Vitamin B12 and Folate Concentrations in Recent-onset Type 2 Diabetes and the Effect of Metformin Treatment

Abstract

Context Vitamin B12 and folate deficiency are not only linked to hematological, neurological, and cardiovascular diseases, but are also associated with insulin resistance. Metformin can decrease vitamin B12 and folate concentrations. Objective To examine (1) effects of short-term metformin treatment on serum holotranscobalamin (holoTC) and folate and (2) their association with insulin sensitivity in recent-onset type 2 diabetes. Design This cross-sectional analysis comprised patients (known disease duration <12 months) on metformin monotherapy (MET, n = 123, 81 males, 53 ± 12 years) or nonpharmacological treatment (NPT, n = 126, 77 males, 54 ± 11 years) of the German Diabetes Study. Main Outcome Measures HoloTC (enzyme-linked immunosorbent assay), cobalamin, and folate (electrochemiluminescence); beta-cell function and whole-body insulin sensitivity, measured during fasting (HOMA-B, HOMA-IR) and intravenous glucose tolerance tests combined with hyperinsulinemic–euglycemic clamp tests. Results HoloTC (105.4 [82.4, 128.3] vs 97 [79.7, 121.9] pmol/L) and folate concentrations (13.4 [9.3, 19.3] vs 12.7 [9.3, 22.0] nmol/L) were similar in both groups. Overall, holoTC was not associated with fasting or glucose-stimulated beta-cell function and insulin-stimulated glucose disposal. Cobalamin measurements yielded similar results in representative subgroups. In NPT but not MET, folate levels were inversely correlated with HOMA-IR (r = –0.239, P = .007). Folate levels did not relate to insulin sensitivity or insulin secretion in the whole cohort and in each group separately after adjustment for age, body mass index, and sex. Conclusions Metformin does not affect circulating holoTC and folate concentrations in recent-onset type 2 diabetes, rendering monitoring of vitamin B12 and folate dispensable, at least during the first 6 months after diagnosis or initiation of metformin.

Associations of Plasma Folate and Vitamin B6 With Blood DNA Methylation Age: An Analysis of One-Carbon Metabolites in the VA Normative Aging Study

“…As previously noted, we observe significant negative age associations with vitamin B 6 , but none with vitamin B 12 . Given that folate is almost always nontoxic to humans, folate deficiency has been the frequent culprit in disease processes including those that are age-related like diabetes and cataracts (40,41). Our observed positive association of folate with GrimAge and PhenoAge seems contrary to this relationship, but the literature contains similar paradoxical folate relationships with other aging markers like mitochondrial DNA copy number and telomere length (42,43).…”

Associations of Homocysteine with B Vitamins and Zinc in Serum Levels of Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study

“…On the other hand, metformin therapy has been reported to decrease serum levels of vitamin B12, and long-term use of metformin is associated with vitamin B12 deficiency. However, metformin does not affect circulating concentrations of vitamin B12 and folic acid at least during the first 6 mo after initiating (30,31). In our study, over half of total subjects were metformin users, but the average of serum vitamin B12 concentrations was within normal ranges.…”

Does Metformin Treatment in Pediatric Population Cause Vitamin B12 Deficiency?

“…Of these, 15 (62.5 %) were female and 9 (37.5 %) were male. The mean age of patients was 13.7 ± 2.3 (10)(11)(12)(13)(14)(15)(16)(17)(18)(19) years. Sixteen patients were diagnosed with metabolic syndrome, and 8 patients suffered from type-2 DM.…”

“…The study, including 700 adult patients, found that holo-TC-II was the best marker of vitamin B12 deficiency 28 . A cross-sectional analysis reported by Kanti et al includes a large study population with diabetes mellitus (123 patients treated with metformin for at least 6 months; and 126 patients with nonpharmacological treatment) which showed that holo-TC-II and cobalamin levels were similar in both groups 18 . However, another study observed no decrease in holo-TC-II levels, while a significant decrease was detected in vitamin B12 levels in patients diagnosed with PCOS 14 .…”