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

Abstract

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.

Western Diet Induced Remodelling of the Tongue Proteome

“…This possibility warrants further investigation. While high expression of AZGP1 in Western diet mice agrees with its known functions in lipid degradation processes and impaired insulin sensitivity in obesity [59,60], AZGP1 was also suggested to be involved in bitter taste perception by Gene Ontology analyses. While the administered Western diet in this study was devoid of any bitterants, it is likely that the long-term consumption of a diet with saturated fat and sweet levels may reduce the sweet tasting cells with no change in the bitter sensing Type II taste receptors [36].…”

Dysglycaemia and South Asian ethnicity: a proteomic discovery and confirmation analysis highlights differences in ZAG

“…The equivocal findings for an association between ZAG and glycaemic control is consistent with the limited evidence available to date. Our own recent systematic review and meta-analysis of 14 studies found that ZAG is lower in individuals with dysglycaemia (NDH, T2DM, metabolic syndrome or poly-cystic ovary syndrome); however, there was a high level of heterogeneity and differences in ZAG disappeared when accounting for differences in BMI (Pearsey et al 2020a). Outside of circulating ZAG, ZAG mRNA has been positively associated with glucose transporter (GLUT)-4 mRNA expression in adipose tissue (Balaz et al 2014) and evidence suggests that ZAG may act on other tissues, in particular human skeletal muscle cells, to aid improved glucose utilization through increased GLUT-4 expression (Russell and Tisdale 2010).…”

Zinc status, insulin resistance and glycoxidative stress in elderly subjects with type 2 diabetes mellitus

“…Understanding the complex role of Zn in glucose homeostasis and subsequent IR and T2DM is at present limited by controversial findings in the literature and the absence of 'gold standard' animal models that could help elucidate the role of Zn and Zn transporters (35). It is acknowledged that, at the pancreatic level, Zn participates in mechanisms involving insulin secretion and action, as a catalytic cofactor for carboxypeptidase H, an enzyme which catalyzes the conversion from proinsulin into insulin.…”