Circulating FGF21 is lower in South Asians compared to Europids with type 2 diabetes mellitus

Endocr Connect. 2024 Dec 1:EC-24-0362. doi: 10.1530/EC-24-0362. Online ahead of print.

Abstract

Objective: Inflammation contributes to the development of type 2 diabetes mellitus (T2DM). While South Asians are more prone to develop T2DM than Europids, the inflammatory phenotype of the South Asian population remains relatively unknown. Therefore, we aimed to investigate potential differences in circulating levels of inflammation-related proteins in South Asians compared to Europids with T2DM.

Method: In this secondary analysis of three randomized controlled trials, relative plasma levels of 73 inflammation-related proteins were measured using the Olink Target Inflammation panel and serum FGF21 concentration using an ELISA kit in Dutch South Asians (n=47) and Dutch Europids (n=49) with T2DM.

Results: Of the 73 inflammation-related proteins, the relative plasma levels of 6 proteins were higher (SCF, CASP-8, CCL28, IFN-gamma, ST1A1, CST5; q-value<0.05), while relative levels of 6 proteins were lower (FGF21, MMP-1, IL8, CCL4, CXCL6, MCP-1; q-value<0.05) in South Asians compared to Europids. Of these, the effect size of FGF21 was the largest, particularly in females. We validated this finding by assessing FGF21 concentration in serum. FGF21 concentration was indeed lower in South Asians compared to Europids with T2DM in both males (-42.2%; P<0.05) and females (-58.5%; P<0.001).

Conclusion: Relative plasma levels of 12 inflammation-related proteins differed between South Asians and Europids with T2DM, with a significantly pronounced reduction in FGF21. In addition, serum FGF21 concentration was significantly lower in South Asian males and females compared to Europids. Whether low FGF21 is an underlying cause or consequence of T2DM in South Asians remains to be determined.