Betaine and B12 intake, glutathione concentration, and MTHFR, PEMT, and MTHFD1 genotypes are associated with diabetes-related parameters in Polish adults

Monika Młodzik-Czyżewska, Artur Szwengiel, Agata Chmurzyńska

Abstract

Background: There is a growing body of evidence on associations between one-carbon metabolism (OCM) and diabetes-related parameters. For this reason, we aimed to examine the associations of plasma choline, betaine, trimethylamine N-oxide (TMAO), glutathione (GSH), serum folate, vitamin B12, DHFR (rs70991108) genotype, MTHFR (rs180113) genotype, MTHFD1 (rs2236225) genotype, PEMT (rs7946 and rs12325817) genotype with fasting glucose level insulin level, and diabetes related indices.

Methods: The study group consisted of 421 Polish adults aged 20-40 years old. Food intake was assessed using a three-day food diary. Plasma concentrations of choline, betaine, and TMAO were determined using ultra-high-performance liquid chromatography electrospray ionization mass spectrometry. Total plasma GSH level was measured using high-performance liquid chromatography. Insulin, folate and vitamin B12 concentrations were estimated using an enzyme-linked immunosorbent assay method. Genotyping was performed using TaqMan probes.

Results: GSH level was negatively associated with insulin (β = -0.11, p < 0.05) and gamma-glutamyltransferase (β = -0.12, p < 0.05), and positively associated with fasting glucose (β = 0.11, p < 0.05). Betaine intake was negatively associated with serum insulin concentration (β = -0.13, p < 0.05) and HOMA-IR (β = -0.12, p < 0.05). Choline intake was negatively associated with insulin (β = -0.17, p < 0.01). Serum folate level was negatively associated with GGTP (β = -0.11; p < 0.05). The MTHFR CC genotype was associated with higher serum insulin level (β = 0.15; p < 0.01) and higher HOMA-IR (β = 0.15, p < 0.01), while the MTHFD1 AA genotype was negatively associated with QUICKI (β = -0.11, p < 0.05).

Conclusions: Our findings suggest that higher GSHl higher intake of betaine, B12, and choline; as well as TT genotype of MTHFR and AA genotype of MTHFD1 are associated with lower diabetes-related parameters among adults.

Keywords: HOMA-IR; MTHFR; diabetes; insulin; one-carbon metabolism.

Journal of Nutrition, 0022-3166, 24, 01113-1, doi: 10.1016/j.tjnut.2024.10.036