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Correlation Between Serum Vitamin B12 Levels and Neuropathic Pain Severity in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study

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Background: Type 2 Diabetes Mellitus (T2DM) is a common metabolic disorder often associated with diabetic peripheral neuropathy manifested by pain, paresthesia and sensory impairment. The first line treatment for T2DM, metformin has been associated with decreased intestinal uptake of vitamin B12 with prolonged use. (de Jager et al., 2010; Reinstatler et al., 2012) Vitamin B12 deficiency may therefore play a role in the neurological dysfunction and aggravate neuropathic symptoms. However, the link between vitamin B12 levels and the severity of neuropathic pain in metformin-treated patients is still not adequately examined. Method: This is a cross-sectional observational study which was conducted at the Department of General Medicine, Guntur General Hospital (GGH), which is a tertiary care teaching hospital serving a diverse semi-urban and rural population. The study was carried out in a period of a year i.e. December 2023 - December 2024. Results: Mean age of participants was 61.1±10.6 years. Vitamin B12 deficiency was seen in 25.6% of the patients and clinical neuropathy (DN4 ≥ 4) was present in 33.6% of the cohort. Neuropathy was much more common in vitamin B12-deficient (81.2%) and normal vitamin B12 level patients (12.6%). Serum vitamin B12 levels had a significant inverse correlation with the VAS pain scores (rs= - 0.527, p < 0.001). Multivariable regression confirmed that lower levels of vitamin B12 were an independent predictor of lower neuropathic pain levels. Conclusion: Vitamin B12 deficiency is seen in high percentages of metformin-treated patients with T2DM and is highly correlated with a greater level of neuropathic pain. Routine monitoring and supplementation may help to decrease neuropathic complications.

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  • Research Article
  • Cite Count Icon 39
  • 10.4088/pcc.08l00707
Vitamin B12Deficiency and Depression in the Elderly
  • Oct 15, 2009
  • The Primary Care Companion to The Journal of Clinical Psychiatry
  • Susan Hanna + 2 more

Vitamin B<sub>12</sub>Deficiency and Depression in the Elderly

  • Research Article
  • Cite Count Icon 24
  • 10.2147/ndt.s399378
Vitamin B12, Folate, Homocysteine, Inflammatory Mediators (Interleukin-6, Tumor Necrosis Factor-α and C-Reactive Protein) Levels in Adolescents with Anxiety or Depressive Symptoms
  • Apr 7, 2023
  • Neuropsychiatric Disease and Treatment
  • Yongjun Tan + 8 more

PurposeTo evaluate the prevalence of abnormal vitamin B12, folate, total homocysteine (tHcy), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) levels, to analyze the relationship between these parameters and the severity of anxiety or depressive symptoms, and to explore the possible factors associated with abnormal levels of these parameters in adolescents with anxiety or depressive symptoms.MethodsAdolescent (aged 12–18 years) outpatients with anxiety or depressive symptoms were recruited. The patient health questionnaire-9 and generalized anxiety disorder scale-7 were used to measure the severity of depression and anxiety. Serum vitamin B12, folate, tHcy, IL-6, TNF-α, and CRP levels were determined.Results128 subjects were recruited. The prevalence of vitamin B12 and folate deficiency, tHcy, TNF-α, IL-6, and CRP elevation was 8.6%, 10.2%, 25.8%, 14.8%, 21.9%, and 10.2%, respectively, in adolescents with anxiety or depressive symptoms. Lower vitamin B12 levels were correlated with a higher risk of severe anxiety and depressive symptoms. The severity of some symptoms of anxiety or depression were weakly correlated with vitamin B12, folate, tHcy, IL-6, and CRP levels. Vitamin B12, folate, and tHcy levels were not associated with inflammatory mediators. Vitamin B12 deficiency was associated with older age and higher tHcy levels. Folate deficiency was associated with elevated tHcy. Elevated tHcy was associated with lower vitamin B12 and folate levels. IL-6 elevation was associated with elevated CRP and TNF-α. CRP elevation was associated with older age, higher BMI, and current drinking.ConclusionLower vitamin B12 levels were correlated with a higher risk of severe anxiety or depressive symptoms. Weak correlations were observed between the severity of some symptoms of anxiety or depression and vitamin B12, folate, tHcy, IL-6, and CRP levels. Vitamin B12, folate, and tHcy levels were related to each other. IL-6 elevation was associated with elevated CRP and TNF-α. CRP elevation was associated with older age, higher BMI, and current drinking.

  • Research Article
  • Cite Count Icon 1
  • 10.7759/cureus.70473
Serum Vitamin B12 Levels as a Risk Factor and Prognostic Marker in Patients With Acute Ischemic Stroke at a Tertiary Care Center in Northern India: A Case-Control Study.
  • Sep 29, 2024
  • Cureus
  • Virendra Atam + 5 more

Objective Stroke is a leading cause of death and disability globally, with its incidence, prevalence, and mortality rising significantly over the past decades. Beyond traditional risk factors, vitamin B12 has garnered attention for its role in stroke prevention due to its influence on homocysteine metabolism. Deficiencies in vitamin B12 are linked to hyperhomocysteinemia, which increases the risk of ischemic stroke. This study aims to compare vitamin B12 and homocysteine levels in stroke patients versus control subjects. Methodology This observational case-control study was conducted at King George's Medical University (KGMU), Lucknow, involving 75 acute ischemic stroke patients and 75 age- and sex-matched controls. Serum vitamin B12 and homocysteine levels were measured, and stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) score. The modified Rankin scale (MRS) evaluated functional outcomes at discharge. Statistical analysis was performed to identify associations between vitamin B12 levels, stroke severity, and patient outcomes. Results Stroke patients had significantly lower vitamin B12 levels (194.24 ± 91.11 pmol/L) and higher homocysteine levels (16.33 ± 3.29 µmol/L) compared to controls (271.13 ± 91.19 pmol/L and 9.76 ± 4.55 µmol/L, respectively). Vitamin B12 levels were lower, and homocysteine levels were higher in patients who died during the study. Additionally, vitamin B12 levels were negatively correlated with MRS scores at discharge and 28 days post-discharge, and positively correlated with NIHSS scores, indicating worse outcomes in patients with lower vitamin B12 levels. Conclusions This study demonstrates a significant association between vitamin B12 deficiency and the occurrence and severity of ischemic stroke. Lower vitamin B12 levels correlated with higher stroke severity and poorer functional outcomes, highlighting the potential role of vitamin B12 in stroke management. Further research is needed to explore the therapeutic implications of vitamin B12 supplementation in reducing stroke risk and improving patient outcomes.

  • Abstract
  • 10.1016/s0016-5085(12)60819-1
Sa1111 Serum Vitamin B12 Levels: Does it Reflect Cellular Deficiency of the Vitamin in Low Normal Range?
  • Apr 18, 2012
  • Gastroenterology
  • Arun Ramaswamy Saraswathy + 3 more

Sa1111 Serum Vitamin B12 Levels: Does it Reflect Cellular Deficiency of the Vitamin in Low Normal Range?

  • Abstract
  • 10.1016/s0016-5085(12)60820-8
Sa1112 CT Attenuation Value of the Fluid Collection Site to Diagnose Infected Pancreatic Fistula After Distal Pancreatectomy
  • Apr 18, 2012
  • Gastroenterology
  • Naohisa Kuriyama + 9 more

Sa1112 CT Attenuation Value of the Fluid Collection Site to Diagnose Infected Pancreatic Fistula After Distal Pancreatectomy

  • Research Article
  • 10.65188/nurexus.1024
Prevalence of Vitamin B12 Deficiency Among Type 2 Diabetes Patients on Metformin Therapy
  • May 31, 2025
  • Journal of MedVerse Research &amp; Practice
  • Vidhyavathi S + 1 more

Introduction: Type 2 diabetes mellitus (T2DM) is increasingly prevalent worldwide, with metformin widely prescribed as the first-line therapy due to its efficacy and safety. However, prolonged use of metformin has been linked to vitamin B12 deficiency, a concern due to its potential to cause neurological and haematological complications, particularly in diabetic patients. This study aims to assess the prevalence of vitamin B12 deficiency among T2DM patients on metformin and examine its association with dosage and duration of therapy. Materials &amp; Methods: A descriptive cross-sectional study was conducted over 18 months (May 2023 to November 2024) at the Government Medical College, Indore. 150 adult T2DM patients on metformin for at least six months were selected via simple random sampling. Patients with confounding factors like strict vegetarian diet, B12 supplementation, or chronic diseases affecting absorption were excluded. Serum vitamin B12 levels were assessed using chemiluminescent immunoassay and classified as deficient (&lt;200 pg/mL), borderline (200–300 pg/mL), or normal (&gt;300 pg/mL). Data were analysed to determine the prevalence and associations with metformin dose and duration. Results: Among 150 patients, those on 1000 mg metformin had significantly lower mean serum vitamin B12 levels (312.47 ± 223.97 pg/mL) compared to those on 500 mg (406.75 ± 309.79 pg/mL) (p = 0.031). Vitamin B12 deficiency was observed in 30% of participants, with a higher prevalence in the 1000 mg group (37.3%) versus the 500 mg group (22.7%) (p = 0.027). Deficiency rates also increased with treatment duration: 15.6% (6 months–1 year), 25.9% (1–3 years), and 46.2% (&gt;3 years), showing a significant trend (p = 0.004). Glycaemic control remained similar across all groups. Conclusion: The study demonstrates a clear association between both higher metformin doses and longer duration of use with lower vitamin B12 levels in T2DM patients. Despite effective glycaemic control, many patients developed vitamin B12 deficiency, reinforcing the need for routine monitoring and early intervention in long-term or high-dose metformin users. Keywords: Type 2 diabetes mellitus, Metformin, Vitamin B12 deficiency, Dose-related effect, Treatment duration, Screening, Cross-sectional study.

  • Research Article
  • Cite Count Icon 3
  • 10.18621/eurj.2015.1.1.1
The Role of Metformin on Serum Vitamin B12 Levels in Patients with Type 2 Diabetes Mellitus
  • Mar 4, 2015
  • The European Research Journal
  • Mitra Niafar + 4 more

Objective. To evaluate the vitamin B12 (VB12) deficiency in patients with type-2 diabetes mellitus (DM-2) using metformin or other hypoglycemic agents. Methods. 400 patients with DM-2 were divided into two arms (N=200/group); 1) those receiving metformin (MET) for at least six months and 2) those receiving hypoglycemic agents other than metformin (OHA). Serum VB12 concentrations were measured. Data were analyzed by using two-sample t-test for numerical data and chi-square with logistic regression analysis for categorical data. Numerical values were expressed as means ± standard deviations. Null hypotheses were rejected at P-values <0.05. Results. Definite biochemical VB12 deficiency (<148 pmol/L) was found in 29/200 (14.5%) of the MET group while it was observed in 4/200 (2%) in the OHA group (P<0.001). Similarly, possible VB12 deficiency (serum concentrations <185 pmol/L) was found in 39 (19.2%) of the MET group and 12 (6%) in the OHA group (p<0.001). There was positive correlation between low VB12 level and metformin administration (R 2 =0.26, p<0.001). Conclusion. Patients with DM-2 on metformin had lower VB12 levels than those on other hypoglycemic drugs. The relation between VB12 deficiency and metformin therapy indicates the need for periodic measurement of serum VB12 levels in patients treated with metformin.

  • Research Article
  • Cite Count Icon 4
  • 10.1111/j.1600-0609.1996.tb01931.x
The deoxyuridine suppression test in HIV-1 positive patients: the role of azydothymidine (AZT).
  • Apr 1, 1996
  • European journal of haematology
  • F García‐Die + 5 more

The deoxyuridine suppression test (dUST) was used to evaluate human immunodeficiency virus type 1 positive (HIV-1) patients with low serum levels of vitamin B12 and/or low red cell folate and to assess any possible interferences of azydothymidine (AZT) in this test. The dUST was studied in 29 HIV-1 positive patients, 18 without low serum vitamin B12 or low red cell folate and 11 with low serum vitamin B12 (6 patients), low red cell folate (4 patients) and 1 case with both. The role of AZT was studied using different concentrations (0.2, 2.5 and 10 microM/ml) in 2 groups: 1 group of 5 patients with vitamin B12 and/or folate deficiency and another group consisting of 13 healthy subjects. Methotrexate (MTX)(50 micrograms/ml) was added to induce a folate megaloblastic pattern in the latter group. Results of the dUST in the HIV-1 group without low levels of serum vitamin B12 fell within the health-related reference interval values. A vitamin B12 deficiency was only detected in 1 case in the HIV-1 group with low serum vitamin B12, although a folate deficiency pattern was observed in the 4 patients with low red cell folate. In the healthy subjects AZT induced a dose-dependent decrease of the MTX-induced folate megaloblastic pattern. The pattern was also observed in the group of patients with vitamin B12 or folate deficiency, although AZT did not entirely interfere with the dUST. The effect of AZT on the dUST was attributed to a decrease in the incorporation of the isotope in the absence of deoxyuridine. The dUST is useful in differentiating vitamin B12 deficient patients from HIV-1 infected patients with low levels of serum vitamin B12.

  • Research Article
  • Cite Count Icon 51
  • 10.1002/gps.1092
Correlations between cognitive, behavioural and psychological findings and levels of vitamin B12 and folate in patients with dementia.
  • Feb 25, 2004
  • International Journal of Geriatric Psychiatry
  • Sebastiaan Engelborghs + 12 more

Associations between low levels of folate and vitamin B12 and cognitive impairment in patients with dementia have been reported. Some studies revealed correlations between low levels of vitamin B12 and behavioural and psychological signs and symptoms of dementia (BPSD) in Alzheimer's disease (AD) patients. Given the lack of studies in frontotemporal dementia (FTD) and on folate and given the methodological shortcomings of former publications, we set up a prospective study. At inclusion, AD (n=152) and FTD (n=28) patients underwent a neuropsychological examination. Behaviour was assessed using a battery of behavioural assessment scales. Determination of serum vitamin B12 and red cell folate levels were performed within a time frame of two weeks of inclusion. In both patient groups, significantly negative correlations between levels of serum vitamin B12 and red cell folate and the degree of cognitive deterioration were found. No correlations with BPSD were found in the AD patient group. In FTD patients, levels of vitamin B12 were negatively correlated with both hallucinations (p=0.022) and diurnal rhythm disturbances (p=0.036). The observed negative correlations between levels of vitamin B12 and folate and cognitive impairment in both AD and FTD patients, raise the possibility of a non-specific etiological role. Although levels of vitamin B12 and folate did not correlate with BPSD in AD patients, negative correlations between serum vitamin B12 levels and BPSD in FTD patients were revealed. Decreased serum vitamin B12 levels may predispose FTD patients to develop hallucinations and diurnal rhythm disturbances.

  • Research Article
  • Cite Count Icon 1
  • 10.1111/jpc.16207
Correlations between serum vitamin B12 and folate levels among mother-infant dyads in Punjab state, North-West India.
  • Sep 13, 2022
  • Journal of Paediatrics and Child Health
  • Inderpal S Grover + 4 more

Adequate vitamin B12 levels in infancy are crucial for normal psychomotor and cognitive development of infants. Our aim was to examine serum vitamin B12, folate and ferritin levels in exclusively breastfed healthy full-term infants (age group: 1-6months), and also investigate their correlation with maternal markers. A cross-sectional study was conducted on 100 exclusively breastfed healthy full-term infants (age group: 1-6months) along with their lactating mothers. Serum vitamin B12, folate and ferritin levels were determined for each mother-infant dyad using enzyme-linked immunosorbent assay. The mean serum vitamin B12, folate and ferritin levels were 512 vs. 535 pg/mL, 15 vs. 12 ng/mL and 313 vs. 114 ng/mL in infants and mothers, respectively. Among 100 infants, 26 (26%) had lower vitamin B12 levels and 5 (5%) had inadequate folate levels. In addition, 22 (22%) of 100 lactating mothers were deficient in vitamin B12 levels and 14 (14%) had inadequate folate levels. We found a statistically significant positive correlation between infant and maternal vitamin B12 (r=0.659, P < 0.001) and folate levels (r=0.51, P < 0.001). Vitamin B12 deficiency was observed in 26% of infants and 22% of lactating mothers. Vitamin B12 and folate levels of infants were positively correlated with maternal levels in the state of Punjab, North-West India. Our findings support that maternal vitamin B12 status can be used as a valuable predictor of infant vitamin B12 status.

  • Abstract
  • 10.1182/blood.v112.11.4278.4278
Vitamin B12 Deficiency in Patients with Chronic Myeloid Leukemia
  • Nov 16, 2008
  • Blood
  • Muhammad K Siddique + 1 more

Vitamin B12 Deficiency in Patients with Chronic Myeloid Leukemia

  • Research Article
  • 10.3329/jdnmch.v26i2.80170
Evaluation of Vitamin B12 Deficiency in Newly Diagnosed Hypothyroid Female Patients in Dhaka City
  • Mar 30, 2020
  • Journal of Dhaka National Medical College &amp; Hospital
  • Farjana Ahmed + 3 more

Background: Vitamin B12 deficiency may remain latent in the early phase of hypothyroidism. Symptoms of neuropathy may occur due to combination of deficiency of thyroxin &amp; vitamin B12 in newly diagnosed hypothyroid female patients. Objectives: To assess the prevalence and clinical features of vitamin B12 deficiency in newly diagnosed hypothyroid female patients in Dhaka. Methods: This cross-sectional study was carried out in the Department of Physiology, Sir Salimullah Medical College (SSMC) between July' 2015 to June' 2016 on 80 newly diagnosed hypothyroid female patients with clinical features of vitamin B12 deficiency. Their serum TSH, FT4, FT3 levels were estimated for assessment of thyroid function status by ELISA method. Vitamin B12 level was also estimated to observe its level by using standard method. The statistical analysis was done by ANOVA test, paired, independent sample't' test. Results: In this study, a total 80 newly diagnosed hypothyroid female patients were evaluated among them 34 patients had low vitamin B12 level. Generalized weakness, impaired memory, depression, numbness and decreased reflexes were more frequently noted in vitamin B12 deficient patient. Additionally 16 subjects were complained of symptoms consistent with vitamin B12 deficiency, but had normal range of vitaminB12 level. Conclusion: The present study revealed that there is a high (approx 42.5%) prevalence of vitamin B12 deficiency in newly diagnosed hypothyroid female patients. Traditional symptoms are not a good guide to determining presence of vitamin B12 deficiency. Screening for vitamin B12 level should be undertaken in all newly diagnosed hypothyroid female patients. Background: Vitamin B12 deficiency may remain latent in the early phase of hypothyroidism. Symptoms of neuropathy may occur due to combination of deficiency of thyroxin &amp; vitamin B12 in newly diagnosed hypothyroid female patients. Objectives: To assess the prevalence and clinical features of vitamin B12 deficiency in newly diagnosed hypothyroid female patients in Dhaka. Methods: This cross-sectional study was carried out in the Department of Physiology, Sir Salimullah Medical College (SSMC) between July' 2015 to June' 2016 on 80 newly diagnosed hypothyroid female patients with clinical features of vitamin B12 deficiency. Their serum TSH, FT4, FT3 levels were estimated for assessment of thyroid function status by ELISA method. Vitamin B12 level was also estimated to observe its level by using standard method. The statistical analysis was done by ANOVA test, paired, independent sample't' test. Results: In this study, a total 80 newly diagnosed hypothyroid female patients were evaluated among them 34 patients had low vitamin B12 level. Generalized weakness, impaired memory, depression, numbness and decreased reflexes were more frequently noted in vitamin B12 deficient patient. Additionally 16 subjects were complained of symptoms consistent with vitamin B12 deficiency, but had normal range of vitaminB12 level. Conclusion: The present study revealed that there is a high (approx 42.5%) prevalence of vitamin B12 deficiency in newly diagnosed hypothyroid female patients. Traditional symptoms are not a good guide to determining presence of vitamin B12 deficiency. Screening for vitamin B12 level should be undertaken in all newly diagnosed hypothyroid female patients. Background: Vitamin B12 deficiency may remain latent in the early phase of hypothyroidism. Symptoms of neuropathy may occur due to combination of deficiency of thyroxin &amp; vitamin B12 in newly diagnosed hypothyroid female patients. Objectives: To assess the prevalence and clinical features of vitamin B12 deficiency in newly diagnosed hypothyroid female patients in Dhaka. Methods: This cross-sectional study was carried out in the Department of Physiology, Sir Salimullah Medical College (SSMC) between July' 2015 to June' 2016 on 80 newly diagnosed hypothyroid female patients with clinical features of vitamin B12 deficiency. Their serum TSH, FT4, FT3 levels were estimated for assessment of thyroid function status by ELISA method. Vitamin B12 level was also estimated to observe its level by using standard method. The statistical analysis was done by ANOVA test, paired, independent sample't' test. Results: In this study, a total 80 newly diagnosed hypothyroid female patients were evaluated among them 34 patients had low vitamin B12 level. Generalized weakness, impaired memory, depression, numbness and decreased reflexes were more frequently noted in vitamin B12 deficient patient. Additionally 16 subjects were complained of symptoms consistent with vitamin B12 deficiency, but had normal range of vitaminB12 level. Conclusion: The present study revealed that there is a high (approx 42.5%) prevalence of vitamin B12 deficiency in newly diagnosed hypothyroid female patients. Traditional symptoms are not a good guide to determining presence of vitamin B12 deficiency. Screening for vitamin B12 level should be undertaken in all newly diagnosed hypothyroid female patients. J. Dhaka National Med. Coll. Hos. 2020; 26 (02): 20-22

  • Discussion
  • Cite Count Icon 23
  • 10.1016/s0002-9343(02)01181-6
Food-cobalamin malabsorption in the elderly
  • Sep 1, 2002
  • The American Journal of Medicine
  • Emmanuel Andrès + 4 more

Food-cobalamin malabsorption in the elderly

  • Abstract
  • Cite Count Icon 1
  • 10.1016/j.jns.2019.10.1256
Profile of vitamin b12 deficiency in a urban neurology clinic in Mumbai, Maharashtra
  • Oct 1, 2019
  • Journal of the Neurological Sciences
  • N Surya + 1 more

Profile of vitamin b12 deficiency in a urban neurology clinic in Mumbai, Maharashtra

  • Research Article
  • 10.62046/gijams.2025.v03i02.006
The Diagnostic Value and Sensitivity of Blood Film in diagnosis of Megaloblastic Anemia
  • Mar 21, 2025
  • Greenfort International Journal of Applied Medical Science
  • Rudhuway A Mtawil + 1 more

Background: Megaloblastic anemia is a type of macrocytic anemia primarily caused by vitamin B12 and/or folate deficiency. Early diagnosis is crucial to prevent complications, particularly neurological impairments associated with vitamin B12 deficiency. Blood film examination is a cost-effective diagnostic tool for identifying macrocytic anemia. Objective: This study evaluates the diagnostic value and sensitivity of blood film in detecting Megaloblastic anemia and its association with vitamin B12 deficiency. Methods: A retrospective cross-sectional observational study was conducted on 31 patients diagnosed with macrocytic anemia using blood film. Laboratory investigations included complete blood count (CBC), red blood cell indices, and serum vitamin B12 levels. Data analysis was performed using statistical software, with significance set at p &lt; 0.05. Results: The median age of patients was 65 years, with 71% being female. The mean hemoglobin level was 7.52 g/dL. Among the patients, 67.7% had macrocytic anemia, while 32.3% had non-macrocytic anemia. A highly significant association was found between macrocytic and vitamin B12 deficiency (p = 0.035). Multivariate analysis confirmed that low vitamin B12 levels were a strong predictor of macrocytic anemia (p = 0.048). Conclusion: Blood film examination is a sensitive and reliable method for diagnosing macrocytic anemia. The study highlights the strong correlation between vitamin B12 deficiency and macrocytosis, reinforcing the importance of routine screening for vitamin B12 levels in anemic patients.

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