Hema Venkataraman

Vitamin B12 deficiency is associated with adverse lipid profile in Europeans and Indians with type 2 diabetes

BackgroundMetformin, a standard therapy in type 2 diabetes, reduces vitamin B12 levels. Studies linking low vitamin B12 levels and cardiovascular disease are equivocal and suggest improving B12 levels may help in primary prevention. The role of vitamin B12 deficiency on cardiovascular risk factors, especially in type 2 diabetes has not been explored. The aim of this study is to investigate whether vitamin B12 deficiency in type 2 diabetes patients is associated with cardiovascular risk factors in two different ethnic groups in UK and India.MethodsType 2 diabetes patients from two secondary care diabetic centres (Europeans - UK and Indians - India) were studied. Serum vitamin B12, folate and biochemical parameters were measured.ResultsThe prevalence rates of vitamin B12 deficiency (<191 ng/L) were 27% and 12% in Europeans and Indians, respectively and higher in metformin treated type 2 diabetes patients. In linear regression analysis, after adjusting for all likely confounding factors, vitamin B12 independently associated with triglycerides in both the populations and cholesterol/HDL ratio in Indians. Logistic regression showed type 2 diabetes patients with vitamin B12 deficiency were at significantly higher odds of having coexisting coronary artery disease (CAD) in Europeans with similar but non-significant trend in Indians, after adjusting for all likely confounding factors.ConclusionsThe prevalence of vitamin B12 deficiency is common in type 2 diabetes patients and is associated with adverse lipid parameters. Type 2 diabetes management guidelines should include the recommendation for regular testing for B12 levels, especially for those on metformin.

Postnatal testing following gestational diabetes: time to replace the oral glucose tolerance test?

Gestational diabetes is associated with up to an eight times increase in risk of future type 2 diabetes: the incidence of type 2 diabetes is 3–24% in the fi rst year postpartum and up to 50% in the fi rst 5 years. Therefore, postnatal testing for these women provides a crucial opportunity for the early detection of diabetes, intervention, and preconceptional care in subsequent pregnancies. Despite this evidence, uptake of postnatal testing for diabetes is poor, with only 23–58% of women with gestational diabetes attending the oral glucose tolerance test (OGTT)—a sharp contrast with the uptake of postnatal cervical screening (94%) and antenatal gestational diabetes screening (98%). Despite this, most international guidelines, including those of the Fifth International Workshop Conference on Gestational Diabetes, the American Diabetes Association (ADA), the Canadian Diabetes Association, and the Australasian Diabetes in Pregnancy Society continue to recommend postnatal OGTT. However, in 2015, the National Institute of Health and Care Excellence (NICE) recommended either a fasting plasma glucose (FPG) or HbA1c test rather than OGTT for postpartum screening. We collected contemporary data from 14 477 women who attended antenatal OGTT during 2009–12 across three UK centres. The appendix contains a summary of our methods. Our results further support the need to investigate alternatives to OGTT. Of 1289 (9%) women diagnosed with gestational diabetes, only 630 (49%) attended a postnatal OGTT. Furthermore, non-attenders were more likely to have increased metabolic risk (table), because multiparity (odds ratio 1·80, 95% CI 1·24–2·58), smoking (2·80, 1·58–4·97), and macrosomia (2·52, 1·46–4·34) were independent predictors of non-attendance at postnatal OGTT after adjustment for maternal BMI, age, glucose concentrations at antenatal OGTT, gestational age, and off spring sex. Other studies have reported that women who did not attend postnatal OGTT were more likely to have had worse glycaemic control and needed insulin during pregnancy than were those who attended. Our fi ndings, combined with previous evidence, suggest that women who do not attend a postnatal OGTT are at increased risk for subsequent type 2 diabetes. We also analysed preliminary data from one of our centres that subsequently adopted HbA1c for postnatal testing in gestational diabetes from December 2013 to assess HbA1c uptake. Of 348 women with gestational diabetes, 217 (62·4%) women attended HbA1c testing, representing an increase of 28% (p<0·0001) compared with OGTT at that centre. Reassuringly, risk characteristics did not diff er between those who attended and failed to attend HbA1c tests (unlike OGTT), suggesting increased uptake of HbA1c by women at high risk of type 2 diabetes postpartum. Barriers to postnatal screening for persisting glucose abnormalities after gestational diabetes mellitus have not been studied extensively. The inconvenience of OGTT and time pressures were the most commonly cited reasons for non-attendance in patient surveys. FPG tests have been recommended as a simpler and cheaper alternative to OGTT. However, FPG requires fasting, is restricted to mornings, and might especially inconvenience mothers with young children. The alternative is a non-fasting HbA1c test. Both ADA and NICE recommend HbA1c for the diagnosis of diabetes in high-risk non-pregnant adults without symptoms and for preconception risk stratifi cation of women with pre-existing diabetes. Studies to assess the role of HbA1c in the postpartum

Vitamin B12 Status among Pregnant Women in the UK and Its Association with Obesity and Gestational Diabetes

Background: To evaluate vitamin B12 and folate status in pregnancy and their relationship with maternal obesity, gestational diabetes mellitus (GDM), and offspring birthweight. Methods: A retrospective case-control study of 344 women (143 GDM, 201 no-GDM) attending a district general hospital and that had B12 and folate levels measured in the early 3rd trimester was performed. Maternal history including early pregnancy body mass index (BMI) and neonatal data (birthweight, sex, and gestational age) was recorded for all subjects. Results: 26% of the cohort had B12 levels <150 pmol/L (32% vs. 22% in the two groups respectively, p < 0.05) while 1.5% were folate deficient. After adjusting for confounders, 1st trimester BMI was negatively associated with 3rd trimester B12 levels. Women with B12 insufficiency had higher odds of obesity and GDM (aOR (95% CI) 2.40 (1.31, 4.40), p = 0.004, and 2.59 (1.35, 4.98), p = 0.004, respectively), although the latter was partly mediated by BMI. In women without GDM, the lowest quartile of B12 and highest quartile of folate had significantly higher adjusted risk of fetal macrosomia (RR 5.3 (1.26, 21.91), p = 0.02 and 4.99 (1.15, 21.62), p = 0.03 respectively). Conclusion: This is the first study from the UK to show that maternal B12 levels are associated with BMI, risk of GDM, and additionally may have an independent effect on macrosomia. Due to the increasing burden of maternal obesity and GDM, longitudinal studies with B12 measurements in early pregnancy are needed to explore this link.

Vitamin B12 status in women of childbearing age in the UK and its relationship with national nutrient intake guidelines: results from two National Diet and Nutrition Surveys

Objective To assess serum B12, folate and the associated homocysteine (Hcy) levels among women of childbearing age in the UK and examine their association with dietary intake in relation to the UK Recommended Nutrient Intakes (RNIs) for B12 and folate. Design Cross-sectional study. Setting Data from two publicly available National Diet and Nutrition Surveys (NDNS 2000/2001 and 2008/2012) were used. These were population-based surveys of randomly selected samples of adults which were carried out in their households. Participants Women of childbearing age (aged 19–39 years), representative of the UK population. Those who were pregnant or breastfeeding were excluded. Outcome measures The associations between micronutrient intakes and blood levels of B12, folate and Hcy were assessed by correlation and stepwise linear regression. B12 intake was divided into quintiles and plotted against blood B12 and Hcy concentrations to determine the threshold of any associations. Results 299 women from the first NDNS cohort had complete intake and biomarker data. The prevalence of serum vitamin B12 (≤150 pmol/L) and serum folate (≤10 nmol/L) deficiency and hyperhomocysteinemia (≥12 µmol/L) was 12.4%, 6.4% and 21.2%, respectively, despite seemingly adequate B12 intakes (median 3.8 μg/day, 96% consumed more than the UK RNI of 1.5 μg/day). B12 concentrations increased across all quintiles of intake with serum levels in quintiles 4 and 5 (median intake 4.9 and 7.1 μg/day, respectively) significantly higher than quintile 1. However, Hcy concentrations levelled off between quintiles 4 and 5. Comparison of micronutrient intake between the two surveys found that folate intake has reduced in the more recent cohort. Conclusions The UK RNI for B12 intake should be increased for women of childbearing age with intakes of around 5–7 μg/day likely to be associated with stable biomarker levels. B12 levels should also be measured in women preconceptionally or in early pregnancy given the high rates of deficiency.

Medicalising pregnancy with new diagnostic criteria for gestational diabetes mellitus: do we need more evidence?

To the Editor:We read with interest the article by Koning et al [1]. The authors report that the additional women diagnosed with gestational diabetes mellitus (GDM) by the WHO 2013 definition (i.e. fasting plasma glucose [FPG] ≥5.1 mmol/l but ≤6.9 mmol/l) were more likely to be obese and have higher BMI and hypertension compared with women with normal glucose tolerance (NGT). They also report, based on unadjusted analysis using χ test and Fisher’s exact tests, that the additional group of women diagnosed by the WHO 2013 FPG criteria (WHO 2013 only fasting glucose: GDM according to new WHO 2013 fasting glucose threshold, but do not meet WHO 1999 criteria) had higher rates of planned Caesarean section and induced labour despite similar unadjusted birthweight, macrosomia and large for gestational age (LGA) rates to the NGT group. The ‘WHO 1999 only 2HG’ group (GDM according to WHO 1999 2HG threshold, but do not meet WHO 2013 criteria), who received treatment for GDM had similar rates of LGA, but lower birthweight and lower rates of macrosomia than the NGT group. Interestingly the NGT group had higher birthweight (unadjusted for gestational age or offspring sex) than those diagnosed as GDM by either criterion but similar LGA rates. Based on these results the authors conclude that treating women with mild fasting hyperglycaemia (FPG 5.1–6.9 mmol/l) would improve outcomes, including LGA. This study has several important limitations that would make this conclusion difficult to make. First, the authors reported differences in crude birthweight and not sexand gestational-age-adjusted birthweight z scores. The crude birthweight (Table 3 in Koning et al [1]) in the additional women diagnosed by the WHO 2013 FPG criteria (WHO 2013 only fasting glucose group) was higher than those in the WHO 1999 only 2HG group. This 143 g lower birthweight in the WHO 1999 only 2HG group was most likely due to the early induction, and hence lower gestational age, because of a diagnostic label of GDM. It is likely that these differences would be insignificant if birthweight z scores for gestational age and sex were used. While the authors discuss that one of the key reasons to recommend a change to the new WHO 2013 criteria is the higher LGA rates in WHO 2013 only FPG group compared with the general population (21% vs 11%), this was not statistically different from the NGT group. In fact, the LGA rates were similar across NGT, WHO 1999 only 2HG and WHO 2013 only fasting glucose groups. Second, this study did not account for the effect on birthweight of the significantly higher pre-pregnancy BMI and obesity rates in the WHO 2013 only fasting glucose group compared with theWHO 1999 only 2HG group. The statistical analysis was by unadjusted χ test/Fisher’s exact tests with no attempt to create a regression model to account for potential * Ponnusamy Saravanan p.saravanan@warwick.ac.uk