Publications by authors named "Hitman G"

Objective: To determine the feasibility of a definitive trial of metformin to prevent type 2 diabetes in the postnatal period in women with gestational diabetes.

Design: A multicentre, placebo-controlled, double-blind randomised feasibility trial with qualitative evaluation.

Setting: Three inner-city UK National Health Service hospitals in London.

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Mitochondrial health and cellular metabolism can heavily influence the onset of senescence in T cells. CD8 EMRA T cells exhibit mitochondrial dysfunction and alterations to oxidative phosphorylation, however, the metabolic properties of senescent CD8 T cells from people living with type 2 diabetes (T2D) are not known. We show here that mitochondria from T2D CD8 T cells had a higher oxidative capacity together with increased levels of mitochondrial reactive oxgen species (mtROS), compared to age-matched control cells.

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Objectives: To determine the feasibility and acceptability of conducting a randomised trial on the effects of myo-inositol in preventing gestational diabetes in high-risk pregnant women.

Design: A multicentre, double-blind, placebo-controlled, pilot randomised trial with nested qualitative evaluation.

Setting: Five inner city UK National Health Service hospitals PARTICIPANTS: Multiethnic pregnant women at 12 and 15 weeks' gestation with risk factors for gestational diabetes.

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Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy Consortium assembled genome-wide association studies of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM.

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The pharmacogenetic effect on cardiovascular disease reduction in response to statin treatment has only been assessed in small studies. In a pharmacogenetic genome wide association study (GWAS) analysis within the Genomic Investigation of Statin Therapy (GIST) consortium, we investigated whether genetic variation was associated with the response of statins on cardiovascular disease risk reduction. The investigated endpoint was incident myocardial infarction (MI) defined as coronary heart disease death and definite and suspect non-fatal MI.

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Size at birth is known to be influenced by various fetal and maternal factors, including genetic effects. South Asians have a high burden of low birth weight and cardiometabolic diseases, yet studies of common genetic variations underpinning these phenotypes are lacking. We generated independent, weighted fetal genetic scores (fGSs) and maternal genetic scores (mGSs) from 196 birth weight-associated variants identified in Europeans and conducted an association analysis with various fetal birth parameters and anthropometric and cardiometabolic traits measured at different follow-up stages (5-6-year intervals) from seven Indian and Bangladeshi cohorts of South Asian ancestry.

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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.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.

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Aims: Gestational diabetes (GDM) is the most common metabolic disorder of pregnancy, requiring complex management and empowerment of those affected. Mobile health (mHealth) applications (apps) are proposed for streamlining healthcare service delivery, extending care relationships into the community, and empowering those affected by prolonged medical disorders to be equal collaborators in their healthcare. This review investigates mHealth apps intended for use with GDM; specifically those powered by artificial intelligence (AI) or providing decision support.

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Background: Gestational diabetes mellitus (GDM) can adversely affect the health of the developing fetus. Women of South Asian origin are particularly at risk of developing GDM. Insulin resistance (IR) contributes to the etiology of GDM, and although studies have shown associations of vitamin B12 (B12) and folate status with GDM and IR, only a limited number of B12 and folate markers have been used.

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Background: Betel-nut consumption is the fourth most common addictive habit globally and there is good evidence linking the habit to obesity, type 2 diabetes (T2D) and the metabolic syndrome. The aim of our pilot study was to identify gene expression relevant to obesity, T2D and the metabolic syndrome using a genome-wide transcriptomic approach in a human monocyte cell line incubated with arecoline and its nitrosated products.

Results: The THP1 monocyte cell line was incubated separately with arecoline and 3-methylnitrosaminopropionaldehyde (MNPA) in triplicate for 24 h and pooled cDNA indexed paired-end libraries were sequenced (Illumina NextSeq 500).

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Introduction: Mothers with gestational diabetes mellitus (GDM) are at increased risk of pregnancy-related complications and developing type 2 diabetes after delivery. Diet and physical activity-based interventions may prevent GDM, but variations in populations, interventions and outcomes in primary trials have limited the translation of available evidence into practice. We plan to undertake an individual participant data (IPD) meta-analysis of randomised trials to assess the differential effects and cost-effectiveness of diet and physical activity-based interventions in preventing GDM and its complications.

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Aim: To assess the efficacy of vitamin D3 or B12 supplementation during pregnancy.

Methods: Pregnant women at 6-14 weeks in the intervention arm received oral high dose intermittent vitamin D3 and/or low dose B12 supplementation if they had vitamin D or vitamin B12 deficiency. The control arm received prescribed dietary instruction only.

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Bayesian networks (BNs) have received increasing research attention that is not matched by adoption in practice and yet have potential to significantly benefit healthcare. Hitherto, research works have not investigated the types of medical conditions being modelled with BNs, nor whether there are any differences in how and why they are applied to different conditions. This research seeks to identify and quantify the range of medical conditions for which healthcare-related BN models have been proposed, and the differences in approach between the most common medical conditions to which they have been applied.

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Information visualisation is transforming data into visual representations to convey information hidden within large datasets. Information visualisation in medicine is underdeveloped. In midwifery, the impact of different graphs on clinicians' and patients' understanding is not well understood.

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Introduction: Up to half of all women diagnosed with gestational diabetes mellitus develop type 2 diabetes within 5 years after delivery. Metformin is effective in preventing type 2 diabetes in high-risk non-pregnant individuals, but its effect when commenced in the postnatal period is not known. We plan to assess the feasibility of evaluating metformin versus placebo in minimising the risk of dysglycaemia including type 2 diabetes after delivery in postnatal women with a history of gestational diabetes through a randomised trial.

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There is a strong push towards standardisation of treatment approaches, care processes and documentation of clinical practice. However, confusion persists regarding terminology and description of many clinical care process specifications which this research seeks to resolve by developing a taxonomic characterisation of clinical care process specifications. Literature on clinical care process specifications was analysed, creating the starting point for identifying common characteristics and how each is constructed and used in the clinical setting.

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It remains unclear whether the increased risk of new-onset type 2 diabetes (T2D) seen in statin users is due to low LDL-C concentrations, or due to the statin-induced proportional change in LDL-C. In addition, genetic instruments have not been proposed before to examine whether liability to T2D might cause greater proportional statin-induced LDL-C lowering. Using summary-level statistics from the Genomic Investigation of Statin Therapy (GIST, n = 40,914) and DIAGRAM (n = 159,208) consortia, we found a positive genetic correlation between LDL-C statin response and T2D using LD score regression (r = 0.

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Background: To assess the maternal characteristics and nutritional status according to body mass index (BMI) at 6-14 weeks of gestation and to examine the relationship between maternal nutritional status in early pregnancy and its impact on neonatal birth weight.

Methods: The investigation was conducted from April 2011 to June 2012 in Dhaka, Bangladesh. A total of 498 primigravida pregnant women participated in the study; women with known diabetes or previous gestational diabetes (GDM) were excluded.

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The worldwide prevalence of diabetes has reached 8.5% among adults, and this is characterised by elevated glucose concentrations and failing insulin secretion. Furthermore, most people with type 2 diabetes are either obese or overweight, with the associated dyslipidaemia contributing to the development of insulin resistance and increased cardiovascular risk.

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Background: Pregnant women with metabolic risk factors are at high risk of complications. We aimed to assess whether a Mediterranean-style diet reduces adverse pregnancy outcomes in high-risk women.

Methods And Findings: We conducted a multicentre randomised trial in 5 maternity units (4 in London and 1 in Birmingham) between 12 September 2014 and 29 February 2016.

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Type 2 diabetes is a global health priority, given that it is driven, in part, by an ageing population, the role of immune senescence has been overlooked. This is surprising, as the functional impairments of senescent T cells show strong similarities to patients with hyperglycaemia. Immune senescence is typified by alterations in T cell memory, such as the accumulation of highly differentiated end-stage memory T cells, as well as a constitutive low-grade inflammation, which drives further immune differentiation.

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Objective: Gestational diabetes is the most common metabolic disorder of pregnancy, and it is important that well-written clinical practice guidelines (CPGs) are used to optimise healthcare delivery and improve patient outcomes. The aim of the study was to assess the methodological quality of hospital-based CPGs on the identification and management of gestational diabetes.

Design: We conducted an assessment of local clinical guidelines in English for gestational diabetes using the Appraisal of Guidelines for Research and Evaluation (AGREE II) to assess and validate methodological quality.

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Context: Vitamin D2 and vitamin D3 have been hypothesized to exert differential effects on vitamin D metabolism.

Objective: To compare the influence of administering vitamin D2 vs vitamin D3 on metabolism of vitamin D3.

Methods: We measured baseline and 4-month serum concentrations of vitamin D3, 25-hydroxyvitamin D3 [25(OH)D3], 25-hydroxyvitamin D2, 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3], 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], and 4β,25-dihydroxyvitamin D3 [4β,25(OH)2D3] in 52 adults randomized to receive a total of four oral bolus doses of 2.

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Introduction: Gestational diabetes increases maternal and offspring complications in pregnancy and cardiovascular complications in the long term. The nutritional supplement -inositol may prevent gestational diabetes; however, further evaluation is required, especially in multiethnic high-risk mothers. Our pilot trial on -inositol to prevent gestational diabetes will evaluate trial processes, assess acceptability to mothers and obtain preliminary estimates of effect and cost data prior to a large full-scale trial.

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Background: Women's groups interventions in Bangladesh reduced neonatal deaths by 38% and improved hygienic delivery, newborn care practices and breast feeding. We explore the longer-term impact of exposure to women's groups during pregnancy on child growth at 2-4 years.

Methods: We performed a cross-sectional survey of child anthropometric measures (analysed as z-scores) among children born to women who had participated in the women's groups interventions while pregnant, compared with an age-matched and sex-matched sample of children born to control mothers.

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