Abstract

Context

Glucagon plays a role in the development of type 2 diabetes, yet its role in prediabetes (preDM) remains uncertain.

Objective

To evaluate glucagon levels in fasting state and its response to glucose inhibition in preDM through meta-analysis.

Methods

A systematic search across Pubmed, Embase, Web of Science, and Cochrane Library identified studies assessing glucagon levels during 75g oral glucose tolerance test (OGTT) in both preDM and normal glucose tolerance (NGT) cohorts. Data on glucagon, glucose and insulin were pooled using random-effect model.

Results

Although glucagon levels decreased in both preDM and NGT groups upon glucose challenge, glucagon levels at 0h, 0.5h, 1h and 1.5h in preDM were significantly higher compared to NGT, despite higher glucose levels at all time points and higher insulin levels at 0h, 1h, 1.5h and 2h during OGTT. Subgroup analysis revealed that in studies using the radioimmunoassay (RIA) method, glucagon levels in preDM were higher at 0.5h and 1h than NGT, while in studies using the Enzyme linked immunosorbent assay (ELISA) method, glucagon levels were similar to those of the NGT group despite higher glucose in preDM compared to NGT. Fasting glucagon level was inadequately suppressed in both impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Responsiveness to glucose inhibition was preserved in IFG, while glucagon level in IGT group at 0.5h after glucose intake was not suppressed and was higher than NGT.

Conclusion

Glucagon was not adequately suppressed during OGTT in preDM. Glucagon dysregulation is a contributing mechanism underlying both IFG and IGT.

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