Contradictory results for concentrations of
vitamin B12, holotranscobalamin (holoTC), and
methylmalonic acid (MMA) have been reported. We tested the hypothesis that the extracellular
vitamin B12 markers are not reflecting the intracellular
vitamin B12-dependent biochemical reactions in individuals with
type 2 diabetes. The study included 92 patients with diabetes and 72 controls with similar age and sex distribution. We measured
vitamin B12 markers [MMA, total serum
vitamin B12, holoTC, total
homocysteine (tHcy)], red blood cell (RBC)-B12, and the plasma concentrations of the methylation markers [
S-adenosylmethionine (SAM) and
S-adenosylhomocysteine (SAH)]. In comparison to controls, diabetic patients showed significantly higher concentrations of plasma SAH (median 15.1 vs. 11.8 nmol/L; p < 0.001) and lower SAM/SAH ratio (9.1 vs. 8.2; p = 0.006). Concentrations of total
vitamin B12 and holoTC did not differ significantly between the groups, but plasma MMA concentrations were significantly higher in diabetics (250 vs. 206 nmol/L). However, RBC-B12 was lower in diabetics compared to controls (median 230 vs. 260 pmol/L; p = 0.001). The inverse correlation between MMA and RBC-B12 was stronger in the controls compared to that in the patients (correlation coefficient in controls R = -0.446, p = 0.001; in patients R = -0.289, p = 0.022).
Metformin treatment was associated with a lower total serum
vitamin B12, but a comparable RBC-B12 and a slightly lower MMA and better methylation index. In conclusion, patients with
type 2 diabetes showed normal extracellular
vitamin B12, but disturbed intracellular B12-dependent biochemical reactions.
Metformin treatment was associated with low serum
vitamin B12 and improved intracellular
vitamin B12 metabolism despite low serum
vitamin B12.