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Comparison of incretin immunoassays with or without plasma extraction: Incretin secretion in Japanese patients with type 2 diabetes.

ABSTRACT:

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Aims/Introduction: The effectiveness of incretin-based therapies in Asian type 2 diabetes requires investigation of the secretion and metabolism of glucose-dependent insulinotropic polypepide (GIP) and glucagon-like peptide 1 (GLP-1). Plasma extractions have been suggested to reduce variability in intact GLP-1 levels among individuals by removing interference that affects immunoassays, although no direct demonstration of this method has been reported. We have evaluated the effects of ethanol and solid-phase extractions on incretin immunoassays. We determined incretin levels during meal tolerance tests in Japanese patients with type 2 diabetes and characterized predictors for incretin secretion.

Materials and methods

Japanese patients with type 2 diabetes (23 anti-diabetic drug-naïve and 18 treated with sulfonylurea [SU] alone) were subjected to meal tolerance tests, and incretin levels were determined by immunoassays with or without extraction.

Results

Intact GLP-1 levels determined by an intact GLP-1 immunoassay with ethanol and solid-phase extractions were lower than those determined without extraction. Intact GLP-1 levels determined by the extractions were highly correlated with each other, much more so than the levels with and without extraction. Total GLP-1 was unaffected by extractions, showing that extractions remove interference only in the case of intact GLP-1. Incretin secretion after meal ingestion was similar between drug-naïve and SU-treated patients. Fasting and postprandial GLP-1 levels were correlated positively with fasting free fatty acids and negatively with dipeptidyl peptidase-4 activity.

Conclusions

Ethanol and solid-phase extractions remove interference for intact GLP-1 immunoassay. SU showed little effect on incretin secretion. GLP-1 and GIP secretion were predicted by different factors. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00141.x, 2012).

SUBMITTER: Yabe D

PROVIDER: S-EPMC4014935 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Incretin hormones (glucose-dependent insulinotropic polypeptide [GIP] and glucagon-like peptide-1 [GLP-1]) play a role in the pathophysiology of type 2 diabetes. Along with their derivatives they have shown therapeutic success in type 2 diabetes, with the potential for further improvements in glycaemic, cardiorenal and body weight-related outcomes. In type 2 diabetes, the incretin effect (greater insulin secretory response after oral glucose than with 'isoglycaemic' i.v. glucose, i.e. with an identical glycaemic stimulus) is markedly reduced or absent. This appears to be because of a reduced ability of GIP to stimulate insulin secretion, related either to an overall impairment of beta cell function or to specific defects in the GIP signalling pathway. It is likely that a reduced incretin effect impacts on postprandial glycaemic excursions and, thus, may play a role in the deterioration of glycaemic control. In contrast, the insulinotropic potency of GLP-1 appears to be much less impaired, such that exogenous GLP-1 can stimulate insulin secretion, suppress glucagon secretion and reduce plasma glucose concentrations in the fasting and postprandial states. This has led to the development of incretin-based glucose-lowering medications (selective GLP-1 receptor agonists or, more recently, co-agonists, e.g. that stimulate GIP and GLP-1 receptors). Tirzepatide (a GIP/GLP-1 receptor co-agonist), for example, reduces HbA1c and body weight in individuals with type 2 diabetes more effectively than selective GLP-1 receptor agonists (e.g. semaglutide). The mechanisms by which GIP receptor agonism may contribute to better glycaemic control and weight loss after long-term exposure to tirzepatide are a matter of active research and may change the pessimistic view that developed after the disappointing lack of insulinotropic activity in people with type 2 diabetes when exposed to GIP in short-term experiments. Future medications that stimulate incretin hormone and other receptors simultaneously may have the potential to further increase the ability to control plasma glucose concentrations and induce weight loss.