The UK Prospective Diabetes Study (UKPDS) epidemiological findings confirmed that T2DM is not a “mild” disease, with roughly 50% of patients having clinically evident complica- tions at diagnosis, emphasising the need for its early detection and treatment. Hyperglycaemia was identified as an independent coronary heart disease risk factor, with progressive hyperglycaemia shown to be a major pathophysiological feature of T2DM, driven by declining beta-cell function. People with T2DM and hypertension were found to be at double jeopardy for any diabetes endpoint, and worsening kidney function was shown to increase the risk of death substantially. The UKPDS 20-year trial results were the first to demon- strate that diabetic complications are not inevitable but can be prevented by more intensive blood glucose control and by metformin therapy, changing T2DM management guide- lines worldwide. The UKPDS also showed that tighter blood pressure control prevents diabetic complications; the benefits of the glucose and blood pressure interventions are additive. The UKPDS 10-year post-trial monitoring study was the first to identify the T2DM glycaemic and metformin legacy effects, with early more intensive therapy having continuing benefits long after the trial terminated. The trial demon- strated the need to achieve good glycaemic control as early as possible to minimise the risk of future complications.
{"title":"brief history of the UK Prospective Diabetes Study","authors":"R. Holman","doi":"10.15277/bjd.2022.359","DOIUrl":"https://doi.org/10.15277/bjd.2022.359","url":null,"abstract":"The UK Prospective Diabetes Study (UKPDS) epidemiological findings confirmed that T2DM is not a “mild” disease, with roughly 50% of patients having clinically evident complica- tions at diagnosis, emphasising the need for its early detection and treatment. Hyperglycaemia was identified as an independent coronary heart disease risk factor, with progressive hyperglycaemia shown to be a major pathophysiological feature of T2DM, driven by declining beta-cell function. People with T2DM and hypertension were found to be at double jeopardy for any diabetes endpoint, and worsening kidney function was shown to increase the risk of death substantially.\u0000The UKPDS 20-year trial results were the first to demon- strate that diabetic complications are not inevitable but can be prevented by more intensive blood glucose control and by metformin therapy, changing T2DM management guide- lines worldwide. The UKPDS also showed that tighter blood pressure control prevents diabetic complications; the benefits of the glucose and blood pressure interventions are additive. The UKPDS 10-year post-trial monitoring study was the first to identify the T2DM glycaemic and metformin legacy effects, with early more intensive therapy having continuing benefits long after the trial terminated. The trial demon- strated the need to achieve good glycaemic control as early as possible to minimise the risk of future complications.","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48656482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reflections on 60 years of caring for people with diabetes","authors":"A. Wright","doi":"10.15277/bjd.2022.362","DOIUrl":"https://doi.org/10.15277/bjd.2022.362","url":null,"abstract":"","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47159379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Although we have treated type 1 diabetes (T1DM) with insulin for more than 100 years, it has been apparent since the discovery of insulitis in the 1960s and islet cell antibodies in 1974 that T1DM is fundamentally an autoimmune disease, not a metabolic disease.1 Almost all other autoimmune diseases, from inflammatory bowel disease to rheumatoid arthritis, are treated with immunotherapy but not T1DM. In large part this is because of the discovery of insulin: unlike most other autoimmune diseases, a replacement therapy exists for T1DM. As a result, the discovery of insulin can be viewed as both a blessing and a curse. It is a “curse” because most of the major drug companies have developed their large immunotherapy portfolios of drugs for autoimmune diseases other than T1DM, including some such as psoriasis or alopecia areata that might be considered less life-threatening. And it is likely that diabetes practitioners are also partly to blame since they fear immunotherapy since it is a treatment with which they are not familiar. It is important to remind ourselves of the challenges of insulin therapy. It is not a drug without risk: deaths still occur from underdosage (DKA) and overdosage (hypoglycaemia). According to ONS data, in 2021 in England and Wales, 44 people under the age of 50 died of DKA and 154 died of hypoglycaemia.2 Set against this, even despite the introduction of CGM and insulin pumps, fewer than 30% of adults and children with diabetes achieve a target HbA1c < 7.0%, or 53 mmol/mol which obviates the risks of longterm complications.3 Furthermore, insulin management consumes millions of hours of patients and healthcare professional time in training, adjustments, testing and decision-making. Despite this, 36% of children and families continue to need psychological support more than five years after diagnosis (NPDA national audit 2018-2019,3 and up to 50% of adults with T1DM report significant diabetes-related distress. 4 There is a large and expanding world of highly selective immunotherapies that does not include the classic immunosuppressents (e.g. cyclosporin, tacrolimus) used in transplantation. Rather, it includes many drugs known as “biologics” that have been widely used and have been very well tolerated in other autoimmune diseases for more than 20 years. Many are monoclonal antibodies, but small molecule inhibitors such as JAK kinase inhibitors are being introduced.5 At least seven selective immunotherapies have shown efficacy in Phase 2 studies in preserving beta cell function from diagnosis compared to controls.6,7 These treatments reduce progression of the underlying disease process but do not cause regrowth of beta cells. In current clinical practice, T1DM is diagnosed at the time that insulin replacement is required. This is late in the disease course, when it is estimated that more than 80% of functional beta cells have been lost. When selective immunotherapy is given at this stage, some impact on insulin dose (and in some
尽管我们用胰岛素治疗1型糖尿病（T1DM）已有100多年的历史，但自20世纪60年代发现胰岛炎和1974年发现胰岛细胞抗体以来，T1DM从根本上说是一种自身免疫性疾病，而不是代谢性疾病，用免疫疗法治疗，但不治疗T1DM。这在很大程度上是因为胰岛素的发现：与大多数其他自身免疫性疾病不同，T1DM有一种替代疗法。因此，胰岛素的发现可以被视为福与祸。这是一个“诅咒”，因为大多数主要制药公司都开发了针对T1DM以外的自身免疫性疾病的大型免疫疗法药物组合，包括一些可能被认为不那么危及生命的银屑病或斑秃。糖尿病从业者可能也要承担部分责任，因为他们害怕免疫疗法，因为这是一种他们不熟悉的治疗方法。提醒我们自己胰岛素治疗的挑战是很重要的。它不是一种没有风险的药物：剂量不足（DKA）和过量（低血糖）仍会导致死亡。根据英国国家统计局的数据，2021年，英格兰和威尔士有44名50岁以下的人死于DKA，154人死于低血糖。2与此相反，即使引入了CGM和胰岛素泵，仍只有不到30%的糖尿病成人和儿童达到目标HbA1c<7.0%，即53 mmol/mol，从而消除了长期并发症的风险。3此外，胰岛素管理消耗了数百万小时的患者和医疗保健专业人员在培训、调整、测试和决策方面的时间。尽管如此，36%的儿童和家庭在确诊后五年以上仍需要心理支持（NPDA 2018-2019年国家审计3，多达50%的T1DM成年人报告了严重的糖尿病相关痛苦移植相反，它包括许多被称为“生物制剂”的药物，这些药物已经被广泛使用，并且在20多年的其他自身免疫性疾病中耐受性很好。许多是单克隆抗体，但正在引入小分子抑制剂，如JAK激酶抑制剂。5与对照组相比，在2期研究中，至少有7种选择性免疫疗法在保护β细胞功能方面显示出有效性。6,7这些疗法可以减少潜在疾病过程的进展，但不会导致β细胞的再生。在目前的临床实践中，T1DM是在需要胰岛素替代的时候被诊断出来的。这是在病程后期，据估计，超过80%的功能性β细胞已经丧失。当在这个阶段给予选择性免疫治疗时，可以看到对胰岛素剂量的一些影响（在一些研究中，还可以看到HbA1c和低血糖率），但现在消除对胰岛素的需求已经太晚了。幸运的是，早期诊断T1DM是可能的。对T1DM患者亲属和普通人群的出生队列进行的多项研究表明，80-90%的无症状儿童如果被发现有两种或两种以上的胰岛自身抗体（包括抗GAD、抗IA-2、抗ZNT8或抗胰岛素），将继续发展为T1DM（图1）。一旦出现低血糖（相当于糖耐量受损），高血糖水平通信地址：Colin M Dayan教授临床糖尿病和代谢教授，加的夫大学，Heath Park，Cardiff，CF14 4XN，英国电子邮件：DayanCM@cardiff.ac.uk
{"title":"beginning of the end for insulin? – enter immunotherapy for T1DM","authors":"C. Dayan","doi":"10.15277/bjd.2022.369","DOIUrl":"https://doi.org/10.15277/bjd.2022.369","url":null,"abstract":"Although we have treated type 1 diabetes (T1DM) with insulin for more than 100 years, it has been apparent since the discovery of insulitis in the 1960s and islet cell antibodies in 1974 that T1DM is fundamentally an autoimmune disease, not a metabolic disease.1 Almost all other autoimmune diseases, from inflammatory bowel disease to rheumatoid arthritis, are treated with immunotherapy but not T1DM. In large part this is because of the discovery of insulin: unlike most other autoimmune diseases, a replacement therapy exists for T1DM. As a result, the discovery of insulin can be viewed as both a blessing and a curse. It is a “curse” because most of the major drug companies have developed their large immunotherapy portfolios of drugs for autoimmune diseases other than T1DM, including some such as psoriasis or alopecia areata that might be considered less life-threatening. And it is likely that diabetes practitioners are also partly to blame since they fear immunotherapy since it is a treatment with which they are not familiar. It is important to remind ourselves of the challenges of insulin therapy. It is not a drug without risk: deaths still occur from underdosage (DKA) and overdosage (hypoglycaemia). According to ONS data, in 2021 in England and Wales, 44 people under the age of 50 died of DKA and 154 died of hypoglycaemia.2 Set against this, even despite the introduction of CGM and insulin pumps, fewer than 30% of adults and children with diabetes achieve a target HbA1c < 7.0%, or 53 mmol/mol which obviates the risks of longterm complications.3 Furthermore, insulin management consumes millions of hours of patients and healthcare professional time in training, adjustments, testing and decision-making. Despite this, 36% of children and families continue to need psychological support more than five years after diagnosis (NPDA national audit 2018-2019,3 and up to 50% of adults with T1DM report significant diabetes-related distress. 4 There is a large and expanding world of highly selective immunotherapies that does not include the classic immunosuppressents (e.g. cyclosporin, tacrolimus) used in transplantation. Rather, it includes many drugs known as “biologics” that have been widely used and have been very well tolerated in other autoimmune diseases for more than 20 years. Many are monoclonal antibodies, but small molecule inhibitors such as JAK kinase inhibitors are being introduced.5 At least seven selective immunotherapies have shown efficacy in Phase 2 studies in preserving beta cell function from diagnosis compared to controls.6,7 These treatments reduce progression of the underlying disease process but do not cause regrowth of beta cells. In current clinical practice, T1DM is diagnosed at the time that insulin replacement is required. This is late in the disease course, when it is estimated that more than 80% of functional beta cells have been lost. When selective immunotherapy is given at this stage, some impact on insulin dose (and in some","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43790790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"What does the next 100 years hold? The perspective of a patient with T1DM","authors":"Tim J. Street","doi":"10.15277/bjd.2022.380","DOIUrl":"https://doi.org/10.15277/bjd.2022.380","url":null,"abstract":"","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45942120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"flash glucose monitoring revolution: the Sat Nav journey","authors":"E. Wilmot","doi":"10.15277/bjd.2022.372","DOIUrl":"https://doi.org/10.15277/bjd.2022.372","url":null,"abstract":"","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47708849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sanger, Hodgkin, Yalow and the impact of insulin analogues","authors":"David Russell - Jones","doi":"10.15277/bjd.2022.361","DOIUrl":"https://doi.org/10.15277/bjd.2022.361","url":null,"abstract":"","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42979448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gazing into the future – what will the next 100 years of diabetes innovation look like? A perspective from industry","authors":"Zoe Cholewa","doi":"10.15277/bjd.2022.375","DOIUrl":"https://doi.org/10.15277/bjd.2022.375","url":null,"abstract":"","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46745286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
80 years after the discovery of insulin, the early noughties The era 80 years after the discovery of insulin, the early noughties, could perhaps be labelled the “Treat to Target” era. The United Kingdom Prospective Diabetes Study (UKPDS), as described elsewhere in this supplement by Professor Rury Holman,1 showed that whilst the microvascular complications were reduced in the intensive arm, the HbA1c relentlessly rose as beta cells relentlessly failed (Figure 1a) no matter whether patients were in the intensive or conventional treatment arm. The study also showed that the lower the HbA1c the less likely there are to be microvascular events (Figure 1b).
{"title":"early noughties - Treating to Target","authors":"B. Ryder","doi":"10.15277/bjd.2022.360","DOIUrl":"https://doi.org/10.15277/bjd.2022.360","url":null,"abstract":"80 years after the discovery of insulin, the early noughties The era 80 years after the discovery of insulin, the early noughties, could perhaps be labelled the “Treat to Target” era. The United Kingdom Prospective Diabetes Study (UKPDS), as described elsewhere in this supplement by Professor Rury Holman,1 showed that whilst the microvascular complications were reduced in the intensive arm, the HbA1c relentlessly rose as beta cells relentlessly failed (Figure 1a) no matter whether patients were in the intensive or conventional treatment arm. The study also showed that the lower the HbA1c the less likely there are to be microvascular events (Figure 1b).","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43832929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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