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.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Diabetic Neuropathies/drug therapy , Metformin/administration & dosage , Peripheral Nervous System Diseases/drug therapy , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/pathology , Diabetic Neuropathies/blood , Diabetic Neuropathies/complications , Diabetic Neuropathies/pathology , Female , Homocysteine/blood , Humans , Male , Metformin/adverse effects , Methylmalonic Acid/metabolism , Middle Aged , Peripheral Nervous System Diseases/blood , Peripheral Nervous System Diseases/complications , Peripheral Nervous System Diseases/pathology , Risk Factors , Vitamin B 12/bloodABSTRACT
BACKGROUND: We investigated SIRT-1 genetic variant and its association with vitamin D level in Egyptian patients with rheumatoid arthritis (RA). METHODS: Seventy Egyptian subjects were enrolled in our study and divided into two groups: RA group (n = 50 patients) and healthy control group (n = 20 subjects). Five milliliter blood sample was withdrawn from each subject followed by laboratory investigation and DNA extraction for SIRT-1 gene polymorphism assessment (rs7895833 A>G, rs7069102 C>G and rs2273773 C>T) and vitamin D level expression. RESULTS: There was statistically significant difference between rheumatoid cases and controls with regard to vitamin D level with 88% of cases showing insufficient vitamin D versus all controls showing sufficient level. SIRT-1 different SNPs rs2273773, rs7895833and rs7069102 genotype frequencies were statistically significant in RA compared to control group (P = 0.001). There was no statistically significant difference between different genotypes of rs2273773, rs7895833 and rs7069102 with regard to vitamin D level. CONCLUSION: We concluded that there is a strong association between SIRT-1 polymorphism genotyping and RA. Vitamin D level was insufficient in Egyptian patients with RA.
