- •Postprandial glicentin and GLP-1 levels are lower in patients with diabetes.
- •Progression to diabetes shows reduction of postprandial glicentin and GLP-1.
- •Glucagon concentrations correlate with visceral fat mass and liver fat%
- •Changes in glicentin and GLP-1 levels correlate with changes in beta cell function.
- •Incretin concentrations in prediabetic state cannot predict future glycaemic traits.
We aimed to compare the concentrations of GLP-1, glucagon and GIP (established regulators of glucose homeostasis) and glicentin (emerging new metabolic marker)during an OGTT in patients with normal glucose tolerance (NGT), prediabetes and diabetes at onset, and one-year before, when all had prediabetes.
GLP-1, glucagon, GIP and glicentin concentrations were measured and compared with markers of body composition, insulin sensitivity and β-cell function at a 5-timepoint OGTT in 125 subjects (30 diabetes, 65 prediabetes, 30 NGT) and in 106 of them one-year before, when all had prediabetes.
At baseline, when all subjects were in prediabetic state, hormonal levels did not differ between groups. One year later, patients progressing to diabetes had lower postprandial increases of glicentin and GLP-1, lower postprandial decrease of glucagon, and higher levels of fasting GIP compared to patients regressing to NGT. Changes in glicentin and GLP-1 AUC within this year correlated negatively with changes in Glucose AUC of OGTT and with changes in markers of beta cell function.
Incretins, glucagon and glicentin profiles in prediabetic state cannot predict future glycemic traits, but prediabetes progressing to diabetes is accompanied by deterioration of postprandial increases of GLP-1 and glicentin.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Diabetes Research and Clinical Practice
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Pharmacotherapy of obesity: available medications and drugs under investigation.Metabolism. 2019; 92: 170-192
- Pharmacotherapy of type 2 diabetes: an update.Metabolism. 2018; 78: 13-42
- Incretin-based therapies in 2021 - current status and perspectives for the future.Metabolism. 2021; 122154843
- Cardiovascular outcomes trials with incretin-based medications: a critical review of data available on GLP-1 receptor agonists and DPP-4 inhibitors.Metabolism. 2020; 111154343
- The rollercoaster history of using physiological and pharmacological properties of incretin hormones to develop diabetes medications with a convincing benefit-risk relationship.Metabolism. 2020; 103154031
- The role of glicentin and oxyntomodulin in human metabolism: new evidence and new directions.J Clin Endocrinol Metab. 2020; 105
- Circulating levels of gastrointestinal hormones in response to the most common types of bariatric surgery and predictive value for weight loss over one year: evidence from two independent trials.Metabolism. 2019; 101153997
- Circulating levels of five proglucagon-derived peptides in response to intravenous or oral glucose or lipids and to a mixed-meal in subjects with normal weight, overweight, and obesity.Clin Nutr. 2022; 41: 1969-1976
- Methods paper: Performance characteristics of novel assays for circulating levels of proglucagon-derived peptides and validation in a placebo controlled cross-over randomized clinical trial.Metabolism. 2022; 129155157
- Targeted analysis of three hormonal systems identifies molecules associated with the presence and severity of NAFLD.J Clin Endocrinol Metab. 2020; 105
- Fasting oxyntomodulin, glicentin, and gastric inhibitory polypeptide levels are associated with activation of reward- and attention-related brain centres in response to visual food cues in adults with obesity: a cross-sectional functional MRI study.Diabetes Obes Metab. 2021; 23: 1202-1207
- Specificity and sensitivity of commercially available assays for glucagon and oxyntomodulin measurement in humans.Eur J Endocrinol. 2014; 170: 529-538
- Specificity and sensitivity of commercially available assays for glucagon-like peptide-1 (GLP-1): implications for GLP-1 measurements in clinical studies.Diab Obes Metab. 2014; 16: 1155-1164
- Different effects of lifestyle intervention in high- and low-risk prediabetes: results of the randomized controlled prediabetes lifestyle intervention study (PLIS).Diabetes. 2021; 70: 2785-2795
American Diabetes, A., 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2018. Diab Care 2018;41(Suppl 1):S13-S27.
- Secretion of glucagon-like peptide-1 in patients with type 2 diabetes mellitus: systematic review and meta-analyses of clinical studies.Diabetologia. 2013; 56: 965-972
- 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.Diabetes. 2015; 64: 2513-2525
- Inappropriate suppression of glucagon during OGTT but not during isoglycaemic i.v. glucose infusion contributes to the reduced incretin effect in type 2 diabetes mellitus.Diabetologia. 2007; 50: 797-805
- Glucagon and other proglucagon-derived peptides in the pathogenesis of obesity.Front Nutr. 2022; 9964406
- Hyperglucagonemia correlates with plasma levels of non-branched-chain amino acids in patients with liver disease independent of type 2 diabetes.Am J Physiol Gastrointest Liver Physiol. 2018; 314: G91-G96
- The glucose dependent insulinotropic polypeptide response to oral glucose and mixed meals is increased in patients with type 2 (non-insulin-dependent) diabetes mellitus.Diabetologia. 1989; 32: 668-677
- Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients.Diabetes. 2001; 50: 609-613
- The evolving story of incretins (GIP and GLP-1) in metabolic and cardiovascular disease: A pathophysiological update.Diabetes Obes Metab. 2021; 23: 5-29
- Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus.J Clin Invest. 1993; 91: 301-307
- Secretion of glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes: systematic review and meta-analysis of clinical studies.Diab Care. 2013; 36: 3346-3352
- Abundance and turnover of GLP-1 producing L-cells in ileal mucosa are not different in patients with and without type 2 diabetes.Metabolism. 2016; 65: 84-91
Published online: March 18, 2023
Accepted: March 16, 2023
Received in revised form: March 1, 2023
Received: January 26, 2023
© 2023 Elsevier B.V. All rights reserved.