S. Manley, Andreas Karwath, John A. Williams, P. Nightingale, J. Webber, R. Raghavan, Alison Barratt, C. Webster, R. Round, I. Stratton, G. Gkoutos, G. Roberts, Samiul Mostafa, Sandip Ghosh
The prevalence of diabetes in Birmingham is 11% but it is 22% in hospital inpatients. Queen Elizabeth Hospital in Birmingham (QEHB) serves a multi-ethnic population with 6% Afro-Caribbean, 19% South Asian and 70% White European. A clinical audit of 18,965 emergency admissions to QEHB showed that 5% were undiagnosed but had admission glucose in the ‘diabetes’ range and 16% were in the ‘at risk’ range. The proportion of Afro-Caribbeans (7%) and South Asians (8%) in the ‘diabetes’ range was higher than White Europeans (5%). Given the magnitude of the problem, this paper explores the issues concerning the use of reflex HbA1c testing in the UK for diagnosis of diabetes in hospital admissions. HbA1c testing is suitable for most patients but conditions affecting red blood cell turnover invalidate the results in a small number of people. However, there are pertinent questions relating to the introduction of such testing in the NHS on a routine basis. Literature searches on a topical question ‘Is hyperglycaemia identified during emergency admission/attendance acted upon?’, were performed from 2016 to 2021 and 2016 to 2022. They identified 21 different, relevant, research papers - 5 from Australia, 9 from Europe including 4 from the UK, 5 from America and 1 each from Canada and Africa. These papers revealed an absence of established procedures for the management and follow-up of routinely detected hyperglycaemia using HbA1c when no previous diabetes diagnosis was recorded. Further work is required to determine the role of reflex HbA1c testing for diagnosis of diabetes in admissions with hyperglycaemia, and the cost-effectiveness and role of point-of-care HbA1c testing.
{"title":"use of HbA1c for new diagnosis of diabetes in those with hyperglycaemia on admission to or attendance at hospital urgently requires research","authors":"S. Manley, Andreas Karwath, John A. Williams, P. Nightingale, J. Webber, R. Raghavan, Alison Barratt, C. Webster, R. Round, I. Stratton, G. Gkoutos, G. Roberts, Samiul Mostafa, Sandip Ghosh","doi":"10.15277/bjd.2022.386","DOIUrl":"https://doi.org/10.15277/bjd.2022.386","url":null,"abstract":"The prevalence of diabetes in Birmingham is 11% but it is 22% in hospital inpatients. Queen Elizabeth Hospital in Birmingham (QEHB) serves a multi-ethnic population with 6% Afro-Caribbean, 19% South Asian and 70% White European.\u0000A clinical audit of 18,965 emergency admissions to QEHB showed that 5% were undiagnosed but had admission glucose in the ‘diabetes’ range and 16% were in the ‘at risk’ range. The proportion of Afro-Caribbeans (7%) and South Asians (8%) in the ‘diabetes’ range was higher than White Europeans (5%). Given the magnitude of the problem, this paper explores the issues concerning the use of reflex HbA1c testing in the UK for diagnosis of diabetes in hospital admissions. HbA1c testing is suitable for most patients but conditions affecting red blood cell turnover invalidate the results in a small number of people.\u0000However, there are pertinent questions relating to the introduction of such testing in the NHS on a routine basis. Literature searches on a topical question ‘Is hyperglycaemia identified during emergency admission/attendance acted upon?’, were performed from 2016 to 2021 and 2016 to 2022. They identified 21 different, relevant, research papers - 5 from Australia, 9 from Europe including 4 from the UK, 5 from America and 1 each from Canada and Africa. These papers revealed an absence of established procedures for the management and follow-up of routinely detected hyperglycaemia using HbA1c when no previous diabetes diagnosis was recorded.\u0000Further work is required to determine the role of reflex HbA1c testing for diagnosis of diabetes in admissions with hyperglycaemia, and the cost-effectiveness and role of point-of-care HbA1c testing.","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45434919","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}
L. Rengarajan, Katrina Nash, E. Ooi, Catherine Cooper, Amy Birchenough, M. Owen, Sanjay Saraf, A. Karamat, P. De, S. Krishnasamy, P. Narendran, P. Kempegowda
Introduction Diabetes-related ketoacidosis (DKA) is a life-threatening complication of diabetes which requires rapid assessment and treatment.1 Although mortality has decreased over the years, DKA still causes considerable morbidity and mortality amongst adults, adolescents and children.2 Existing quality improvement projects (QIP) have demonstrated that use of evidence-based protocols and order sets is able to improve outcomes associated with DKA management.3,4 However, we did not find any studies demonstrating sustainable improvements over a long period. People presenting with DKA represent a considerable financial and resource burden.5 Reducing the duration of DKA would therefore substantially reduce the disease and resource burden associated with diabetes.
{"title":"Sustaining improvement in diabetes-related ketoacidosis management through a Quality Improvement ProjectSustaining improvement in diabetic ketoacidosis management through Quality Improvement Project","authors":"L. Rengarajan, Katrina Nash, E. Ooi, Catherine Cooper, Amy Birchenough, M. Owen, Sanjay Saraf, A. Karamat, P. De, S. Krishnasamy, P. Narendran, P. Kempegowda","doi":"10.15277/bjd.2022.398","DOIUrl":"https://doi.org/10.15277/bjd.2022.398","url":null,"abstract":"Introduction Diabetes-related ketoacidosis (DKA) is a life-threatening complication of diabetes which requires rapid assessment and treatment.1 Although mortality has decreased over the years, DKA still causes considerable morbidity and mortality amongst adults, adolescents and children.2 Existing quality improvement projects (QIP) have demonstrated that use of evidence-based protocols and order sets is able to improve outcomes associated with DKA management.3,4 However, we did not find any studies demonstrating sustainable improvements over a long period. People presenting with DKA represent a considerable financial and resource burden.5 Reducing the duration of DKA would therefore substantially reduce the disease and resource burden associated with diabetes.","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44857234","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}
The origins of diabetes medications provide an intriguing catalogue of clinical serendipity and scientific design. Use of insulin (beyond 1922) gave recognition to insulin resistance and the categorisation of type 2 diabetes (T2DM). The first sulphonylurea (carbutamide, 1956) emerged from its use as an antibacterial sulphonamide prone to cause hypoglycaemia, and biguanides were first used to treat diabetes in 1957 despite their glucose-lowering properties having been known since the 1920s. Alpha-glucosidase inhibitors arose from a screening programme for amylase inhibitors by Bayer in the 1970s and acarbose was introduced in 1990. The first thiazolidinedione (ciglitazone; not developed) was identified in a screening programme for triglyceride-lowering compounds by Takeda in the late 1970s and gave rise to pioglitazone (approved 1999), although first to market was troglitazone (from Warner Lambert 1997, withdrawn 2000). Exendin, an analogue of the incretin hormone glucagon-like peptide-1 (GLP-1), was identified in 1992 in the saliva of a lizard (Heloderma suspectum), and took until 2005 to be marketed as exenatide. To promote the efficacy of endogenous GLP-1, its rapid inactivation by the enzyme dipeptidylpeptidase-4 (DPP4) was blocked by clever molecular design of the first DPP4 inhibitors (vildagliptin and sitagliptin, approved in 2006). SGLT2 inhibitors are based on phlorizin, identified in apple tree bark (1835) and modified (2000) to avoid intestinal degradation: further modifications to increase selectivity against SGLT2 gave dapagliflozin and canagliflozin - approved 2012 and 2013, respectively, in Europe.
{"title":"origins of type 2 diabetes medications","authors":"Clifford J Bailey","doi":"10.15277/bjd.2022.388","DOIUrl":"https://doi.org/10.15277/bjd.2022.388","url":null,"abstract":"The origins of diabetes medications provide an intriguing catalogue of clinical serendipity and scientific design. Use of insulin (beyond 1922) gave recognition to insulin resistance and the categorisation of type 2 diabetes (T2DM). The first sulphonylurea (carbutamide, 1956) emerged from its use as an antibacterial sulphonamide prone to cause hypoglycaemia, and biguanides were first used to treat diabetes in 1957 despite their glucose-lowering properties having been known since the 1920s. Alpha-glucosidase inhibitors arose from a screening programme for amylase inhibitors by Bayer in the 1970s and acarbose was introduced in 1990. The first thiazolidinedione (ciglitazone; not developed) was identified in a screening programme for triglyceride-lowering compounds by Takeda in the late 1970s and gave rise to pioglitazone (approved 1999), although first to market was troglitazone (from Warner Lambert 1997, withdrawn 2000). Exendin, an analogue of the incretin hormone glucagon-like peptide-1 (GLP-1), was identified in 1992 in the saliva of a lizard (Heloderma suspectum), and took until 2005 to be marketed as exenatide. To promote the efficacy of endogenous GLP-1, its rapid inactivation by the enzyme dipeptidylpeptidase-4 (DPP4) was blocked by clever molecular design of the first DPP4 inhibitors (vildagliptin and sitagliptin, approved in 2006). SGLT2 inhibitors are based on phlorizin, identified in apple tree bark (1835) and modified (2000) to avoid intestinal degradation: further modifications to increase selectivity against SGLT2 gave dapagliflozin and canagliflozin - approved 2012 and 2013, respectively, in Europe.","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48001130","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}
U. Dashora, P. Kempegowda, A. Li, S. Harris, E. Castro, R. Hillson, C. Jones, K. Dhatariya
Introduction: The annual National Diabetes Inpatient Audit (NaDIA and NaDIA-Harms) in the UK continues to show significant problems with patient care. During the COVID pandemic patient care has been even more difficult. New initiatives are urgently required to improve inpatient safety for people with diabetes. Method: The Joint British Diabetes Societies for Inpatient Care (JBDS-IP) organised the seventh national Rowan Hillson Inpatient Safety Award on the theme of “the best interventions: redesigning, rebuilding and maintaining safe inpatient diabetes care during COVID”. Result: The winner was the DEKODE team, led by Dr Punith Kempegowda from University Hospitals Birmingham NHS Foundation Trust, for their innovative quality improvement project across hospitals during COVID to improve diabetes-related ketoacidosis (DKA) management and study DKA in people with COVID. Adherence to national guidance improved in some hospitals, with falls in hypoglycaemia, and overall there was a significant improvement in awareness about DKA amongst junior doctors. The King’s College NHS Foundation Trust team, led by Adrian Li and colleagues, received the highly commended award for their innovative project of remote blood glucose (BG) monitoring across healthcare boundaries. This improved diabetes control and tackled health inequalities. Summary and conclusion: These and similar schemes need to be developed, promoted and shared to improve safety for people with diabetes admitted in hospital during COVID times.
{"title":"The Rowan Hillson Inpatient Safety Award 2022 The best interventions: redesigning, rebuilding and maintaining safe inpatient diabetes care during COVID","authors":"U. Dashora, P. Kempegowda, A. Li, S. Harris, E. Castro, R. Hillson, C. Jones, K. Dhatariya","doi":"10.15277/bjd.2022.389","DOIUrl":"https://doi.org/10.15277/bjd.2022.389","url":null,"abstract":"Introduction: The annual National Diabetes Inpatient Audit (NaDIA and NaDIA-Harms) in the UK continues to show significant problems with patient care. During the COVID pandemic patient care has been even more difficult. New initiatives are urgently required to improve inpatient safety for people with diabetes. Method: The Joint British Diabetes Societies for Inpatient Care (JBDS-IP) organised the seventh national Rowan Hillson Inpatient Safety Award on the theme of “the best interventions: redesigning, rebuilding and maintaining safe inpatient diabetes care during COVID”. Result: The winner was the DEKODE team, led by Dr Punith Kempegowda from University Hospitals Birmingham NHS Foundation Trust, for their innovative quality improvement project across hospitals during COVID to improve diabetes-related ketoacidosis (DKA) management and study DKA in people with COVID. Adherence to national guidance improved in some hospitals, with falls in hypoglycaemia, and overall there was a significant improvement in awareness about DKA amongst junior doctors. The King’s College NHS Foundation Trust team, led by Adrian Li and colleagues, received the highly commended award for their innovative project of remote blood glucose (BG) monitoring across healthcare boundaries. This improved diabetes control and tackled health inequalities. Summary and conclusion: These and similar schemes need to be developed, promoted and shared to improve safety for people with diabetes admitted in hospital during COVID times.","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":"50 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67138968","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}
Aim: Diabetic foot ulcers (DFU) are linked to morbidity, decreased mobility, and feelings of isolation, powerlessness and sadness. The aim of this study was to explore the prevalence of anxiety and depression symptoms in adult patients with DFU. Method(s): Patients with DFU attending our multidisciplinary diabetic foot clinic from February 14th to March 14th, 2022 were invited to complete a questionnaire which included sociodemographic questions, the Patient Health Questionnaire-9 (PHQ-9) scale to assess depression and the Generalized Anxiety Disorder scale (GAD-7) to assess anxiety. For each scale, a cut-off total score of 10 was used to identify those who met the criteria for anxiety and depression. Result(s): 60 patients completed the questionnaire. 83.25% of the participants reported that their diabetes foot care had not been affected by the COVID-19 pandemic. 25% reported moderate to severe anxiety symptoms, 10% reported mild anxiety symptoms while 65% reported no or minimal anxiety symptoms. Regarding depression, 30% reported moderate to severe depressive symptoms, 10% reported mild depressive symptoms, while 60% reported no or minimal depression (Figure 1). Patients with other co-morbidities were three times more likely to report depression compared to those without other co-morbidities (OR=3.2;95% CI 1.10-10.26). Patients younger than 50 years were nearly nine times more likely to report anxiety compared to those aged 60 years or above (adjusted OR=8.9;95% CI: 1.01-86.41) taking into account other variables. Conclusion(s): The prevalence of depression and anxiety in this cohort of patients with DFU was low, but the severity was moderate to severe in those who were affected. Patients with other co-morbidities and those younger than 50 years have worse mental health status. This finding needs to be taken into account in the management of patients with DFU. Attempts to reduce anxiety and/or depression could improve the quality of life of DFU patients.
目的:糖尿病足溃疡(DFU)与发病率、活动能力下降、孤立感、无力感和悲伤感有关。本研究的目的是探讨成年DFU患者焦虑和抑郁症状的患病率。方法:邀请2022年2月14日至3月14日在我院多学科糖尿病足门诊就诊的DFU患者完成一份问卷，包括社会人口学问题、患者健康问卷-9 (PHQ-9)量表(用于评估抑郁)和广泛性焦虑障碍量表(GAD-7)量表(用于评估焦虑)。对于每个量表，用10分的截止总分来确定那些符合焦虑和抑郁标准的人。结果:60例患者完成问卷调查。83.25%的参与者报告说，他们的糖尿病足护理没有受到COVID-19大流行的影响。25%报告有中度至重度焦虑症状，10%报告有轻度焦虑症状，65%报告没有或只有轻微焦虑症状。关于抑郁症，30%报告中度至重度抑郁症状，10%报告轻度抑郁症状，而60%报告无抑郁或轻度抑郁(图1)。与无其他合并症的患者相比，有其他合并症的患者报告抑郁的可能性是无其他合并症患者的三倍(or =3.2;95% CI 1.10-10.26)。考虑到其他变量，50岁以下的患者报告焦虑的可能性是60岁或以上患者的近9倍(调整后or =8.9;95% CI: 1.01-86.41)。结论:该队列DFU患者抑郁和焦虑患病率较低，但患者的严重程度为中度至重度。患有其他合并症的患者和年龄小于50岁的患者精神健康状况较差。这一发现需要在DFU患者的管理中加以考虑。尝试减少焦虑和/或抑郁可以改善DFU患者的生活质量。
{"title":"Abstracts from ABCD Conference","authors":"A. Two","doi":"10.15277/bjd.2022.393","DOIUrl":"https://doi.org/10.15277/bjd.2022.393","url":null,"abstract":"Aim: Diabetic foot ulcers (DFU) are linked to morbidity, decreased mobility, and feelings of isolation, powerlessness and sadness. The aim of this study was to explore the prevalence of anxiety and depression symptoms in adult patients with DFU. Method(s): Patients with DFU attending our multidisciplinary diabetic foot clinic from February 14th to March 14th, 2022 were invited to complete a questionnaire which included sociodemographic questions, the Patient Health Questionnaire-9 (PHQ-9) scale to assess depression and the Generalized Anxiety Disorder scale (GAD-7) to assess anxiety. For each scale, a cut-off total score of 10 was used to identify those who met the criteria for anxiety and depression. Result(s): 60 patients completed the questionnaire. 83.25% of the participants reported that their diabetes foot care had not been affected by the COVID-19 pandemic. 25% reported moderate to severe anxiety symptoms, 10% reported mild anxiety symptoms while 65% reported no or minimal anxiety symptoms. Regarding depression, 30% reported moderate to severe depressive symptoms, 10% reported mild depressive symptoms, while 60% reported no or minimal depression (Figure 1). Patients with other co-morbidities were three times more likely to report depression compared to those without other co-morbidities (OR=3.2;95% CI 1.10-10.26). Patients younger than 50 years were nearly nine times more likely to report anxiety compared to those aged 60 years or above (adjusted OR=8.9;95% CI: 1.01-86.41) taking into account other variables. Conclusion(s): The prevalence of depression and anxiety in this cohort of patients with DFU was low, but the severity was moderate to severe in those who were affected. Patients with other co-morbidities and those younger than 50 years have worse mental health status. This finding needs to be taken into account in the management of patients with DFU. Attempts to reduce anxiety and/or depression could improve the quality of life of DFU patients.","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":"114 3","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41294917","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":"Why are GLP-1 receptor agonists in short supply?","authors":"Clifford J. Bailey","doi":"10.15277/bjd.2022.382","DOIUrl":"https://doi.org/10.15277/bjd.2022.382","url":null,"abstract":"","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45182375","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}
M. Gulamhussein, Ridwaan Sohawon, H. Travers, M. Wall
Diabetic foot disease (DFD) is a leading cause of acute sepsis and has long-term consequences for patients. It poses a strain on health resources in both the developed and developing world, with a significant impact on patient quality of life due to the associated complications of DFD and the often multiple interventions required to control infection and preserve limb tissue. Although there is evidence in the literature regarding early detection and prompt management of this debilitating condition, there is little structured evidence on how to gain accurate tissue sampling with processing to allow targeted antimicrobial therapy from minor amputations where bone cultures have been sent. Methods: A literature review was conducted to establish the publications on intra-operative bone sampling and processing taken during diabetic foot minor amputations and the pathways described for processing sample acquisition. Findings: Thirty papers were identified which highlighted some of the processes involved in the procurement of intraoperative tissue samples. No published paper reported a complete pathway for the ascertainment of samples, transfer and processing of these specimens. Conclusion: There is no published consistent pathway published for procurement of intra-operative diabetic foot specimens, for their storage, transportation and processing. Without documented, reproducible processes, it is difficult to interpret published results. This makes planning for targeted antibiotic therapy more difficult.
{"title":"Intra-operative tissue sampling and microbiological analyses during minor lower limb amputations in patients with diabetes are poorly reported and difficult to interpret","authors":"M. Gulamhussein, Ridwaan Sohawon, H. Travers, M. Wall","doi":"10.15277/bjd.2022.383","DOIUrl":"https://doi.org/10.15277/bjd.2022.383","url":null,"abstract":"Diabetic foot disease (DFD) is a leading cause of acute sepsis and has long-term consequences for patients. It poses a strain on health resources in both the developed and developing world, with a significant impact on patient quality of life due to the associated complications of DFD and the often multiple interventions required to control infection and preserve limb tissue. Although there is evidence in the literature regarding early detection and prompt management of this debilitating condition, there is little structured evidence on how to gain accurate tissue sampling with processing to allow targeted antimicrobial therapy from minor amputations where bone cultures have been sent.\u0000Methods: A literature review was conducted to establish the publications on intra-operative bone sampling and processing taken during diabetic foot minor amputations and the pathways described for processing sample acquisition.\u0000Findings: Thirty papers were identified which highlighted some of the processes involved in the procurement of intraoperative tissue samples. No published paper reported a complete pathway for the ascertainment of samples, transfer and processing of these specimens.\u0000Conclusion: There is no published consistent pathway published for procurement of intra-operative diabetic foot specimens, for their storage, transportation and processing. Without documented, reproducible processes, it is difficult to interpret published results. This makes planning for targeted antibiotic therapy more difficult.","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47607661","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}
N. Shah, Thushari Bandara, Harshal Deshmukh, Lucy Batten, C. Walton, T. Sathyapalan
Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a class of anti-hyperglycaemic agents widely used in the treatment of type 2 diabetes mellitus (T2DM). They function by reducing renal glucose reabsorption and thereby promote urinary glucose excretion, resulting in improvement in glycaemic control. In large-scale clinical trials, SGLT2i have been shown to reduce cardiovascular mortality, non-fatal myocardial infarction and stroke significantly. In addition, clinical evidence suggests that they are renal protective as their use reduces the relative risk of end-stage renal disease and death from renal causes. These positive results have led to a rapid uptake of SGLT2i in clinical practice. Recently, clinical studies and case reports have suggested a link between SGLT2i therapy and erythrocytosis. The authors discuss possible mechanisms at cellular level that may cause erythrocytosis and explore its clinical relevance in people living with T2DM who are taking SGLT2i therapy.
{"title":"Sodium-glucose co-transporter 2 inhibitors and erythrocytosis: a review","authors":"N. Shah, Thushari Bandara, Harshal Deshmukh, Lucy Batten, C. Walton, T. Sathyapalan","doi":"10.15277/bjd.2022.384","DOIUrl":"https://doi.org/10.15277/bjd.2022.384","url":null,"abstract":"Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a class of anti-hyperglycaemic agents widely used in the treatment of type 2 diabetes mellitus (T2DM). They function by reducing renal glucose reabsorption and thereby promote urinary glucose excretion, resulting in improvement in glycaemic control. In large-scale clinical trials, SGLT2i have been shown to reduce cardiovascular mortality, non-fatal myocardial infarction and stroke significantly. In addition, clinical evidence suggests that they are renal protective as their use reduces the relative risk of end-stage renal disease and death from renal causes. These positive results have led to a rapid uptake of SGLT2i in clinical practice. Recently, clinical studies and case reports have suggested a link between SGLT2i therapy and erythrocytosis. The authors discuss possible mechanisms at cellular level that may cause erythrocytosis and explore its clinical relevance in people living with T2DM who are taking SGLT2i therapy.","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48186554","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}
LEADER was a landmark cardiovascular outcome trial with the GLP-1 receptor agonist liraglutide, which demonstrated significant reductions in major adverse cardiovascular events (MACE, a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke), driven by a reduction in cardiovascular deaths and accompanied by a significant reduction in all-cause mortality. Shortly afterwards, the SUSTAIN-6 trial with once-weekly semaglutide demonstrated non-inferiority for MACE, with a nominal reduction in MACE that was driven by a reduction in the risk of non-fatal strokes. Since then, a further six cardiovascular trials have been published with GLP-1 receptor agonists, with major differences in study design and outcomes. Four trials have been performed with once-weekly formulations. The EXSCEL trial with once-weekly exenatide showed non-inferiority for MACE, but not superiority, with a reduction in all-cause mortality which was an exploratory outcome. The Harmony Outcomes trial with albiglutide demonstrated significant reductions in MACE, driven by reductions in fatal or non-fatal myocardial infarction. REWIND, with dulaglutide, also demonstrated significant reductions in MACE, this time driven by reductions in strokes. The AMPLITUDE-O trial with efpeglenatide showed significant reductions in MACE, but none of the individual components of MACE was significantly reduced as a secondary endpoint, and in contrast to other trials there was also a significant reduction in heart failure events. The fifth trial was the PIONEER 6 trial with the oral formulation of semaglutide, and this showed non-inferiority for MACE, but not superiority, with reductions in cardiovascular deaths and all-cause mortality which were secondary outcomes. Finally, FREEDOM-CVO with a subcutaneous mini-pump of exenatide showed non-inferiority for MACE and MACE plus hospitalisation for unstable angina. A reduction in albuminuria was seen in several of these trials, but there was no definite effect on eGFR or end-stage renal disease. Meta-analysis of the cardiovascular outcome trials with GLP-1 receptor agonists has demonstrated significant reductions in MACE, cardiovascular death, fatal or non-fatal stroke, fatal or non-fatal myocardial infarction, and all-cause mortality. It remains unclear why updated guidance from NICE on the management of T2DM in adults fails to acknowledge these evidence-based cardiovascular benefits.
{"title":"Series: Cardiovascular outcome trials for diabetes drugs.","authors":"M. Fisher","doi":"10.15277/bjd.2022.387","DOIUrl":"https://doi.org/10.15277/bjd.2022.387","url":null,"abstract":"LEADER was a landmark cardiovascular outcome trial with the GLP-1 receptor agonist liraglutide, which demonstrated significant reductions in major adverse cardiovascular events (MACE, a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke), driven by a reduction in cardiovascular deaths and accompanied by a significant reduction in all-cause mortality. Shortly afterwards, the SUSTAIN-6 trial with once-weekly semaglutide demonstrated non-inferiority for MACE, with a nominal reduction in MACE that was driven by a reduction in the risk of non-fatal strokes. Since then, a further six cardiovascular trials have been published with GLP-1 receptor agonists, with major differences in study design and outcomes.\u0000Four trials have been performed with once-weekly formulations. The EXSCEL trial with once-weekly exenatide showed non-inferiority for MACE, but not superiority, with a reduction in all-cause mortality which was an exploratory outcome. The Harmony Outcomes trial with albiglutide demonstrated significant reductions in MACE, driven by reductions in fatal or non-fatal myocardial infarction. REWIND, with dulaglutide, also demonstrated significant reductions in MACE, this time driven by reductions in strokes. The AMPLITUDE-O trial with efpeglenatide showed significant reductions in MACE, but none of the individual components of MACE was significantly reduced as a secondary endpoint, and in contrast to other trials there was also a significant reduction in heart failure events. The fifth trial was the PIONEER 6 trial with the oral formulation of semaglutide, and this showed non-inferiority for MACE, but not superiority, with reductions in cardiovascular deaths and all-cause mortality which were secondary outcomes. Finally, FREEDOM-CVO with a subcutaneous mini-pump of exenatide showed non-inferiority for MACE and MACE plus hospitalisation for unstable angina. A reduction in albuminuria was seen in several of these trials, but there was no definite effect on eGFR or end-stage renal disease.\u0000Meta-analysis of the cardiovascular outcome trials with GLP-1 receptor agonists has demonstrated significant reductions in MACE, cardiovascular death, fatal or non-fatal stroke, fatal or non-fatal myocardial infarction, and all-cause mortality. It remains unclear why updated guidance from NICE on the management of T2DM in adults fails to acknowledge these evidence-based cardiovascular benefits.","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41852529","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}
The article by Miles Fisher in this edition of the British Journal of Diabetes discusses cardiovascular outcome trials (CVOTs) which have examined the impact of GLP-1RAs in type 2 diabetes (T2DM). He queries ‘why updated guidance from NICE...fails to acknowledge the evidence-based cardiovascular benefits’. Indeed, clinicians in the UK will be puzzled as to why this class of glucose-lowering therapy is now a first-line option in European and North American guidelines for people with T2DM at high cardiovascular risk, but remains well down the pecking order in NICE guideline (NG) 28.1-3 This editorial will provide a short précis of the history of GLP-1RAs and NICE and try to explain the current impasse. The National Institute of Clinical Excellence (NICE) was established in 1999 to ‘diffuse the postcode lottery’ of healthcare (for example, varying access to medicines according to where people lived) and serves the National Health Services (NHS) in England, Northern Ireland and Wales. Since its set-up, there have been two changes in name, the National Institute for Health and Clinical Excellence (2005) and the National Institute for Health and Care Excellence (2013) but the abbreviation of NICE has stood the test of time and is a globally recognised brand. Well over fifty countries world-wide access guidelines produced by NICE rather than doing their own in-depth assessment of new medicines.4 When it was launched, NICE inherited various guidelines for the management of T2DM, which were rebadged. It produced its first clinical guideline for T2DM (CG66) in 2008.5 This was rapidly followed by the release of CG87 in May 2009, which was a short update on the ‘newer agents’ for blood glucose lowering.6 This guideline included exenatide, given twice daily, which was the first GLP-1RA to be licensed in the UK (in 2007). Exenatide was positioned as a third-line ‘alternative’ add-on therapy to be considered after insulin, a thiazolidinedione or a dipeptidyl peptase-4 inhibitor and it was only sanctioned for use with metformin and a sulfonylurea. CG87 introduced the body mass index (BMI) cut-off of 35 Kg/m2 for GLP-1RAs, which was not based on data from clinical trials but was the BMI at which the average cost of a long-acting insulin analogue was the same as BD exenatide. NICE also introduced ‘stopping rules’ where exenatide should be withheld when a reduction of at least 1% (11mmol/mol) in HbA1c and weight loss of at least 3% initial body weight was not achieved after six months. Stopping rules have not been recommended for any other glucose-lowering class. The next NICE guidance for the management of T2DM (NG28) was published in 2015 and is best remembered for the furore created by the recommendation of repaglinide as firstline treatment for people intolerant of metformin.7,8 In the preceding six years, GLP-1RAs had been added to the glucoselowering algorithm by means of single technology appraisals (TAs). These individual assessments by NICE had a more bind
Miles Fisher在本期《英国糖尿病杂志》上发表的文章讨论了心血管结果试验（CVOT），该试验检测了GLP-1RA对2型糖尿病（T2DM）的影响。他质疑“为什么NICE更新了指南。。。未能承认循证心血管益处”。事实上，英国的临床医生会感到困惑，为什么这类降糖治疗现在是欧洲和北美指南中针对心血管高危T2DM患者的一线选择，但在NICE指南（NG）28.1-3中排名靠后。这篇社论将简要介绍GLP-1RA和NICE的历史，并试图解释目前的僵局。国家临床卓越研究所（NICE）成立于1999年，旨在“分散医疗保健的邮政编码抽签”（例如，根据人们的居住地不同获得药物的机会），并为英格兰、北爱尔兰和威尔士的国家医疗服务体系（NHS）服务。自成立以来，名称发生了两次变化，即国家健康与临床卓越研究所（2005年）和国家健康与护理卓越研究院（2013年），但NICE的缩写经受住了时间的考验，是一个全球公认的品牌。全球有50多个国家制定了NICE获得指南，而不是自己对新药进行深入评估。4当它推出时，NICE继承了T2DM管理的各种指南，这些指南被重新调整了。它于2008年制定了首个T2DM临床指南（CG66）。5随后，CG87于2009年5月迅速发布，这是对降血糖“新药物”的简短更新。6该指南包括艾塞那肽，每天两次，这是第一个在英国获得许可的GLP-1RA（2007年）。艾塞那肽被定位为继胰岛素、噻唑烷二酮或二肽基肽酶-4抑制剂之后考虑的第三线“替代”添加疗法，它只被批准与二甲双胍和磺酰脲一起使用。CG87引入了GLP-1RA的体重指数（BMI）临界值35 Kg/m2，这不是基于临床试验的数据，而是长效胰岛素类似物的平均成本与BD艾塞那肽相同的BMI。NICE还引入了“停止规则”，即当HbA1c减少至少1%（11mmol/mol），且六个月后初始体重未减少至少3%时，应停止使用艾塞那肽。停止规则没有被推荐用于任何其他降血糖类别。下一份NICE关于T2DM（NG28）管理的指南于2015年发布，人们最怀念的是瑞格列奈作为二甲双胍不耐受人群一线治疗的推荐所引起的轰动。7,8在过去的六年里，GLP-1RA通过单一技术评估（TA）被添加到葡萄糖代谢算法中。NICE的这些个人评估比其指导方针具有更具约束力的法律地位，因为TA的积极建议要求临床委托小组提供资金。因此，利拉鲁肽（TA2032010）、艾塞那肽缓释剂（TA2482012）和利西那肽（2013）都被批准使用，尽管NICE将利拉鲁的剂量限制在最大1.2mg OD，因为该剂量与BD艾塞那苷的获取成本相同。9-11然而，GLP-1RA在降糖算法中的总体地位没有变化。在各种三重口服组合或胰岛素后，它们仍然是一种可供考虑的第三线选择，甚至没有提到不能耐受二甲双胍或二甲双胍禁忌的人。证明其优越性的第一个降血糖治疗CVOT是对恩帕列嗪（一种钠-葡萄糖共转运蛋白2（SGLT2）抑制剂）的EMPA-REG结果研究，该试验在2015年12月NG28上市前三个月发表。12 NG28没有考虑这些阳性数据，但这并不重要，因为NICE承诺每两年定期更新一次，而且更多的CVOT数据正在酝酿中。事实上，2016年利拉鲁肽（LEADER）和每周一次的西格鲁肽（SUSTAIN 6）都有阳性CVOT。13,14杜拉鲁肽（REWIND）的阳性优势CVOT于2019年发表，英国斯旺西斯旺西大学医学院1所
{"title":"The place of Glucagon-like 1 peptide receptor agonists (GLP-1RAs) in the new NICE guidelines – what is going on?","authors":"Stephen C. Bain","doi":"10.15277/bjd.2022.381","DOIUrl":"https://doi.org/10.15277/bjd.2022.381","url":null,"abstract":"The article by Miles Fisher in this edition of the British Journal of Diabetes discusses cardiovascular outcome trials (CVOTs) which have examined the impact of GLP-1RAs in type 2 diabetes (T2DM). He queries ‘why updated guidance from NICE...fails to acknowledge the evidence-based cardiovascular benefits’. Indeed, clinicians in the UK will be puzzled as to why this class of glucose-lowering therapy is now a first-line option in European and North American guidelines for people with T2DM at high cardiovascular risk, but remains well down the pecking order in NICE guideline (NG) 28.1-3 This editorial will provide a short précis of the history of GLP-1RAs and NICE and try to explain the current impasse. The National Institute of Clinical Excellence (NICE) was established in 1999 to ‘diffuse the postcode lottery’ of healthcare (for example, varying access to medicines according to where people lived) and serves the National Health Services (NHS) in England, Northern Ireland and Wales. Since its set-up, there have been two changes in name, the National Institute for Health and Clinical Excellence (2005) and the National Institute for Health and Care Excellence (2013) but the abbreviation of NICE has stood the test of time and is a globally recognised brand. Well over fifty countries world-wide access guidelines produced by NICE rather than doing their own in-depth assessment of new medicines.4 When it was launched, NICE inherited various guidelines for the management of T2DM, which were rebadged. It produced its first clinical guideline for T2DM (CG66) in 2008.5 This was rapidly followed by the release of CG87 in May 2009, which was a short update on the ‘newer agents’ for blood glucose lowering.6 This guideline included exenatide, given twice daily, which was the first GLP-1RA to be licensed in the UK (in 2007). Exenatide was positioned as a third-line ‘alternative’ add-on therapy to be considered after insulin, a thiazolidinedione or a dipeptidyl peptase-4 inhibitor and it was only sanctioned for use with metformin and a sulfonylurea. CG87 introduced the body mass index (BMI) cut-off of 35 Kg/m2 for GLP-1RAs, which was not based on data from clinical trials but was the BMI at which the average cost of a long-acting insulin analogue was the same as BD exenatide. NICE also introduced ‘stopping rules’ where exenatide should be withheld when a reduction of at least 1% (11mmol/mol) in HbA1c and weight loss of at least 3% initial body weight was not achieved after six months. Stopping rules have not been recommended for any other glucose-lowering class. The next NICE guidance for the management of T2DM (NG28) was published in 2015 and is best remembered for the furore created by the recommendation of repaglinide as firstline treatment for people intolerant of metformin.7,8 In the preceding six years, GLP-1RAs had been added to the glucoselowering algorithm by means of single technology appraisals (TAs). These individual assessments by NICE had a more bind","PeriodicalId":42951,"journal":{"name":"British Journal of Diabetes","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48885119","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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