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Zinc-alpha2-glycoprotein, dysglycaemia and insulin resistance: a systematic review and meta-analysis

Lookup NU author(s): Katherine Bowden-Brown


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© 2020, The Author(s).To systematically review the current literature investigating associations between zinc-alpha2-glycoprotein (ZAG) and dysglycaemia (including type 2 diabetes (T2DM), poly-cystic-ovary syndrome (PCOS), pre-diabetes or insulin resistance). This included relationships between ZAG and continuous measures of insulin and glucose. Additionally, we performed a meta-analysis to estimate the extent that ZAG differs between individuals with or without dysglycaemia; whilst examining the potential influence of adiposity. A systematic search was performed on four databases for studies on circulating ZAG concentrations in adult human populations, comparing healthy controls to individuals with dysglycaemia. Key characteristics, including the mean ZAG concentrations (mg∙L−1), and any correlational statistics between ZAG and continuous measures of glucose, glycated haemoglobin (HbA1c) or insulin were extracted. Meta-analyses were performed to compare metabolically healthy controls to cases, and on studies that compared controls and cases considered overweight or obese (body mass index (BMI) ≥25 kg.m2). 1575 papers were identified and 14 studies (16 cohorts) were considered eligible for inclusion. Circulating ZAG was lower in individuals with dysglycaemia compared to metabolically healthy controls (−4.14 [−8.17, −0.11] mg.L−1; I2 = 98.5%; p < 0.001). When using data from only studies with overweight or obese groups with or without dysglycaemia (three studies (four cohorts); pooled n = 332), the difference in circulating ZAG was no longer significant (−0.30 [−3.67, 3.07] mg. L−1; I2 = 28.0%; p = 0.225). These data suggest that ZAG may be implicated in dysglycaemia, although there was significant heterogeneity across different studies and the mediating effect of adiposity cannot be excluded. Therefore, more research is needed before robust conclusions can be drawn.

Publication metadata

Author(s): Pearsey HM, Henson J, Sargeant JA, Davies MJ, Khunti K, Suzuki T, Bowden-Davies KA, Cuthbertson DJ, Yates TE

Publication type: Review

Publication status: Published

Journal: Reviews in Endocrine and Metabolic Disorders

Year: 2020

Pages: epub ahead of print

Online publication date: 07/05/2020

Acceptance date: 02/04/2016

ISSN (print): 1389-9155

ISSN (electronic): 1573-2606

Publisher: Springer


DOI: 10.1007/s11154-020-09553-w

PubMed id: 32377863


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