Inadequate Glucagon Suppression During OGTT in Prediabetes: A Systematic Review and Meta-analysis

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

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

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

Although glucagon levels decreased in both preDM and NGT groups upon glucose challenge, glucagon levels at 0 hours, 0.5 hours, 1 hour, and 1.5 hours in preDM were significantly higher compared to NGT, despite higher glucose levels at all time points and higher insulin levels at 0 hours, 1 hour, 1.5 hours, and 2 hours during OGTT. Subgroup analysis revealed that in studies using the radioimmunoassay method, glucagon levels in preDM were higher at 0.5 hours and 1 hour than NGT, while in studies using the 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 0.5 hours after glucose intake was not suppressed and was higher than NGT.

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