scholarly journals Profiling immuno-metabolic mediators of vitamin B12 deficiency among metformin-treated type 2 diabetic patients in Ghana

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0249325
Author(s):  
Samuel Asamoah Sakyi ◽  
Edwin Ferguson Laing ◽  
Richard Mantey ◽  
Alexander Kwarteng ◽  
Eddie-Williams Owiredu ◽  
...  

Background The association between prolong metformin usage and B12 deficiency has been documented. However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed substantial disparity among studies due to varied study definitions of vitamin B12 deficiency. Metformin blocks the calcium dependent absorption of the vitamin B12-Intrinsic Factor complex at the terminal ileum. Lack of intrinsic factor due to the presence of auto-antibodies to parietal cells (IFA) could lead to vitamin B12 deficiency and subsequently cause peripheral neuropathy. We investigated the prevalence of vitamin B12 deficiency using more sensitive, combined markers of vitamin B12 status (4cB12) and the immuno-biochemical mediators of vitamin B12 deficiency. Methods In this observational study, 200 consecutive consenting metformin-treated T2DM patients, aged 35 and above, attending the diabetic clinic at KATH were recruited. Vitamin B12 deficiency was classified based on the Fedosov age-normalized wellness quotient. Anthropometric measurement was taken as well as blood samples for immunological and biochemical mediators. Peripheral neuropathy was assessed using the Michigan Neuropathy Screening Instrument (MNSI). Statistical analysis was performed using the R Language for Statistical Computing. Results Using the combined indicator (4cB12), the prevalence of metformin induced vitamin B12 deficiency was 40.5% whilst the prevalence of MNSI-Q and MNSI-PE diabetic neuropathy was 32.5% and 6.5% respectively. Participants with vitamin B12 deficiency had significantly higher levels of IFA, GPA, TNF-α, TC, LDL and albumin compared to those with normal vitamin B12 levels (p < 0.05). Correlation analysis revealed a statistically significant negative association between 4cB12 and the immunological markers [IFA (rs = -0.301, p<0.0001), GPA (rs = -0.244, p = 0.001), TNF-α (rs = -0.242, p = 0.001) and IL-6 (rs = -0.145, p = 0.041)]. Likewise, 4cB12 was negatively associated with TC (rs = -0.203, p = 0.004) and LDL (rs = -0.222, p = 0.002) but positively correlated with HDL (rs = 0.196, p = 0.005). Conclusion Vitamin B12 deficiency and diabetic neuropathy are very high among metformin-treated T2DM patients and it is associated with increased GPA, IFA, TNF-α and cardiometabolic risk factors (higher LDL and TC and lower HDL). Upon verification of these findings in a prospective case-control study, it may be beneficial to include periodic measurement of Vitamin B12 using the more sensitive combined indicators (4cB 12) in the management of patients with T2DM treated with metformin in Ghana.

2020 ◽  
Author(s):  
Samuel Sakyi ◽  
Edwin F. Laing ◽  
Richard Mantey ◽  
Alexander Kwarteng ◽  
Eddie-Williams Owiredu ◽  
...  

Abstract Background: The association between prolong metformin usage and B12 deficiency has been documented. However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed substantial disparity among studies due to varied study definitions of vitamin B12 deficiency. Metformin blocks the calcium dependent absorption of the vitamin B12-Intrinsic Factor complex at the terminal ileum. Lack of intrinsic factor due to the presence of auto-antibodies to parietal cells (IFA) could lead to vitamin B12 deficiency and subsequently cause peripheral neuropathy. We investigated the prevalence of vitamin B12 deficiency using more sensitive, combined markers of vitamin B12 status (4cB12) and the immuno-biochemical mediators of vitamin B12 deficiency.Methods: In this observational study, 200 consecutive metformin-treated T2DM patients, aged 35 and above, attending the diabetic clinic at KATH were recruited. Vitamin B12 deficiency was classified based on the Fedosov age-normalized wellness quotient. Anthropometric measurement was taken as well as blood samples for immunological and biochemical mediators. Peripheral neuropathy was assessed using the Michigan Neuropathy Screening Instrument (MNSI). Statistical analysis was performed using the R Language for Statistical Computing version 3.6.0. Results: Using the combined indicator (4cB12), the prevalence of metformin induced vitamin B12 deficiency was 40.5% whilst the prevalence of MNSI-Q and MNSI-PE diabetic neuropathy was 67.5% and 93.5% respectively. Participants with vitamin B12 deficiency had significantly higher levels of IFA, GPA, TNF-α, TC, LDL and albumin compared to those with normal vitamin B12 levels (p < 0.05). Correlation analysis revealed a statistically significant negative association between 4cB12 and the immunological markers [AIF (rs= -0.301, p<0.0001), GPA (rs= -0.244, p=0.001), TNF-α (rs= -0.242, p=0.001) and IL-6 (rs= -0.145, p=0.041)]. Likewise, 4cB12 was negatively associated with TC (rs= -0.203, p=0.004) and LDL (rs= -0.222, p=0.002) but positively correlated with HDL (rs= 0.196, p=0.005).Conclusion: Vitamin B12 deficiency and diabetic neuropathy are very high among metformin-treated T2DM patients and it is associated with increased GPA, IFA, TNF-α and cardiometabolic risk factors (higher LDL and TC and lower HDL). It is imperative Ghana include routine measurement of Vitamin B12 deficiency using the more sensitive combined indicators (4cB12), in the management of T2DM patients on metformin.


2016 ◽  
Vol 20 (1) ◽  
pp. 16-20
Author(s):  
Mohammed Noorjahan ◽  
Kandregula Madhavi ◽  
Chandran Priscilla ◽  
Shaik A Jabeen

ABSTRACT Diabetic neuropathy is the most common and debilitating microvascular complication leading to nontraumatic amputations. Identifying the role of vitamin B12 in the etiology of neuropathy is crucial because simple vitamin B12 replacement may reverse neurologic symptoms if confirmed. Large proportion of vegetarians and patients on metformin have been associated with lowering of vitamin B12 levels. We have undertaken study on 60 vegetarian subjects between the age of 30 and 60 years, 20 healthy controls, 20 type 2 diabetes mellitus patients who were on metformin with peripheral neuropathy (DMWN), and 20 diabetics without peripheral neuropathy (DMWON). Vitamin B12, homocysteine, and folate levels were measured, and holotranscobalamin (holoTC) is also included, to improve the diagnosis of tissue vitamin B12 status, as holoTC is the biologically active fraction and more sensitive index of vitamin B12 status than total vitamin B12 itself. Complete history and clinical evaluation for neuropathy and electroneuromyography were recorded. Results In the DMWN group, vitamin B12 levels were significantly higher than in the DMWON group and controls [1013 (564-1501) pmol/l, 387 (245-731) pmol/l, and 305 (234-472) pmol/l respectively]. Similarly, serum holoTC was also found to be significantly higher in the DMWN [203.8 (129-300) pmol/l] group compared with the DMWON [94.4 (42.2-230.6) pmol/l] group and controls [74 (40-170) pmol/l]. Whereas mean levels of homocysteine and folate did not show any significant difference between groups, significant increase in fasting blood sugar and HbA1c was seen in the DMWN group compared with DMWON group and controls. Duration of diabetes is also significantly more in DMWN group compared with DMWON group. Conclusion We found that vitamin B12 and holoTC levels were high in patients with DMWN and DMWON groups compared with controls. Our study demonstrated that peripheral neuropathy was not associated with vitamin B12 deficiency in diabetics. These findings merit further research on a larger population to investigate into the cause of diabetic neuropathy, the factors involved, and benefit of vitamin B12 supplementation in these patients. Key messages Vitamin B12 status has no association with diabetic peripheral neuropathy. How to cite this article Noorjahan M, Madhavi K, Priscilla C, Jabeen SA. Vitamin B12 and Holotranscobalamin Levels in Diabetic Peripheral Neuropathy Patients. Indian J Med Biochem 2016;20(1):16-20.


2019 ◽  
Vol 12 (12) ◽  
pp. e229380
Author(s):  
Gareth Hughes ◽  
Ed Moran ◽  
Martin J Dedicoat

A 27-year-old woman presented with confusion, agitation and fever. Having initially been treated as an infective encephalitis case her initial and subsequent lumbar punctures revealed cerebrospinal fluid with a worsening pleocytosis and elevated protein. It was initially felt she had been suffering from tuberculous meningitis and started on treatment it later became apparent that she had a severe vitamin B12 deficiency related to recreational nitrous oxide use. She also was noted to have a peripheral neuropathy. After replacing her vitamin B12 and later stopping her tuberculous medication once cultures were negative her cognition and peripheral neuropathy continued to improve.


Introduction: Type 2 diabetes has multifactorial complications, in which hyperhomocysteinemia is an emerging risk factor that may be secondary to various conditions such as vitamin B12 deficiency, which appears oftenly as an asymptomatic setting and less specific in diabetics. Vitamin B12 deficiency definition has been revisited because its level does not reflect the intracellular status of vitamin B12, and an intracellular cofactor must be included systematically. Subclinical deficiency of vitamin B12 has recently been identified as a new clinic-biological entity that can affect micro and macro-angiopathic complications of diabetes indirectly through hyperhomocysteinemia. Materials and methods: 40 diabetic patients were screened for an infra-clinicalvitaminB12 deficiency subdivided into two groups each containing 16 patients, the first group having a deficit and the second having a normal level of vitamin B12. They were compared according to the frequency of micro-antipathy (retinopathy, nephropathy, peripheral neuropathy). Results: No significant difference was found for the different microangiopathic lesions; nevertheless the subclinical deficit seems to be a risk factor for peripheral neuropathy. Conclusion: In this study with a very modest sample. We attempted to approach the link between the borderline deficit of vitamin B12 and micro-angiopathic complications. In these results, even though the risk trend does not seem to be developing, the prospects for more extensive studies, both prospective and fundamental, should be encouraged.


Author(s):  
R. Arun

Metformin use over time reduces vitamin B12 levels, according to several studies, and its clinical manifestation can be mistaken as diabetic peripheral neuropathy. In order to investigate vitamin-B12 deficiency in type II diabetic patients with long-term metformin treatment, a link between vitamin B12 and peripheral neuropathy, and to evaluate the quality of life in (T2DM) patients, the current study was done. At Sree Balaji Medical College and Hospital's outpatient and inpatient departments, a prospective observational case-control research was done. The study included 35 healthy volunteers (controls) and 35 Type 2 diabetes patients who had been on metformin for more than six months (cases). Patients' venous blood samples were collected in K2 EDTA vacutainers and centrifuged at 1500 rpm for 10 minutes, settled plasma was transferred into cryo-vials, and parameters such as Vitamin-B12, HbA1c, and CBP were estimated and this is used to conduct the statistical analysis. The prevalence of blood vitamin B12 deficiency and borderline deficiency in T2DM patients is 20.5 percent, while the mean HbA1C values in our study T2DM subjects are 9.07 percent, indicating either poor diabetes control or poor metformin drug compliance. Vitamin B12 insufficiency was found in 83 percent of T2DM patients who had been using metformin for 1 to 10 years. The reliability test was used to assess their quality of life, and the results revealed that the study participants' quality of life was poor.


2016 ◽  
Vol 12 (6) ◽  
pp. 22
Author(s):  
Wafa'a Jamil Abu Jama'ah ◽  
Motazbellah Fat'hi Alzu'bi ◽  
Alaa Rfeefan Alabbad ◽  
Alaa Mohammed Al Mrayat ◽  
Ola Ahmad Aldmour ◽  
...  

The aim of the present study was to study the association of metformin dose with peripheral neuropathy in diabetic patients at Jordanian Royal Medical Services. A retrospective study was conducted to collect data from files of 392 diabetic patients at Jordanian Royal Medical Services. A working sheet was created for each patient that included the following information: gender, age, peripheral neuropathy, vitamin B12 status, metformin use, and metformin dose. Data were analyzed using SPSS version 20. Data were represented as frequencies and percentages for categorical variables such as gender, and vitamin B12 status; means and standard deviations for continuous variables such as age. The relationships between variables were examined using Chi-Square, and One Way Anova. Significance was considered at alpha level <0.05. Study findings showed that the prevalence of diabetic peripheral neuropathy among participants was about 43%. Vitamin B12 deficiency was about 7%. Diabetic peripheral neuropathy was significantly associated with gender (p=0.018). No significant associations were observed between peripheral neuropathy and vitamin B12 or metformin dose. Taken together, the results of the present study showed that treatment with metformin did not lead to vitamin B12 deficiency, although the prevalence of diabetic peripheral neuropathy was relatively high (about 43%).


2015 ◽  
Vol 23 (7) ◽  
pp. 1843-1850 ◽  
Author(s):  
Janet M. Schloss ◽  
Maree Colosimo ◽  
Caroline Airey ◽  
Luis Vitetta

Author(s):  
Nishant Kumar Singh ◽  
Hirni J. Patel ◽  
Mohit Buddhadev ◽  
S P Srinivas Nayak ◽  
Gunosindhu Chakraborthy

Peripheral nerves are susceptible to damage by a wide array of toxins, medications, and vitamin deficiencies. Vitamin B12 (VB12) deficiency neuropathy is a rare debilitating disease that affects mostly the elderly. It is important to consider these etiologies when approaching patients with a variety of neuropathic presentations in this review were have included most relevant and latest information on mechanisms causing Peripheral neuropathy in VB12 deficiency. We also have included cardiovascular disorders and their management. Hyperhomocysteinemia has been implicated in endothelial dysfunction and cardiovascular disease. The association of homocysteine (Hcy) and VB12 with cardiovascular risk factors in patients with coronary artery disease (CAD) has also been studied Keywords: Peripheral Neuropathy, Vitamin B12 Deficiency, Cardiovascular Disease and Homocysteine.


2021 ◽  
Vol 12 (2) ◽  
pp. 54-58
Author(s):  
Vinay Krishnamurthy ◽  
Akhila Rao Kerekoppa

Background: Diabetes is one of the largest global health emergencies of the 21st century. Prevalence of anemia in diabetic patients is two to three times higher than for patients with comparable renal impairment and iron stores in the general population. Aims and Objective: This study was done to analyse the prevalence of anemia and its profile in patients with preserved renal function. Materials and Methods: One-hundred diabetic patients with anemia with normal renal functions were selected. Complete blood count, peripheral blood smear, iron studies, vitamin B12 levels were assessed. Diabetic control was monitored by HbA1c. Patients were identified to have specific type of anemia, based on iron profile and vitamin B12 levels. Severity of anemia was also assessed. Appropriate statistical tests were applied to analyse the results. Results: Mean age of subjects in the study group was 53.4±13.6 years. The mean haemoglobin level was 9.41±2.18 g/dl. Out of the 100 cases, 43 patients had iron deficiency anemia, 40 patients had anemia of inflammation, and 8 patients had vitamin B12 deficiency, 8 patients had combined iron and vitamin B12 deficiency, and 1 patient had pancytopenia. Mean HbA1c was higher in iron deficient individuals with a significant p value and mean HbA1c was lower in Vitamin B12 deficient individuals. Among the cases, 16% had mild anemia, 61% had moderate anemia, and 23% had severe anemia. Severe anemia had a significantly lower HbA1c, which was statistically significant. Conclusion: According to our study, iron deficiency anemia was the commonest, followed by anemia of inflammation in diabetic patients with preserved renal function. Diabetes being a pro-inflammatory state had a higher incidence of anemia of inflammation compared to general population. We have to identify and acknowledge the higher prevalence of Anemia of Inflammation in diabetic patients in the absence of renal dysfunction.


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