Betaine and B12 Intake, Glutathione Concentration, and MTHFR, PEMT, and MTHFD1 Genotypes Are Associated with Diabetes-Related Parameters in Polish Adults

• Published in: The Journal of nutrition 2025-01, Vol.155 (1), p.111-121
• Main Authors: Mlodzik-Czyzewska, Monika A, Szwengiel, Artur, Chmurzynska, Agata
• Format: Article
• Language: English
• Subjects: Adults; Betaine; Choline; Cyanocobalamin; Diabetes; Diabetes mellitus; Dihydrofolate reductase; Enzyme-linked immunosorbent assay; Fasting; Folic acid; Food intake; Genotype & phenotype; Genotypes; Genotyping; Glucose; Glutathione; High performance liquid chromatography; HOMA-IR; Insulin; Ionization; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Methylenetetrahydrofolate dehydrogenase; Methylenetetrahydrofolate reductase; MTHFR; N-Methyltransferase; Nutrition; one-carbon metabolism; Parameter sensitivity; Phosphatidylethanolamine; Phosphatidylethanolamine N-methyltransferase; Reductases; Risk factors; Trimethylamine; Vitamin B12; γ-Glutamyltransferase
• ISSN: 0022-3166; 1541-6100; 1541-6100
• DOI: 10.1016/j.tjnut.2024.10.036

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, dihydrofolate reductase (rs70991108) genotype, methylenetetrahydrofolate reductase (MTHFR) (rs180113) genotype, methylenetetrahydrofolate dehydrogenase (MTHFD1) (rs2236225) genotype, and phosphatidylethanolamine N-methyltransferase (rs7946 and rs12325817) genotype with fasting glucose level, insulin level, and diabetes-related indices. The study group consisted of 421 Polish adults aged 20–40 y. Food intake was assessed using a 3-d food diary. Plasma concentrations of choline, betaine, and TMAO were determined by ultra-high-performance liquid chromatography-electrospray ionization mass spectrometry. The total plasma GSH level was measured by high-performance liquid chromatography. Insulin, folate, and vitamin B12 concentrations were estimated by enzyme-linked immunosorbent assay method. Genotyping was performed with TaqMan probes. GSH level was negatively associated with insulin (β = −0.11, P < 0.05) and gamma-glutamyl transferase (GGTP) (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 methylenetetrahydrofolate reductase (MTHFR) CC genotype was associated with higher serum insulin levels (β = 0.15; P < 0.01) and higher HOMA-IR (β = 0.15, P < 0.01), whereas the MTHFD1 AA genotype was negatively associated with Quantitative Insulin Sensitivity Check Index (β = −0.11, P < 0.05). Our findings suggest that higher GSH level and higher intake of betaine, B12, and choline, as well as the TT genotype of MTHFR and the AA genotype of MTHFD1, are associated with lower diabetes-related parameters among adults.