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

J Clin Endocrinol Metab. 2020 Jun 1;105(6):dgaa150. doi: 10.1210/clinem/dgaa150.

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.

Trial registration: ClinicalTrials.gov NCT01055093.

Keywords: beta-cell function; folate; holotranscobalamin; insulin sensitivity; metformin; vitamin B12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood*
  • Blood Glucose / analysis
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / epidemiology
  • Diabetes Mellitus, Type 1 / pathology*
  • Female
  • Folic Acid / blood*
  • Folic Acid Deficiency / physiopathology*
  • Follow-Up Studies
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin Resistance
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Vitamin B 12 / blood*
  • Vitamin B 12 Deficiency / physiopathology*
  • Young Adult

Substances

  • Biomarkers
  • Blood Glucose
  • Hypoglycemic Agents
  • Metformin
  • Folic Acid
  • Vitamin B 12

Associated data

  • ClinicalTrials.gov/NCT01055093