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 candecrease vitamin B12 and folate concentrations.Objective: To examine (1) effects of short-term metformin treatment on serumholotranscobalamin (holoTC) and folate and (2) their association with insulin sensitivity inrecent-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 nonpharmacologicaltreatment (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, measuredduring fasting (HOMA-B, HOMA-IR) and intravenous glucose tolerance tests combined withhyperinsulinemic-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 notassociated with fasting or glucose-stimulated beta-cell function and insulin-stimulated glucosedisposal. Cobalamin measurements yielded similar results in representative subgroups. In NPTbut not MET, folate levels were inversely correlated with HOMA-IR (r =-0.239, P =.007). Folatelevels did not relate to insulin sensitivity or insulin secretion in the whole cohort and in eachgroup separately after adjustment for age, body mass index, and sex.Conclusions: Metformin does not affect circulating holoTC and folate concentrations in recentonset type 2 diabetes, rendering monitoring of vitamin B12 and folate dispensable, at least duringthe first 6 months after diagnosis or initiation of metformin.