Time in range (TIR) is gaining ground as an outcome measure in type 1 diabetes trials. However, i... more Time in range (TIR) is gaining ground as an outcome measure in type 1 diabetes trials. However, inclusion of TIR raises several issues for trial design. In this article, the authors begin by defining TIR and describing the current international consensus around TIR targets. They then expand on evidence for the validity of TIR as a primary clinical trial outcome before concluding with some practical, ethical, and logistical implications.
The first systems for continuous glucose monitoring (CGM) became available over 15 years ago. Man... more The first systems for continuous glucose monitoring (CGM) became available over 15 years ago. Many then believed CGM would revolutionize the use of intensive insulin therapy in diabetes; however, progress toward that vision has been gradual. Although increasing, the proportion of individuals using CGM rather than conventional systems for self-monitoring of blood glucose on a daily basis is still low in most parts of the world. Barriers to uptake include cost, measurement reliability (particularly with earlier-generation systems), human factors issues, lack of a standardized format for displaying results, and uncertainty on how best to use CGM data to make therapeutic decisions. This Scientific Statement makes recommendations for systemic improvements in clinical use and regulatory (pre- and postmarketing) handling of CGM devices. The aim is to improve safety and efficacy in order to support the advancement of the technology in achieving its potential to improve quality of life and h...
Epidemiological data on obesity are needed, particularly in patients with type 2 diabetes mellitu... more Epidemiological data on obesity are needed, particularly in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular (CV) risk. We used the baseline data of liraglutide effect and action in diabetes: evaluation of CV outcome results-A long term Evaluation (LEADER) (a clinical trial to assess the CV safety of liraglutide) to investigate: (i) prevalence of overweight and obesity; (ii) relationship of the major cardiometabolic risk factors with anthropometric measures of adiposity [body mass index (BMI) and waist circumference (WC)]; and (iii) cardiometabolic treatment intensity in relation to BMI and WC. LEADER enrolled two distinct populations of high-risk patients with T2DM in 32 countries: (1) aged ≥50 years with prior CV disease; (2) aged ≥60 years with one or more CV risk factors. Associations of metabolic variables, demographic variables and treatment intensity with anthropometric measurements (BMI and WC) were explored using regression models (ClinicalTrials.gov id...
Insulin pump therapy, also known as continuous subcutaneous insulin infusion (CSII), is an import... more Insulin pump therapy, also known as continuous subcutaneous insulin infusion (CSII), is an important and evolving form of insulin delivery, which is mainly used for people with type 1 diabetes. However, even with modern insulin pumps, errors of insulin infusion can occur due to pump failure, insulin infusion set (IIS) blockage, infusion site problems, insulin stability issues, user error, or a combination of these. Users are therefore exposed to significant and potentially fatal hazards: interruption of insulin infusion can result in hyperglycemia and ketoacidosis; conversely, delivery of excessive insulin can cause severe hypoglycemia. Nevertheless, the available evidence on the safety and efficacy of CSII remains limited. The European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) have therefore joined forces to review the systems in place for evaluating the safety of pumps from a clinical perspective. We found that useful information held...
Aims/hypothesis Imbalances in glucose metabolism are hallmarks of clinically silent prediabetes (... more Aims/hypothesis Imbalances in glucose metabolism are hallmarks of clinically silent prediabetes (defined as impaired fasting glucose and/or impaired glucose tolerance) representing dysmetabolism trajectories leading to type 2 diabetes. CD26/dipeptidyl peptidase 4 (DPP4) is a clinically proven molecular target of diabetes-controlling drugs but the DPP4 gene control of dysglycaemia is not proven. Methods We dissected the genetic control of post-OGTT and insulin release responses by the DPP4 gene in a Portuguese population-based cohort of mainly European ancestry that comprised individuals with normoglycaemia and prediabetes, and in mouse experimental models of Dpp4 deficiency and hyperenergetic diet. Results In individuals with normoglycaemia, DPP4 single-nucleotide variants governed glycaemic excursions (rs4664446, p=1.63x10−7) and C-peptide release responses (rs2300757, p=6.86x10−5) upon OGTT. Association with blood glucose levels was stronger at 30 min OGTT, but a higher associatio...
Background: The long-term burden of self-management in type 2 diabetes can impact quality of life... more Background: The long-term burden of self-management in type 2 diabetes can impact quality of life. Aims: To examine associations between demographic and clinical factors, anxiety/depression and perception of health in people with type 2 diabetes. Methods: Retrospective analyses of anonymised data from completed clinical trials provided by the diabetes subsection of Virtual International Cardiovascular and Cognitive Trials Archive (VICCTA). Data on demographics, polypharmacy, HbA1c, anxiety/depression (EQ-5D-3L) and perception of health (EQ-5D-3L VAS) were extracted. Regression analyses explored associations amongst polypharmacy, HbA1c and quality of life (anxiety/depression and health perception) at baseline. Results: In 2783 participants with type 2 diabetes (median age 66 years (IQR 61–70), n=1,595 (57%) male), female sex and Caucasian/European ethnicity were each associated with increased anxiety/depression and lower EQ-5D-3L VAS scores. Following adjustment for covariates, each ...
Background: The risks of, and risk factors for, COVID-19 disease associated with diabetes are poo... more Background: The risks of, and risk factors for, COVID-19 disease associated with diabetes are poorly quantified. Methods: We identified as cases all those in Scotland with a positive SARS-CoV-2 nucleic acid test in the national laboratory database and anyone else with a death certificate mentioning COVID-19. Seven controls matched for age, sex and general practice were selected per case. Data were linked to the national diabetes register, hospitalisation and critical care unit (CCU) databases. Analyses focused on those with COVID-19 requiring critical care or dying. Analyses were by conditional and unconditional logistic regression. Findings: 0.3% (n=845) of those with diabetes had developed severe or fatal COVID-19, representing rate ratios of 3.86 (2.74, 5.45) in type 1 and 1.69 (1.56, 1.84) in type 2 diabetes. Rates were almost threefold in the most versus least socioeconomically deprived quintiles of the population. Most (77%) cases had another recognised co-morbidity such as he...
Abstract When the COVID‐19 pandemic hit the UK, hospital diabetes clinics ground abruptly to a ha... more Abstract When the COVID‐19 pandemic hit the UK, hospital diabetes clinics ground abruptly to a halt and many diabetologists were effectively conscripted on to front‐line emergency care. Their contribution was key to the ability of acute medical services to be rapidly redesigned and continuously adapted during the peak. This was a simple imperative as “lockdown” kicked in, usual out‐patient clinical activity ceased, and emergency admissions with the new virus surged.
Time in range (TIR) is gaining ground as an outcome measure in type 1 diabetes trials. However, i... more Time in range (TIR) is gaining ground as an outcome measure in type 1 diabetes trials. However, inclusion of TIR raises several issues for trial design. In this article, the authors begin by defining TIR and describing the current international consensus around TIR targets. They then expand on evidence for the validity of TIR as a primary clinical trial outcome before concluding with some practical, ethical, and logistical implications.
The first systems for continuous glucose monitoring (CGM) became available over 15 years ago. Man... more The first systems for continuous glucose monitoring (CGM) became available over 15 years ago. Many then believed CGM would revolutionize the use of intensive insulin therapy in diabetes; however, progress toward that vision has been gradual. Although increasing, the proportion of individuals using CGM rather than conventional systems for self-monitoring of blood glucose on a daily basis is still low in most parts of the world. Barriers to uptake include cost, measurement reliability (particularly with earlier-generation systems), human factors issues, lack of a standardized format for displaying results, and uncertainty on how best to use CGM data to make therapeutic decisions. This Scientific Statement makes recommendations for systemic improvements in clinical use and regulatory (pre- and postmarketing) handling of CGM devices. The aim is to improve safety and efficacy in order to support the advancement of the technology in achieving its potential to improve quality of life and h...
Epidemiological data on obesity are needed, particularly in patients with type 2 diabetes mellitu... more Epidemiological data on obesity are needed, particularly in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular (CV) risk. We used the baseline data of liraglutide effect and action in diabetes: evaluation of CV outcome results-A long term Evaluation (LEADER) (a clinical trial to assess the CV safety of liraglutide) to investigate: (i) prevalence of overweight and obesity; (ii) relationship of the major cardiometabolic risk factors with anthropometric measures of adiposity [body mass index (BMI) and waist circumference (WC)]; and (iii) cardiometabolic treatment intensity in relation to BMI and WC. LEADER enrolled two distinct populations of high-risk patients with T2DM in 32 countries: (1) aged ≥50 years with prior CV disease; (2) aged ≥60 years with one or more CV risk factors. Associations of metabolic variables, demographic variables and treatment intensity with anthropometric measurements (BMI and WC) were explored using regression models (ClinicalTrials.gov id...
Insulin pump therapy, also known as continuous subcutaneous insulin infusion (CSII), is an import... more Insulin pump therapy, also known as continuous subcutaneous insulin infusion (CSII), is an important and evolving form of insulin delivery, which is mainly used for people with type 1 diabetes. However, even with modern insulin pumps, errors of insulin infusion can occur due to pump failure, insulin infusion set (IIS) blockage, infusion site problems, insulin stability issues, user error, or a combination of these. Users are therefore exposed to significant and potentially fatal hazards: interruption of insulin infusion can result in hyperglycemia and ketoacidosis; conversely, delivery of excessive insulin can cause severe hypoglycemia. Nevertheless, the available evidence on the safety and efficacy of CSII remains limited. The European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) have therefore joined forces to review the systems in place for evaluating the safety of pumps from a clinical perspective. We found that useful information held...
Aims/hypothesis Imbalances in glucose metabolism are hallmarks of clinically silent prediabetes (... more Aims/hypothesis Imbalances in glucose metabolism are hallmarks of clinically silent prediabetes (defined as impaired fasting glucose and/or impaired glucose tolerance) representing dysmetabolism trajectories leading to type 2 diabetes. CD26/dipeptidyl peptidase 4 (DPP4) is a clinically proven molecular target of diabetes-controlling drugs but the DPP4 gene control of dysglycaemia is not proven. Methods We dissected the genetic control of post-OGTT and insulin release responses by the DPP4 gene in a Portuguese population-based cohort of mainly European ancestry that comprised individuals with normoglycaemia and prediabetes, and in mouse experimental models of Dpp4 deficiency and hyperenergetic diet. Results In individuals with normoglycaemia, DPP4 single-nucleotide variants governed glycaemic excursions (rs4664446, p=1.63x10−7) and C-peptide release responses (rs2300757, p=6.86x10−5) upon OGTT. Association with blood glucose levels was stronger at 30 min OGTT, but a higher associatio...
Background: The long-term burden of self-management in type 2 diabetes can impact quality of life... more Background: The long-term burden of self-management in type 2 diabetes can impact quality of life. Aims: To examine associations between demographic and clinical factors, anxiety/depression and perception of health in people with type 2 diabetes. Methods: Retrospective analyses of anonymised data from completed clinical trials provided by the diabetes subsection of Virtual International Cardiovascular and Cognitive Trials Archive (VICCTA). Data on demographics, polypharmacy, HbA1c, anxiety/depression (EQ-5D-3L) and perception of health (EQ-5D-3L VAS) were extracted. Regression analyses explored associations amongst polypharmacy, HbA1c and quality of life (anxiety/depression and health perception) at baseline. Results: In 2783 participants with type 2 diabetes (median age 66 years (IQR 61–70), n=1,595 (57%) male), female sex and Caucasian/European ethnicity were each associated with increased anxiety/depression and lower EQ-5D-3L VAS scores. Following adjustment for covariates, each ...
Background: The risks of, and risk factors for, COVID-19 disease associated with diabetes are poo... more Background: The risks of, and risk factors for, COVID-19 disease associated with diabetes are poorly quantified. Methods: We identified as cases all those in Scotland with a positive SARS-CoV-2 nucleic acid test in the national laboratory database and anyone else with a death certificate mentioning COVID-19. Seven controls matched for age, sex and general practice were selected per case. Data were linked to the national diabetes register, hospitalisation and critical care unit (CCU) databases. Analyses focused on those with COVID-19 requiring critical care or dying. Analyses were by conditional and unconditional logistic regression. Findings: 0.3% (n=845) of those with diabetes had developed severe or fatal COVID-19, representing rate ratios of 3.86 (2.74, 5.45) in type 1 and 1.69 (1.56, 1.84) in type 2 diabetes. Rates were almost threefold in the most versus least socioeconomically deprived quintiles of the population. Most (77%) cases had another recognised co-morbidity such as he...
Abstract When the COVID‐19 pandemic hit the UK, hospital diabetes clinics ground abruptly to a ha... more Abstract When the COVID‐19 pandemic hit the UK, hospital diabetes clinics ground abruptly to a halt and many diabetologists were effectively conscripted on to front‐line emergency care. Their contribution was key to the ability of acute medical services to be rapidly redesigned and continuously adapted during the peak. This was a simple imperative as “lockdown” kicked in, usual out‐patient clinical activity ceased, and emergency admissions with the new virus surged.
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