scholarly journals Profiling Immuno-Metabolic Mediators of Vitamin B12 Deficiency Among Metformin-Treated Type II Diabetes Patients in Ghana

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.

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.


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.


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.


Author(s):  
Saskia LM van Loon ◽  
Anna M Wilbik ◽  
Uzay Kaymak ◽  
Edwin R van den Heuvel ◽  
Volkher Scharnhorst ◽  
...  

Background Methylmalonic acid (MMA) can detect functional vitamin B12 deficiencies as it accumulates early when intracellular deficits arise. However, impaired clearance of MMA from blood due to decreased glomerular filtration rate (eGFR) also results in elevated plasma MMA concentrations. Alternative to clinical trials, a data mining approach was chosen to quantify and compensate for the effect of decreased eGFR on MMA concentration. Methods Comprehensive data on patient’s vitamin B12, eGFR and MMA concentrations were collected ( n = 2906). The relationship between vitamin B12, renal function (eGFR) and MMA was modelled using weighted multiple linear regression. The obtained model was used to estimate the influence of decreased eGFR on MMA. Clinical impact was examined by comparing the number of patients labelled vitamin B12 deficient with and without adjustment in MMA. Results Adjusting measured MMA concentrations for eGFR in the group of patients with low-normal vitamin B12 concentrations (90–300 pmol/L) showed that the use of unadjusted MMA concentrations overestimates vitamin B12 deficiency by 40%. Conclusions Through a data mining approach, the influence of eGFR on the relation between MMA and vitamin B12 can be quantified and used to correct the measured MMA concentration for decreased eGFR. Especially in the elderly, eGFR-based correction of MMA may prevent over-diagnosis of vitamin B12 deficiency and corresponding treatment.


2012 ◽  
Vol 4 (2) ◽  
pp. 326-328
Author(s):  
M Wadhwani ◽  
S Beri ◽  
A Saili ◽  
S Garg

Background: Homocystinuria is a rare metabolic disorder charcterised by excess homocysteine in the urine. Vitamin B12 deficiency has diverse cutaneous, nervous and ophthalmic manifestations. Objective: To report a case of homocystinuria masquerading as vitamin B 12 deficiency. Case: We hereby are presenting an interesting case of a 4 year old boy who was being treated for Vitamin B 12 deficiency on the basis of history of delayed milestone, abdominal pain and hyperpigmentation of skin which was diagnosed as homocystinuria. Conclusion: It is important to carry out ophthalmological examination in every case of megaloblastic anemia if associated with blurring of vision and mental retardation.DOI: http://dx.doi.org/10.3126/nepjoph.v4i2.6554 Nepal J Ophthalmol 2012; 4 (8): 326-328


Author(s):  
Raquel Aparicio-Ugarriza ◽  
Gonzalo Palacios ◽  
Monika Alder ◽  
Marcela González-Gross

AbstractVitamin B


2020 ◽  
Vol 2 (8) ◽  
pp. 01-03
Author(s):  
Rateesh Sareen

Vitamin B12 assay is one of the most frequently ordered tests particularly as a part of regular medical checkups. The deficiency is rampant in vegetarian population. It is of immense importance that laboratories establish their own reference interval (RI) of analyte specially Vitamin B12 as a diagnosis of Vitamin B12 deficiency based on RI of kit insert inadvertently leads to unnecessary treatment or work up. A blind reliance on RI of kit insert should be discouraged as they do not take into account population characteristics and do not truly reflect RI specific to the population under study.


1961 ◽  
Vol 200 (1) ◽  
pp. 99-101 ◽  
Author(s):  
B. L. O'Dell ◽  
B. A. Erickson ◽  
P. M. Newberne ◽  
L. M. Flynn

A vitamin B12 deficiency in weanling rats, which reduced their average weight to one-half that of controls, decreased liver concentration of nonprotein sulfhydryl (NPSH) compounds about 10% but had no effect on concentration of disulfide compounds. Fasting did not accentuate the effect of the deficiency. Dams severely depleted of B12 produced offspring whose livers contained significantly less NPSH and correspondingly more nonprotein disulfide (NPSS) compounds than controls. Thus the decreased concentration of NPSH on the B12-deficient liver was accounted for as NPSS. Vitamin B12 deficiency had no effect on the rate of anaerobic glycolysis in liver and brain tissues.


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