Metformin and statin use associate with plasma protein N-glycosylation in people with type 2 diabetes. Issue 1 (2nd July 2020)

• Record Type: Journal Article
• Authors: Singh, Sunny S; Naber, Annemieke; Dotz, Viktoria; Schoep, Emma; Memarian, Elham; Slieker, Roderick C; Elders, Petra J M; Vreeker, Gerda; Nicolardi, Simone; Wuhrer, Manfred; Sijbrands, Eric J G; Lieverse, Aloysius G; 't Hart, Leen M; van Hoek, Mandy
• Is Part Of: BMJ open diabetes research and care. Volume 8:Issue 1(2020)
• Publication Date: 2020-07-02
• Subjects: glycosylated proteins -- glycosylation -- metformin -- lipid medication; Diabetes -- Periodicals; 616.462005
• DOI: 10.1136/bmjdrc-2020-001230
• Languages: English
• ISSNs: 2052-4897

Abstract

Abstract : Introduction: Recent studies revealed N -glycosylation signatures of type 2 diabetes, inflammation and cardiovascular risk factors. Most people with diabetes use medication to reduce cardiovascular risk. The association of these medications with the plasma N -glycome is largely unknown. We investigated the associations of metformin, statin, ACE inhibitor/angiotensin II receptor blocker (ARB), sulfonylurea (SU) derivatives and insulin use with the total plasma N -glycome in type 2 diabetes. Research design and methods: After enzymatic release from glycoproteins, N -glycans were measured by matrix-assisted laser desorption/ionization mass spectrometry in the DiaGene (n=1815) and Hoorn Diabetes Care System (n=1518) cohorts. Multiple linear regression was used to investigate associations with medication, adjusted for clinical characteristics. Results were meta-analyzed and corrected for multiple comparisons. Results: Metformin and statins were associated with decreased fucosylation and increased galactosylation and sialylation in glycans unrelated to immunoglobulin G. Bisection was increased within diantennary fucosylated non-sialylated glycans, but decreased within diantennary fucosylated sialylated glycans. Only few glycans were associated with ACE inhibitor/ARBs, while none associated with insulin and SU derivative use. Conclusions: We conclude that metformin and statins associate with a total plasma N -glycome signature in type 2 diabetes. Further studies are needed to determine the causality of these relations, and future N -glycomic research should consider medication a potential confounder.