Investigations into dysglycaemia and ethnic health disparities using mass spectrometry based plasma proteomics and targeted assay analysis

<div>Background:</div><div>Mass Spectrometry (MS) - proteomics is emerging in diabetes research. Ethnicity is an important factor in the development of dysglycaemia, with South Asians (SA) in particular at increased risk. The use of MS-proteomics to compare ethnic differences in dysglycaemia is under-researched and may aid in understanding disease aetiology.</div><div>Aims:</div><div>1. To investigate differences in the fasting proteomes of white European (WE) and SA adults with either normal glycaemic control or non-diabetic hyperglycaemia.</div><div>2. To verify and validate the identified proteins to confirm differences.</div><div>3. To quantify the role of the verified protein(s) in dysglycaemia in existing literature</div><div>4. To examine associations of the protein(s) with energy expenditure (EE) and consumption of a plant-based diet.</div><div>5. To investigate differences in the post-prandial proteomes of WE and SA adults in response to an acute physical activity intervention.</div><div>Key findings:</div><div>1. MS-proteomic analysis identified zinc-alpha-2-glycoprotein (ZAG) as being lower in SA versus WE and lower in individuals with NDH versus NGC.</div><div>2. Targeted verification/validation analyses ZAGs confirmed differences between WE and SA individuals but not glycaemic control.</div><div>3. The current literature demonstrates that circulating ZAG was lower in dysglycaemic individuals but this was attenuated after body mass index adjustment.</div><div>4. ZAG was inversely associated with exercise-related EE and adopting a plant-based diet resulted in lower ZAG.</div><div>5. Post-prandial proteome analysis identified 60 proteins that may explain mechanisms for disease-risk differences between ethnicities, in response to physical activity and ethnicity/physical activity interaction.</div><div>Conclusions:</div><div>Fasting proteomic differences were explored in WEs and SAs and differing level of dysglycaemia, highlighting ZAG as a protein of interest. Associations between ZAG and lifestyle factors relating to glycaemic control were then explored. The post-prandial proteome of WE and SA adults was also investigated to determine protein mechanisms for ethnic health disparities and responses to physical activity.</div>