Edwin Gale

Edwin Gale
University of Bristol | UB · Centre for Child and Adolescent Health

About

289
Publications
35,238
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21,859
Citations
Citations since 2017
5 Research Items
4317 Citations
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20172018201920202021202220230200400600
20172018201920202021202220230200400600
20172018201920202021202220230200400600
Introduction
Skills and Expertise

Publications

Publications (289)
Article
Every young researcher dreams of making a great discovery, but few achieve it. If they do, success does not guarantee happiness. There is little satisfaction in discovering something if others get the credit, and those who achieve fame must face the ‘winner’s curse’ of living up to their reputation. Few discoveries have been more dramatic than the...
Chapter
Type 1 diabetes results from insulin deficiency, although some residual insulin secretion is present at diagnosis and a minority of people retain limited function even after many years of diabetes. Preservation or regeneration of beta cells is a prime goal of diabetes research. Healthy individuals vary in their insulin sensitivity, i.e. the amount...
Article
Full-text available
To determine whether trial publications of glucose lowering drugs are dominated by a small group of highly prolific authors ("supertrialists") and to identify some of their characteristics. Bibliographic analysis of trial publications. We searched PubMed for all randomised controlled trials (RCTs) relating to glucose lowering drugs published betwee...
Article
Over the past few years, substantial clinical data have been presented showing that incretin-based therapies are effective glucose-lowering agents. Specifically, glucagon-like peptide 1 receptor agonists demonstrate an efficacy comparable to insulin treatment with minimal hypoglycemia and have favorable effects on body weight. Thus, many of the unm...
Chapter
Recognisable features of the diabetes syndrome can be identified in some of the ancient Hindu, Graeco-Roman and mediaeval Arab literature, but it was frequently confused with other causes of excessive urination. Greater understanding came with the rediscovery of the sweet taste of the urine in the seventeenth century. Chemical tests for glycosuria...
Article
We set out to estimate the prevalence rate of insulin use in the UK population, the total number of people in the UK who use insulin, the proportion of users with type 1 and type 2 diabetes, and changes between 1991 and 2010. Patients receiving prescriptions for insulin were identified in the Clinical Practice Research Datalink and attributed a dia...
Article
Full-text available
I, on behalf of Butler et al. (1), thank Bjerre Knudsen et al. (2) for their comments and accept their statement that liraglutide was not withdrawn before euthanasia of the monkeys. Nyborg et al. (3) reported routine pathological examination in the pancreas of young healthy members of three species. A single transverse section of the midpart of the...
Article
Transparency is what we need In a linked investigation (doi:10.1136/bmj.f3680), Cohen shines a spotlight on the safety of the incretins—drugs for the treatment of diabetes that mimic or enhance the biological effects of glucagon-like peptide-1 (GLP-1).1 Her investigation raises important questions as to the nature of the dialogue between drug comp...
Article
There is ample evidence that environmental factors are involved in the aetiology of type 1 diabetes, but the nature and timing of the interactions are poorly understood. The intrauterine environment is known to play a role in the later development of type 2 diabetes, and this review considers a possible role in type 1 diabetes. Autoimmune type 1 di...
Article
Full-text available
There is no question that incretin-based glucose-lowering medications have proven to be effective glucose-lowering agents. Glucagon-like peptide 1 (GLP-1) receptor agonists demonstrate an efficacy comparable to insulin treatment and appear to do so with significant effects to promote weight loss with minimal hypoglycemia. In addition, there are sig...
Article
Drug safety falls victim to the three monkey paradigm Investment companies knew that the Food and Drug Administration safety database carried a signal for acute pancreatitis with the antidiabetic drug exenatide (a glucagon-like peptide 1 (GLP-1) agonist) in 2006, a year before the agency alerted doctors1—a curious reflection on the way we mix bus...
Article
A 68 year old woman with a body mass index (weight (kg)/(height (m))2) of 31 has a five year history of type 2 diabetes. She is reasonably active but takes treatment for hypertension, hyperlipidaemia, and angina. She has signs of early diabetic background retinopathy. Her current treatment for diabetes is with metformin 850 mg twice daily and glicl...
Article
The International Diabetes Federation (IDF) is an umbrella organisation of more than 200 national diabetes associations in over 160 countries, and states its mission as being “to promote diabetes care, prevention and a cure worldwide”. In pursuing this mission, it can proudly point to many highly successful initiatives, helping to raise awareness,...
Article
Edwin Gale’s analysis of registered post-marketing studies of new treatments for diabetes showed that studies of insulin analogues have involved some 400 000 participants worldwide. One company recruited nearly 360 000 individuals. Most studies were performed in middle or low income countries, had limited scientific value, and promoted wider use of...
Article
Full-text available
GLP-1–based therapies are the most promising new treatment for type 2 diabetes to have been introduced in recent years. Long-term outcome studies are not yet available, but in the interim they have cleared many—although not all—of the hurdles for acceptability, efficacy, and safety. GLP-1 is a proglucagon-derived peptide secreted from the L cells o...
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Full-text available
Substantial evidence suggests that people with type 2 diabetes have an increased risk of developing several types of cancers. These associations may be due to a number of direct and indirect mechanisms. Observational studies of these associations, including the potential role for glucose-lowering therapy, are being increasingly reported, but face a...
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In this paper we address methodological aspects of aetiological importance in the link between diabetes and mortality in patients with cancer. We identified nine key points on the cancer pathway at which confounding may arise-cancer screening use, stage at diagnosis, cancer treatment selection, cancer treatment complications and failures, peri-trea...
Article
The hypothesis that a virus might in some way be involved in the causation of type 1 diabetes has a long history, but decades of research have failed to resolve the issue beyond reasonable doubt. Viruses could potentially play a primary role in the pathogenesis of type 1 diabetes by initiating autoimmunity, a secondary role by promoting established...
Article
Type 2 diabetes is associated with an increased risk of several types of cancer and with reduced survival after cancer diagnosis. We examined the hypotheses that survival after a diagnosis of solid-tumor cancer is reduced in those with diabetes when compared with those without diabetes, and that treatment with metformin influences survival after ca...
Article
The diabetes pandemic increasingly affects low and middle income countries, where most of those affected have type 2 diabetes. Cheap generic versions of current first line treatments, metformin and sulfonylureas, are widely available so why does this not apply to insulin? Human insulin is off patent, is relatively simple to manufacture, and WHO re...
Article
Both respondents suggest that there may be benefit to be gained from intensified glucose control in subgroups of patients with type 2 diabetes—younger patients, those with a shorter disease duration, and those without evidence of complications. The conclusions of a meta-analysis can be considered applicable only to individuals with similar characte...
Article
Rosiglitazone is the second of the marketed thiazolidinediones to fall from grace, and its demise bears an uncanny resemblance to the earlier downfall of troglitazone. Both narratives demonstrate the inadequacy of a regulatory system that is mandated to place a higher value on commercial secrecy than on patient safety.
Data
Estimated effects of intensified glycaemic control on measurements of event rates
Article
The purpose of this study was to characterize the financial cost and efficacy of primary care treatment for diabetes in the United Kingdom from 1997 to 2007. Retrospective data were analysed for people with Type 1 and Type 2 diabetes along with matched control subjects using data from The Health Improvement Network. Costs were attributed from publi...
Article
Full-text available
Cancer has overtaken cardiovascular disease as the leading cause of death in individuals under the age of 65 in the general population, but it is still overshadowed by cardiovascular disease in those with diabetes. People with type 2 diabetes are nonetheless more likely to develop cancer—and to die from it—than members of the general population, so...
Article
The higher risk of type 1 diabetes in the offspring of older mothers is well known but still unexplained
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This article presents the conclusions of a WHO Expert Consultation that evaluated the utility of the 'metabolic syndrome' concept in relation to four key areas: pathophysiology, epidemiology, clinical work and public health. The metabolic syndrome is a concept that focuses attention on complex multifactorial health problems. While it may be conside...
Article
Full-text available
The risk of developing a range of solid tumours is increased in type 2 diabetes, and may be influenced by glucose-lowering therapies. We examined the risk of development of solid tumours in relation to treatment with oral agents, human insulin and insulin analogues. This was a retrospective cohort study of people treated in UK general practices. Th...
Article
The incidence of type 1 diabetes in children younger than 15 years is increasing. Prediction of future incidence of this disease will enable adequate fund allocation for delivery of care to be planned. We aimed to establish 15-year incidence trends for childhood type 1 diabetes in European centres, and thereby predict the future burden of childhood...
Article
The UK Prospective Diabetes Study (UKPDS) set out to establish whether improved glucose control could alleviate the macrovascular and microvascular complications of diabetes and to compare the relative merits of diet, oral glucose-lowering agents or insulin in achieving this objective. The study broke many of the rules of trial design, not least by...
Article
As this survey indicates, the congenital rubella syndrome undoubtedly predisposes to diabetes in later life. A high proportion of the reported cases, mostly described in very brief summary (Table 1) presented under the age of 5 years, in children who were for the most part markedly underweight at birth. These were often reported to be in diabetic k...
Article
Type 2 diabetes and lesser degrees of glucose intolerance are associated with insulin resistance, central obesity, hypertension, and dyslipidaemia. The term metabolic syndrome describes the same constellation, with or without glucose intolerance. Although these associations are well established, their pathophysiological basis remains unclear, and n...
Article
The aim of this study was to evaluate the prognostic significance of autoantibodies to IA-2beta (IA2betaA) in a large, well-characterised population of islet cell antibody (ICA)-positive relatives followed for 5 years in the European Nicotinamide Diabetes Intervention Trial. Autoantibodies to insulin (IAA), glutamate decarboxylase (GADA) and IA-2 (...
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Insulin resistance can modulate progression to type 1 diabetes in individuals with ongoing islet autoimmunity. We wanted to see whether measures of insulin resistance improved risk assessment in islet cell antibody (ICA)-positive relatives when added to other immune and metabolic markers. The retrospective cohort analysis included 213 family member...
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We assessed the effect upon A1C of recruitment to a clinical trial in patients with diabetes who had been screened and interviewed to determine eligibility but whose therapy was otherwise unchanged. Eligible trials were selected from the global program of an insulin manufacturer. Included were studies in which patients were seen on a single screeni...
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Maternal cells have recently been found in the circulation and tissues of mothers' immune-competent children, including in adult life, and is referred to as maternal microchimerism (MMc). Whether MMc confers benefits during development or later in life or sometimes has adverse effects is unknown. Type 1 diabetes (T1D) is an autoimmune disease that...
Article
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There is an unexplained excess of type 1 diabetes and other organ-specific autoimmune diseases in children with Down's syndrome, but the immunogenetic characteristics of diabetes in Down's syndrome have not been investigated. We studied the frequency of islet autoantibodies in 106 children with Down's syndrome and no history of autoimmunity and ana...
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Aims/hypothesis To examine the role of additional immune, genetic and metabolic risk markers in determining risk of diabetes in islet cell antibody (ICA)-positive individuals with a family history of type 1 diabetes recruited into the European Nicotinamide Diabetes Intervention Trial. Methods Five hundred and forty-nine first-degree relatives with...
Article
Raised risks of several cancers have been found in patients with type II diabetes, but there are few data on cancer risk in type I diabetes. We conducted a cohort study of 28 900 UK patients with insulin-treated diabetes followed for 520 517 person-years, and compared their cancer incidence and mortality with national expectations. To analyse by di...
Article
The full potential of cadaveric islet transplantation will only be realized by avoiding both pretransplant insults programming islets for subsequent death and posttransplant triggers for apoptosis and necrosis. The immediate blood mediated inflammatory response causes significant islet loss in the immediate posttransplant period. However, if we foc...
Article
To test the effect of continuing metformin on weight gain and glycaemic control in patients with poorly controlled Type 2 diabetes who need to start insulin. Patients with Type 2 diabetes on maximum tolerated oral agents referred for insulin conversion were recruited from hospital diabetes clinics into a double-blind randomized placebo-controlled t...
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The pubertal peak in onset of type 1 diabetes occurs earlier in girls than boys. We postulated that this sex difference might be mediated in part by estrogen or by genes regulated by estrogen, such as the interleukin-6 (IL6) gene. Previous studies concerning the role of an estrogen-sensitive single nucleotide polymorphism (SNP) in the IL6 promoter...
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We have recently shown that permanent neonatal diabetes can be caused by activating mutations in KCNJ11 that encode the Kir6.2 subunit of the beta-cell ATP-sensitive K(+) channel. Some of these patients were diagnosed after 3 months of age and presented with ketoacidosis and marked hyperglycemia, which could have been diagnosed as type 1 diabetes....
Article
The incidence of childhood type 1 diabetes has risen over the past 50 years. We compared the frequency of HLA class II haplotypes in 194 patients diagnosed more than 50 years ago and 582 age-matched and sex-matched individuals diagnosed between 1985 and 2002. The proportion of high-risk susceptibility genotypes was increased in the earlier cohort (...
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Full-text available
The autoimmune disease process leading to childhood-onset type 1 diabetes appears to start in infancy, and decisions on treatment to prevent initiation of autoimmunity will need to be based on genetic susceptibility alone. We set out to quantify the absolute risk associated with human leukocyte antigen (HLA) DRB1-DQA1-DQB1 class II genotypes and to...
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‘The consumer of knowledge can never know what a dicky thing knowledge is until he has tried to produce it’. F.J. Roethlisberger, investigator at Hawthorne There is a familiar anecdote that relates, with variations, that experiments with improved factory lighting increased the productivity of workers. The outcome seemed clear until someone turned...
Article
Background Results of studies in animals and human beings suggest that type 1 diabetes is preventable. Nicotinamide prevents autoimmune diabetes in animal models, possibly through inhibition of the DNA repair enzyme poly-ADP-ribose polymerase and prevention of β-cell NAD depletion. We aimed to assess whether high dose nicotinamide prevents or delay...
Article
### Type 1 diabetes is potentially preventable Both the name and that notion emerged in the mid-1970s, when it became clear that this form of diabetes has an autoimmune basis. Studies in identical twins showed that two of three initially unaffected cotwins would remain nondiabetic, an experiment of nature implying that type 1 diabetes was a diseas...

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