Diabetic neuropathy is not associated with homocysteine, folate, vitamin B12 levels, and MTHFR C677T mutation in type 2 diabetic outpatients taking metformin

Russo, Giuseppina T.; Giandalia, Annalisa; Romeo, Elisabetta L.; Scarcella, C.; Gambadoro, N.; Zingale, Rosalia; Forte, F.; Perdichizzi, Giuseppa; Alibrandi, Angela; Cucinotta, Domenico

doi:10.1007/s40618-015-0365-9

Cited by 44 publications

(46 citation statements)

References 39 publications

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“…Among these factors, current therapies, peripheral neuropathy, reduced vision (caused by peripheral retinopathy and cataracts), hypoglycaemia, decreased muscle performance, diabetic foot, orthostatic hypotension, polyuria and nocturia, causing falls especially at night, reduction of reflexes, stroke, and cognitive impairment may all play an important role [19, 20]. Moreover, diabetes is associated with a delay in the wound healing [21], altered biochemical properties, and a reduction of cell proliferation and of collagen content in bone callus [22].…”

Section: Potential Pathophysiological Basis Of the Increased Fractmentioning

confidence: 99%

Fracture Risk in Type 2 Diabetes: Current Perspectives and Gender Differences

Russo

Giandalia

Romeo

et al. 2016

International Journal of Endocrinology

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Type 2 diabetes mellitus (T2DM) is associated with an increased risk of osteoporotic fractures, resulting in disabilities and increased mortality. The pathophysiological mechanisms linking diabetes to osteoporosis have not been fully explained, but alterations in bone structure and quality are well described in diabetic subjects, likely due to a combination of different factors. Insulin deficiency and dysfunction, obesity and hyperinsulinemia, altered level of oestrogen, leptin, and adiponectin as well as diabetes-related complications, especially peripheral neuropathy, orthostatic hypotension, or reduced vision due to retinopathy may all be associated with an impairment in bone metabolism and with the increased risk of fractures. Finally, medications commonly used in the treatment of T2DM may have an impact on bone metabolism and on fracture risk, particularly in postmenopausal women. When considering the impact of hypoglycaemic drugs on bone, it is important to balance their potential direct effects on bone quality with the risk of falling-related fractures due to the associated hypoglycaemic risk. In this review, experimental and clinical evidence connecting bone metabolism and fracture risk to T2DM is discussed, with particular emphasis on hypoglycaemic treatments and gender-specific implications.

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Section: Potential Pathophysiological Basis Of the Increased Fractmentioning

confidence: 99%

Fracture Risk in Type 2 Diabetes: Current Perspectives and Gender Differences

Russo

Giandalia

Romeo

et al. 2016

International Journal of Endocrinology

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“…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.…”

Section: Diabetic Polyneuropathymentioning

confidence: 55%

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

Román-Pintos

Villegas-Rivera

Rodríguez-Carrizález

et al. 2016

Journal of Diabetes Research

186

152

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Diabetic polyneuropathy (DPN) is defined as peripheral nerve dysfunction. There are three main alterations involved in the pathologic changes of DPN: inflammation, oxidative stress, and mitochondrial dysfunction. Inflammation induces activation of nuclear factor kappa B, activator protein 1, and mitogen-activated protein kinases. Oxidative stress induced by hyperglycemia is mediated by several identified pathways: polyol, hexosamine, protein kinase C, advanced glycosylation end-products, and glycolysis. In addition, mitochondrial dysfunction accounts for most of the production of reactive oxygen and nitrosative species. These free radicals cause lipid peroxidation, protein modification, and nucleic acid damage, to finally induce axonal degeneration and segmental demyelination. The prevalence of DPN ranges from 2.4% to 78.8% worldwide, depending on the diagnostic method and the population assessed (hospital-based or outpatients). Risk factors include age, male gender, duration of diabetes, uncontrolled glycaemia, height, overweight and obesity, and insulin treatment. Several diagnostic methods have been developed, and composite scores combined with nerve conduction studies are the most reliable to identify early DPN. Treatment should be directed to improve etiologic factors besides reducing symptoms; several approaches have been evaluated to reduce neuropathic impairments and improve nerve conduction, such as oral antidiabetics, statins, and antioxidants (alpha-lipoic acid, ubiquinone, and flavonoids).

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“…A possible reason for this finding may be due to the direct neuroprotective effect of metformin through its glucose-lowering effect and antihyperglycemic-independent, direct anti-neuropathic impact on neurons including inhibition of oxidative stressrelated apoptotic cell death [36,37]. Studies by Ahmed et al in South Africa and Russo et al in Italy [38,39] also found no significant difference in the presence of neuropathy between subjects with normal vitamin B 12 levels and those with vitamin B 12 deficiency. Additionally, though classical B 12 deficiency is associated with clinical symptoms such as anemia and peripheral neuropathy, these symptoms are usually absent in those with only biochemical vitamin B 12 deficiency [33].…”

Section: Discussionmentioning

confidence: 97%

Vitamin B₁₂ deficiency in type 2 diabetic patients on metformin: a cross-sectional study from South-Western part of Ghana

Yakubu

Laing

Nsiah

et al. 2019

Alexandria Journal of Medicine

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Introduction: Metformin is the most widely administered anti-diabetic medication among type 2 diabetes mellitus (T2DM) patients. However, metformin induces vitamin B12 malabsorption which may increase the risk of vitamin B12 deficiency among T2DM patients. We determined the prevalence of vitamin B12 deficiency and related risk factors among Ghanaian T2DM patients on metformin therapy. Methods: This cross-sectional study recruited 196 T2DM patients attending the outpatient diabetic clinic at the Effia Nkwanta Regional Hospital, Ghana. Fasting venous blood was collected for biochemical analysis. Vitamin B12 deficiency was defined as serum B12 <100 pg/ml and methylmalonic acid (MMA) ≥ 0.4µmol/L. Results: The prevalence of vitamin B12 deficiency based on serum vitamin B12, MMA, and the combination of both methods were 32.1%, 14.8%, and 14.3%, respectively. Longer duration of metformin use [5-9 years; aOR= 2.83, 95% CI (1.03-7.81), p=0.045 and ≥10 years; aOR= 4.17, 95% CI (1.41-12.33), p=0.010], higher daily dose of metformin [1000-2000 mg/day; aOR= 1.34, 95% CI (0.25-2.74), p=0.038 and >2000 mg/day; aOR= 1.13, 95% CI (0.39-2.97), p=0.047], and very high body fat [aOR= 2.98, 95% CI (1.47-6.05), p=0.020] were significantly associated with increased odds of vitamin B12 deficiency. For daily dose of metformin, a cutoff value of 1500 mg/day presented with a sensitivity, specificity, and AUC of 71.4%, 40.1%, and 0.54 (95% CI, 0.53-0.54), respectively, in predicting vitamin B12 deficiency. A ≥ six (6) years duration of metformin therapy presented with a sensitivity, specificity, and AUC of 70.4%, 62.9%, and 0.66 (95% CI, 0.57-0.75), respectively, in predicting vitamin B12 deficiency. Conclusion: Vitamin B12 deficiency is high among T2DM patients on metformin therapy in Ghana. There is the need for regular monitoring of vitamin B12 levels especially in T2DM patients on metformin daily dose of ≥ 1500 mg for duration of therapy ≥ 6 years.

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Diabetic neuropathy is not associated with homocysteine, folate, vitamin B12 levels, and MTHFR C677T mutation in type 2 diabetic outpatients taking metformin

Cited by 44 publications

References 39 publications

Fracture Risk in Type 2 Diabetes: Current Perspectives and Gender Differences

Fracture Risk in Type 2 Diabetes: Current Perspectives and Gender Differences

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

Vitamin B₁₂ deficiency in type 2 diabetic patients on metformin: a cross-sectional study from South-Western part of Ghana

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Diabetic neuropathy is not associated with homocysteine, folate, vitamin B12 levels, and MTHFR C677T mutation in type 2 diabetic outpatients taking metformin

Cited by 44 publications

References 39 publications

Fracture Risk in Type 2 Diabetes: Current Perspectives and Gender Differences

Fracture Risk in Type 2 Diabetes: Current Perspectives and Gender Differences

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

Vitamin B12 deficiency in type 2 diabetic patients on metformin: a cross-sectional study from South-Western part of Ghana

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Vitamin B₁₂ deficiency in type 2 diabetic patients on metformin: a cross-sectional study from South-Western part of Ghana