Prevalence of vitamin B12 deficiency in type 2 diabetic patients using metformin: a cross-sectional study / Prevalência de deficiência de vitamina B12 em pacientes diabéticos do tipo 2 usando metformina: um estudo transversal

ABSTRACT: CONTEXT AND OBJECTIVE: The prevalence of vitamin B12 deficiency varies from 5.8% to 30% among patients undergoing long-term treatment with metformin. Because of the paucity of data on Brazilian patients, this study aimed to determine the frequency of B12 deficiency and related factors among Brazilian patients with type 2 diabetes mellitus (T2DM) using metformin. DESIGN AND SETTING: Cross-sectional study at a public university hospital. METHODS: Patients with T2DM and a control group of non-diabetics were included. Serum B12 levels were measured and biochemical B12 deficiency was defined as serum levels < 180 pg/ml. Associations between B12 deficiency and age, duration of T2DM, duration of use and dosage of metformin, and use of proton pump inhibitors (PPIs) or histamine H2 antagonists were determined. RESULTS: 231 T2DM patients using metformin (T2DM-met) and 231 controls were included. No difference in the frequency of PPI or H2-antagonist use was seen between the groups. B12 deficiency was more frequent in the T2DM-met group (22.5% versus 7.4%) and this difference persisted after excluding PPI/H2-antagonist users (17.9% versus 5.6%). The factors that interfered with serum B12 levels were PPI/H2-antagonist use and duration of metformin use ≥ 10 years. Use of PPI/H2-antagonists was associated with B12 deficiency, with an odds ratio of 2.60 (95% confidence interval, 1.34-5.04). CONCLUSIONS: Among T2DM patients, treatment with metformin and concomitant use of PPI/H2-antagonists are associated with a higher chance of developing B12 deficiency than among non-diabetics.

RESUMO: CONTEXTO E OBJETIVO: A prevalência de deficiência de vitamina B12 varia de 5,8% a 30% nos pacientes em tratamento a longo prazo com metformina. Devido à escassez de dados em pacientes brasileiros, este estudo determinou a frequência de deficiência de B12 e fatores relacionados em pacientes brasileiros com diabetes mellitus tipo 2 (DM2) usando metformina. TIPO DE ESTUDO E LOCAL: Estudo transversal em hospital público universitário. MÉTODOS: Pacientes com DM2 e um grupo controle de não diabéticos foram incluídos. Os níveis séricos de vitamina B12 foram dosados e deficiência bioquímica de B12 foi definida como níveis séricos < 180 pg/ml. Foi investigada a associação entre deficiência de B12 e idade, duração do DM2, duração do uso e dose de metformina, uso de inibidores de bomba de prótons (IBP) ou antagonistas dos receptores histamínicos H2 (antagonistas-H2). RESULTADOS: 231 pacientes DM2 usando metformina (DM2-met) e 231 controles foram incluídos. Não houve diferença na frequência de uso de IBP/antagonistas-H2 entre os grupos. Deficiência de B12 foi mais frequente no grupo DM2-met (22,5% versus 7,4%) e essa diferença persistiu após exclusão dos usuários de IBP/antagonistas-H2 (17,9% versus 5,6%). Fatores que interferiram nos níveis séricos de B12 foram: uso de IBP/antagonistas-H2 e duração do uso de metformina ≥ 10 anos. O uso de IBP/antagonistas-H2 associou-se com deficiência de B12, com um risco relativo de 2,60 (95% intervalo de confiança, 1,34-5,04). CONCLUSÕES: Considerando pacientes com DM2, o tratamento com metformina e uso concomitante de IBP/antagonistas-H2 estão associados com maior chance de desenvolver deficiência de B12 quando comparado aos não diabéticos.

Nutritional status of iron, vitamin B12, folate, retinol and anemia in children 1 to 11 years old: Results of the Ensanut 2012 / Estado nutricional de hierro, vitamina B12, folato, retinol y anemia en niños de 1 a 11 años: Resultados de la Ensanut 2012

Objective. To describe the frequency of anemia, iron, vitamin B12, folate, retinol and predictors of anemia among Mexican children from Ensanut 2012. Materials and methods. Hemoglobin, ferritin, CRP, vitamin B12, retinol and folate concentrations were measured in 2 678 children aged 1-4 y and 4 275 children aged 5-11 y. Adjusted logistic regression models were constructed to assess the risk for anemia and micronutrient deficiencies. Results. In preschoolers and scholars, the overall prevalence of anemia was 20.4 and 9.7%, iron deficiency 14 and 9.3%, low vitamin B12 (LB12S) 1.9 and 2.6%; Folate 0.30 and 0%, and retinol depletion (VADp) 15.7 and 2.3%, respectively. ID and VADp were negatively associated with Hb (coefficient: -0.38 and -0.45, p<0.05); a higher log-CRP was associated with higher risk for anemia and VADp (OR=1.13 and OR=2.1, p<0.05, respectively). Conclusions. Iron deficiency, anemia and VADp are some of the main nutritional problems among Mexican infants.

Objetivo. Describir la frecuencia de anemia, deficiencia de hierro, vitamina B12, folato, retinol y predictores de la anemia en niños mexicanos de la Ensanut 2012. Material y métodos. Se midieron las concentraciones de hemoglobina, ferritina, PCR, vitamina B12, retinol y folato en 2 678 niños de 1-4 años y 4 275 niños de 5-11 años. Se construyeron modelos de regresión logística para evaluar el riesgo de anemia y deficiencias de micronutrientes. Resultados. La prevalencia de anemia en preescolares y escolares fue 20.4 y 9.7%; deficiencia de hierro (DH) 14 y 9.3%; baja concentración de vitamina B12 (BCB12) 1.9 y 2.6%; folato 0.30 y 0%, y depleción de vitamina A (DpVA), 15.7 y 2.3%, respectivamente. La DH y DpVA se asociaron negativamente con la Hb (coeficiente: -0.38 y -0.45, p<0.05); a mayor log-PCR, mayor riesgo de anemia y DpVA (OR=1.13 y OR=2.1, p<0.05, respectivamente). Conclusiones. DH, anemia y DpVA son algunos de los principales problemas de nutrición en niños mexicanos.

Prevalence of iron, folate, and vitamin B12 deficiencies in 20 to 49 years old women: Ensanut 2012 / Prevalencia de deficiencias de hierro, folato y vitamina B12 en mujeres de 20 a 49 años: Ensanut 2012

Objective. To describe the prevalence of iron, folate, and B12 deficiencies in Mexican women of reproductive age from the National Health and Nutrition Survey (Ensanut) 2012. Materials and methods. Data came from a national probabilistic survey, representative from rural and urban areas, and different age groups. Blood samples were obtained from 4 263, 20 to 49 years old women for serum ferritin, vitamin B12 and serum folate concentrations. The prevalence of deficiencies, was assessed using adjusted logistic regression models. Results. The deficiency of folate was 1.9% (95%CI 1.3-2.8), B12 deficiency was 8.5% (95%CI 6.7-10.1) and iron deficiency was 29.4% (95%CI 26.5-32.2). No differences were found when compared with 2006, 24.8% (95%CI 22.3-27.2). Conclusions. The vitamin B12 deficiency is still a problem for women of reproductive age and their offspring in Mexico, while folate deficiency disappeared as a problem. Iron deficiency needs prevention and fortification strategies.

Objetivo. Describir las prevalencias de deficiencias de hierro, folato y B12 en mujeres mexicanas en edad reproductiva de la Encuesta Nacional de Salud y Nutrición (Ensanut) 2012. Material y métodos. Datos derivados de una encuesta probabilística nacional, representativa del área rural y urbana por grupos de edad. Se obtuvo una submuestra de sangre en 4 263 mujeres de 20 a 49 años de edad para medir las concentraciones séricas de ferritina, vitamina B12 y folato. Las deficiencias fueron evaluadas mediante regresiones logísticas múltiples ajustadas. Resultados. La prevalencia de deficiencias de folatos fue de 1.9% (IC95% 1.3-2.8) y vitamina B12 de 8.5% (IC95% 6.7-10.1). La deficiencia de hierro no fue diferente a la de 2006: 29.4% (IC95% 26.5-32.2) vs 24.8% (IC95% 22.3-27.2). Conclusiones. La prevalencia de deficiencias de hierro y vitamina B12 todavía representan un problema en mujeres mexicanas (20-49), mientras que la deficiencia de folato ha dejado de ser un problema de salud pública. Aún se requieren estrategias de prevención en México.

Vitamin B12 deficiency & levels of metabolites in an apparently normal urban south Indian elderly population.

Background & objectives: There is no published literature on the extent of vitamin B12 deficiency in elderly Indians as determined by plasma vitamin B12 levels and methylmalonic acid (MMA) levels. Vitamin B12 deficiency is expected to be higher in elderly Indians due to vegetarianism, varied socio-economic strata and high prevalence of Helicobacter pylori infection. We therefore, studied the dietary habits of south Indian urban elderly population and measured vitamin B12, MMA red cell folate and homocysteine (Hcy) levels. Methods: Healthy elderly urban subjects (175, >60 yr) were recruited. Detailed history, physical examination and neurological assessment were carried out. Food Frequency Questionnaire (FFQ) for dietary analysis for daily intake of calories, vitamin B12, folate and detailed psychological assessment for cognitive functions was carried out. Blood samples were analyzed for routine haematology and biochemistry, vitamin B12, red cell folate, MMA and Hcy. Results: The mean age of the study population was 66.3 yr. Median values for daily dietary intake of vitamin B12 and folate were 2.4 and 349.2 μg/day respectively. Sixty two (35%) participants consumed multivitamin supplements. Plasma vitamin B12 level and the dietary intake of vitamin B12 was significantly correlated (P=0.157). Plasma vitamin B12 and Hcy were inversely correlated (P= -0.509). Red cell folate was inversely correlated with Hcy (P= -0.550). Significant negative correlation was observed between plasma vitamin B12 and MMA in the entire study population (P= -0.220). Subjects consuming vitamin supplements (n=62) had significantly higher plasma vitamin B12 levels, lower MMA levels and lower Hcy levels. There was no significant correlation between plasma vitamin B12, MMA, Hcy and red cell folate and any of the 10 cognitive tests including Hindi Mental Status Examination (HMSE). Interpretation & conclusions: Our study is indicative of higher vitamin B12 (2.4 μg/day) intakes in urban south Indian population. Thirty five per cent of the study population consumed multivitamin supplements and therefore, low plasma vitamin B12 levels were seen only in 16 per cent of the study subjects. However, MMA was elevated in 55 per cent and Hcy in 13 per cent of the subjects.

[Folic acid and vitamin B12 status in healthy preschool children in Tehran, Iran, 2010]

A deficiency of folate or vitamin B12, particularly in tissues with a high cell replication rate, could inhibit RNA and DNA synthesis, DNA methylation, as well as cell maturation. Therefore, a sufficient intake of these vitamins in childhood is of vital importance. Since there are no published reports on the status of folic acid and vitamin B12 in Iranian children, the present study was conducted to assess serum and red blood cells concentrations and some related factors in healthy 3-6 year old children in Tehran, Iran, 2010. This was a cross-sectional, descriptive-analytical study, in which 228 children, 3-6 year old [105 girls and 123 boys], were selected by random systematic cluster sampling from 20 [out of 270] day-care centers in Tehran. A 2-ml non-fasting blood sample was drawn from each child and analyzed for serum and red blood cell folate and vitaminB12 by the RIA method. SPSS.16 was used for data analysis, the statistical tests being t-test, Chi-square and ANOVA. There were no significant differences between the 2 sexes with regard to age, weight, height, BMI, RBC folate, or serum folate and vitamin B12 levels. Based on the serum folate level, 9.6% and 37.8% of the children suffered from severe and mild deficiency, respectively; 52.6% had normal folate serum levels. The data also showed that 97.4% of the children had a normal serum vitamin B12 level, only 2.6% being mildly deficient. As judged by the RBC folate level, of 105 children [60 boys and 45 girls], 1% and 37% had severe and mild deficiency, respectively, an absolute majority [62%] having normal levels. The distributions of serum folate, serum vitaminB12, and RBC folate levels were not statistically different between boys and girls. Similarly, no associations were observed between the RBC folate level, serum folate level, or serum vitamin B12 level and age, weight, height, family size, birth order, or head of the family. There were positive significant correlations between serum folate on the one hand and RBC folate [r=0.4, p<0.001] and serum vitamin B12 [r=0.8, p<0.001] on the other hand. Furthermore, folate, RBC folate, and serum vitamin B12 were all positively related to father's education [p=0.01], mother's education [p=0.008] and father's job status [p<0.027]. In addition, the vitamin levels were higher in children of the working mothers, as compared to those of non-working mothers [p<0.036]. There were no differences between the 2 groups with regard to other variables. Folate deficiency is highly prevalent, while the deficiency of vitamin B12 is low, among Tehrani preschoolers. It is recommended to design and implement suitable intervention programs. Major components of such programs should be mothers' nutrition education and improving family food consumption patterns with particular emphasis on optimum utilization of folate sources, particularly vegetables

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.

High prevalence of mild hyperhomocysteinemia and folate, B12 and B6 deficiencies in an urban population in Karachi, Pakistan

To find out the prevalence of hyperhomocysteinemia, and deficiencies of folate, vitamin B6 and vitamin B12 in an urban population in Karachi, Pakistan. In a pre and post experimental study, eight hundred and seventy-two apparently healthy adults [aged 18-60 years; 355 males and 517 females] were recruited from a low-income urban locality in East of Karachi from February 2006 to March 2007. Fasting venous blood was obtained. Serum was analyzed for folate and vitamin B12. Plasma was analyzed for pyridoxal phosphate [PLP, coenzymic form of B6] and total homocysteine. A group of vitamin-deficient individuals [n=194] was given 3-week supplementation with folic acid [5mg/day], methycobalamin [0.5mg/day] and pyridoxine hydrochloride [vitamin B6, 50 mg/day]. After supplementation, serum/plasma levels of folate, vitamin B12, PLP and homocysteine were again determined. Prevalence of hyperhomocysteinemia [>15micromol/l] was 32%. Similarly percent values of folate deficiency [<3.5ng/ml], vitamin B6 deficiency [PLP<20 nmol/l] and vitamin B12 deficiency [<200pg/ml] in the study population were 27.5%, 33.7% and 9.74%, respectively. Hyperhomocysteinemia was associated with male sex, folate deficiency, vitamin B12 deficiency [OR [95%CI], 8.3[5.7-12.1]; 2.5[1.76-3.58]; 2.6[1.5-4.5], respectively]. A 3-week supplementation with folic acid, methycobalamin and pyridoxine hydrochloride in vitamin-deficient subjects decreased plasma homocysteine levels by 37%. High prevalence estimates of folate, vitamin B12, and vitamin B6 deficiencies appear to be the major determinants of hyperhomocysteinemia in a low income general population in Karachi

Isolated vitamin B12 deficiency due to pernicious anemia in a patient with celiac sprue: a case report

Celiac sprue or Celiac disease is an autoimmune enteropathy often seen in patients are sensitive to gluten. Usually due to impaired absorption of iron and folic acid at the proximal of small intestine, iron deficiency anemia and megaloblastic anemia is common, but vitamin B 12 deficiency is rarely reported. We will describe the case that in addition to have celiac disease, without deficiency of iron and folic acid, has deficient vitamin B 12 due to severe pernicious anemia and improved dramatically to treatment with injection of vitamin B12. 38-years-old male patient with complaints of weakness and malaise and abdominal pain is referred. Initial tests indicated patient have megaloblastic anemia caused by vitamin B12 deficiency. With stomach and deuodenal biopsy and serological antibody titration studies including anti-parietal cell antibody, anti-endomysial antibody and tissue transglutaminase, accompanied with pernicious anemia and celiac disease was proved. After diagnosis, patients treated with intramuscular vitamin B12 and regimen without gluten, after one month significant improvements in clinical symptoms and laboratory found

High frequency of low serum levels of vitamin B [12] among patients attending Jordan University Hospital

This study aimed to estimate the status of serum vitamin B[12] level in patients attending Jordan University Hospital in Amman, and to examine the relationship with demographic data, chronic illness, dietary habits, haematological parameters and symptoms related to vitamin B[12] levels. A total of 838 patients completed a questionnaire and gave blood samples; 44.6% were vitamin B[12] deficient [< 180 pg/mL] and 34.2% had hypovitaminosis [180-300 pg/mL]. Vitamin B[12] deficiency was associated with memory impairment, low meat intake and strict vegetarian [vegan] diets. The high frequency of low vitamin B[12] warrants the development of a strategy to correct this problem in Jordan

Nutritional factors associated with anaemia in pregnant women in northern Nigeria.

This study was conducted to assess the relative contribution of iron, folate, and B 12 deficiency to anaemia in pregnant women in sub-Saharan Africa. In total, 146 pregnant women, who attended two antenatal clinics in Gombe, Nigeria, were recruited into the study. The majority (54%) of the women were in the third trimester. Blood samples were obtained for determination of haematocrit and for measurement of serum iron, total iron-binding capacity, ferritin, folate, vitamin B12, and homocysteine. Malaria was present in 15 (9.4%) women. Based on a haemoglobin value of<105 g/L, 44 (30%) women were classified as anaemic. The major contributing factor to anaemia was iron deficiency based on the serum concentration of ferritin (<10 ng/mL). The mean homocysteine concentration for all subjects was 14.1 pmol/L, and homocysteine concentrations were inversely correlated with concentrations of folate and vitamin B 12. The serum homocysteine increased markedly at serum vitamin B12 levels below 250 pmol/L. The most common cause of anaemia in the pregnant women in northern Nigeria was iron deficiency, and the elevated concentrations of homocysteine were most likely due to both their marginal folate and vitamin B12 status.

Vitamin B12 deficiency and hyperhomocysteinemia in rural and urban Indians.

BACKGROUND: Low vitamin B12 concentration in South Asian Indians is common, but the exact prevalence is not known. AIM: To investigate prevalence and associations of low vitamin B12 concentration and hyperhomocysteinemia in rural and urban Indian men living in and around Pune, Maharashtra. METHOD: We studied 441 middle-aged men (149 rural, 142 slum and 150 urban middle-class residents, mean age 39 y). Data on lifestyle, socio-economic status, nutrition and medical history were obtained. Circulating concentrations of vitamin B12, folate, ferritin, total homocysteine (tHcy), and haematological indices, and cardiovascular risk variables were measured. RESULTS: Median plasma B12 concentration was low (110 pmol/L): Overall, 67% of men had low vitamin B12 concentration (<150 pmol/L) and 58% had hyperhomocysteinemia (>15 micromol/L). Of the urban middle class, 81% had low vitamin B12 concentration and 79% had hyperhomocysteinemia. Low vitamin B12 concentration contributed 28% to the risk of hyperhomocysteinemia (population attributable risk) while low red cell folate contributed 2%. Vegetarians had 4.4 times (95% CI 2.1, 9.4) higher risk of low vitamin B12 concentrations and 3.0 times (95% CI 1.4, 6.5) higher risk of hyperhomocysteinemia compared to those who ate non-vegetarian foods frequently. Urban middle-class residence was an additional independent risk factor of hyperhomocysteinemia (odds ratio 7.6 (95% CI 2.5, 22.6), compared to rural men). Low vitamin B12 concentration was related to lower blood haemoglobin concentration and higher mean corpuscular volume, but macrocytic anemia was rare. CONCLUSION: Low vitamin B12 concentration and hyperhomocysteinemia are common in Indian men, particularly in vegetarians and urban middle class residents. Further studies are needed to confirm these findings in other parts of India.

Relationships of vitamin B1, B12, folate and the cognitive ability of the Thai rural elderly.

The comparisons of the levels of vitamin B1, B12 and folate between the elderly with good and poor cognitive ability are the goals of this study. 203 subjects enrolled in 3 geriatric centers of Ratchaburi province and nearby were recruited. All the subjects were tested with structured Thai Mini Mental State Examination (TMSE) questionnaire by trained examiners. With the cut off point of 23 out of 30 in TMSE, 31 per cent were designated as poor cognitive group. Radiodilution assay was used to determine the level of serum B12 and red cell folate while the TPP effect was processed by spectrophotometry. The prevalence of vitamin B1, B12 and folate deficiency were 30.2 per cent, 3.8 per cent and 8.2 per cent consecutively. None of the studied vitamin levels was shown to be significantly different between the poor and good cognitive group suggesting no proved indication to the use of vitamin B1, B12 and folate in the healthy elderly with poor cognitive function.

Concentración de hemoglobina y nutrientes en una población estudiantil adolescente de bajos recursos económicos. Relación el rendimiento academico / Concentration of hemoglobin and nutrients in a low income adolescent population and its relationship with academic achievement

Se estudiaron las concentraciones de hemoglobina y de nutrientes séricos necesarios para la eritripoyesis (hierro, ácido fólico y vitamina B12) de 199 adolescentes (126 de sexo femenino y 73 de sexo masculino pertenecientes a una población estudiantil de Educación Básica y de bajos recursos económicos, con la finalidad de observar si existe alguna relación entre los valores de los parámetros mencionados y el rendimiento académico. El 8,5% de la población presentó anemia, con ligera predominancia en el sexo masculino (9,5%). Sin embargo, en el sexo femenino se halló mayor déficit de hierro, saturación de transferrina y ferritina (20,6; 19,8; y 24,2% respectivamente). El 29,6% de la población presentó deficiencia de uno o más parámetros de hierro. La deficiencia de folato fue de 24,6% en las hembras y 28,7% en los varones. La deficiencia de vitamina B12 similar en ambos sexos (3,9 y 5,4%). La anemia por deficiencia de hierro fue la más frecuente, predominado en el sexo femenino (70%) aunque un 29,4% de los adolescentes anémicos tenía defiencia combinada con folato. En el grupo no anémico la defiencia de hierro fue más importante en las mujeres (31%), en cambio, en la deficiencia de ácido fólico hubo un ligero predominio en los varones (27,3%). Como indicadores del rendimiento estudiantil se utilizaron el Promedio Final de Notas y el Indice de Rendimiento Académico (IRA), el primero fue de 10,9 ñ 2,4 (escala de 0 a 20 puntos) y el segundo de 0,70 ñ 0,3 (calculado por la relación de materias aprobadas sobre materias cursadas), lo que señala un bajo rendimiento estudiantil. No se encontró correlación significativa entre el Promedio Final de Notas, el IRA y los valores de hemoglobina y nutrientes en la población estudiantil, como tampoco cuando se agruparon en anémicos y no anémicos, y entre aquellos con deficiencia nutricional y los normales. Sin embargo, se halló correlación negativa y significativa entre los indicadores académicos y la edad de las estudiantes (p < 0,001). El presente trabajo revela una alta prevalencia de anemia, deficiencia de hierro y de folato en la población estudiantil de bajos recursos económicos y que no parece guardar relación con el rendimiento académico, el cual fue similar en los estudiantes normales y aquellos con deficiencia nutricional. Los resultados sugieren que en el grupo estudiado, el bajo rendimiento pueden estar influyendo además de los nutricionales otros factores como: calidad de la enseñanza y codiciones ind