To define the threshold for excess glucose variability (GV), one of the main features of dysglycemia in diabetes.
A total of 376 persons with diabetes investigated at the University Hospital of ...Montpellier (Montpellier, France) underwent continuous glucose monitoring. Participants with type 2 diabetes were divided into several groups-groups 1, 2a, 2b, and 3 (
= 82, 28, 65, and 79, respectively)-according to treatment:
) diet and/or insulin sensitizers alone;
) oral therapy including an insulinotropic agent, dipeptidyl peptidase 4 inhibitors (group 2a) or sulfonylureas (group 2b); or
) insulin. Group 4 included 122 persons with type 1 diabetes. Percentage coefficient of variation for glucose (%CV = (SD of glucose)/(mean glucose) × 100) and frequencies of hypoglycemia (interstitial glucose <56 mg/dL 3.1 mmol/L) were computed.
Percentages of CV (median interquartile range; %) increased significantly (
< 0.0001) from group 1 (18.1 15.2-23.9) to group 4 (37.2 31.0-42.3). In group 1, the upper limit of %CV, which served as reference for defining excess GV, was 36%. Percentages of patients with %CVs above this threshold in groups 2a, 2b, 3, and 4 were 0, 12.3, 19.0, and 55.7%, respectively. Hypoglycemia was more frequent in group 2b (
< 0.01) and groups 3 and 4 (
< 0.0001) when subjects with a %CV >36% were compared with those with %CV ≤36%.
A %CV of 36% appears to be a suitable threshold to distinguish between stable and unstable glycemia in diabetes because beyond this limit, the frequency of hypoglycemia is significantly increased, especially in insulin-treated subjects.
The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) convened a writing group to develop a consensus statement on the management of type 1 diabetes in ...adults. The writing group has considered the rapid development of new treatments and technologies and addressed the following topics: diagnosis, aims of management, schedule of care, diabetes self-management education and support, glucose monitoring, insulin therapy, hypoglycaemia, behavioural considerations, psychosocial care, diabetic ketoacidosis, pancreas and islet transplantation, adjunctive therapies, special populations, inpatient management and future perspectives. Although we discuss the schedule for follow-up examinations and testing, we have not included the evaluation and treatment of the chronic microvascular and macrovascular complications of diabetes as these are well-reviewed and discussed elsewhere. The writing group was aware of both national and international guidance on type 1 diabetes and did not seek to replicate this but rather aimed to highlight the major areas that healthcare professionals should consider when managing adults with type 1 diabetes. Though evidence-based where possible, the recommendations in the report represent the consensus opinion of the authors.
Graphical abstract
Measurement of glycated hemoglobin (HbA
) has been the traditional method for assessing glycemic control. However, it does not reflect intra- and interday glycemic excursions that may lead to acute ...events (such as hypoglycemia) or postprandial hyperglycemia, which have been linked to both microvascular and macrovascular complications. Continuous glucose monitoring (CGM), either from real-time use (rtCGM) or intermittently viewed (iCGM), addresses many of the limitations inherent in HbA
testing and self-monitoring of blood glucose. Although both provide the means to move beyond the HbA
measurement as the sole marker of glycemic control, standardized metrics for analyzing CGM data are lacking. Moreover, clear criteria for matching people with diabetes to the most appropriate glucose monitoring methodologies, as well as standardized advice about how best to use the new information they provide, have yet to be established. In February 2017, the Advanced Technologies & Treatments for Diabetes (ATTD) Congress convened an international panel of physicians, researchers, and individuals with diabetes who are expert in CGM technologies to address these issues. This article summarizes the ATTD consensus recommendations and represents the current understanding of how CGM results can affect outcomes.
Cell-free transcription-translation systems have great potential for biosensing, yet the range of detectable chemicals is limited. Here we provide a workflow to expand the range of molecules ...detectable by cell-free biosensors through combining synthetic metabolic cascades with transcription factor-based networks. These hybrid cell-free biosensors have a fast response time, strong signal response, and a high dynamic range. In addition, they are capable of functioning in a variety of complex media, including commercial beverages and human urine, in which they can be used to detect clinically relevant concentrations of small molecules. This work provides a foundation to engineer modular cell-free biosensors tailored for many applications.
More than 500 million adults suffer from diabetes worldwide, and this number is constantly increasing. Diabetes causes 5 million deaths per year and huge healthcare costs per year. β-cell death is ...the major cause of type 1 diabetes. β-cell secretory dysfunction plays a key role in the development of type 2 diabetes. A loss of β-cell mass due to apoptotic death has also been proposed as critical for the pathogenesis of type 2 diabetes. Death of β-cells is caused by multiple factors including pro-inflammatory cytokines, chronic hyperglycemia (glucotoxicity), certain fatty acids at high concentrations (lipotoxicity), reactive oxygen species, endoplasmic reticulum stress, and islet amyloid deposits. Unfortunately, none of the currently available antidiabetic drugs favor the maintenance of endogenous β-cell functional mass, indicating an unmet medical need. Here, we comprehensively review over the last ten years the investigation and identification of molecules of pharmacological interest for protecting β-cells against dysfunction and apoptotic death which could pave the way for the development of innovative therapies for diabetes.
Summary Background Intensive basal-bolus insulin therapy has been shown to improve glycaemic control and reduce the risk of long-term complications that are associated with type 1 diabetes mellitus. ...Insulin degludec is a new, ultra-longacting basal insulin. We therefore compared the efficacy and safety of insulin degludec and insulin glargine, both administered once daily with mealtime insulin aspart, in basal-bolus therapy for type 1 diabetes. Methods In an open-label, treat-to-target, non-inferiority trial, undertaken at 79 sites (hospitals and centres) in six countries, adults (aged ≥18 years) with type 1 diabetes (glycated haemoglobin HbA1c ≤10% 86 mmol/mol), who had been treated with basal-bolus insulin for at least 1 year, were randomly assigned in a 3:1 ratio, with a computer-generated blocked allocation sequence, to insulin degludec or insulin glargine without stratification by use of a central interactive response system. The primary outcome was non-inferiority of degludec to glargine, assessed as a reduction in HbA1c after 52 weeks, with the intention-to-treat analysis. This trial is registered with ClinicalTrials.gov , number NCT00982228. Findings Of 629 participants, 472 were randomly assigned to insulin degludec and 157 to insulin glargine; all were analysed in their respective treatment groups. At 1 year, HbA1c had fallen by 0·40% points (SE 0·03) and 0·39% points (0·07), respectively, with insulin degludec and insulin glargine (estimated treatment difference −0·01% points 95% CI −0·14 to 0·11; p<0·0001 for non-inferiority testing) and 188 (40%) and 67 (43%) participants achieved a target HbA1c of less than 7% (<53 mmol/mol). Rates of overall confirmed hypoglycaemia (plasma glucose <3·1 mmol/L or severe) were similar in the insulin degludec and insulin glargine groups (42·54 vs 40·18 episodes per patient-year of exposure; estimated rate ratio degludec to glargine 1·07 0·89 to 1·28; p=0·48). The rate of nocturnal confirmed hypoglycaemia was 25% lower with degludec than with glargine (4·41 vs 5·86 episodes per patient-year of exposure; 0·75 0·59 to 0·96; p=0·021). Overall serious adverse event rates (14 vs 16 events per 100 patient-years of exposure) were similar for the insulin degludec and insulin glargine groups. Interpretation Insulin degludec might be a useful basal insulin for patients with type 1 diabetes because it provides effective glycaemic control while lowering the risk of nocturnal hypoglycaemia, which is a major limitation of insulin therapy. Funding Novo Nordisk.
Aims
To describe glycaemic control and diabetes management in adults with type 1 diabetes (T1DM), in a real‐life global setting.
Materials and Methods
Study of Adults' GlycEmia (SAGE) was a ...multinational, multicentre, single visit, noninterventional, cross‐sectional study in adult patients with T1DM. Data were collected at a single visit, analysed according to predefined age groups (26–44, 45–64 and ≥65 years) and reported across different regions. The primary endpoint was the proportion of participants achieving HbA1c less than 7.0 % in each age group. Secondary endpoints included incidence of hypoglycaemia, severe hypoglycaemia and severe hyperglycaemia leading to diabetic ketoacidosis (DKA) and therapeutic management of T1DM.
Results
Of 3903 included participants, 3858 (98.8%) were eligible for the study. Overall, 24.3% (95% confidence interval CI: 22.9–25.6) of participants achieved the glycaemic target of HbA1c less than 7.0 %, with more participants achieving this target in the 26–44 years group (27.6% 95% CI: 25.5–29.8). Target achievement was highest in Eastern and Western Europe, and lowest in the Middle East. The incidence of hypoglycaemia and of severe hyperglycaemia leading to DKA tended to decrease with age, and varied across regions. Age and regional differences were observed in therapeutic management, including types of device/insulin usage, frequency of insulin dose adjustment and technology usage.
Conclusions
Glycaemic control remains poor in adults with T1DM globally. Several areas of treatment may be optimised to improve outcomes, including supporting patient self‐management of insulin therapy, increasing use of technologies such as CGM, and greater provision of healthcare support.
Automated insulin delivery (AID) systems, so-called closed-loop systems or artificial pancreas, are based upon the concept of insulin supply driven by blood glucose levels and their variations ...according to body glucose needs, glucose intakes and insulin action. They include a continuous glucose monitoring device which provides a signal to a control algorithm tuning insulin delivery from an infusion pump. The control algorithm is the key of the system since it commands insulin administration in order to maintain blood glucose in a predefined target range and close to a near-normal glucose level. The last two decades have shown dramatic advances toward the use in free life of AID systems for routine care of type 1 diabetes through step-by-step demonstrations of feasibility, safety and efficacy in successive hospital, transitional and outpatient trials. Because of the constraints of pharmacokinetics and dynamics of subcutaneous insulin delivery, the currently available AID systems are all ‘hybrid’ or ‘semi-automated’ insulin delivery systems with a need of meal and exercise announcements in order to anticipate rapid glucose variations through pre-meal bolus or pre-exercise reduction of infusion rate. Nevertheless, these AID systems significantly improve time spent in a near-normal range with a reduction of the risk of hypoglycemia and the mental load of managing diabetes in everyday life, representing a milestone in insulin therapy. Expected progression toward fully automated, further miniaturized and integrated, possibly implantable on long-term and more physiological closed-loop systems paves the way for a
functional cure
of type 1 diabetes.
The promise for real precision medicine is contingent on innovative technological solutions to diagnosis and therapy. In the post‐genomic era, rational and systematic approaches to biological design ...could provide new ways to dynamically probe, monitor, and interface human pathophysiology. Emerging as a mature field increasingly transitioning to the clinics, synthetic biology integrates engineering principles to build sensors, control circuits, and actuators within the biological substrate according to clinical specifications. A particularly tantalizing goal is to develop novel versatile, programmable and autonomous diagnostic devices intertwined with therapy and personalized for the patient to get closest, finest, and most comprehensive diagnostic information and medical procedures. Here, we discuss how synthetic biology could be preparing the future of medicine, supporting and speeding up the development of diagnostics with novel capabilities to bring direct improvement from the clinical laboratory to the patient, while addressing healthcare evolution and global health concerns.
Courbet, Renard and Molina comment on the prospects of precision medicine and how synthetic biology could be preparing the future of medicine by providing innovative technological solutions to diagnosis and therapy.
Insulin pump therapy (continuous subcutaneous insulin infusion CSII) is now an established form of intensive insulin treatment. It is pertinent to ask, however, if multiple daily injection (MDI) ...regimens based on new long-acting insulin analogs such as glargine and detemir have now replaced the need for CSII. In type 1 diabetes, CSII reduces the frequency of severe hypoglycemia compared with isophane-based MDIs, but the rate of severe hypoglycemia is usually similar on glargine- or detemir-based MDIs compared with isophane-based MDIs. CSII reduces A1C and glycemic variability compared with isophane-based MDIs; but glargine and detemir do not improve A1C or variability in many patients, particularly those who are prone to hypoglycemia. Head-to-head comparisons of CSII with MDI based on glargine indicate lower A1C, fructosamine, or glucose levels on CSII. It can be concluded that long-acting insulin analogs have not yet replaced the need for insulin pump therapy in type 1 diabetes, and CSII is the best current therapeutic option for some type 1 diabetic subjects. In type 2 diabetes, CSII and MDI produce similar glycemic control, although there is little study of MDI based on long-acting analogs compared with pumps. It is possible that CSII will be beneficial in selected patient groups with type 2 diabetes, but this requires further study.
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