A pancreatic extract which was successful in lowering glucose in diabetes was developed and commercialized with leader-ship from the University of Toronto in 1921-1922. The active principle remained unknown, though it was assumed to be the ‘insulin’ (or ‘isletin’ or ‘insuline’) identified microscopically in the islets of Langerhans from work in the previous 50 years. Within four years the active principle was crystallized by Abel and co-workers, and convincing proof given that it was a peptide. Determining the amino acid sequence of this relatively small protein proved a 30-year task for science, due to the confounding effects of two short chains united by di-sulphide bridges. Even then it was a mystery how the sequence related to insulin activity. That remained the case when the early X-ray diffraction work in the 1930s by Crowfoot (Hodgkin) matured in 1969 with the determination of the 3-dimensional structure of the insulin hexamer. Meanwhile 25 years of work, much in industry, invented useful extended-acting insulin preparations and, over an even longer time course, insulin preparations of high enough purity to be non-immunogenic in clinical practice. In the 1960s and 1970s work on radioimmunoassay and on glucose clamps provided tools that would prove critical to the further development of insulin as a medication over its second 50 years.
{"title":"From muck to molecule: insulin discovery over 50 years","authors":"Philip Home","doi":"10.15277/bjd.2022.354","DOIUrl":"https://doi.org/10.15277/bjd.2022.354","url":null,"abstract":"A pancreatic extract which was successful in lowering glucose in diabetes was developed and commercialized with leader-ship from the University of Toronto in 1921-1922. The active principle remained unknown, though it was assumed to be the ‘insulin’ (or ‘isletin’ or ‘insuline’) identified microscopically in the islets of Langerhans from work in the previous 50 years. Within four years the active principle was crystallized by Abel and co-workers, and convincing proof given that it was a peptide. Determining the amino acid sequence of this relatively small protein proved a 30-year task for science, due to the confounding effects of two short chains united by di-sulphide bridges. Even then it was a mystery how the sequence related to insulin activity. That remained the case when the early X-ray diffraction work in the 1930s by Crowfoot (Hodgkin) matured in 1969 with the determination of the 3-dimensional structure of the insulin hexamer. Meanwhile 25 years of work, much in industry, invented useful extended-acting insulin preparations and, over an even longer time course, insulin preparations of high enough purity to be non-immunogenic in clinical practice. In the 1960s and 1970s work on radioimmunoassay and on glucose clamps provided tools that would prove critical to the further development of insulin as a medication over its second 50 years.","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42956161","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}
This article was written as a contribution to mark the centenary of the first administration of insulin to a human in 1922. Writing from an Aberdeen perspective, an introductory passage will place emphasis on the role of JJR MacLeod, under whose supervision the discovery of insulin by Banting and Best was made. The major thrust of the article, however, will be on the cloning and sequencing of the human insulin gene, and the impact it had on the scientific career of the author. It initiated a journey to find alternative therapies for diabetes that led sequentially though gene therapy, embryonic stem cell-derived islets, and reprogramming. Our experience in these areas will be described, with emphasis on the strengths and weaknesses of each of these approaches.
{"title":"journey from the insulin gene to reprogramming pancreatic tissue","authors":"K. Docherty","doi":"10.15277/bjd.2022.371","DOIUrl":"https://doi.org/10.15277/bjd.2022.371","url":null,"abstract":"This article was written as a contribution to mark the centenary of the first administration of insulin to a human in 1922. Writing from an Aberdeen perspective, an introductory passage will place emphasis on the role of JJR MacLeod, under whose supervision the discovery of insulin by Banting and Best was made. The major thrust of the article, however, will be on the cloning and sequencing of the human insulin gene, and the impact it had on the scientific career of the author. It initiated a journey to find alternative therapies for diabetes that led sequentially though gene therapy, embryonic stem cell-derived islets, and reprogramming. Our experience in these areas will be described, with emphasis on the strengths and weaknesses of each of these approaches.","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49605063","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}
Who would have thought? Surgery as a ‘cure for type 2 diabetes (T2DM)’. I would like to introduce one of my patients, Sarah, a 46year-old woman. She presented 10 years ago, living with obesity (BMI 44) and poorly controlled T2DM. She had been taking insulin for eight years, plus additional GLP-1 agonists and metformin. She underwent several lifestyle interventions for weight loss with little success. She subsequently underwent a Roux-en-Y gastric bypass (RYGB) and was able to come off all insulin and oral antiglycaemic medications. She only takes the recommended multivitamin replacement post-bariatric surgery now. Her HbA1c has been well controlled for several years.
{"title":"Fat: bariatric surgery and procedures","authors":"B. McGowan","doi":"10.15277/bjd.2022.368","DOIUrl":"https://doi.org/10.15277/bjd.2022.368","url":null,"abstract":"Who would have thought? Surgery as a ‘cure for type 2 diabetes (T2DM)’. I would like to introduce one of my patients, Sarah, a 46year-old woman. She presented 10 years ago, living with obesity (BMI 44) and poorly controlled T2DM. She had been taking insulin for eight years, plus additional GLP-1 agonists and metformin. She underwent several lifestyle interventions for weight loss with little success. She subsequently underwent a Roux-en-Y gastric bypass (RYGB) and was able to come off all insulin and oral antiglycaemic medications. She only takes the recommended multivitamin replacement post-bariatric surgery now. Her HbA1c has been well controlled for several years.","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48510908","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":"Life of RD Lawrence (1892-1968) - pioneering doctor and survivor of diabetes","authors":"Hugo Lawrence","doi":"10.15277/bjd.2022.353","DOIUrl":"https://doi.org/10.15277/bjd.2022.353","url":null,"abstract":"","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46827913","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: the next 100 years of training from the YDEF perspective","authors":"Giulia Argentesi","doi":"10.15277/bjd.2022.378","DOIUrl":"https://doi.org/10.15277/bjd.2022.378","url":null,"abstract":"","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47688418","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}
Impaired awareness of hypoglycaemia (IAH), defined either clinically as the loss of subjective awareness of hypoglycaemia before the onset of cognitive impairment or biochemically as the loss of symptom perception until plasma glucose has fallen below 3 mmol/L (54 mg/dl), is the major modifiable risk factor for severe hypoglycaemia in T1DM and possibly in insulin-treated T2DM. This paper tells the story of IAH, its pathogenesis and its implications and the treatment strategies used to address it.
{"title":"Impaired awareness of hypoglycaemia","authors":"S. Amiel","doi":"10.15277/bjd.2022.358","DOIUrl":"https://doi.org/10.15277/bjd.2022.358","url":null,"abstract":"Impaired awareness of hypoglycaemia (IAH), defined either clinically as the loss of subjective awareness of hypoglycaemia before the onset of cognitive impairment or biochemically as the loss of symptom perception until plasma glucose has fallen below 3 mmol/L (54 mg/dl), is the major modifiable risk factor for severe hypoglycaemia in T1DM and possibly in insulin-treated T2DM. This paper tells the story of IAH, its pathogenesis and its implications and the treatment strategies used to address it.","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47950734","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":"1993 - The Diabetes Control and Complications Trial (DCCT)","authors":"B. Ryder","doi":"10.15277/bjd.2022.357","DOIUrl":"https://doi.org/10.15277/bjd.2022.357","url":null,"abstract":"2022;","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48678491","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 – the next 100 years. Perspectives from diabetologists","authors":"R. Ryder, E. Wilmot, T. Crabtree","doi":"10.15277/bjd.2022.399","DOIUrl":"https://doi.org/10.15277/bjd.2022.399","url":null,"abstract":"","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48874059","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}
Introduction In 2015 Dana Lewis, a person with diabetes, developed her own hybrid-closed loop system and began the #WeAreNotWaiting movement (Figure 1). These systems, often called “do-it-yourself” artificial pancreas systems (DIY APS) or open-source closed-loop automated insulin delivery systems, combine an insulin pump, a sensor and an algorithm to maintain glucose levels in range. Whilst early versions were “hybrid” – in other words they still required manual bolusing-the newer versions of the algorithm have been used as a fully-closed loop (no bolus required!) by some individuals. An article written in 2019 provides further detail on these systems and some of the issues associated with them.1 These systems filled a gap by circumnavigating the approvals that commercial companies require in order to launch similar systems. There are three systems commonly encountered: OpenAPS, AndroidAPS and Loop.1 At the time of writing all three systems are unapproved and unregulated. When these systems first entered UK services the evidence was limited. However, self-reported outcomes from users of the systems were encouraging from both glycaemia and safety points of view.2-4 At that time, the approach taken across UK diabetes services was inconsistent and guidelines from the General Medical Council and others were unclear.5 Work was undertaken to explore the opinions of UK healthcare professionals; initial position statements were produced by Diabetes UK and other organisations to support users of these systems.6,7 We also explored the concerns of individuals with diabetes commencing the use of these systems, and were able to demonstrate that they were less concerned with safety and
{"title":"#We are not waiting - DIY APS Do-It-Yourself Artificial Pancreas Systems: The story so far","authors":"T. Crabtree, B. Ryder, E. Wilmot","doi":"10.15277/bjd.2022.373","DOIUrl":"https://doi.org/10.15277/bjd.2022.373","url":null,"abstract":"Introduction In 2015 Dana Lewis, a person with diabetes, developed her own hybrid-closed loop system and began the #WeAreNotWaiting movement (Figure 1). These systems, often called “do-it-yourself” artificial pancreas systems (DIY APS) or open-source closed-loop automated insulin delivery systems, combine an insulin pump, a sensor and an algorithm to maintain glucose levels in range. Whilst early versions were “hybrid” – in other words they still required manual bolusing-the newer versions of the algorithm have been used as a fully-closed loop (no bolus required!) by some individuals. An article written in 2019 provides further detail on these systems and some of the issues associated with them.1 These systems filled a gap by circumnavigating the approvals that commercial companies require in order to launch similar systems. There are three systems commonly encountered: OpenAPS, AndroidAPS and Loop.1 At the time of writing all three systems are unapproved and unregulated. When these systems first entered UK services the evidence was limited. However, self-reported outcomes from users of the systems were encouraging from both glycaemia and safety points of view.2-4 At that time, the approach taken across UK diabetes services was inconsistent and guidelines from the General Medical Council and others were unclear.5 Work was undertaken to explore the opinions of UK healthcare professionals; initial position statements were produced by Diabetes UK and other organisations to support users of these systems.6,7 We also explored the concerns of individuals with diabetes commencing the use of these systems, and were able to demonstrate that they were less concerned with safety and","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45519088","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":"Fat – pharmacological therapies","authors":"Stephen C. Bain","doi":"10.15277/bjd.2022.367","DOIUrl":"https://doi.org/10.15277/bjd.2022.367","url":null,"abstract":"J","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2022-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43943650","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：