Publications
81 results found
Alonso AM, Cork SC, Phuah P, et al., 2024, The vagus nerve mediates the physiological but not pharmacological effects of PYY3-36 on food intake, Molecular Metabolism, Vol: 81, ISSN: 2212-8778
Peptide YY (PYY3-36) is a post-prandially released gut hormone with potent appetite-reducing activity, the mechanism of action of which is not fully understood. Unravelling how this system physiologically regulates food intake may help unlock its therapeutic potential, whilst minimising unwanted effects. Here we demonstrate that germline and post-natal targeted knockdown of the PYY3-36 preferring receptor (neuropeptide Y (NPY) Y2 receptor (Y2R)) in the afferent vagus nerve is required for the appetite inhibitory effects of physiologically-released PYY3-36, but not peripherally administered pharmacological doses. Post-natal knockdown of the Y2R results in a transient body weight phenotype that is not evident in the germline model. Loss of vagal Y2R signalling also results in altered meal patterning associated with accelerated gastric emptying. These results are important for the design of PYY-based anti-obesity agents.
Hirani D, Alabdulkader S, Miras AD, et al., 2023, What can functional brain imaging teach us about remission of type 2 diabetes?, Diabet Med, Vol: 40
AIMS: With a paradigm shift in attitudes towards type 2 diabetes (T2D), 'weight loss responsive' diabetes is now thought of as a curable disease state. As a result, national programmes are being orchestrated to induce T2D remission soon after diagnosis with aggressive dietary interventions-such as very low-calorie diets (VLCD). However, dietary interventions to achieve weight loss and diabetes remission lack the same long-term sustainability and cardiovascular risk reduction evidence as bariatric surgery. This review aims to explore how brain imaging has contributed to our understanding of human eating behaviours and how neural correlates are affected by T2D. METHODS: We summarise functional MRI (fMRI) studies looking at human eating behaviour and obesity. We explore how these neural correlates are affected by insulin resistance and T2D itself as well as its different treatment approaches. Finally, we comment on the need for more personalised approaches to maintaining metabolic health and how fMRI studies may inform this. CONCLUSION: fMRI studies have helped to fashion our understanding of the neurobiology of human appetite and obesity. Improving our understanding of the neural implications of T2D that promote disadvantageous eating behaviours will enable prevention of disease as well as mitigation against a vicious cycle of metabolic dysfunction and associated cognitive complications.
Yaganoglu S, Kalyviotis K, Vagena-Pantoula C, et al., 2023, Author Correction: Highly specific and non-invasive imaging of Piezo1-dependent activity across scales using GenEPi, Nature Communications, Vol: 14, ISSN: 2041-1723
Alhakami A, Salem V, Alateeq D, et al., 2023, The Arab COVID-19 Anxiety Syndrome Scale (C-19ASS): COVID-19 anxiety syndrome and psychological symptoms in the Saudi Arabian population, CLINICAL PSYCHOLOGY & PSYCHOTHERAPY, Vol: 30, Pages: 1083-1094, ISSN: 1063-3995
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- Citations: 4
Pantazis P, Pantazis P, Yaganoglu S, et al., 2023, Highly specific and non-invasive imaging of Piezo1-dependent activity across scales using GenEPi, Nature Communications, Vol: 14, Pages: 1-16, ISSN: 2041-1723
Mechanosensing is a ubiquitous process to translate external mechanical stimuliinto biological responses. Piezo1 ion channels are directly gated by mechanical forces and playan essential role in cellular mechanotransduction. However, readouts of Piezo1 activity aremainly examined by invasive or indirect techniques, such as electrophysiological analyses andcytosolic calcium imaging. Here, we introduce GenEPi, a genetically-encoded fluorescentreporter for non-invasive optical monitoring of Piezo1-dependent activity. We demonstrate thatGenEPi has high spatiotemporal resolution for Piezo1-dependent stimuli from the single-celllevel to that of the entire organism. GenEPi reveals transient, local mechanical stimuli in theplasma membrane of single cells, resolves repetitive contraction-triggered stimulation ofbeating cardiomyocytes within microtissues, and allows for robust and reliable monitoring of Piezo1-dependent activity in vivo. GenEPi will enable non-invasive optical monitoring ofPiezo1 activity in mechanochemical feedback loops during development, homeostaticregulation, and disease.
Hirani D, Salem V, Khunti K, et al., 2023, Newly detected diabetes during the COVID-19 pandemic: What have we learnt?, BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 37, ISSN: 1521-690X
Tomas Catala A, Bitsi S, Manchanda Y, et al., 2023, Divergent acute versus prolonged pharmacological GLP-1R responses in adult beta cell-specific β-arrestin 2 knockout mice, Science Advances, Vol: 9, Pages: 1-23, ISSN: 2375-2548
The glucagon-like peptide-1 receptor (GLP-1R) is a major type 2 diabetes therapeutic target. Stimulated GLP-1Rs are rapidly desensitized by β-arrestins, scaffolding proteins that not only terminate G protein interactions but also act as independent signaling mediators. Here, we have assessed in vivo glycemic responses to the pharmacological GLP-1R agonist exendin-4 in adult β cell–specific β-arrestin 2 knockout (KO) mice. KOs displayed a sex-dimorphic phenotype consisting of weaker acute responses that improved 6 hours after agonist injection. Similar effects were observed for semaglutide and tirzepatide but not with biased agonist exendin-phe1. Acute cyclic adenosine 5′-monophosphate increases were impaired, but desensitization reduced in KO islets. The former defect was attributed to enhanced β-arrestin 1 and phosphodiesterase 4 activities, while reduced desensitization co-occurred with impaired GLP-1R recycling and lysosomal targeting, increased trans-Golgi network signaling, and reduced GLP-1R ubiquitination. This study has unveiled fundamental aspects of GLP-1R response regulation with direct application to the rational design of GLP-1R–targeting therapeutics.
Distaso W, Malik MMAH, Semere S, et al., 2022, Diabetes self-management during the COVID-19 pandemic and its associations with COVID-19 anxiety syndrome, depression and health anxiety, Publisher: WILEY, ISSN: 0742-3071
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- Citations: 3
Frampton J, Izzi-Engbeaya C, Salem V, et al., 2022, The acute effect of glucagon on components of energy balance and glucose homoeostasis in adults without diabetes: a systematic review and meta-analysis, International Journal of Obesity, Vol: 46, Pages: 1948-1959, ISSN: 0307-0565
ObjectiveUsing a systematic review and meta-analysis, we aimed to estimate the mean effect of acute glucagon administration on components of energy balance and glucose homoeostasis in adults without diabetes.MethodsCENTRAL, CINAHL, Embase, MEDLINE, PubMed, and Scopus databases were searched from inception to May 2021. To be included, papers had to be a randomised, crossover, single- or double-blind study, measuring ad libitum meal energy intake, energy expenditure, subjective appetite, glucose, and/or insulin following acute administration of glucagon and an appropriate comparator in adults without diabetes. Risk of bias was assessed using the Revised Cochrane Risk of Bias Tool for Randomized trials with additional considerations for cross-over trials. Certainty of evidence was assessed using the GRADE approach. Random-effect meta-analyses were performed for outcomes with at least five studies. This study is registered on PROSPERO (CRD42021269623).ResultsIn total, 13 papers (15 studies) were considered eligible: energy intake (5 studies, 77 participants); energy expenditure (5 studies, 59 participants); subjective appetite (3 studies, 39 participants); glucose (13 studies, 159 participants); insulin (12 studies, 147 participants). All studies had some concerns with regards to risk of bias. Mean intervention effect of acute glucagon administration on energy intake was small (standardised mean difference [SMD]: –0.19; 95% CI, –0.59 to 0.21; P = 0.345). Mean intervention effect of acute glucagon administration on energy expenditure (SMD: 0.72; 95% CI, 0.37–1.08; P < 0.001), glucose (SMD: 1.11; 95% CI, 0.60–1.62; P < 0.001), and insulin (SMD: 1.33; 95% CI, 0.88–1.77; P < 0.001) was moderate to large.ConclusionsAcute glucagon administration produces substantial increases in energy expenditure, and in circulating insulin and glucose concentrations. However, the effect of acute g
Salem V, AlHusseini N, Razack HIA, et al., 2022, Prevalence, risk factors, and interventions for obesity in Saudi Arabia: A systematic review, OBESITY REVIEWS, Vol: 23, ISSN: 1467-7881
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- Citations: 26
Salem V, Hirani D, Lloyd C, et al., 2022, Why are women still leaving academic medicine? A qualitative study within a London Medical School, BMJ Open, Vol: 12, ISSN: 2044-6055
Objectives: To identify factors that influenced women who chose to leave academic medicine.Design and main outcome measures: Independent consultants led a focus group of women in medicine who had left academia after completion of their postgraduate research degree at Imperial College London Faculty of Medicine. Thematic analysis was performed on the transcribed conversations.Participants and setting: Nine women physicians who completed a postgraduate degree (MD or PhD) at a large London Medical School and Academic Health Sciences Centre, Imperial College London, but did not go on to pursue a career in academic medicine.Results: Influences to leave clinical academia were summarised under eight themes—career intentions, supervisor support, institutional human resources support, inclusivity, work–life balance, expectations, mentors and role models, and pregnancy and maternity leave.Conclusion: The women in our focus group reported several factors contributing to their decision to leave clinical academia, which included lack of mentoring tailored to specific needs, low levels of acceptance for flexible working to help meet parental responsibilities and perceived explicit gender biases. We summarise the multiple targeted strategies that Imperial College London has implemented to promote retention of women in academic medicine, although more research needs to be done to ascertain the most effective interventions.
Suba K, Patel YS, Roberts A, et al., 2022, The Role of Intraislet Glucagon in Pulsatile Insulin Secretion, Publisher: AMER DIABETES ASSOC, ISSN: 0012-1797
Witt CE, Mena S, Honan LE, et al., 2022, Low-Frequency Oscillations of In Vivo Ambient Extracellular Brain Serotonin, CELLS, Vol: 11
Misky A, Shah R, Meeran K, et al., 2022, Understanding concepts of generalism and specialism amongst medical students at a research-intensive London Medical School, BMC Medical Education, Vol: 22, Pages: 1-11, ISSN: 1472-6920
BackgroundMany prominent UK medical organisations have identified a need for more generalist clinicians to address the complex requirements of an aging society. We sought to clarify attitudes towards “Specialists” and “Generalists” amongst medical students and junior doctors at Imperial College School of Medicine.MethodsA survey exploring medical students’ beliefs was followed up by qualitative analysis of focus groups of medical students and Imperial-graduate foundation year doctors.ResultsFirst year medical students associated specialists with academia and higher income, and generalists with ease of training and job availability. Senior (Years 5/6) medical students associated specialists even more firmly with broader influence and academic work, whilst generalists were assigned lower prestige but the same workload as specialists. The medicalstudent focus group discussed concepts of Generalism pertaining only to Primary Care. In contrast, the foundation year doctor focus group revealed that Generalism was now seen to include some hospital care, and the perception that generalists sat lower in a knowledge hierarchy had been challenged.ConclusionPerceptions that Generalism is associated with lower prestige in the medical profession are already present at the very start of medical school and seem to be reinforced during undergraduate training. In early postgraduate clinical practice, the perceived knowledge and prestige hierarchy lessens. These findings can help inform curriculum redesign and the promotion of Generalism as a rewarding career aspiration.
Eng PC, Distaso W, Durreshahwar H, et al., 2022, The benefit of dexamethasone in patients with COVID-19 infection is preserved in patients with diabetes., Diabetes, Obesity and Metabolism: a journal of pharmacology and therapeutics, Vol: 24, Pages: 1385-1389, ISSN: 1462-8902
Dexamethasone significantly reduces mortality1 and is now standard treatment for patients with COVID-19 who require supplemental oxygen and/or mechanical ventilation. However, supraphysiological doses of glucocorticoids may exacerbate dysglycaemia and precipitate hyperglycaemic complications, particularly in those with or at risk of Type 2 diabetes2. The RECOVERY trial1 reported a low incidence of hyperglycaemic complications (2/1996, 0.1%), although the real-world incidence is likely to be much higher3. Type 2 diabetes itself increases the risk of severe COVID-194, and hyperglycaemia independently predicts poor outcomes5. We investigated the possibility that patients with diabetes may derive less survival benefit from steroid therapy in the setting of severe COVID-19 infection
Izzi-Engbeaya C, Salem V, 2021, Commentary: 'Diversity of invited speakers at endocrinology conferences', CLINICAL ENDOCRINOLOGY, ISSN: 0300-0664
Kim A, Knudsen JG, Madara JC, et al., 2021, Arginine-vasopressin mediates counter-regulatory glucagon release and is diminished in type 1 diabetes, eLife, Vol: 10, Pages: 1-29, ISSN: 2050-084X
Insulin-induced hypoglycemia is a major treatment barrier in type-1 diabetes (T1D). Accordingly, it is important that we understand the mechanisms regulating the circulating levels of glucagon. Varying glucose over the range of concentrations that occur physiologically between the fed and fuel-deprived states (8 to 4 mM) has no significant effect on glucagon secretion in the perfused mouse pancreas or in isolated mouse islets (in vitro), and yet associates with dramatic increases in plasma glucagon. The identity of the systemic factor(s) that elevates circulating glucagon remains unknown. Here, we show that arginine-vasopressin (AVP), secreted from the posterior pituitary, stimulates glucagon secretion. Alpha-cells express high levels of the vasopressin 1b receptor (V1bR) gene (Avpr1b). Activation of AVP neurons in vivo increased circulating copeptin (the C-terminal segment of the AVP precursor peptide) and increased blood glucose; effects blocked by pharmacological antagonism of either the glucagon receptor or V1bR. AVP also mediates the stimulatory effects of hypoglycemia produced by exogenous insulin and 2-deoxy-D-glucose on glucagon secretion. We show that the A1/C1 neurons of the medulla oblongata drive AVP neuron activation in response to insulin-induced hypoglycemia. AVP injection increased cytoplasmic Ca2+ in alpha-cells (implanted into the anterior chamber of the eye) and glucagon release. Hypoglycemia also increases circulating levels of AVP/copeptin in humans and this hormone stimulates glucagon secretion from human islets. In patients with T1D, hypoglycemia failed to increase both copeptin and glucagon. These findings suggest that AVP is a physiological systemic regulator of glucagon secretion and that this mechanism becomes impaired in T1D.
de Jesus DS, Mak TCS, Wang Y-F, et al., 2021, Dysregulation of the Pdx1/Ovol2/Zeb2 axis in dedifferentiated β-cells triggers the induction of genes associated with epithelial-mesenchymal transition in diabetes, Molecular Metabolism, Vol: 53, ISSN: 2212-8778
OBJECTIVE: β-cell dedifferentiation has been revealed as a pathological mechanism underlying pancreatic dysfunction in diabetes. We previously showed that increased miR-7 levels trigger β-cell dedifferentiation and diabetes. We used β-cell-specific miR-7 overexpressing mice (Tg7) to test the hypothesis that loss of β-cell identity triggered by miR-7 overexpression alters islet gene expression and islet microenvironment in diabetes. METHODS: We performed bulk and single-cell RNA sequencing (RNA-seq) in islets obtained from β-cell-specific miR-7 overexpressing mice (Tg7). We carried out loss- and gain-of-function experiments in MIN6 and EndoC-bH1 cell lines. We analysed previously published mouse and human T2D data sets. RESULTS: Bulk RNA-seq revealed that β-cell dedifferentiation is associated with the induction of genes associated with epithelial-to-mesenchymal transition (EMT) in prediabetic (2-week-old) and diabetic (12-week-old) Tg7 mice. Single-cell RNA-seq (scRNA-seq) indicated that this EMT signature is enriched specifically in β-cells. These molecular changes are associated with a weakening of β-cell: β-cell contacts, increased extracellular matrix (ECM) deposition, and TGFβ-dependent islet fibrosis. We found that the mesenchymal reprogramming of β-cells is explained in part by the downregulation of Pdx1 and its inability to regulate a myriad of epithelial-specific genes expressed in β-cells. Notable among genes transactivated by Pdx1 is Ovol2, which encodes a transcriptional repressor of the EMT transcription factor Zeb2. Following compromised β-cell identity, the reduction in Pdx1 gene expression causes a decrease in Ovol2 protein, triggering mesenchymal reprogramming of β-cells through the induction of Zeb2. We provided evidence that EMT signalling associated with the upregulation of Zeb2 expression is a molecular feature of islets in T2D subjects. CONCLUSIONS: Our study indicates that m
Akalestou E, Suba K, Lopez-Noriega L, et al., 2021, Intravital imaging of islet Ca2+ dynamics reveals enhanced beta cell connectivity after bariatric surgery in mice (vol 12, 5165, 2021), Nature Communications, Vol: 12, Pages: 1-1, ISSN: 2041-1723
Salem V, McDonagh J, Avis E, et al., 2021, Scientific medical conferences can be easily modified to improve female inclusion: a prospective study., The Lancet Diabetes and Endocrinology, Vol: 9, Pages: 556-559, ISSN: 2213-8595
Akalestou E, Suba K, Lopez-Noriega L, et al., 2021, Intravital imaging of islet Ca2+ dynamics reveals enhanced beta cell connectivity after bariatric surgery in mice, Nature Communications, Vol: 12, Pages: 1-13, ISSN: 2041-1723
Bariatric surgery improves both insulin sensitivity and secretion and can induce diabetes remission. However, the mechanisms and time courses of these changes, particularly the impact on β cell function, are difficult to monitor directly. In this study, we investigated the effect of Vertical Sleeve Gastrectomy (VSG) on β cell function in vivo by imaging Ca2+ dynamics in islets engrafted into the anterior eye chamber. Mirroring its clinical utility, VSG in mice results in significantly improved glucose tolerance, and enhanced insulin secretion. We reveal that these benefits are underpinned by augmented β cell function and coordinated activity across the islet. These effects involve changes in circulating GLP-1 levels which may act both directly and indirectly on the β cell, in the latter case through changes in body weight. Thus, bariatric surgery leads to time-dependent increases in β cell function and intra-islet connectivity which are likely to contribute to diabetes remission.
Marzook A, Chen S, Pickford P, et al., 2021, Evaluation of efficacy- versus affinity-driven agonism with biased GLP-1R ligands P5 and exendin-F1, Biochemical Pharmacology, Vol: 190, Pages: 1-12, ISSN: 0006-2952
The glucagon-like peptide-1 receptor (GLP-1R) is an important regulator of glucose homeostasis and has been successfully targeted for the treatment of type 2 diabetes. Recently described biased GLP-1R agonists with selective reductions in β-arrestin versus G protein coupling show improved metabolic actions in vivo. However, two prototypical G protein-favouring GLP-1R agonists, P5 and exendin-F1, are reported to show divergent effects on insulin secretion. In this study we aimed to resolve this discrepancy by performing a side-by-side characterisation of these two ligands across a variety of in vitro and in vivo assays. Exendin-F1 showed reduced acute efficacy versus P5 for several readouts, including recruitment of mini-G proteins, G protein-coupled receptor kinases (GRKs) and β-arrestin-2. Maximal responses were also lower for both GLP-1R internalisation and the presence of active GLP-1R-mini-Gs complexes in early endosomes with exendin-F1 treatment. In contrast, prolonged insulin secretion in vitro and sustained anti-hyperglycaemic efficacy in mice were both greater with exendin-F1 than with P5. We conclude that the particularly low acute efficacy of exendin-F1 and associated reductions in GLP-1R downregulation appear to be more important than preservation of endosomal signalling to allow sustained insulin secretion responses. This has implications for the ongoing development of affinity- versus efficacy-driven biased GLP-1R agonists as treatments for metabolic disease.
Israni A, Jones B, Salem V, et al., 2021, IMPACT OF PCSK9 INHIBITORS ON HYPERCHOLESTEROLAEMIC PATIENTS AT A TERTIARY CENTRE LIPID, Publisher: ELSEVIER IRELAND LTD, Pages: E176-E176, ISSN: 0021-9150
Imbernon M, Saponaro C, Helms HCC, et al., 2021, Tanycytes Control the Hypothalamic Uptake and Metabolic Actions of Liraglutide, Publisher: WILEY, Pages: E237-E237, ISSN: 0894-1491
Salem V, Demetriou L, Behary P, et al., 2021, Weight loss by low calorie diet versus gastric bypass surgery in people with diabetes results in divergent brain activation patterns: an functional MRI study, Diabetes Care, Vol: 44, Pages: 1842-1851, ISSN: 0149-5992
OBJECTIVE: Weight loss achieved with very-low-calorie diets (VLCDs) can produce remission of type 2 diabetes (T2D), but weight regain very often occurs with reintroduction of higher calorie intakes. In contrast, bariatric surgery produces clinically significant and durable weight loss, with diabetes remission that translates into reductions in mortality. We hypothesized that in patients living with obesity and prediabetes/T2D, longitudinal changes in brain activity in response to food cues as measured using functional MRI would explain this difference.RESEARCH DESIGN AND METHODS: Sixteen participants underwent gastric bypass surgery, and 19 matched participants undertook a VLCD (meal replacement) for 4 weeks. Brain responses to food cues and resting-state functional connectivity were assessed with functional MRI pre- and postintervention and compared across groups.RESULTS: We show that Roux-en-Y gastric bypass surgery (RYGB) results in three divergent brain responses compared with VLCD-induced weight loss: 1) VLCD resulted in increased brain reward center food cue responsiveness, whereas in RYGB, this was reduced; 2) VLCD resulted in higher neural activation of cognitive control regions in response to food cues associated with exercising increased cognitive restraint over eating, whereas RYGB did not; and 3) a homeostatic appetitive system (centered on the hypothalamus) is better engaged following RYGB-induced weight loss than VLCD.CONCLUSIONS: Taken together, these findings point to divergent brain responses to different methods of weight loss in patients with diabetes, which may explain weight regain after a short-term VLCD in contrast to enduring weight loss after RYGB.
Chabosseau PL, Martinez-Sanchez A, Leclerc I, et al., 2021, Repetitive Ca2+Waves Emanate from a Stable Leader Cell in Mouse Islets, 81st Virtual Scientific Sessions of the American-Diabetes-Association (ADA), Publisher: AMER DIABETES ASSOC, ISSN: 0012-1797
Bitsi S, Suba K, Mohamed N, et al., 2021, β-arrestin-2 Deletion Influences GLP-1 Receptor Signaling in Pancreatic β Cells In Vivo, 81st Virtual Scientific Sessions of the American-Diabetes-Association (ADA), Publisher: AMER DIABETES ASSOC, ISSN: 0012-1797
Salem V, Demetriou L, Behary P, et al., 2021, Weight loss by low-calorie diet versus gastric bypass surgery in people with diabetes results in divergent brain activation patterns which may explain differences in long-term outcomes: an FMRI study, The Diabetes UK Professional Conference 2021, Publisher: Wiley, Pages: 1-1, ISSN: 0742-3071
Objective: Clinically significant weight loss can produce remission of type 2 diabetes. Bariatric surgery (specifically, Roux-en-Y gastric bypass, RYGB) produces durable weight loss that translates into reductions in mortality. In contrast, weight regain is very common after very low-calorie diets (VLCD). No study has investigated longitudinal changes in brain activity using functional MRI in patients living with obesity and prediabetes/type 2 diabetes to explain this difference.Methods: Visual food cue responses and resting state connectivity was assessed with functional MRI pre- and post-intervention and compared between 16 participants who underwent gastric bypass surgery and 19 age, gender, and disease stage matched participants who undertook a VLCD for 4 weeks.Results: Brain responses to RYGB-induced weight loss diverge from those induced by VLCD in three domains: (i) dieting resulted in increased responsiveness to visual food cues in reward areas whereas after RYGB this was reduced; (ii) dieting therefore engaged greater activation of brain regions involved in cognitive control, associated with the need to exercise increased restraint over eating; and (iii) a homeostatic appetitive system (centred on the hypothalamus) was better engaged following RYGB-induced weight loss than dieting.Conclusion: This study provides a holistic view of multiple divergent brain responses to different methods of weight loss in patients with diabetes, which may explain weight regain after a short-term VLCD in contrast with the enduring weight loss after RYGB.
Misra S, Khozoee B, Huang-Jiawei P, et al., 2021, Comparison of diabetic ketoacidosis in adults, during the SARS-CoV-2 outbreak and over the same time period for the 3 preceding years, Diabetes Care, Vol: 44, Pages: e29-e31, ISSN: 0149-5992
Izzi-Engbeaya C, Distaso W, Amin A, et al., 2021, Adverse outcomes in COVID-19 and diabetes – a retrospective cohort study from three London Teaching hospitals, BMJ Open Diabetes Research and Care, Vol: 9, Pages: 1-10, ISSN: 2052-4897
INTRODUCTION: Patients with diabetes mellitus admitted to hospital with COVID-19 have poorer outcomes. However, the drivers for this are not fully elucidated. We performed detailed characterisation of COVID-19 patients to determine clinical and biochemical factors that may be the drivers of poorer outcomes. RESEARCH DESIGN AND METHODS: Retrospective cohort study of 889 consecutive inpatients diagnosed with COVID-19 between 9th March 2020 and 22nd April 2020 in a large London NHS Trust. Unbiased multivariate logistic regression analysis was performed to determine variables that were independently and significantly associated with increased risk of death and/or ICU admission within 30 days of COVID-19 diagnosis. RESULTS: 62% of patients in our cohort were of non-White ethnic backgrounds and the diabetes prevalence was 38%. 323 (36%) patients met the primary outcome of death/admission to the intensive care unit (ICU) within 30 days of COVID-19 diagnosis. Male gender, lower platelet count, advancing age and higher Clinical Frailty Scale (CFS) score (but not diabetes) independently predicted poor outcomes on multivariate analysis. Antiplatelet medication was associated with a lower risk of death/ICU admission. Factors that were significantly and independently associated with poorer outcomes in patients with diabetes were co-existing ischaemic heart disease, increasing age and lower platelet count. CONCLUSIONS: In this large study of a diverse patient population, comorbidity (i.e. diabetes with ischaemic heart disease; increasing CFS score in older patients) were major determinants of poor outcomes with COVID-19. Antiplatelet medication should be evaluated in randomised clinical trials amongst high-risk patient groups.
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