The relationship between exacerbated diabetic peripheral neuropathy and metformin treatment in type 2 diabetes mellitus

Manal Mohammed Hashem,Abdelfattah Kasem Nassar,Ahmed Esmael,Mohammed El-Sherif

doi:10.1038/s41598-021-81631-8

Manal Mohammed Hashem, Abdelfattah Kasem Nassar + Show 2 more

Open Access

https://doi.org/10.1038/s41598-021-81631-8

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Abstract

Metformin-treated diabetics (MTD) showed a decrease in cobalamin, a rise in homocysteine, and methylmalonic acid, leading to accentuated diabetic peripheral neuropathy (DPN). This study aimed to determine whether or not metformin is a risk factor for DPN. We compared MTD to non-metformin-treated diabetics (NMTD) clinically using the Toronto Clinical Scoring System (TCSS), laboratory (methylmalonic acid, cobalamin, and homocysteine), and electrophysiological studies. Median homocysteine and methylmalonic acid levels in MTD vs. NMTD were 15.3 vs. 9.6 µmol/l; P < 0.001 and 0.25 vs. 0.13 µmol/l; P = 0.02, respectively with high statistical significance in MTD. There was a significantly lower plasma level of cobalamin in MTD than NMTD. Spearman’s correlation showed a significant negative correlation between cobalamin and increased dose of metformin and a significant positive correlation between TCSS and increased dose of metformin. Logistic regression analysis showed that MTD had significantly longer metformin use duration, higher metformin dose > 2 g, higher TCSS, lower plasma cobalamin, and significant higher homocysteine. Diabetics treated with metformin for prolonged duration and higher doses were associated with lower cobalamin and more severe DPN.

Highlights

Metformin-treated diabetics (MTD) showed a decrease in cobalamin, a rise in homocysteine, and methylmalonic acid, leading to accentuated diabetic peripheral neuropathy (DPN)
We prospectively identified patients diagnosed with Type 2 DM (T2DM) who were treated with metformin for more than 6 months
There was no important difference between both groups regarding differences in the disease severity, the duration of diabetes, and duration of diabetic PN (P = 0.9 and 0.82 respectively (Table 1)

Summary

Introduction

Metformin-treated diabetics (MTD) showed a decrease in cobalamin, a rise in homocysteine, and methylmalonic acid, leading to accentuated diabetic peripheral neuropathy (DPN). Homocysteine is a sulfur-containing amino acid formed during the metabolism of methionine[7] It is associated with cardiac and vascular illness produced in different ways like the increase of blood coagulation, oxidative stress, endothelial impairment, and cardiomyocyte impairment[8,9,10]. Liu et al stated that the duration of diabetes, age, hemoglobin A1c, and diabetic retinopathy are associated with significantly increased risks of DPN among diabetic patients[18] It affects approximately half of patients with diabetes[19]. Our study intends to distinguish the serum level of cobalamin, methylmalonic acid and homocysteine changes in Metformin-treated diabetics (MTD) and to evaluate the connection between the severity of DPN and the long-term utilization of metformin

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