Study of Vitamin B ₁₂ deficiency and peripheral neuropathy in metformin-treated early Type 2 diabetes mellitus

Abstract

Background:Long-term therapy with metformin was shown to decrease the Vitamin B12 level and manifested as peripheral neuropathy.Aim:The aim of this study is to define the prevalence of Vitamin B12 deficiency in early Type 2 diabetic patients (duration ≤5 years or drug treatment ≤3 years) and the relationship among metformin exposure and levels of cobalamin (Cbl), folic acid, and homocysteine (Hcy) with severity of peripheral neuropathy.Methodology:This is a cross-sectional study involving randomly selected ninety patients (male 56, female 34) between age groups of 35 and 70 years, comparing those who had received >6 months of metformin (Group A) (n = 35) with those without metformin (Group B) (n = 35) and patients taking metformin with other oral hypoglycemic agent (Group C) (n = 20). Comparisons were made clinically, biochemically (serum Cbl, fasting Hcy, and folic acid), and with electrophysiological measures (nerve conduction studies of all four limbs). Comorbidities contributing to neuropathy were excluded from the study.Results:Group A patients (54.28%) were prone to develop peripheral neuropathy comparing Group B (28.57%) and Group C (35%). There was significantly low plasma level of Cbl in Group A (mean 306.314 pg/ml) than in Group B (mean 627.543 pg/ml) and Group C (mean 419.920 pg/ml). There was insignificant low-level plasma folic acid in Group A (16.47 ng/ml) than in Group B (16.81 ng/ml) and Group C (22.50 ng/ml). There was significantly high level of Hcy in Group A (mean 17.35 µmol/L) and Group C (mean 16.99 µmol/L) than in Group B (mean 13.22 µmol/L). Metformin users even for 2 years showed evidence of neuropathy on nerve conduction velocity though their body mass index and postprandial blood sugar were maintained. There was significant difference in between groups regarding plasma Cbl, folic acid, and Hcy level as significance level <0.05 in all three groups (F [2, 87] = 28.1, P = 0.000), (F [2, 87] = 7.43, P = 0.001), (F [2, 87] = 9.76, P = 0.000). Post hoc study shows significant (P < 0.05) lowering of Cbl and Hcy level in Group A (mean = 306.314, standard deviation [SD] = 176.7) than in Group C (mean = 419.92, SD = 208.23) and Group B (mean = 627.543, SD = 168.33).Discussion:Even short-term treatment with metformin causes a decrease in serum Cbl folic acid and increase in Hcy, which leads to peripheral neuropathy in Type 2 diabetes patients. A multicenter study with heterogeneous population would have increased the power of the study. We suggest prophylactic Vitamin B12 and folic acid supplementation or periodical assay in metformin user.

Diabetic Polyneuropathy in Type 2 Diabetes Mellitus: Inflammation, Oxidative Stress, and Mitochondrial Function

“…The prevalence of vitamin B12 deficiency was 28.1%; however, there was no association between vitamin B12 deficiency and DPN, and Metformin dose did not confer an increase risk on DPN presence [129]. Similar results were reported by other authors, with controversial results, but without strong evidence that vitamin B12 deficiency influences the presence or severity of peripheral neuropathy [130–132]. We recommend supplementation with vitamin B12 in those patients with long-term use of Metformin (≥10 years) or concomitant use of PPI/H2A, and evidence of clinical DPN.…”

Investigation of the vitamin b12 deficiency with peripheral neuropathy in the type 2 diabetes mellitus using metformin

“…Vitamin B12 deficiency may lead to neuropsychiatric and hematological abnormalities. The relationship between vitamin B12 deficiency and peripheral neuropathy has been shown in previous studies [ 6 – 7 ].…”

Metformin Use Is Not Associated With B12 Deficiency or Neuropathy in Patients With Type 2 Diabetes Mellitus in Qatar

“…Indeed, the recent 2017 ADA position statement on diabetic neuropathy has emphasized the importance of excluding B 12 deficiency in patients with diabetic neuropathy ( 13 ). However, there are conflicting reports on the association between Metformin-induced B 12 deficiency and neuropathy, with some reports showing an association ( 14 , 15 ) while others have refuted this ( 11 , 16 – 18 ). Furthermore, in a recent study from Turkey, while the prevalence of B 12 deficiency was 38.4% there was no difference in B 12 levels in those with and without neuropathy ( 19 ).…”