Role of Maternal Serum Vitamin B12 Concentration with Risk of Developing Gestational Diabetes Mellitus

AIM: To determine concurrent changes in serum methylmalonic acid (MMA) and vitamin B12 concentrations of ewes and their lambs on cobalt-deficient properties, subsequent to cobalt supplementation. METHODS: Three experiments were carried out on two farms. Groups of ewes (n=25−50) were either supplemented with cobalt bullets during late pregnancy, 23–47 days before the mean lambing date, or left unsupplemented. In two experiments, lambs from within each group were supplemented directly by vitamin B12 injection at 3-weekly intervals from birth, and in the third experiment by injection with micro-encapsulated vitamin B12 at tailing and 3 months later. Pasture samples were obtained for analysis of cobalt content at each sampling time. Blood samples were obtained and liveweight recorded from ewes and lambs at approximately monthly intervals. On one farm (two experiments), liver and milk samples were obtained from ewes and liver samples from lambs. RESULTS: Serum vitamin B12 concentrations in unsupplemented ewes fell below 250 pmol/L during early lactation in all experiments and mean concentrations as low as 100 pmol/L were recorded. MMA concentration was maintained below 2 μmol/L in serum from supplemented ewes but increased to mean concentrations ranging from 7 to14 μmol/L at the nadir of serum vitamin B12 concentration during peak lactation. A significant liveweight response to supplementation was recorded in ewes on one property, and the vitamin B12 concentration in the ewes' milk and in the livers of their lambs more than doubled. No liveweight-gain response to supplementation was observed in lambs on this property. Mean serum MMA concentrations in lambs ranged from <2 in supplemented, to 19.2 μmol/L in unsupplemented lambs, and the latter had concurrent serum vitamin B12 concentrations of >300 pmol/L. Pasture cobalt concentration was lowest at 0.04–0.09 μg/kg dry matter (DM) on the property on which responses in lambs occurred but considerably higher (>0.09 μg/kg DM) on the property on which responses in ewes occurred. On the second property, serum vitamin B12 concentrations in lambs at tailing were extremely low (100 pmol/L), irrespective of supplementation of dams with cobalt. Mean serum MMA concentration was increased to 20 and 42 μmol/L in lambs from supplemented and non-supplemented ewes, respectively. Weight-gain response to direct supplementation of lambs with vitamin B12 occurred during suckling in the latter, but not the former. Lambs from ewes supplemented with vitamin B12 showed a much bigger increase in serum vitamin B12 concentrations a month after supplementation than did lambs from unsupplemented ewes (+1,400 pmol/L vs +650 pmol/L). CONCLUSIONS: Serum MMA concentration gave a more precise indication of responsiveness to vitamin B12 or cobalt supplementation than serum vitamin B12 concentrations in ewes and lambs. Neither very low serum vitamin B12 nor elevated MMA concentrations were necessarily indicative of responsiveness to supplementation in suckling lambs, but the latter gave an early indication of impending responsiveness. Supplementation of the ewe with a cobalt bullet appeared to protect the growth performance of the lamb for 90 days and influence the subsequent serum vitamin B12 response in the lamb to vitamin B12 supplementation. CLINICAL SIGNIFICANCE: Supplementing ewes with cobalt bullets in late pregnancy can improve the vitamin B12 status of their lambs, and modify their response to vitamin B12 supplementation.

Gestational diabetes mellitus (GDM) is described as a glucose intolerance of variable severity which begun or was firstly recognized during gravidity. Two major metabolic disorders, insulin resistance and β-cell dysfunction, currently play major role in pathogenesis of GDM. Our intention was to investigate total serum homocysteine and vitamin B12 levels in pregnant women with GDM and non-diabetic gravid women. Serum homocysteine and vitamin B12 levels were prospectively measured in a total of 79 pregnant women, 60 of whom were diagnosed with GDM, and 19 of whom were healthy controls. Serum homocysteine levels were analyzed by ELISA. Vitamin B12 concentrations were determined by chemiluminescent immunoassay, and lipids were determined enzymatically. GDM and control groups did not differ in terms of the serum homocysteine levels (median 7.24 vs 7.97 umol/L, respectively, p = 0.15). Nor did we find any association between serum homocysteine levels and BMI (r = 0.06, p = 0.55, respectively). There was no correlation between serum homocysteine and fasting serum glucose (r = 0.3, p = 0.8, respectively). There was no relationship between serum homocysteine concentrations and glycosylated hemoglobin (HgbA1c) levels (r = 0.06, p = 0.67, respectively). Serum vitamin B12 concentrations did not differ between the GDM and control groups (median 286 vs 262 pg/mL, respectively, p = 0.17). We found that levels of Vitamin B12 correlated inversely with fasting serum glucose concentrations (r = -0.44, p = 0.0009). Vitamin B12 concentrations increased along with LDL (r = 0.27, p = 0.043) and HDL (r = 0.38, p = 0.004) levels, however were inversely correlated with serum triglycerides (r = -0.34, p = 0.009). GDM patients with low Vitamin B12 values tend to have higher fasting serum glucose and altered lipid profiles (high triglycerides, low HDL and LDL). In women with GDM, serum homocysteine levels are not associated with HbA1c level, fasting glycemia, or BMI.

AIM: To compare serum analyses of vitamin B12 and methylmalonic acid (MMA) as indices of cobalt/vitamin B12 deficiency in lambs around weaning. METHODS: Lambs on five properties, considered to be cobalt- deficient, were supplemented with either cobalt bullets, or short- or long-acting vitamin B12 preparations. Blood samples, and in some cases liver biopsies, and liveweights were obtained at monthly intervals. Serum samples were assayed for vitamin B12 and MMA and liver for vitamin B12 concentrations. Pasture cobalt concentrations were measured on three of the properties. RESULTS: Pasture cobalt concentrations were generally maintained below 0.07 μg/g dry matter (DM) on the properties sampled. Growth responses to supplementation were observed on only 2/5 properties, despite serum vitamin B12 concentrations being within the currently used ’marginal‘ reference range (336–499 pmol/L) for at least 3 months on all properties and in the deficient reference range (0–335 pmol/L) for at least 2 months on all farms except one. Serum MMA concentrations in supplemented lambs were <2 μmol/L, except in those animals sampled 1 month after receiving treatment with a short-acting vitamin B12 injection. Serum MMA concentrations in unsupplemented animals on properties on which no growth response to supplementation occurred generally reached peak levels of between 4 and 7 μmol/L at the nadir of serum vitamin B12 concentration. When a growth response was observed, differences in weight gain between supplemented and unsupplemented lambs occurred as mean serum MMA concentrations increased from 9 to 14 μmol/L. On one property where supplementation commenced before weaning, normal growth rates were maintained despite serum vitamin B12 concentrations of 140 pmol/L and serum MMA concentrations in excess of 40 μmol/L serum. CONCLUSIONS: The possibility that current serum vitamin B12 references ranges for diagnosis of cobalt deficiency are set too high and lead to over-diagnosis of responsiveness to cobalt/ vitamin B12 supplementation is discussed. The suggestion is made that serum MMA concentrations in excess of 9–14 μmol/L will provide a more reliable diagnostic test for cobalt deficiency. However, there was sufficient variation between properties in the relationships between cobalt concentrations of pasture and serum vitamin B12 or MMA concentrations to require more rigorous testing of the reliability of using serum MMA concentration for this purpose. The possibility that differences in rumen fermentation and therefore propionate and vitamin B12 production could be involved is discussed. The measurement of serum MMA and vitamin B12 appears to be of little value whilst the lamb is still suckling. CLINICAL SIGNIFICANCE: Serum MMA concentration may offer advantages over serum vitamin B12 concentrations in the diagnosis of a cobalt/vitamin B12 responsiveness in weaned lambs.

Objectives: Studies on the relationship between vitamin B12 and gestational diabetes mellitus (GDM) have shown different results. Given the lack of research in this area in Iran and the inconsistent findings of studies carried out in other nations, this study was conducted in light of the significance of the problem, particularly with regard to the health of expectant mothers. Materials and Methods: This case-control study was performed on 120 pregnant women referred to Ayatollah Rouhani hospital in Babol, private offices, and health centers to evaluate the vitamin B12 level in women with and without GDM. GDM was defined as 1) after oral ingestion of 75g glucose, fasting plasma glucose level (PGL) &gt;92 mg/dL, 1-hour PGL &gt;180mg/dL, or 2-hour PGL &gt;153mg/ dL during 24-28 weeks of gestational age, or 2) in the 100-g oral glucose tolerance test (OGTT), PGL &gt;195 mg/dL, one-hour PGL &gt;180 mg/dL, 2-hour PGL &gt;155, and 3-hour PGL &gt;140, and GDM was diagnosed if there were at least 2 out of 4 mentioned cases. According to the above definition, pregnant women with GDM were placed in the case group, while those without GDM were placed in the control group. After 8 hours of fasting, intravenous blood samples were taken and sent to the laboratory for measurement, and vitamin B12 deficiency was considered &lt;99 pg/dL after 28 gestational weeks. Results: Vitamin B12 deficiency was prevalent in 14.2% of 120 pregnant women studied. Vitamin B12 deficiency was more common in GDM women than in non-GDM women (58.8%-41.2%). A normal level of vitamin B12 could act as a protective factor against GDM. The vitamin B12 levels increased in the 30- to 40-year-old women with GDM. In other age groups, vitamin B12 levels were higher in non-GDM women than in GDM women. Among 17 women with vitamin B12 deficiency, 52.9% had a fasting PGL &gt;92. Conclusions: The results of the present study suggest that measuring vitamin B12 levels may aid in the early diagnosis of GDM and prevent maternal and fetal complications.

Hyperhomocysteinaemia is a well-known risk factor for venous thromboembolic disease (VTD). However, it is not clear whether homocysteine (Hc) itself or a related metabolite or a cofactor is primarily responsible for VTD. We carried out a case-control study to investigate whether vitamin concentrations that are involved in the Hc metabolism are associated or not with an elevated risk of VTD. Case-control study. We measured serum vitamin B12, folate, creatinine and albumin concentrations and plasma Hc concentrations in 101 consecutive patients with VTD, diagnosed by image tests and 101 control subjects, matched for age and sex. Serum vitamin B12 concentrations were significantly lower in VTD patients than in the control subjects. There were no differences in plasma Hc or serum folate concentrations between the groups. Among the male subgroup aged more than 70 years, serum vitamin B12 concentrations were significantly lower (240.88 +/- 103.07 vs. 421.20 +/- 314.31 pmol L(-1); P = 0.03) and plasma Hc concentrations were significantly higher (13.1 +/- 4.18 vs. 10.56 +/- 3.06 micromol L(-1); P =0.04) in VTD patients than in the control group. On multivariate analysis, in patients aged more than 70 years, serum vitamin B12 concentrations were independently associated with VTD. Compared with the highest quartile of vitamin B12 (>512.6 pmol L(-1)) the odds ratio (OR) for VTD in the lowest quartile (<230.9 pmol L(-1)) was 3.8 (95% CI 1.44-10.18; P = 0.01). In the VTD group, lowest vitamin B12 concentrations (percentile 10 <152.8 pmol L(-1)) were associated with the factor V Leiden mutation (OR = 6.07, 95% CI 0.93-38.55; P = 0.04). Measuring vitamin B12 concentrations in elderly males may help in identifying people at risk of venous thromboembolism in our population.

Aim. To obtain information on serum and liver vitamin B12 and urinary methylmalonic acid concentrations as diagnostic tests to predict a weight gain response to supplementation with vitamin B12 in young dairy cattle when grazing pasture of low cobalt content. Methodology. Forty dairy cattle (12 Friesian, 14 Friesian × Jersey and 14 Jersey) were allocated to two equal sized groups, treated and untreated, based on liveweight. At monthly intervals for 14 months, all animals were weighed, their serum and urine sampled, their liver biopsied and the pasture sampled from the paddocks they were grazing and going to graze. Serum and liver were assayed for Vitamin B12 concentrations. For the first 5 months of the trial, urine was assayed for methylmalonic acid concentrations. Both washed and unwashed pasture samples were assayed for cobalt concentrations. Results. No weight gain response occurred to Vitamin B12 supplementation in young growing cattle grazing pasture with a cobalt concentration of 0.04-0.06 mg/kg DM. For 5 months of the trial, liver Vitamin B12 concentrations from untreated calves were in the range 75-220 nmol/kg and serum vitamin B12 concentrations were as low as 72 pmol/1. There was no associated growth response to supplementation. Conclusion. Further trials involving young cattle grazing pastures with cobalt concentrations less than 0.04 mg/kg DM are required to reliably determine liver and serum Vitamin B12 concentrations at which growth responses to Vitamin B12 or cobalt supplementation are likely under New Zealand pastoral grazing conditions.

Deficiencies of folate and vitamin B12 lead to an elevated serum concentration of homocysteine which has been associated with many diseases including cardiovascular disease. Laboratory algorithms often include initial testing of serum folate and vitamin B12. Reference intervals for these vitamins can vary significantly among populations for which dietary intakes may be different. The aim of this study was to establish reference intervals in a Norwegian population and to assess the folate and vitamin B12 status related to reference intervals. Blood samples were taken from 144 healthy volunteers aged 18 - 65 years. A questionnaire provided data of medication, medical history, vitamin supplementation, alcohol consumption, and use of oral contraceptives and others. Serum folate and vitamin B12 concentrations were measured on the Abbott Architect i2000. Reference values were calculated using the bootstrap method. Results of serum folate, vitamin B12, and homocysteine from 1190 individuals from regional primary health care centers were evaluated related to reference values and the proportion of individuals with deficiency was estimated. Mean serum concentrations of folate and vitamin B12 were 11.9 nmol/L and 328 pmol/L, respectively. Men were found to have statistically significant higher vitamin B12 concentrations than women. 95%-reference intervals were calculated to 5.2 - 29.2 nmol/L for folate and 133 - 595 pmol/L for vitamin B12. 1.1% of the study population has serum vitamin B12-concentrations < 133 pmol/L and 3.4% has serum folate concentrations < 5.2 nmoI/L. The serum reference intervals for folate and vitamin B12 for a healthy, not vitamin-supplemented adult population were determined from 144 subjects. The application of these intervals will assist in the evaluation of folate and vitamin status.

SummaryInadequate vitamin B12 status in a pregnant woman increases the risk for adverse maternal and fetal outcomes. The use of serum vitamin B12 concentration alone to assess vitamin B12 status in pregnant women is unreliable because of the decrease in serum vitamin B12 levels in normal pregnancy. The combination of serum vitamin B12 and methylmalonic acid (MMA) concentrations may provide a better estimate of vitamin B12 status. We obtained blood samples from 98 pregnant women in the third trimester at an antenatal clinic in Jos, Nigeria. All subjects were taking iron and folate supplements. Twelve of the subjects had a serum vitamin B12 concentration <148 pmol/l and 18 subjects had a serum MMA level >271 nmol/l. Using a combination of low serum vitamin B12 and elevated MMA concentrations, eight subjects were classified as having subclinical vitamin B12 deficiency. Because of the potential harmful consequences of vitamin B12 deficiency in pregnant women, it would be advisable to add vitamin B12 supplements to the existing regimen of folate and iron supplements currently provided to pregnant women in Nigeria.

Background:Studies conducted in the USA have demonstrated that micronutrients such as folate and vitamin B12 play a significant role in modifying the natural history of high-risk human papillomaviruses (HR-HPVs), the causative agent for developing invasive cervical cancer (CC) and its precursor lesions.Objective:The purpose of the current study was to investigate whether these micronutrients have similar effects on HR-HPV infections in Indian women.Methods:The associations between serum concentrations of folate and vitamin B12 and HR-HPV infections were evaluated in 724 women who participated in a CC screening study in the southern state of Andhra Pradesh, India. Serum folate and vitamin B12 concentrations were measured by using a competitive radio-binding assay. Digene hybrid capture 2 (HC2) assay results were used to categorize women into two groups, positive or negative for HR-HPVs. Unconditional logistic regression models specified a binary indicator of HC2 (positive/negative) as the dependent variable and serum folate concentrations combined with serum vitamin B12 concentrations as the independent predictor of primary interest. Models were fitted, adjusting for age, education, marital status, parity, type of fuel used for cooking and smoking status.Results:Women with higher concentrations of serum folate (>6 ng/mL) and vitamin B12 (>356 pg/mL) were at lower risk of being positive for HR-HPVs compared to those with serum folate ≤6 ng/mL and serum vitamin B12 ≤ 356 pg/mL (odds ratio = 0.26; 95% confidence interval: 0.08–0.89; P = 0.03).Conclusions:These results demonstrated that improving folate and vitamin B12 status in Indian women may have a beneficial impact on the prevention of CC. Micronutrient based interventions for control of HR-HPV infections may represent feasible alternatives to vaccine based approaches to HPV disease prevention, which are currently unaffordable for use in resource limited areas in rural India.

To explore the effect of subchronic combined oral exposure of titanium dioxide nanoparticles and glucose on levels of serum folate and vitamin B12 in young SD rats. At first, the physical and chemical properties of titanium dioxide nanoparticles, such as particle size, shape, crystal form and agglomeration degree in solution system, were characterized in detail. Eighty 4-week-old young SD rats were randomly divided into 8 groups (10 rats in each group, half male and half female). The rats were exposed to titanium dioxide nanoparticles through intragastric administration at 0, 2, 10 and 50 mg/kg body weight with or without 1.8 g/kg glucose daily for 90 days. At last, the concentrations of serum folate and vitamin B12 were detected. Titanium dioxide nanoparticles were anatase crystals, closely spherical shape, with an average particle size of (24±5) nm. In male young rats, compared with the control group, the serum folate concentration was significantly increased when exposed to titanium dioxide nanoparticles (10 mg/kg) and glucose. The difference was statistically significant (P<0.05). However, in female and male young rats, compared with glucose (1.8 g/kg) exposure group, titanium dioxide nanoparticles (50 mg/kg) and glucose significantly reduced the serum folate concentration. The difference was statistically significant (P<0.05). Through statistical analysis of factorial design and calculation of interaction, obvious antagonistic effect was observed between titanium dioxide nanoparticles and glucose on the serum folate concentration in the young female SD rats. The combined oral exposure of titanium dioxide nanoparticles and glucose had little effect on the concentration of serum vitamin B12 in the young SD rats, with no significant interaction between the two substances. It was only found that titanium dioxide nanoparticles (2 mg/kg) and glucose significantly increased the serum vitamin B12 concentration, compared with glucose (1.8 g/kg) exposure group. The difference was statistically significant (P<0.05). Subchronic combined oral exposure of titanium dioxide nanoparticles and glucose had an obvious antagonistic effect on serum folate concentrations in young SD rats.

Background: Inflammatory bowel disease (IBD) patients may be at risk of vitamin B12 and folate insufficiencies, as these micronutrients are absorbed in the small intestine, which is affected by IBD. However, a consensus has not been reached on the association between IBD and serum folate and vitamin B12 concentrations. Methods: In this study, a comprehensive search of multiple databases was performed to identify studies focused on the association between IBD and serum folate and vitamin B12 concentrations. Studies that compared serum folate and vitamin B12 concentrations between IBD and control patients were selected for inclusion in the meta-analysis. Results: The main outcome was the mean difference in serum folate and vitamin B12 concentrations between IBD and control patients. Our findings indicated that the average serum folate concentration in IBD patients was significantly lower than that in control patients, whereas the mean serum vitamin B12 concentration did not differ between IBD patients and controls. In addition, the average serum folate concentration in patients with ulcerative colitis (UC) but not Crohn’s disease (CD) was significantly lower than that in controls. This meta-analysis identified a significant relationship between low serum folate concentration and IBD. Conclusions: Our findings suggest IBD may be linked with folate deficiency, although the results do not indicate causation. Thus, providing supplements of folate and vitamin B12 to IBD patients may improve their nutritional status and prevent other diseases.

Exploring the Link of Serum Vitamin B12, Folate, and Homocysteine Concentrations in Individuals with Multiple Sclerosis: An Umbrella Meta-analysis of Case-control Studies.

Association of Serum Folate and Vitamin B12 Concentrations with Obesity in Chinese Children and Adolescents*

Aim: Our aim is to study the behavior, diet, and physical activity patterns among gestational diabetes mellitus (GDM) and non-GDM women. Materials and Methods: A survey was conducted among GDM and non-GDM women from multispeciality hospitals and maternal clinics using a purposive sampling criterion. A validated interview schedule was used to obtain details of readiness for pregnancy, perception of managing pregnancy, concerns in pregnancy, degree of depression, food preferences, shopping of food, eating out, cooking, current nutrient intake, food consumption pattern, type, duration and frequency of physical activity, and rest periods of GDM and non-GDM women. Results: Majority of GDM and non-GDM women showed readiness for motherhood. GDM women exhibited greater confidence and importance toward making lifestyle changes during pregnancy. The pregnancy-related concerns were more common among GDM women. The mean energy and protein intake was lower than the recommended dietary allowance (RDA) among GDM women compared to their counterparts. On the contrary, carbohydrate consumption exceeded RDA among both groups. The total fat intake, including visible and invisible fat among GDM women, met the RDA; however, it exceeded the RDA among non-GDM women. The RDA for calcium, iron, and fiber showed significant difference compared to RDA among both groups. Physical activity patterns did not show any significant difference among GDM and non-GDM women and were unsatisfactory in both groups. Conclusion: The study recommends the need for psychological support, proper medical nutrition therapy, and adequate physical activity for GDM and non-GDM women.

Aim. To determine the effect of increasing the Vitamin B12 status of the ewe on the Vitamin B12 supply to the suckling lamb. Methods. The Vitamin B12 status of the ewe was increased during gestation and lactation by three injections of a long- acting preparation of Vitamin B12 microencapsulated in an organic acid polymer. The Vitamin B12 status of the ewes and suckling lambs was assessed from changes in serum and liver Vitamin B12 concentrations. Results. Compared to untreated animals, serum and liver Vitamin B12 concentrations of the treated ewes were increased at least 70% during gestation. Foetal liver Vitamin B12 concentrations were increased 270%. Over the lactation, ewe serum and milk Vitamin B12 concentrations were increased at least 200% and 44%, respectively. The liver Vitamin B12 stores of the new born lambs from Vitamin B,,-treated ewes were depleted within 58 days. There were no significant differences in the serum vitamin B12 concentrations of suckling lambs from vitamin B12-treated and untreated ewes. Conclusion. Ewes with a high vitamin B12 status will ensure an adequate supply of vitamin B12 to their lambs for at least the first 30 days of life. Clinical significance. In flocks grazing Co-deficient pastures, treating ewes with a long-acting vitamin B12 supplement at mating will prevent Vitamin B12 (Co) deficiency in ewes, as well as their lambs, until they can be treated at tailing at 4-6 weeks of age.