757","article-title":"Multiple factors related to the secretion of glucagon-like peptide-1","volume":"2015","author":"Wang","year":"2015","journal-title":"Int J Endocrinol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1124","article-title":"Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance","volume":"57","author":"Vollmer","year":"2008","journal-title":"Diabetes"},{"key":"B36","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1136\/bmjdrc-2016-000352","article-title":"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","volume":"5","author":"Yeow","year":"2017","journal-title":"BMJ Open Diabetes Res Care"},{"key":"B37","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s12933-021-01274-x","article-title":"Stronger association of triglyceride glucose index than the homa-ir with arterial stiffness in patients with type 2 diabetes: A real-world single-centre study","volume":"20","author":"Wang","year":"2021","journal-title":"Cardiovas Diabetol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1016\/j.atherosclerosis.2006.12.018","article-title":"Ethnic differences in the ability of triglyceride levels to identify insulin resistance","volume":"196","author":"Sumner","year":"2008","journal-title":"Atherosclerosis"},{"key":"B39","doi-asserted-by":"publisher","first-page":"796","DOI":"10.2337\/dc13-0598","article-title":"Body composition is the main determinant for the difference in type 2 diabetes pathophysiology between Japanese and caucasians","volume":"37","author":"M\u00f8ller","year":"2014","journal-title":"Diabetes Care"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e173","DOI":"10.1038\/nutd.2015.24","article-title":"Ethnic differences in insulin sensitivity and beta-cell function among Asian men","volume":"5","author":"Tan","year":"2015","journal-title":"Nutr Diabetes"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-0592","article-title":"Impact of glucose tolerance status, sex, and body size on glucose absorption patterns during ogtts","volume":"36","author":"F\u00e6rch","year":"2013","journal-title":"Diabetes Care"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067578","article-title":"Glucagon-like peptide-1 secretory function as an independent determinant of blood pressure: Analysis in the tanno-sobetsu study","volume":"8","author":"Yoshihara","year":"2013","journal-title":"PloS One"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.114.04718","article-title":"Glucagon-like peptide-1 and blood pressure in young and healthy adults from the general population","volume":"65","author":"Krisai","year":"2015","journal-title":"Hypertension"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.ypmed.2017.05.025","article-title":"Healthy lifestyle and glucagon-like peptide-1 in young and healthy adults: A population-based study","volume":"101","author":"Krisai","year":"2017","journal-title":"Prev Med"},{"key":"B45","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1007\/s11906-015-0621-6","article-title":"Glp-1 agonists and blood pressure: A review of the evidence","volume":"18","author":"Goud","year":"2016","journal-title":"Curr Hypertens. Rep"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2004.02172.x","article-title":"Impaired circulating glucagon-like peptide-1 response to oral glucose in women with previous gestational diabetes","volume":"62","author":"Forbes","year":"2005","journal-title":"Clin Endocrinol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1046\/j.1365-2265.2003.01675.x","article-title":"Comparisons of leptin, incretins and body composition in obese and lean patients with hypopituitarism and healthy individuals","volume":"58","author":"Mersebach","year":"2003","journal-title":"Clin Endocrinol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c180013","article-title":"Physiology of the incretin hormones, gip and glp-1-Regulation of release and posttranslational modifications","volume":"9","author":"Holst","year":"2019","journal-title":"Compr Physiol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.961432\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T17:41:37Z","timestamp":1662745297000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.961432\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,9]]},"references-count":48,"alternative-id":["10.3389\/fendo.2022.961432"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.961432","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,9]]},"article-number":"961432"}}