Abstract

Background: Type 2 diabetes mellitus (T2DM) patients on metformin (the first line therapy to treat T2DM) are prone to have low serum B12 as evident from western literature. There is limited evidence from India regarding the same. Symptoms of B12 deficiency can manifest as hematological and neurological manifestations. The study was planned to understand the association of B12 deficiency, anemia and neuropathy among T2DM patients on metformin. Aim: To assess the magnitude of B12 deficiency and study it in relation to anemia and peripheral neuropathy (PN) among T2DM patients on metformin. Method: A hospital based cross sectional survey of 245 T2DM adults on metformin from a tertiary health care hospital of Delhi was conducted for PN assessment by Michigan Neuropathy Screening Instrument (MNSI). After meeting the inclusion and exclusion criteria, 155 subjects gave fasting blood samples for estimation of Vitamin B12, HbA1c,Hemoglobin and cell morphology by chemiluminescent enzyme immunoassay (C.L.I.A), HPLC and C.B.C respectively. Results: The prevalence of B12 deficiency (B12≤200pg/ml) was 52% among T2DM adults on metformin. Odds Ratio of B12 deficiency and vegetarian diet was 2.33(C.I. 1.22-4.47) (p<0.05). Anemia was present in 40% but it was not associated with B12 deficiency as there were no cases of macrocytic anemia. The prevalence of PN was 38% by PN score ≥2.5 and the mean PN scores was 2.14 ± 1.98.There was 39.2% low grade PN (PN score > 0 ≤ 2.5) followed by high grade PN (34.3%) (PN score >2.5).By Receiver Operating Curve (ROC) analysis serum B12 has shown fair test performance in predicting PN scores of 2.25 (p<0.001). Discussion: The prevalence of vitamin B12 deficiency in T2DM adults on metformin in our study is higher than that reported in other countries. The higher prevalence of B12 deficiency in our study (52 %) is not stunning owing to the higher prevalence of vitamin B12 deficiency in general population in India. The prevalence of B12 deficiency in T2DM patients in our study is more than other Indian studies on metformin. This study showed that though metformin lowers serum B12 but this had no impact on hematological parameter (hemoglobin and cell morphology) assessed in our study. Similar results have been reported by an Indian study and study from the other country. In our study the vitamin B12 deficiency was associated with PN in T2DM adults on metformin which is similar to the finding of a multi centric study from an Asian country Pakistan and several studies from other countries It can be said from our study that vitamin B12 test has fair chance of predicting PN among T2DM patients on metformin and taking a decision regarding which patients should be referred to a neurologist for electrophysiological studies. Conclusions: Metformin use was associated with biochemical B12 deficiency but not with clinical B12 deficiency as none had macrocytic anemia. Those who were B12 deficient were probable to have PN scores of 2.5 by MNSI physical assessment score. Serum B12 screening and use of MNSI for PN is recommended in T2DM patients on metformin.

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