Search

A significant number of cardiovascular outcome trials have been published to support decision-making regarding treatment options after or alongside metformin in people with type 2 diabetes (T2DM), specifically targeting prevention of adverse cardiovascular and renal outcomes. The latest NICE guidelines recommend the use of sodium-glucose transport inhibitors (SGLT2i) in patients with cardiovascular diseases, heart failure and chronic kidney disease with diabetes and recommends the use of glucagon-like polypeptide receptor agonists (GLP-1RA) only in a selected group of patients. A comprehensive summary of the various trials, structured around patient characteristics and clinical outcomes, can help to compare the various classes of drugs and drugs within the class. Since the drug acquisition cost within a class is generally the same in the UK, the drug with the best available evidence in the class should be chosen to maximise clinical benefit for the patient. Clinical phenotyping, a process of aligning a patient to the inclusion criteria and the desired clinical outcomes of a trial, can guide the choice of the best drug within a class.

Vitamin B12 has multiple biochemical functions including in the one-carbon cycle generating a methyl group for DNA methylation, and metabolism of fatty acids and amino acids to generate energy via the citric acid cycle. The aim of our study was to use a combined epigenomic and transcriptomic approach to identify novel genes mediating the effect of B12 on adipogenesis.\ud \ud Human pre-adipocytes (CHUB-S7) were treated with a range of B12 (0–500 nM) concentrations from the day of cell seeding until harvesting in discovery and validation experiments prior to genome-wide methylation analysis using the Illumina HumanMethylation 450Beadchip. For transcriptomic analysis, RNA-seq libraries were run on the Illumina HiSeq 2500. To further investigate the expression of any genes on human adipogenesis, a second human preadipocyte strain was studied (SGBS) by real-time quantitative PCR (qRT-PCR).\ud \ud A combined epigenetic and transcriptomic approach in differentiated human pre-adipocyte cell line, CHUB-S7, identified that the Human cartilage chitinase 3-like protein 2 (CHI3L2) gene was hypo-methylated and had increased expression in low B12 conditions. Furthermore, there was an approximately 1000-fold increase in CHI3L2 expression in the early days of adipocyte differentiation, which paralleled an increase of lipid droplets in differentiated SGBS cells and an increased expression level of markers of mature adipocytes.\ud \ud In summary, we have identified a potential role of the human cartilage chitinase 3-like protein 2 (CHI3L2) in adipocyte function in the presence of low B12 levels.

Gestational diabetes mellitus (GDM) diagnosed during the first trimester of pregnancy is called 'early pregnancy Gestational Diabetes Mellitus' (eGDM). The burden of eGDM has only been studied sporadically. This review aims to understand the global burden of eGDM in terms of prevalence, risk factors, pregnancy outcomes, treatment and postpartum dysglycemia. METHODS: A review of epidemiologic studies reporting on early GDM screening as per Joanna Briggs Institute (JBI) methodology for prevalence reviews was conducted. A customized search strategy was used to search electronic databases namely, PubMed, CINAHL, EMBASE, Cochrane Library, Scopus, MEDLINE, Ovid, ScienceDirect, and Google Scholar. Three independent reviewers reviewed studies using Covidence software. Observational studies irrespective of study design and regardless of diagnostic criteria were included. Quality of evidence was appraised, and findings were synthesized.Of 58 included studies, 41 reported a prevalence of eGDM, ranging from 0.7 to 36.8%. Body mass index (BMI), previous history of GDM, family history of diabetes and multiparity were reported as eGDM risk factors. Adverse pregnancy outcomes associated with eGDM were macrosomia, caesarean delivery, induction of labour, hypertension, preterm delivery, and shoulder dystocia. The incidence of postpartum dysglycemia and the need for insulin was higher in women with eGDM. The risk of bias was moderate. Heterogeneity of studies is a limitation. Meta-analysis was not performed.There is heterogeneity in the prevalence of eGDM and intrapartum and postpartum ill effects for the mother and the offspring. There is a need to develop a universal screening protocol for eGDM.

Dapagliflozin is the first novel SGLT2 inhibitor for the treatment of Type 2 diabetes. The aim of this study was to evaluate its effectiveness and safety in a real-life clinical setting. We analyze data from four hospitals on patients initiated on dapagliflozin. HbA1c, weight and daily insulin dosage was recorded at baseline and 6 months follow-up.229 patients received dapagliflozin. At baseline, mean HbA1c was 82mmol/mol(186) and mean weight was 102 kg(n=159).The average reduction in HbA1c at 6 months (n=121) was 13mmol/mol whereas the average reduction in weight(n=96) was 2kg.A mean reduction in daily insulin requirement(n=41) by 12 units(13%) at 6 months compared to baseline was noted. Nine patients developed candidiasis, eight developed UTI, five reported symptoms of thirst and five developed hypoglycaemia out of which four were on insulin and one on gliclazide. Ten patients discontinued(4%) dapagliflozin due to side effects. Our results confirm that dapagliflozin can be used safely and effectively in a real-life setting. Keywords: Dapagliflozin, real world, SGLT2, Type 2 diabetes. Continuous...

Background/Aims: Rise in global incidence of obesity impacts metabolic health. Evidence from human and animal models show association of vitamin B12 (B12) deficiency with elevated BMI and lipids. Human adipocytes demonstrated dysregulation of lipogenesis by low B12 via hypomethylation and altered microRNAs. It is known de novo hepatic lipogenesis plays a key role towards dyslipidaemia, however, whether low B12 affects hepatic metabolism of lipids is not explored. \ud \ud Methods: HepG2 was cultured in B12-deficient EMEM medium and seeded in different B12 media: 500nM(control), 1000pM(1nM), 100pM and 25pM(low) B12. Lipid droplets were examined by Oil Red O (ORO) staining using microscopy and then quantified by elution assay. Gene expression were assessed with real-time quantitative polymerase chain reaction (qRT-PCR) and intracellular triglycerides were quantified using commercial kit (Abcam, UK) and radiochemical assay. Fatty acid composition was measured by gas chromatography and mitochondrial function by seahorse XF24 flux assay. \ud \ud Results: HepG2 cells in low B12 had more lipid droplets that were intensely stained with ORO compared with control. The total intracellular triglyceride and incorporation of radio-labelled-fatty acid in triglyceride synthesis were increased. Expression of genes regulating fatty acid, triglyceride and cholesterol biosynthesis were upregulated. Absolute concentrations of total fatty acids, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), trans-fatty acids and individual even-chain and odd-chain fatty acids were significantly increased. Also, low B12 impaired fatty acid oxidation and mitochondrial functional integrity in HepG2 compared with control. \ud \ud Conclusion: Our data provide novel evidence that low B12 increases fatty acid synthesis and levels of individual fatty acids, and decreases fatty acid oxidation and mitochondrial respiration, thus resulting in dysregulation of lipid metabolism in HepG2. This highlights the potential significance of de novo lipogenesis and warrants possible epigenetic mechanisms of low B12.

BACKGROUND AND AIMS The SURE programme of observational real-world studies is investigating once-weekly (OW) subcutaneous semaglutide in routine clinical practice across a diverse type 2 diabetes (T2D) patient population, including those with chronic kidney disease. This pooled post-hoc analysis of SURE Canada, Denmark/Sweden, Switzerland and UK evaluated OW semaglutide use and outcomes according to kidney function at semaglutide initiation. METHOD The SURE studies (all ∼30 weeks’ duration) enrolled adults (≥18 years) with T2D who received OW semaglutide and other anti-hyperglycaemic drugs prescribed at physician discretion; pooled data were analysed to determine change from baseline to end of study (EOS) in HbA1c and body weight (BW) by estimated glomerular function rate (eGFR) subgroups ( RESULTS Data from 913 patients with median (interquartile range) age of 61 (54–68) years and T2D duration of 11.0 (6.2–17.2) years were included. Patients with eGFR CONCLUSION OW semaglutide provided clinically relevant glycaemic control and BW improvements, and was well tolerated, in patients with varying degrees of kidney impairment at treatment initiation in a real-world setting. These findings support semaglutide use in routine clinical practice regardless of patients’ kidney function.

The COVID-19 pandemic has required rapid transformation and adaptation of healthcare services. Women with gestational diabetes mellitus (GDM) are one of the largest high-risk groups accessing antenatal care. In reformulating the care offered to those with GDM, there is a need to balance the sometimes competing requirement of lowering the risk of direct viral transmission against the potential adverse impact of service changes. We suggest pragmatic options for screening of GDM in a pandemic setting based on blood tests, and risk calculators applied to underlying risk factors. Alternative models for antenatal care provision for women with GDM, including targeting high-risk groups, early lifestyle interventions and remote monitoring are provided. Testing options and their timing for postpartum screening in women who had GDM are also considered. Our suggestions are only applicable in a pandemic scenario, and usual guidelines and care pathways should be re-implemented as soon as possible and appropriate.

Serum progesterone sulfates were evaluated in the etiology of gestational diabetes mellitus (GDM). Serum progesterone sulfates were measured using ultra-performance liquid chromatography–tandem mass spectrometry in four patient cohorts: 1) the Hyperglycemia and Adverse Pregnancy Outcomes study; 2) London-based women of mixed ancestry and 3) U.K.-based women of European ancestry with or without GDM; and 4) 11–13 weeks pregnant women with BMI ≤25 or BMI ≥35 kg/m2 with subsequent uncomplicated pregnancies or GDM. Glucose-stimulated insulin secretion (GSIS) was evaluated in response to progesterone sulfates in mouse islets and human islets. Calcium fluorescence was measured in HEK293 cells expressing transient receptor potential cation channel subfamily M member 3 (TRPM3). Computer modeling using Molecular Operating Environment generated three-dimensional structures of TRPM3. Epiallopregnanolone sulfate (PM5S) concentrations were reduced in GDM (P < 0.05), in women with higher fasting plasma glucose (P < 0.010), and in early pregnancy samples from women who subsequently developed GDM with BMI ≥35 kg/m2 (P < 0.05). In islets, 50 µmol/L PM5S increased GSIS by at least twofold (P < 0.001); isosakuranetin (TRPM3 inhibitor) abolished this effect. PM5S increased calcium influx in TRPM3-expressing HEK293 cells. Computer modeling and docking showed identical positioning of PM5S to the natural ligand in TRPM3. PM5S increases GSIS and is reduced in GDM serum. The activation of GSIS by PM5S is mediated by TRPM3 in both mouse and human islets.

The American Diabetes Association guidelines for the management of type 2 diabetes mellitus recommends treating patients with atherosclerotic cardiovascular diseases, heart failure or diabetic kidney disease with sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists, irrespective of the baseline HbA1c, to reduce adverse renal and cardiovascular outcomes. Initiation of such therapies have a significant cost impact on health economies. Cost of gain in quality-adjusted life-years is normally used for cost effectiveness for a particular drug. In the absence of head-to-head comparisons, prescribers may go for the cheapest option, which may not necessarily be the right decision. We propose using the calculated ‘YoDa’ (Years of Drug administration) as an easily comparable metric between the drug accrual cost and clinical outcomes. YoDa is calculated as a product of numbers needed to treat and the median duration in years that the trial ran over, to accrue the positive clinical outcomes. Clinical phenotyping of the patient to the specific inclusion and exclusion criteria of relevant clinical trials could guide the clinician to choose the most appropriate therapy. We also propose a series of steps or ‘deliberations’, which a clinician should consider in making a final choice of sodium-glucose co-transporter-2 inhibitor therapy. A comprehensive summary of the sodium-glucose co-transporter-2 inhibitor trials, clinical phenotyping and YoDa calculations for various significant clinical outcomes could assist making evidence-based, patient-individualised and cost-effective management plans for diabetes care. Video abstract Informing and Empowering Patients and Clinicians to Make Evidence-Supported Outcome-Based Decisions in Relation to SGLT2 Inhibitor Therapies: The Use of The Novel Years of Drug administration (YoDa) Concept Supplementary Information The online version contains supplementary material available at 10.1007/s40261-021-01105-7.

Dapagliflozin is the first novel sodium glucose co transporter 2 inhibitor for the treatment of Type 2 diabetes. The aim of this audit was to evaluate its effectiveness and safety in a real-life clinical setting.We analyze data from four UK district general hospitals on patients initiated on dapagliflozin. HbA1c, weight and daily insulin dosage was recorded at baseline and 6 months follow-up.At baseline, mean HbA1c was 82±19.21mmol/mol(9.7%) and mean weight was 102±18.1kg. The average reduction in HbA1c at 6 months was 13±7.23 mmol/mol (1%) whereas the average reduction in weight was 2 ±2.02 kg.. A mean reduction in daily insulin requirement by 12±8.3 units at 6 months compared to baseline was noted. There were certain complications in patients taking insulin and gliclazide including candidiasis, urinary tract infection and hypoglycaemia, and 4% patients discontinued dapagliflozin due to side effects.Our results confirm that dapagliflozin can be used safely and effectively in a real-life setting.

Background Gestational diabetes mellitus (GDM) is diagnosed during pregnancy, and women with a history of GDM are at a higher risk of developing type 2 diabetes mellitus (T2DM). Prevention strategies focused on lifestyle modification help to reduce long-term complications. Self-management technology-based interventions can support behaviour change and diabetes control. The Baby Steps programme, a randomised controlled trial intervention offering group education and access to a mobile web application, was evaluated to explore user experience of the app and barriers and facilitators to app usability. Methods Ten semi-structured interviews and four focus group discussions were conducted with 23 trial participants between 2018 and 2019. Interviews and focus group discussions were audiotaped, transcribed and independently analysed. The analysis was informed by thematic analysis, with the use of the Nvivo 12 software. Results Themes identified were: (1) GDM and post-pregnancy support from healthcare services; (2) Impact of Baby Steps app on lifestyle changes; (3) Facilitators and barriers to the usability of the Baby Steps app. The Baby Steps app served as a motivator for increasing self-management activities and a tool for monitoring progress. Peer support and increased awareness of GDM and T2DM enhanced engagement with the app, while poor awareness of all the components of the app and low technical skills contributed to low usability. Conclusions This study documents experiences from existing GDM support, user experiences from using the Baby Steps app, and the barriers and facilitators to app usability. The app was both a motivational and a monitoring tool for GDM self-management and T2DM prevention. Peer support was a key trait for enhanced engagement, while barriers were low technical skills and poor awareness of the app components. A digital app, such as the Baby Steps app, could strengthen existing face-to-face support for the prevention of T2DM. The results also have wider implications for digital support technologies for all self-management interventions. Further research on the effect of specific components of apps will be required to better understand the long term impact of apps and digital interventions on self-management behaviours and outcomes. Trial registration ISRCTN, ISRCTN17299860. Registered on 5 April 2017.

BackgroundGestational diabetes mellitus (GDM) affects over 4% of pregnancies in England. We investigated GDM epidemiology within ethnically diverse population and the current offer of services to women with previous GDM to reduce their type 2 diabetes mellitus (T2DM) risk.Methods(i) Analysis of routinely collected maternity data examining GDM incidence and risk factors; (ii) local authority self-assessment questionnaire on public health interventions targeting women with previous GDM and (iii) service development discussions regarding the current pathway and areas for improvement.ResultsOf 9390 births between 2014 and 2018, 6.8% had a record of GDM. High body mass index (BMI), maternal age, and ethnicity (South Asian and some mixed ethnic backgrounds) were independent predictors of GDM. There were no public health commissioned services specifically targeting women with previous GDM. Weaknesses in transition from secondary to primary care and areas for improvement when screening for GDM were identified.ConclusionsGDM burden in this population was high. Awareness should be raised on the importance of regular glucose testing and lifestyle modification to delay or prevent progression to T2DM, particularly within high risk groups. The potential for health visitors to contribute to this should be explored. Commissioners should review evidence to develop a flexible lifestyle services model to meet the specific needs of these women.

We have analysed a 6100-year record of benthic and planktonic foraminifera from inner neritic sediments from Core SK291/GC13, off the Goa coast, eastern Arabian Sea, to understand the response of benthic foraminifera to shallow-marine processes. The benthic foraminiferal assemblage is dominated by Nonion cf. asterizans, Ammonia beccarii, A. gaimardii and Virgulinella fragilis, which have been selected on the basis of a population of 10% or more in any three samples analysed. The planktonic foraminiferal population is sporadic and rare, with Globigerinoides ruber as the predominant species showing a variable trend. The foraminiferal proxies combined with total organic carbon (wt%) and δ13C and δ18O values of Ammonia gaimardii suggest distinct variations, indicating changes in productivity and salinity in the shallow eastern Arabian Sea. The coastal waters off Goa were relatively warmer and less saline between 6100 and 4600, or perhaps to 4200, calibrated years before the present (cal yr BP), corresponding to a stronger monsoon in South and East Asia. The shallow sea was cooler from ~4200 to 2600 cal yr BP in the study area, coinciding with a lower sea surface temperature in the northeastern Arabian Sea and an arid phase in the Indian subcontinent. From 2900 to 2600 cal yr BP the study core exhibits the impacts of short-term cold events, which have earlier been observed in the northeastern Arabian Sea, off Pakistan. During the Little Ice Age, the shallow sea off Goa was less productive.

Climate variability has played a vital role in the expansion and collapse of human civilizations across the World since ancient times. The Indus Civilization in South Asia has been the focus of investigations to archaeologists, historians, and anthropologists. But little attention was paid earlier to the role of climate variability in shaping the course of this well-established urban civilization. In this paper, we have presented a review of literature to understand various factors that affected the evolution of this cultural enigma. We suggest that the climate change in the region was a major controlling factor in determining the fate of Indus civilization settlements. The transformation of hunter-gatherers into pastoral community between 7000 and 3200 B.C.E., the establishment of village habitations along the Indus River and its tributaries in the Early Harappan phase, urbanization and shifting towards Ghaggar-Hakra rivers in the Mature Harappan phase, and final displacement towards Ganga-Yamuna doab (interfluve) region as village culture were largely modulated by the changing strength of the Indian summer monsoon and amount of precipitation in the region.

The liver mass constitutes hepatocytes expressing receptors for vitamin B12 (B12)-bound transporters in circulation. However, intrahepatic and circulating B12 interrelationship levels remain unclear. We assessed the intracellular B12 levels at various circulating B12 concentrations in human HepG2 cell-line and liver tissue levels of B12 in the C57BL/6 mouse model. In HepG2 cells treated with a range of B12 concentrations, the intracellular and circulatory B12 levels, transcript and protein levels of B12 receptor (CD320) and transporter (TCN2) were determined using immunoassays, qRT-PCR and Western blot, respectively. Similar assessments were done in plasma and liver tissue of C57BL/6 mice, previously fed a diet of either a high or low B12 (30.82 µg B12/kg and 7.49 µg B12/kg, respectively) for 8–10 weeks. The physiological B12 status (0.15–1 nM) resulted in increased levels of intracellular B12 in HepG2 cells compared to supraphysiological levels of B12 (&gt, 1 nM). Gene and protein expression of CD320 and TCN2 were also higher at physiological levels of B12. Progressively increasing extracellular B12 to supraphysiological levels led to relative decreased levels of intracellular B12, lower expression of gene and protein levels of CD320 and TCN2. Similar results were observed in liver tissue from mice fed on a low B12 diet verses high B12 diet. These findings suggest that unlike supraphysiological B12, physiological levels of B12 in the extracellular media or circulation accelerates active transport of B12, and expression of CD320 and TCN2, resulting in higher relative uptake of B12 in hepatocytes.

Childhood obesity is a growing epidemic. Early identification of high-risk groups will allow for the development of prevention strategies. Cord blood adipocytokines have been previously examined as biomarkers predicting future obesity. We conducted a systematic review looking at the association between cord blood leptin and adiponectin with adiposity up to 5 years of age. A literature review was performed between January 1994 and August 2020 using two bibliographic databases (Medline/Pubmed and EMBASE) and was registered on PROSPERO (CRD42017069024). Studies using skinfold thickness and direct methods of assessing body composition in full term neonates were considered. Partial correlation and multiple regression models were used to present the results. Meta-analysis was performed, were possible, using a random effects model. Cochran’s Q test was used to assess heterogeneity and I2 statistics to calculate the percentage of variation across studies. The potential for publication bias was assessed using funnel plots. Data from 22 studies were retrieved and reviewed by two independent reviewers. Cord blood leptin was positively associated with adiposity at birth (r = 0.487; 95% CI: 0.444, 0.531) but was inversely related to adiposity up to 3 years of age. The association was not sustained at 5 years. There was a weak positive association between adiponectin in cord blood and adiposity at birth (r = 0.201; 95% CI: 0.125, 0.277). No correlation was found between cord blood adiponectin in young children, but data were limited. This review supports that cord blood leptin and adiponectin are associated with adiposity at birth. The results of this study provide insight into the role of adipocytokines at birth on future metabolic health and their potential use as risk stratification tools.

This study aimed to test the feasibility and to identify barriers and facilitators towards adherence of a text messaging intervention for postnatal care in India. Mixed methods research involving both quantitative and qualitative methods were used. A survey questionnaire for feasibility and focus group interviews to identify the barriers and facilitators to the intervention were conducted. The top three reasons for activation of service were: helped the new mother to understand the changes (95%); provided continuation of care (90%) and clarified conflicting information (89%). Over 90% read the messages daily. 80% were happy with the message frequency. About 75% shared the content with others. The main reasons for non-activation were: 30% had technical issues, 15% did not think it would be useful, 17% did not have time to activate and for 5%, husbands made the decision. These findings were triangulated through the qualitative focus groups. The main themes identified via the focus groups were: (1) reliable, current information; (2) issues and themes well aligned with new mothers’ needs and priorities; (3) expanded the repertoire of information sources available; and (4) high-quality accessible information. The satisfaction and trust rates were high. This technology may be useful for health information intervention in specific postnatal areas.

Introduction. Gestational diabetes is a common complication, whose incidence is growing globally. There is a pressing need to obtain more data on GDM in low- and middle-income countries, especially amongst high-risk populations, as most of the data on GDM comes from high-income countries. With the growing awareness of the role HIV plays in the progression of noncommunicable diseases and the disproportionate HIV burden African countries like Kenya face, investigating the potential role HIV plays in increasing dysglycemia amongst pregnant women with HIV is an important area of study. Methods. The STRiDE study is one of the largest ever conducted studies of GDM in Kenya. This study enrolled pregnant women aged between 16 and 50 who were receiving care from public and private sector facilities in Eldoret, Kenya. Within this study, women received venous testing for glycosylated hemoglobin (HbA1c) and fasting glucose between 8- and 20-week gestational age. At their 24-32-week visit, they received a venous 75 g oral glucose tolerance test (OGTT). Because of the pressing need to assess the burden of GDM within the population of pregnant women with HIV, a nested case-control study design was used. Pregnant women with HIV within the larger STRiDE cohort were matched to non-HIV-infected women within the STRiDE cohort at a 1 : 3 ratio based on body mass index, parity, family history of GDM, gestational age, and family history of hypertension. The measurements of glucose from the initial visit (fasting glucose and HbA1c) and follow-up visit (OGTT) were compared between the two groups of HIV+ cases and matched HIV- controls. Results. A total of 83 pregnant women with HIV were well matched to 249 non-HIV-infected women from the STRiDE cohort with marital status being the only characteristic that was statistically significantly different between the two groups. Statistically significant differences were not observed in the proportion of women who developed GDM, the fasting glucose values, the HbA1c, or OGTT measurements between the two groups. Discussion. Significant associations were not seen between the different measures of glycemic status between pregnant women with and without HIV. While significant differences were not seen in this cohort, additional investigation is needed to better describe the association of dysglycemia with HIV, especially in Kenyan populations with a higher prevalence of GDM.

Gestational diabetes, the most common medical disorder in pregnancy, is defined as glucose intolerance resulting in hyperglycaemia that begins or is first diagnosed in pregnancy. Gestational diabetes is associated with increased pregnancy complications and long-term metabolic risks for the woman and the offspring. However, the current diagnostic and management strategies recommended by national and international guidelines are mainly focused on short-term risks during pregnancy and delivery, except the Carpenter-Coustan criteria, which were based on the risk of future incidence of type 2 diabetes post-gestational diabetes. In this Personal View, first, we summarise the evidence for long-term risk in women with gestational diabetes and their offspring. Second, we suggest that a shift is needed in the thinking about gestational diabetes; moving from the perception of a short-term condition that confers increased risks of large babies to a potentially modifiable long-term condition that contributes to the growing burden of childhood obesity and cardiometabolic disorders in women and the future generation. Third, we propose how the current clinical practice might be improved. Finally, we outline and justify priorities for future research.

An abnormal lipid profile is an independent risk factor for cardiovascular diseases. The relationship between vitamin B12 deficiency and lipid profile is inconclusive, with most studies conducted in unhealthy populations. In this study, we aimed to assess the relationship between serum vitamin B12 levels and lipid profiles in a cross-sectional study that included 341 apparently healthy Saudi women, aged 19&ndash, 30 years, from different colleges at King Saud University, Saudi Arabia. Sociodemographic, anthropometric, biochemical, and lifestyle data were collected, including diet and physical activity. Serum vitamin B12 deficiency was defined as serum B12 level of &lt, 148 pmol/L. The prevalence of vitamin B12 deficiency was approximately 0.6%. Using multivariable linear regression models, serum vitamin B12 levels were found to be inversely associated with total cholesterol (B = &minus, 0.26, p &lt, 0.001), low-density lipoprotein cholesterol levels (B = &minus, 0.30, 0.001), and triglyceride (B = &minus, 0.16, 0.01) after adjusting for potential confounders, while obesity indices of body mass index, central obesity, and fat percentage showed no association. Therefore, we conclude that low serum vitamin B12 levels are independently associated with abnormal lipid profiles in healthy young Saudi women. Further interventional studies are needed to determine whether improving serum vitamin B12 levels in a healthy population can improve lipid profiles.

Vitamin B12 (B12) is a micronutrient essential for one-carbon (1C) metabolism. B12 deficiency disturbs the 1C cycle and alters DNA methylation which is vital for most metabolic processes. Studies show that B12 deficiency may be associated with obesity, insulin resistance and gestational diabetes; and with obesity in child-bearing women. We therefore hypothesised that the associations between B12 deficiency, BMI and the metabolic risk could be mediated through altered 1C metabolites in early pregnancy. We explored these associations in two different early pregnancy cohorts in the UK (cohort 1; n = 244 and cohort 2; n = 60) with anthropometric data at 10–12 weeks and plasma/serum sampling at 16–18 weeks. B12, folate, total homocysteine (tHcy), methionine, MMA, metabolites of 1C metabolism (SAM, SAH) and anthropometry were measured. B12 deficiency (