Screening For Vitamin B12 Deficiency Research Articles

Individuals Diagnosed With Type 2 Diabetes Mellitus and the Status of Vitamin B12 Deficiency: A Review.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder with a multifactorial etiology and a significant global burden. In recent years, emerging evidence has suggested a potential link between T2DM and vitamin B12 deficiency, raising concerns about its impact on disease progression, management, and associated complications. This comprehensive review critically examines the current understanding of the prevalence, risk factors, clinical implications, and management strategies related to vitamin B12 deficiency in individuals diagnosed with T2DM. The review begins by providing an overview of the epidemiology of T2DM and its associated complications, underscoring the need for comprehensive management approaches. Subsequently, it delves into the physiology of vitamin B12, including its sources, absorption mechanisms, and biological functions, laying the groundwork for understanding the potential implications of deficiency in T2DM. A thorough analysis of the literature is conducted to elucidate the prevalence and risk factors of vitamin B12 deficiency in individuals with T2DM, considering factors such as age, duration of diabetes, medication use (e.g., metformin), dietary patterns, and comorbidities. Special attention is given to the role of metformin, the first-line therapy for T2DM, in precipitating or exacerbating vitamin B12 deficiency through mechanisms involving alterations in the gut microbiota and intestinal absorption. The review further explores the clinical manifestations and diagnostic challenges associated with vitamin B12 deficiency in the context of T2DM, emphasizing the importance of recognizing subtle symptoms and implementing appropriate screening protocols. It discusses the potential implications of vitamin B12 deficiency on glycemic control, diabetic neuropathy, cognitive function, cardiovascular health, and overall quality of life in individuals with T2DM. In addressing the management of vitamin B12 deficiency in T2DM, the review examines various therapeutic strategies, including oral and parenteral supplementation, dietary modifications, and lifestyle interventions. It critically evaluates the evidence supporting routine screening for vitamin B12 deficiency in individuals with T2DM and discusses controversies surrounding optimal supplementation protocols, dosing regimens, and monitoring strategies. Furthermore, the review highlights gaps in current knowledge and identifies areas for future research, such as the long-term effects of vitamin B12 supplementation on clinical outcomes in T2DM, the impact of genetic factors on vitamin B12 metabolism, and the potential role of personalized interventions. Overall, this review consolidates existing evidence and provides insights into the complex relationship between T2DM and vitamin B12 deficiency, aiming to inform clinical practice, enhance patient care, and guide future research endeavors in this important area of metabolic medicine.

A Retrospective Evaluation of the Predictive Value of Newborn Screening for Vitamin B12 Deficiency in Symptomatic Infants Below 1 Year of Age.

The sensitivity of newborn screening (NBS) in detecting infants that later develop symptomatic vitamin B12 deficiency is unknown. We evaluated the predictive value using NBS algorithms in detecting infants that later were clinically diagnosed with symptomatic B12 deficiency. Furthermore, we investigated whether being born in a hospital using nitrous oxide (N2O) as pain relief in labor may have had an impact on total homocysteine at NBS. We retrospectively retrieved NBS data and analyzed total homocysteine, methylmalonic acid and methyl citrate on stored NBS dried blood spots (DBS) of 70 infants diagnosed with symptomatic B12 deficiency and compared them to 646 matched and 434 unmatched DBS controls to evaluate the Austrian and Heidelberg B12 NBS algorithms. The sensitivity of NBS in detecting infants later diagnosed with symptomatic B12 deficiency at median age 10.9 weeks was ≤10%. Total homocysteine was higher in DBS for the unmatched controls who were born in hospitals providing N2O compared to in hospitals not providing N2O, with median total homocysteine 4.0 µmol/L compared to 3.5 µmol/L (n = 434, 95% CI 0.04-0.87, p = 0.03). NBS algorithms were unable to identify most infants diagnosed with symptomatic B12 deficiency after the neonatal period. Being born in hospitals providing N2O may impact total homocysteine at NBS.

Methylmalonic acid analysis using urine filter paper samples to screen for metabolic vitamin B12 deficiency in older adults.

Aim: Methylmalonic acid (MMA) analysis in urine represents a noninvasive approach to screening for vitamin B12 deficiency in older adults. A method allowing the analysis of MMA/creatinine in fasting urine collected on filter paper was developed/validated. Method: Dry urine specimens were eluted using a solution containing internal standards, filtrated and analyzed by ultra-performance LC-MS/MS. Results: The method allowed the chromatographic separation of MMA from succinic acid. Dried urine samples were stable for 86days at room temperature. The MMA/creatinine ratios measured in urine collected on filter paper were highly correlated with values derived from the corresponding liquid specimens. Conclusion: This robust filter paper method might greatly improve the accessibility and cost-effectiveness of vitamin B12 deficiency screening in older adults.

The epidemiology and importance of vitamin B12 screening in diabetic patients

Peripheral neuropathy is a commonly reported chronic adverse event among diabetes mellitus (DM) patients secondary to poor glycemic control. It might also result secondary to deficiency of vitamin B12, reportedly common among diabetic patients. Deficiency of vitamin B12 might result from prolonged metformin administration in patients with type II DM (T2DM). It might also result from reduced absorption and impaired metabolism-related events in type I DM (T1DM) patients. This occurs secondary to the presence of associated autoimmune disorders. Vitamin B12 deficiency is a commonly encountered condition among diabetic patients, both T1DM and T2DM, with variable etiologies. Our current study discussed the epidemiology and importance of screening of vitamin B12 in these patients. However, our findings show that screening is not commonly practiced in different settings. Therefore, awareness is low about the benefits and complications of this practice. Therefore, further research is encouraged to alleviate the quality of care in diabetic patients. Screening for vitamin B12 deficiency might intervene against any potential complications, including irreversible, painful, and potentially disabling nerve injury. Accordingly, it is recommended that screening should be initiated since the start of metformin administration and every year or when relevant clinical manifestations were reported.

Frequency of Vitamin B12 and Red Cell Folate Deficiency in Macrocytic Anaemia

Background: Macrocytosis refers to a condition in which red blood cells are larger than normal, with or without anemia. Macrocytic anemia occur due to variety of illnesses and requires further clinical and laboratory assessment. Both folate and vitamin B12 have been known to cause macrocytic anemia since the deficiencies of these two vitamins are very common in Pakistan, it would be imperative to investigate their role in causing megaloblastic anemia.Objective: To determine the frequency of vitamin B12 and folate deficiencies in cases of macrocytic anemia.Material and Methods: This is a descriptive cross-sectional study conducted in the | department of medicine of Abbasi Shaheed hospital from January 2012 to June 2012. A total of 95 patients (65 males and 30 females) with an age of above 13 years, who admitted with macrocytic anemia (MCV>96) with hemoglobin < 12 mg/dl in females and < 13 mg/dl in males were enrolled and data pertaining to complete blood count, serum level of vitamin B12 and RBC folate were analyzed. Result: A total of 95 patients (65 males and 30 females) with hemoglobin < 12 mg/dl in females and < 13 mg/dl in males were taken. Mostly were non vegetarian and majority of the patients belongs to age group of 34-54 years. It was found that 69 patients (48 males and 21 females) from total of 95 had vitamin B12 deficiency which is 72.6% and 43 patients (20 males and 23 females) from total of 95 had folate deficiency which is 45.26%.Conclusion: Our study concludes that vitamin B12 is a major contributing factor of macrocytic anemia in our population. Dietary insufficiency, poor absorption and increase demand might be contributing to high prevalence of vitamin B12 deficiency in our population. Therefore our medical community should seriously consider the merit of early screening for vitamin B12 deficiency and take precautions against the clinical consequences of vitamin B12 deficiency.

Newborn Screening for Vitamin B12 Deficiency in Germany—Strategies, Results, and Public Health Implications

To evaluate a systematic newborn screening (NBS) strategy for vitamin B12 deficiency. In a prospective single-center NBS study, a systematic screening strategy for vitamin B12 deficiency was developed and evaluated. Tandem-mass spectrometry screening was complemented by 2 second-tier strategies, measuring methylmalonic/3-OH-propionic/methylcitric acid, and homocysteine from dried blood spots. In a cohort of 176 702 children screened over 27months, 33 children were detected by NBS in whom (maternal) vitamin B12 deficiency was confirmed. Homocysteine was the most sensitive marker for vitamin B12 deficiency, but only combination with a second-tier strategy evaluating methylmalonic acid allowed for detection of all 33 children. Mothers were of various ethnic origins, and 89% adhered to a balanced diet. Treatment in children was performed predominantly by oral vitamin B12 supplementation (84%), and all children remained without clinical symptoms at short-term follow-up. Vitamin B12 deficiency is a treatable condition but can cause severe neurologic sequelae in infants if untreated. The proposed screening strategy is feasible and effective to identify moderate and severe cases of vitamin B12 deficiency. With an incidence of 1:5355 newborns, vitamin B12 deficiency is more frequent than inborn errors of metabolism included in NBS panels. Treatment of vitamin B12 deficiency is easy, and additional benefits can be achieved for previously undiagnosed affected mothers. This supports inclusion of vitamin B12 deficiency into NBS but also stresses the need for increased awareness of vitamin B12 deficiency in caregivers of pregnant women.

Extremely severe vitamin B12 deficiency

Aim: Vitamin B12 (cobalamin) is nutrient from the vitamin B complex family. It is essential in the human body for deoxyribonucleic acid (DNA) synthesis and for cellular energy production. Vitamine B12 deficiency is decrease in its serum concentration below 220 pmol/L, and it can be present in various range of hematologic and systemic symptoms and signs. The aim of this article is to provide extensive information on extreme forms of deficiency of vitamin B12. Case report: 83-year-old men presented with fatigue, intolerance of physical activity, vertigo, paresthesia in fingers, dispersion, epigastric pain, vomitting and loss of apetite. Vital parameters were within normal range, and physical examination did not reveal any patological findings, except icterus of sclera and subicterus of skin. Urgent laboratory findings showed erythrocytes 1.18 x 1012/L (4.34-5.72 x 1012/L), hemoglobin 50 g/L (138-175 g/L), mean corpuscular volume (MCV) 123.6 fL (83.0-97.2 fL), vitamin B12 < 61 pmol/L (220-665 pmol/L). Patient started parenteral therapy with vitamin B12. After 5 days, rapid increase in reticulocyte count was observed, with haemogram stabilization within 6 weeks. In a follow-up period of two years, the patient had no symptoms. Conclusion: We presented patient with extreme deficiency of vitamin B12. Screening for vitamin B12 deficiency should be established in each patient with macrocytic anemia, even with slightly elevated MCV.

Prevention of Micronutrient Deficiencies in Young Children: Consensus Statement from Infant and Young Child Feeding Chapter of Indian Academy of Pediatrics

Micronutrient deficiencies have significant impact on the overall health and well-being of society and potential targets for supplementations. It is important to formulate a consensus statement in view of current evidence, and put in place strategies to meet targets. To formulate by endorsement or adoption and disseminate a consensus statement for prevention of micronutrients deficiencies in young children for office practices from an Indian perspective. A National Consultative Meeting was convened by Infant and Young Child Feeding Chapter (IYCF) of Indian Academy of Pediatrics (IAP) on 17 December, 2016 at Mumbai. IYCF chapter, IAP, United Nations Children Fund, National Institute of Nutrition and Government of India were the participating agencies; and participants representing different parts of India were included. Micronutrient deficiencies are widespread. For its prevention proper maternal and infant-young child feeding strategies need to be practiced. Encourage delayed cord clamping, dietary diversification, germinated foods, soaking and fermentation processes. Existing Iron, Vitamin A, Zinc supplementation and universal salt iodization programs need to be scaled up, especially in high risk groups. Universal vitamin D supplementation need to be in place; though, the dose needs more research. Vitamin B12 deficiency screening and supplementation should be practiced only in high-risk groups. Availability of appropriately fortified foods needs to be addressed urgently.

Vitamin B12 deficiency and the knowledge and practice of physicians regarding screening for vitamin B12 deficiency among type 2 diabetic patients on metformin in selected hospitals in Riyadh, Saudi Arabia.

Background/Aim:The worldwide prevalence of diabetes is high including Saudi Arabia. One standard first-line treatment for diabetes is metformin, which was reported to increase the risk for vitamin B12 deficiency. We wanted to determine the prevalence of vitamin B12 deficiency in metformin-treated type 2 diabetes mellitus patients.Methods:We conducted a cross-sectional study at the diabetic clinics of four hospitals in Riyadh, Saudi Arabia. Type 2 diabetes mellitus patients who were on metformin for at least 1 year were included in the study. Associations between B12 deficiency and age, duration of type 2 diabetes mellitus (T2DM), duration of use and dosage of metformin, and use of proton pump inhibitors (PPIs) were determined.Results:Of 363 T2DM patients, 206 (56.7%) were males and 157 (43.3%) were females, mean age was 53.72 ± 11.31 years, the mean duration of T2DM was 9.89 ± 7.32 years, and the mean duration of metformin use was 9.84 ± 7.29 years. There were 205 patients 56.5% who had a daily dose of 750 mg of metformin. The most commonly used oral hypoglycemic agent was gliclizide only in 138 (38.4%) of patients. There were 107 patients (29.5%) who were on PPIs. There were 210 patients (57.9%) who were on vitamin B12 supplementation, of which 111 (30.6%) had a daily dose of 200 mcg. The use of vitamin B12 supplement, duration of T2DM and duration of metformin use was significantly higher among females. The use of vitamin B12 supplement was significant among patients who were 46 years old and above. There were only 16 patients (4.4%) who had available serum vitamin B12 levels. Only 44.0% of the physician respondents know the current recommendation of American Diabetes Association on vitamin B12 screening and supplementation among diabetic patients, and 21.0% never prescribe vitamin B12 to their patients.Conclusion:Routine testing for serum vitamin B12 level is not practiced in our institution. A large percentage of physicians are not aware of the current recommendations of the American Diabetic Association (ADA) regarding vitamin B12 supplementation and screening. Thus, there is a need for doctors involved in the management of diabetes to keep abreast with guidelines and current recommendations and routinely monitor vitamin B12 levels particularly those who were on long-term takers of metformin and the elderly patients to optimize management of diabetes and its complications.

Failure of the holotranscobalamin assay in vitamin B12-deficient patients

AbstractBackgroundIt has been demonstrated that vitamin B12 determinations fail, especially in patients with pernicious anemia with high titers of intrinsic factor antibody. Consistent with this finding, we observed a case of falsely normal holotranscobalamin (HoloTC) results in a patient with pernicious anemia and severe vitamin B12 deficiency. We aimed to investigate whether such a situation can also be seen in other individuals.MethodsWithin the frameworks of the SENIORLAB study and routine samples from a mixed patient population referred to a laboratory for investigation of B12 status, we searched for study participants displaying a normal HoloTC level (≥50 pmol/L) together with a decreased total vitamin B12 level (<125 pmol/L). Thereafter, we determined whether samples with discrepant biochemical markers (i.e. low vitamin B12, normal HoloTC) also had increased functional markers of vitamin B12 deficiency (methyl malonic acid [MMA], homocysteine [Hcy]) and/or a low value of Fedosov’s combined indicator of vitamin B12 status (<−0.5).ResultsThe prevalence of a normal HoloTC level and low total vitamin B12 level among the group of healthy seniors (n=1451) was 0.21% (95% confidence interval [CI], CI, 0.08–0.6%). Among the 106,635 routine samples with concurrent HoloTC and total vitamin B12 determination, 176 (i.e. 0.17%, 95% CI, 0.14–0.19%) had discrepant biochemical markers. Among them, 24 who were identified as having discrepant biochemical markers and a diagnosis of vitamin B12 deficiency could be confirmed with functional markers.ConclusionsInitial and isolated screening for vitamin B12 deficiency using a HoloTC cut-off of ≥50 pmol/L in a small subset of patients may reveal false-negative (normal) results, meaning that patients with vitamin B12 deficiency may remain undetected.

Maternal and neonatal vitamin B12 deficiency detected by expanded newborn screening

Infant vitamin B12 deficiency can manifest as a severe neurodegenerative disorder and is usually caused by maternal deficiency due to vegetarian diet or pernicious anaemia. Its early recognition and treatment can prevent potentially serious and irreversible neurologic damage. Biochemically, vitamin B12 deficiency leads to an accumulation of methylmalonic acid, homocysteine, and propionylcarnitine. Expanded newborn screening using tandem mass spectrometry may identify neonatal and maternal vitamin B12 deficiency by measurement of propionylcarnitine and other metabolites in the dried blood spot sample of newborns. To summarize our experiences gained by screening for vitamin B12 deficiency. Clinical and laboratory data of vitamin B12-deficient infants diagnosed in Szeged Screening Centre were retrospectively analysed. In Hungary, expanded newborn screening was introduced in 2007. Since then approximately 395 000 newborns were screened in our centre and among them, we identified four newborns with vitamin B12 deficiency based on their screening results. In three cases an elevated propionylcarnitine level and in the fourth one a low methionine level were indicative of vitamin B12 deficiency. We also detected an additional vitamin B12-deficient infant with neurological symptoms at 4 months of age, after a normal newborn screening, because of elevated urinary methylmalonic acid concentration. Vitamin B12 deficiency was secondary to maternal autoimmune pernicious anaemia in all the five infants. As a result of the recognized cases the incidence of infant vitamin B12 deficiency in the East-Hungarian region was 1.26/100 000 births, but the real frequency may be higher. Conslusions: Optimizing the cut off values of current screening parameters and measuring of methylmalonic acid and/or homocysteine in the dried blood spot, as a second tier test, can improve recognition rate of vitamin B12 deficiency. Orv Hetil. 2017; 158(48): 1909-1918.

Vitamin B12 deficiency among vegetarian and non-vegetarian diabetic population receiving prolonged Metformin based oral hypoglycemic agents therapy

Background: Diabetes is a group of metabolic disorder that share the phenotype of hyperglycemia. Over the period of time the metabolic dysregulation associated with diabetes mellitus causes secondary pathophysiological changes in multiple organs like heart, blood vessels, eyes, kidney and nerves resulting in various complications. However, a common potential interaction of metformin with vitamin B-12 is well documented but is poorly studied by the physicians who prescribe metformin to their diabetic patients. Since vitamin B-12 deficiency is common among vegan population as compared to population consuming food of animal origin (meat, fish and dairy products). But in this article, it has been studied that metformin cause vitamin B-12 deficiency even in non-vegetarian population. The aim of this study was to asses’ vitamin B12 deficiency among vegetarian and non-vegetarian diabetic population receiving prolonged Metformin based oral hypoglycaemic agents therapy. It was a cross sectional study done in Department of Medicine, UPUMS, Saifai, Etawah, Uttar Pradesh, India.Methods: Study done among patients of type 2 diabetes mellitus of age group 30-60 years on prolonged metformin based OHA therapy and having peripheral neuropathy were included in study. Data was analysed on SPSS Version 22.0 and p value obtained.Results: Statistical analysis of 93 patients included in study showed that vitamin B12 deficiency is common among the vegetarian (56.52%) and non-vegetarian (35.71%) population but the difference is not statistically significant (p value=0.29) which is more in favour of metformin associated vitamin B12 deficiency in non-vegetarian population.Conclusions: Vitamin B12 deficiency is common in diabetes patients on metformin based OHA therapy hence we recommend routine screening for Vitamin B12 deficiency in such diabetes patients.

Vitamin B12 deficiency among adult diabetic patients in Uganda: relation to glycaemic control and haemoglobin concentration.

BackgroundVitamin B12 deficiency is highly prevalent among adult individuals with diabetes yet screening is infrequent in Uganda. There are currently no published data regarding the prevalence of vitamin B12 deficiency and its associated factors among adult individuals with diabetes in sub-Saharan Africa. This study aimed at describing the prevalence and factors associated with vitamin B12 deficiency among this patient population in a resource constrained setting in sub-Saharan Africa.MethodsIn this cross-sectional study, 280 eligible study participants attending the outpatient diabetic clinic at Mulago national referral and teaching hospital in Kampala, Uganda were enrolled. Their socio-demographic, clinical and laboratory data was collected using a pre-tested questionnaire.ResultsThe majority of the study participants were female (68.9 %), with a median age of 50 (IQR: 40–58) years. The mean (SD) serum vitamin B12 levels was 472.0 (16.4) pg/ml. The prevalence of vitamin B12 deficiency was 10.7 %. Hemoglobin level < 12 g/dl (AOR 3.38; 95 % CI 1.38–8.32, p value = 0.008) and glycated hemoglobin ≥ 7 % (AOR 3.29; 1.44–7.51, p value = 0.005) were associated with vitamin B12 deficiency.ConclusionsVitamin B12 deficiency is prevalent in approximately 1 in 10 of adult individuals with diabetes in Uganda. We recommend screening for vitamin B12 deficiency among diabetic patients in Uganda especially those with low hemoglobin concentrations and glycated hemoglobin levels ≥ 7 %.

Folate, vitamin B12 and Homocysteine status in the post-folic acid fortification era in different subgroups of the Brazilian population attended to at a public health care center.

BackgroundFolate and vitamin B12 are essential nutrients, whose deficiencies are considerable public health problems worldwide, affecting all age groups. Low levels of these vitamins have been associated with high concentrations of homocysteine (Hcy) and can lead to health complications. Several genetic polymorphisms affect the metabolism of these vitamins. The aims of this study were to assess folate, vitamin B12 and homocysteine status in distinct Brazilian individuals after the initiation of folic acid fortification by Brazilian authorities and to investigate the effects of RFC1 A80G, GCPII C1561T and MTHFR C677T polymorphisms on folate, vitamin B12 and Hcy levels in these populations.MethodsA total of 719 individuals including the elderly, children, as well as pregnant and lactating women were recruited from our health care center. Folate, vitamin B12 and Hcy levels were measured by conventional methods. Genotype analyses of RFC1 A80G, GCPII C1561T and MTHFR C677T polymorphisms were performed by PCR-RFLP.ResultsThe overall prevalence of folate and vitamin B12 deficiencies were 0.3% and 4.9%, respectively. Folate deficiency was observed only in the elderly (0.4%) and pregnant women (0.3%), whereas vitamin B12 deficiency was observed mainly in pregnant women (7.9%) and the elderly (4.2%). Plasma Hcy concentrations were significantly higher in the elderly (33.6%). Pregnant women carrying the MTHFR 677TT genotype showed lower serum folate levels (p = 0.042) and higher Hcy levels (p = 0.003). RFC1 A80G and GCPII C1561T polymorphisms did not affect folate and Hcy levels in the study group. After a multivariate analysis, Hcy levels were predicted by variables such as folate, vitamin B12, gender, age and RFC1 A80G polymorphism, according to the groups studied.ConclusionOur results suggest that folate deficiency is practically nonexistent in the post-folic acid fortification era in the subgroups evaluated. However, screening for vitamin B12 deficiency may be particularly relevant in our population, especially in the elderly.

P-084 An Educational Intervention With Enhanced Use of Electronic Medical Records Improves Screening for Vitamin B12 Deficiency in Crohn’s Disease

Individuals with Crohn’s disease (CD) are at increased risk for vitamin B12 malabsorption. It is recommended that physicians evaluate vitamin B12 levels in CD patients. There is data to suggest that vitamin B12 levels are inconsistently measured in CD patients. This study evaluated the rate of physicians’ vitamin B12 assessment prior to and following an educational intervention at an urban, university medical center. Database I, created in 2009, obtained vitamin B12 levels in consecutive Crohn’s patients during a 1 year period. There were no exclusion criteria. Patients’ intestinal involvement (terminal ileum, only colonic) was documented. Patients’ confidentiality was maintained. An educational intervention that focused on obtaining vitamin B12 levels in Crohn’s patients was conducted during the past year. The intervention included a didactic lecture addressing potential nutrient deficiencies in Crohn’s disease and enhanced utilization of electronic medical records that incorporated structured notes for inflammatory bowel disease. Database II, created in 2014, obtained vitamin B12 levels in consecutive Crohn’s patients during a 9 month period. There were no exclusion criteria. Patients’ intestinal involvement (terminal ileum, only colonic) was documented. Patients’ confidentiality was maintained. Statistical analysis using Fisher Exact Test was performed with significance set at P < 0.05. The study was approved by the University IRB. Database 1 included 108 Crohn’s patients (74 with ileal involvement, 34 with only colonic involvement). 45 (41.6%) had vitamin B12 measured. In the 74 patients with ileal involvement, 37 had vitamin B12 measured. In the 34 with only colonic involvement, 8 had vitamin B12 measured. There was a significant difference (P = 0.0117) in the rate at which Vitamin B12 was measured in individuals with ileal and those with colonic involvement. Database 2 included 38 Crohn’s patients (29 with ileal involvement, 9 with only colonic involvement). 29 (76.3%) had vitamin B12 measured. In the 29 with ileal involvement, 21 had vitamin B12 measured. In the 9 with only colonic involvement, 8 had vitamin B12 measured. There was no significant difference (P = 0.4105) in the rate at which vitamin B12 was measured in individuals with ileum and those with colonic involvement. Following the educational intervention, significantly more (P = 0.0003) Crohn’s patients had vitamin B12 measured. There was a significant difference in the rate at which both individuals with ileal disease (P = 0.0480) and colonic disease (P = 0.0006) had vitamin B12 measured. It is recommended that vitamin B12 level be measured in CD patients, supplementing when deficiency or insufficiency is identified. This study revealed that an educational intervention with enhanced use of electronic medical records improved vitamin B12 screening and documentation. Nevertheless, the rate of screening remains suboptimal. It is possible that some patients may have had laboratory tests that were obtained by providers outside of the university practice. Continued efforts to encourage physicians' adherence to guidelines recommending vitamin B12 measurement with improvement of medical record documentation can optimize clinical outcome.

Vitamin B12 deficiency among patients with diabetes mellitus: is routine screening and supplementation justified?

Vitamin B12 is an essential micronutrient required for optimal hemopoetic, neuro-cognitive and cardiovascular function. Biochemical and clinical vitamin B12 deficiency has been demonstrated to be highly prevalent among patients with type 1 and type 2 diabetes mellitus. It presents with diverse clinical manifestations ranging from impaired memory, dementia, delirium, peripheral neuropathy, sub acute combined degeneration of the spinal cord, megaloblastic anemia and pancytopenia. This review article offers a current perspective on the physiological roles of vitamin B12, proposed pathophysiological mechanisms of vitamin B12 deficiency, screening for vitamin B12 deficiency and vitamin B12 supplementation among patients with diabetes mellitus.

Screening for metabolic vitamin B12 deficiency by holotranscobalamin in patients suspected of vitamin B12 deficiency: a multicentre study

Vitamin B(12) deficiency occurs frequently, especially among the elderly. However, screening for vitamin B(12) deficiency is hampered by poor sensitivity of the existing total vitamin B(12) assay. Methylmalonic acid (MMA) is considered as the most representative indicator of metabolic vitamin B(12) deficiency and is used as such in this study. The aim of this study was to validate the clinical usefulness of holotranscobalamin (holoTC) as an initial screening assay for metabolic vitamin B(12) deficiency in a mixed patient population. Three hundred and sixty blood samples were collected by five Dutch hospitals. Vitamin B(12) and holoTC in serum were measured (AxSYM; Abbott). MMA in serum was measured by tandem mass spectrometry (LC-MS/MS). Receiver operating curve (ROC) analysis demonstrated a greater area under the curve (AUC) for holoTC than for vitamin B(12) in detecting vitamin B(12) deficiency characterized by three predefined cut-off levels of MMA. A cut-off value of 32 pmol/L of holoTC resulted in the highest sensitivity (83%) with acceptable specificity (60%) in detecting MMA concentrations above 0.45 μmol/L. The combination of vitamin B(12) and holoTC did not improve diagnostic accuracy at this cut-off level. HoloTC has a better diagnostic accuracy than vitamin B(12) and can replace the existing vitamin B(12) assay as a primary screening test in patients suspected of vitamin B(12) deficiency. Critical evaluation of cut-off values of holoTC indicated that a cut-off value of 32 pmol/L can be considered in screening for metabolic vitamin B(12) deficiency (defined by MMA > 0.45μmol/L) in a mixed patient population.

Renal impairment compromises the use of total homocysteine and methylmalonic acid but not total vitamin B12 and holotranscobalamin in screening for vitamin B12 deficiency in the aged

Vitamin B(12) deficiency and renal impairment are common in the aged, and therefore the screening test for vitamin B(12) deficiency should not be affected by renal function. Renal impairment has been associated with increased concentrations of plasma total homocysteine and methylmalonic acid, as well as increased total vitamin B(12) and holotranscobalamin concentrations. The effect of renal impairment on vitamin B(12)-related biochemical variables was assessed in 1011 aged subjects. Renal function as indicated by serum cystatin C correlated strongly with plasma total homocysteine (r(s)=0.53, p<0.001) and serum methylmalonic acid (r(s)=0.27, p<0.001), but not with serum total vitamin B(12) (r(s)=-0.04, p=0.227) or holotranscobalamin (r(s)=-0.01, p=0.817). Either total vitamin B(12) or holotranscobalamin rather than homocysteine or methylmalonic acid should be used when screening an aged population prone to renal impairment.

Measurement of Total Vitamin B12 and Holotranscobalamin, Singly and in Combination, in Screening for Metabolic Vitamin B12 Deficiency

The standard screening test for vitamin B12 deficiency, measurement of total plasma vitamin B12, has limitations of sensitivity and specificity. Plasma vitamin B12 bound to transcobalamin (holoTC) is the fraction of total vitamin B12 available for tissue uptake and therefore has been proposed as a potentially useful alternative indicator of vitamin B12 status. We compared the diagnostic accuracy of total vitamin B12, holoTC, and a combination of both measures to screen for metabolic vitamin B12 deficiency in an elderly cohort (age > or = 60 years). Plasma methylmalonic acid and homocysteine were used as indicators of vitamin B12 deficiency. Low total vitamin B12 (< 148 pmol/L) and low holoTC (< 35 pmol/L) were observed in 6.5% and 8.0%, and increased methylmalonic acid (> 350 nmol/L) and homocysteine (> 13 micromol/L) were observed in 12.1% and 17.0% of the study participants. In multiple regression models, holoTC explained 5%-6% more of the observed variance in methylmalonic acid and homocysteine than did total vitamin B12 (P < or = 0.004). ROC curve analysis indicated that total vitamin B12 and holoTC were essentially equivalent in their ability to discriminate persons with and without vitamin B12 deficiency. Individuals with low concentrations of both total vitamin B12 and holoTC had significantly higher concentrations of methylmalonic acid and homocysteine than did individuals with total vitamin B12 and/or holoTC within the reference intervals (P < 0.001). HoloTC and total vitamin B12 have equal diagnostic accuracy in screening for metabolic vitamin B12 deficiency. Measurement of both holoTC and total vitamin B12 provides a better screen for vitamin B12 deficiency than either assay alone.

Should we monitor vitamin B12 levels in patients who have had end-ileostomy for inflammatory bowel disease?

We examined whether vitamin B12 levels are low following surgery in those patients who have had end-ileostomy for inflammatory bowel disease. This prospective observational study used the database of a university teaching hospital to identify patients with inflammatory bowel disease with an end-ileostomy constructed more than 30 months previously. Precise diagnosis, disease distribution and details of their surgery were collected from case notes of the 39 eligible patients (18 Crohn's disease, 17 ulcerative colitis, 4 indeterminate colitis). Mean duration since ileostomy formation was 12.53 years. Patients found to be vitamin B12 deficient underwent further investigations to ascertain the cause of their vitamin B12 deficiency (<150 ng/l). There was no significant difference between serum vitamin B12 levels in patients with Crohn's disease and those in patients with ulcerative colitis following end ileostomy formation. Two patients (5.1%) were identified as having vitamin B12 deficiency. One of these had had a panproctocolectomy for Crohn's disease, followed by subsequent resection for ileal obstruction and ongoing small intestinal disease. The other had had colectomy for ulcerative colitis, in whom no cause other than the ileostomy was found for the vitamin B12 deficiency. There was no significant correlation between serum vitamin B12 levels and duration of ileostomy overall or in the disease subgroups. We do not recommend routine screening for vitamin B12 deficiency in this group of patients unless they have undergone additional small bowel resection or have ongoing small bowel inflammation.