Polineuropatia diabética assintomática induzida pelo uso crônico de metformina e correlação com vitamina B12 / Asymptomatic diabetic polyneuropathy induced by chronic metformin use and correlation with vitamin B12

Introdução: Diabetes Mellitus é doença metabólica, caracterizada pela deficiência absoluta ou relativa de insulina, que acomete cerca de 382 milhões de pessoas em todo mundo, tendo uma das complicações mais comuns a polineuropatia. A Metformina, medicamento amplamente utilizado como tratamento do Diabetes, foi descrita como responsável, em algumas literaturas, por causar ou agravar deficiência de vitamina B12, que está similarmente relacionada ao desenvolvimento de polineuropatia.Métodos: Nesse sentido, foi conduzido um estudo no município de Soledade ­ RS, com objetivo de verificar se essa relação é condizente com a realidade da localidade. Foram escolhidos 58 pacientes, dos quais 30 responderam questionários adaptados baseados na literatura e na Classificação de Neuropatia de Michigan (MNSS-Brasil), então colhidos 5 ml de sangue venoso da fossa antecubital, preparado soro do qual uma alíquota foi separada para determinação bioquímica da vitamina B12.Resultados: Analisando os resultados, a maioria dos pacientes analisados apresentou sintomas de polineuropatia, e 10% deste, deficiência vitamínica.Conclusão: nenhuma variável explicou a correlação do uso crônico da Metformina, dose e gênero com a deficiência da vitamina B12, o que indica que não há evidências fortes o suficiente que sustentem esse fato, de acordo com as particularidades da localidade analisada.

Introduction: Diabetes Mellitus is a metabolic disease, characterized by absolute or relative insulin deficiency, which affects about 382 million people, with polyneuropathy being one of the most common complications. Metformin, a drug widely used as a treatment for diabetes, has been described as responsible, in some literature, for causing or aggravating vitamin B12 deficiency, which is similarly related to the development of polyneuropathy.Methods: In this sense, a study was conducted in Soledade ­ RS, in order to verify whether this relationship is consistent with the reality of the locality. Fifty-eight patients were selected, of which 30 answered adapted questionnaires based on the literature and on the Michigan Neuropathy Classification (MNSS-Brazil), then 5 ml of venous blood was collected from the antecubital fossa, serum prepared from which an aliquot was separated for biochemical determination of the vitamin B12.Results: Analyzing the results, most of these patients presented symptoms of polyneuropathy and, 10% of them, vitamin deficiency.Conclusion: no variable explained the correlation of chronic use of Metformin, dose and gender with vitamin B12 deficiency, which indicates that there is not enough evidence to support this fact, according to the particularities of the analyzed locality.

Manifestaciones neurológicas del déficit de vitamina B12 en pediatría / Neurological manifestations of vitamin B12 deficiency in pediatrics

Introducción: El déficit de vitamina B12 genera un proceso de desmielinización neuronal, manifestándose con anormalidades cerebrales y degeneración del cordón espinal. En pediatría, las manifestaciones neurológicas son una de las formas de presentación. Usualmente, se observa en niños alimentados con lactancia materna exclusiva cuyas madres tienen escaso consumo de alimentos de origen animal. Objetivo: Describir las manifestaciones neurológicas del déficit vitamínico e identificar factores de riesgo alimentario. Pacientes y método: Se realizó un estudio de serie de casos de 6 pacientes internados en el Hospital Garrahan con deficiencia de vitamina B12 en el periodo comprendido entre julio 1996 y diciembre 2013 cuyo diagnóstico se realizó mediante determinación sérica de vitamina B12. Resultados: La edad media de presentación de los síntomas fue de 3,6 meses. El 83.3% de los pacientes presentaron convulsiones, 60% las manifestaron de forma exclusiva y en el 40% se asociaron a hipotonía y pérdida de pautas madurativas. Un 16.7% presentó hipotonía más pérdida de pautas sin presentar convulsiones. Respecto de la alimentación, la totalidad recibía lactancia materna, el 83.3% de forma exclusiva, el 16.7% asociada a leche maternizada. En cuanto a la dieta de las madres de pacientes alimentados con pecho materno exclusivo, el 40% realizaba dieta vegetariana estricta, en otro 40% no se hallaron datos relacionados con su alimentación, pero se diagnosticó déficit de vitamina B12 por dosaje sérico, y el 20% restante refería recibir dieta general. Conclusión: Ante el aumento de la incidencia de la población vegetariana/vegana, se debería considerar la deficiencia de vitamina B12 ante pacientes con manifestaciones neurológicas de etiología desconocida, dado que es una enfermedad con un tratamiento inocuo y efectivo, y se evidencia mejoría clínica, y de los parámetros de laboratorio en todos los casos (AU)

Introduction: Vitamin B12 deficiency may cause a process of neuronal demyelination associated with brain abnormalities and degeneration of the spinal cord. In pediatrics, neurological manifestations are one of the forms of presentation. It is usually observed in exclusively breast fed children whose mothers do not consume food of animal origin. Aim: To describe neurological manifestations of vitamin B12 deficiency and identify nutritional risk factors. Patients and method: A series of 7 patients admitted to Hospital Garrahan with vitamin B12 deficiency diagnosed by vitamin B12 serum level testing were evaluated between July and December of 1996-2013. Results: Mean age at symptom presentation was 3,6 months. Overall, 83.3% of the patients presented with seizures, in 60% as the only symptom and in 40% associated with hypotonia and developmental delay. Hypotonia and developmental delay without seizures were observed in 16.7%. A single patient presented with pancytopenia only. All infants were breastfed, 83.3% exclusively, 16.7% in combination with formula, and the remaining 14.3% in combination with food. Regarding the diet of the mothers of the exclusively breastfed children, 40% followed a strict vegetarian diet, for another 40% no data on their diet were available but they were diagnosed with vitamin B12 based on serum values, and the remaining 20% followed a general diet. Conclusion: As the incidence of vegetarianism/veganism is increasing in the population, vitamin B12 deficiency should be considered in patients with neurological symptoms of unclear etiology, as treatment of the condition is innocuous and effective and leads to clinical and laboratory parameter improvement in all cases (AU)

Mielopatia por deficiência de cobalamina: resolução clínica e de imagem / Cobalamin deficiency myelopathy: clinical and imaging resolution

Embora o quadro clássico de mielopatia por deficiência de vitaminaB12 seja a degeneração subaguda combinada da medula, a manifestaçãoclínica pode ser variável. Homem branco de 36 anos de idade com hipotireoidismo e vitiligo apresentou dormência nas mãos de início súbito. Exame físico: sinal de Lhermitte e hipoestesia nas palmas. Evidenciada alteração de sinal na ressonância magnética (RM) da medula cervical. Foram evidenciados nível sérico de vitamina B12 de 150 pg/mL, gastrite atrófica e hemograma normal. Paciente foi tratado com reposição intramuscular de vitamina B12. Após seis meses, houve remissão completa dos sintomas com normalização do exame de imagem em um ano. O presente caso ilustra discreta alteração clínica e lesão extensa na RM (dissociação entre a clínica e o exame de imagem) na deficiência de B12. A melhora dos sintomas precedeu a resolução da alteração no exame de imagem, no presente caso.

Although the classic manifestation of myelopathy due to vitamin B12deficiency is a subacute combined degeneration of the spinal cord, the clinical manifestation may be varied. A 36-year-old white man with hypothyroidism and vitiligo presented sudden onset of numbness in hands. Physical examination: Lhermitte's sign and hypoesthesia in palms. Signal change on magnetic resonance image (MRI) of the cervical spinal cord was evidenced. Serum vitamin B12 of 150 pg/mL, gastric atrophy and normal hemogram were shown. The patient was treated with intramuscular vitamin B12 replacement. After six months there was complete remission of the symptoms, and within one year the MRI was normal. This case illustrates mild clinical signs and extensive changes on MRI (dissociation between clinic and image) in B12 deficiency. Resolution of MRI was observed after the clinical signs, in the present case.

Association of Vitamin B12 Deficiency and Metformin Use in Patients with Type 2 Diabetes

We evaluated the prevalence of vitamin B12 deficiency and associated factors in type 2 diabetes patients using metformin. A total of 799 type 2 diabetes patients using metformin was enrolled. Vitamin B12 and folate levels were quantified by chemiluminescent enzyme immunoassay. Vitamin B12 deficiency was defined as vitamin B12 4 ng/mL). The prevalence of vitamin B12 deficiency in metformin-treated type 2 diabetes patients was 9.5% (n = 76), and the mean vitamin B12 level was 662.5 +/- 246.7 pg/mL. Vitamin B12 deficient patients had longer duration of metformin use (P or = 2,000 mg were 2.52 (95% CI, 1.27-4.99, P = 0.008) and 3.80 (95% CI, 1.82-7.92, P or = 10 yr were 4.65 (95% CI, 2.36-9.16, P 1,000 mg) and longer durations (> or = 4 yr) of treatment.

Vitamin B12 deficiency in India: Mean corpuscular volume is an unreliable screening parameter.

Background. Vitamin B12 deficiency is thought to be more common than was previously believed, but there are little data from India on this. It has protean clinical manifestations, and raised mean corpuscular volume (MCV) is commonly used by physicians as an indicator for megaloblastic anaemia caused by vitamin B12 deficiency. We evaluated the clinical profiles of our patients with vitamin B12 deficiency and tried to ascertain how useful MCV and the peripheral smear were in diagnosis. Methods. We evaluated the clinical picture, haematology indices and peripheral smear findings of 117 patients with low vitamin B12 levels. Serum folic acid, ferritin values and biopsy findings of some patients were also assessed. Results. Patients were commonly detected to have reduced levels of serum vitamin B12 during the work-up for anaemia (n=45) or for neurological symptoms (n=31). Of the 94 cases in which smears were examined, 26 showed macrocytes and hypersegmented neutrophils were present in 24. Twentysix patients showed a raised MCV, 50 patients had an MCV within the reference range and 28 had low MCV. Pancytopenia was present in 5 patients. Concomitant iron deficiency, as judged by serum ferritin levels, was present in 18 patients. Conclusion. Vitamin B12 deficiency is not uncommon in India. It is often diagnosed during the work-up for a haematological disorder or for neurological symptoms. MCV is unreliable as a screening parameter for the presumed diagnosis of macrocytic anaemia, which is associated with vitamin B12 deficiency.

Megaloblastic anemia: Back in focus.

Megaloblastic anemia (MA), in most instances in developing countries, results from deficiency of vitamin B12 or folic acid. Over the last two to three decades, incidence of MA seems to be increasing. Of the two micronutrients, folic acid deficiency contributed to MA in a large majority of cases. Now deficiency of B12 is far more common. In addition to anemia, occurrence of neutropenia and/or thrombocytopenia is increasingly being reported. Among cases presenting with pancytopenia, MA stands out as an important (commonest cause in some series) cause. This article focuses on these and certain other aspects of MA. Possible causes of increasing incidence of MA are discussed. Observations on other clinical features like neurocognitive dysfunction, associated hyperhomocysteinemeia and occurrence of tremors and thrombocytosis during treatment are highlighted.

Comparison between serum holotranscobalamin and total vitamin B12 as indicators of Vitamin B12 status

This study aims to assess the usefulness of serum holotranscobalamin [holo TC], the fraction of vitamin B12 that is available for tissue uptake, compared with total vitamin B12 in patients investigated for vitamin B12 disorders. Serum samples were randomly selected from 76 patients [48females, 28 males; age range 12-69 years] referred to the Clinical Biochemistry Laboratory, Royal Hospital for the assessment of vitamin B12 status. For each patient, serum total vitamin B12 was determined by chemiluminescent microparticle immunoassay on Architect 2000 analyzer and holo TC[active vitamin B12] level was determined by microparticle enzyme immunoassay on Axsym analyzer [both from Abbott, USA]. Comparison of the data was conducted to reflect the mean, standard deviation [SD] and correlation coefficient between the two groups. The mean [SD] for serum holo TC and total vitamin B12 were 46.5[32.2] pmol/L and 316.3[165.6] pmol/L respectively. There was a significant correlation between holo TC and total vitamin B12 [r=0.765, P<0.001] and the regression equation was expressed as; y= a+bx [i.e: holot TC = 1.5+0.14 total vitamin B12]. Also, the results were assessed for any misclassification when comparing holo TC and the total vitamin B12 in terms of whether each or both values agree or disagree for classifying the patients as having normal or abnormal [low or high] results, based on the cut-off thresholds of the kit's quoted reference range for holo TC of 9-123 pmol/L and for total vitamin B12 of 140-600 pmol/L. Accordingly, in69 [90.8%] samples, there was a parallel agreement/ classification of results, both being normal or abnormal. In 61 [80.4%] patients, both results were normal, whereas in 4 [5.2%] patients, both results were high, and in 4 [5.2%] patients both results were low. However, in 7[9.8%] cases, there was disagreement/ misclassification of results; 6 [7.8%] patients, holo TC was normal while total vitamin B12 was low, and in 1 [1.4%] patient, holo TC was normal while total vitamin B12 was low, and in 1 [1.4%] patient, holo TC was normal while total vitamin B 12 was high. It can be recommended that holo TC and total vitamin B 12, alone and in combination, have almost equal diagnostic efficiency reflector of vitamin B 12 status. Further comparison studies based on a gold standard method for classifying vitamin B 12 status are worth considering

Relationship between the Levels of Holotranscobalamin and Vitamin B12 / 대한진단검사의학회지

To date, the determination of serum vitamin B12 levels has been the most common laboratory test for the assessment of vitamin B12 status; however, the diagnostic accuracy of this test is low. To obtain a more sensitive marker, a new test to measure holotranscobalamin (holoTC) levels has been introduced. In this study, we assessed 45 patients for whom a vitamin B12 test had been requested and 139 anemic patients. We investigated the associations between the levels of homocysteine (Hcy) and those of holoTC, serum vitamin B12, and folate and assessed the diagnostic value of holoTC levels as a marker for vitamin B12 deficiency. We also determined the precision of the AxSYM holoTC assay by calculating the coefficient of variance (CV). The within-run and between-run precision values were excellent, as all CV values were less than 3.5%. The holoTC levels were low (12 micromol/L) indicated vitamin B12 deficiency. Thus, the holoTC levels were more sensitive than the serum vitamin B12 levels for indicating vitamin B12 status. If the serum vitamin B12 level is 151-300 pmol/L, the levels of holoTC alone or in combination with serum vitamin B12 levels are likely to be more useful markers than serum vitamin B12 levels alone.

lnfantile dyskinesia and vitamin B12 deficiency

We report an 11-months old female infant, failure to thrive, developmentally delayed, who presented to Prince Ali hospital in the south of Jordan with chorea involving right side of the face, and right upper limb, found to have megaloblastic anemia due to vitamin B12 deficiency

RAEB-t in young adults--a rare entity.

Refractory anemia with excess blasts in transformation (RAEB-t) in young adults is a rare entity. RAEB-t presenting with megaloblastic erythropoiesis should be differentiated from nutritional B12 and folic acid deficiency and from acute erythroleukemia. We report two cases in the present article.

Investigación de la deficiencia de hierro en pacientes con insuficiencia renal crónica en hemodiálisis / Investigation of iron deficiency in patients with chronic kidney failure in hemodialysis

Se estudiaron 19 pacientes con IRC, en hemodiálisis entre 1 y 108 meses. Siete eran mujeres (22-65 años) y 12 varones (22-66 años). La causa de la IRC fue GNC 4, PNC 3, nefroangioesclerosis 3, GNMP 2, uropatía obstructiva 2, indeterminada 2, poliquistosis 1, nefronoptisis 1 y GNPD 1. Nueve pacientes habían recibido transfusiones en el año previo al estudio, pero ninguno había sido tratado con hierro ni con eritropoyetina. La hemocitometría se realizó con un analizador electrónico, también se midió la ferremia, la transferinemia, la ferritina sérica, y el hierro medular en una proporción de los casos. Se observó una correlación significativa entre la ferritina sérica y el hierro medular. La asociación VCM menor de 80 fl y HCM menor de 27 pg tuvo valor predictivo para deficiencia de hierro (ferritina sérica menor de 30 ng/ml y/o hierro medular menor de dos cruces), con 60% de sensibilidad y 100% de especificidad. La ferremia y la saturación de la transferrina no fueron útiles para el diagnóstico de deficiencia de hierro en la IRCHD. Cinco de los 19 pacientes estudiados tenían deficiencia de hierro (26%), y 2 de ellos respondieron favorablemente a la administración parenteral del mismo. El empleo racional de la eritropoyetina recombinante, para el tratamiento de la anemia en la IRCHD, hace necesario investigar la posible deficiencia de hierro así como de otros factores hemopoyéticos en estos pacientes

Anemia megaloblastica en el Hospital 2 de Mayo: agosto 1984 - abril 1987 / Megaloblastic anemia in the Hospital 2 de Mayo: August 1984 - april 1987

Se estudian 34 casos de Anemia Megaloblástica por deficiencia de vitamina B12 y/o ácida fólico, atendido a diferentes parámetros hematológicos, bioquímicos, clínicos y otros datos complementarios comparando los resultados obtenidos con lo publicado en la literatura médica. Los datos más relevantes que se ha obtenido se pueden concretar diciendo que la Anemia Megaloblástica es una enfermedad de ligero predominio femenino y con preferencias por las edades avanzadas. Las manifestaciones de anemia son las alteraciones clínicas más frecuentemente encontradas. Se trata generalmente de anemias marcadas acompañadas de discretas leucopenia y trombocitopenia. En nuestro medio se tipifica la etiología y a todos los pacientes se les trata con la administración simultánea de vitamina B12 y ácido fólico. La incidencia real de esta anemia es difícil de establecer, puesto que los tratamientos polivitamínicos administrados muchas veces de forma indiscriminada pueden enmascarar un número elevado de casos, sobre todo en el ámbito extrahospitalario