Serum vitamin B12, distal symmetrical polyneuropathy and anaemia in type 2 diabetes: the Fremantle Diabetes Study Phase 2

Background: There are limited data relating to the effects of metformin-associated vitamin B12 deficiency on the risk of distal symmetrical polyneuropathy (DSPN) and megaloblastic anaemia in well-characterised community-based cohorts.Aims: To assess inter-relationships between metformin therapy, vitamin B12 defi- ciency assessed using serum active B12 concentrations, and DSPN and anaemia in 1492 Fremantle Diabetes Study Phase 2 (FDS2) participants with type 2 diabetes.Methods: Prevalence rates of vitamin B12 deficiency (total <80 pmol/L, active <23 pmol/L) and borderline deficiency (total z80 and s200 pmol/L, active z23 and s35 pmol/L) were determined using baseline sera. The relationship between vitamin B12 status and both DSPN and anaemia was assessed using multivariable analyses.Results: Most FDS2 participants (94.4%) were vitamin B12 replete (total serum con-centration >200 pmol/L, active >35 pmol/L), 2.0% were deficient (total <80 pmol/L, active <23 pmol/L) and the remainder (3.6%) borderline. Although metformin treat-ment increased the odds of deficiency (4.2%, 3.1% borderline) in a dose-dependent fashion (odds ratio (95% confidence interval) 39.4 (4.90-316) for >2000 mg daily com-pared with no treatment; P < 0.001), there was no significant association between vita-min B12 status and DSPN, anaemia (haemoglobin s130 g/L males, s120 g/L females), haemoglobin concentration or mean corpuscular volume (P z 0.147). Metformin increased the likelihood of anaemia, especially at high doses, independent of vitamin B12 deficiency.Conclusions: Since nutritional sources likely attenuate metformin-associated vitamin B12 malabsorption and its clinical sequelae in developed countries such as Australia, there is no need for routine/opportunistic serum vitamin B12 screening in metformin-treated patients.