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

Background:

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.

Aims:

1. To investigate differences in the fasting proteomes of white European (WE) and SA adults with either normal glycaemic control or non-diabetic hyperglycaemia.

2. To verify and validate the identified proteins to confirm differences.

3. To quantify the role of the verified protein(s) in dysglycaemia in existing literature

4. To examine associations of the protein(s) with energy expenditure (EE) and consumption of a plant-based diet.

5. To investigate differences in the post-prandial proteomes of WE and SA adults in response to an acute physical activity intervention.

Key findings:

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.

2. Targeted verification/validation analyses ZAGs confirmed differences between WE and SA individuals but not glycaemic control.

3. The current literature demonstrates that circulating ZAG was lower in dysglycaemic individuals but this was attenuated after body mass index adjustment.

4. ZAG was inversely associated with exercise-related EE and adopting a plant-based diet resulted in lower ZAG.

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.

Conclusions:

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.