Background:
A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data.
Methods:
We ...assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low–glucose and low-glucose hypoglycemia; very high–glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation.
Results:
The analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals.
Conclusion:
The GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.
Aims/hypothesis
The risk of complications and medical consequences of type 2 diabetes are well known. Hospital costs have been identified as a key driver of total costs in studies of the economic ...burden of type 2 diabetes. Less evidence has been generated on the impact of individual diabetic complications on the overall societal burden. The objective of this study was to analyse costs of hospital-based healthcare (inpatient and outpatient care) and work absence related to individual macrovascular and microvascular complications of type 2 diabetes in Sweden in 2016.
Methods
Data for 2016 were retrieved from a Swedish national retrospective observational database cross-linking individual-level data for 1997–2016. The database contained information from population-based health, social insurance and socioeconomic registers for 392,200 people with type 2 diabetes and matched control participants (5:1). Presence of type 2 diabetes and of diabetes complications were derived using all years, 1997–2016. Costs of hospital-based care and of absence from work due to diabetes complications were estimated for the year 2016. Regression analysis was used for comparison with control participants to attribute absence from work to individual complications, and to account for joint presence of complications.
Results
Use of hospital care for complications was higher in type 2 diabetes compared with control participants in 2016: 26% vs 12% had ≥1 hospital contact; there were 86,104 vs 24,608 outpatient visits per 100,000 people; and there were 9894 vs 2546 inpatient admissions per 100,000 people (all
p
< 0.001). The corresponding total costs of hospital-based care for complications were €919 vs €232 per person (
p
< 0.001), and 74.7% of costs were then directly attributed to diabetes (€687 per person). Regression analyses distributed the costs of days absent from work across diabetes complications per se, basic type 2 diabetes effect and unattributed causes. Diabetes complications amounted to €1317 per person in 2016, accounting for possible complex interactions (25% of total costs of days absent). Key drivers of costs were the macrovascular complications angina pectoris, heart failure and stroke; and the microvascular complications eye diseases, including retinopathy, kidney disease and neuropathy. Early mortality in working ages cost an additional €579 per person and medications used in risk-factor treatment amounted to €418 per person.
Conclusions/interpretation
The economic burden of complications in type 2 diabetes is substantial. Costs of absence from work in this study were found to be greater than of hospital-based care, highlighting the need for considering treatment consequences in a societal perspective in research and policy.
Graphical abstract
Summary Background For patients with type 2 diabetes who do not achieve target glycaemic control with conventional insulin treatment, advancing to a basal–bolus insulin regimen is often recommended. ...We aimed to compare the efficacy and safety of long-acting glucagon-like peptide-1 receptor agonist dulaglutide with that of insulin glargine, both combined with prandial insulin lispro, in patients with type 2 diabetes. Methods We did this 52 week, randomised, open-label, phase 3, non-inferiority trial at 105 study sites in 15 countries. Patients (aged ≥18 years) with type 2 diabetes inadequately controlled with conventional insulin treatment were randomly assigned (1:1:1), via a computer-generated randomisation sequence with an interactive voice-response system, to receive once-weekly dulaglutide 1·5 mg, dulaglutide 0·75 mg, or daily bedtime glargine. Randomisation was stratified by country and metformin use. Participants and study investigators were not masked to treatment allocation, but were unaware of dulaglutide dose assignment. The primary outcome was a change in glycated haemoglobin A1c (HbA1c ) from baseline to week 26, with a 0·4% non-inferiority margin. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT01191268. Findings Between Dec 9, 2010, and Sept 21, 2012, we randomly assigned 884 patients to receive dulaglutide 1·5 mg (n=295), dulaglutide 0·75 mg (n=293), or glargine (n=296). At 26 weeks, the adjusted mean change in HbA1c was greater in patients receiving dulaglutide 1·5 mg (−1·64% 95% CI −1·78 to −1·50, −17·93 mmol/mol −19·44 to −16·42) and dulaglutide 0·75 mg (−1·59% −1·73 to −1·45, −17·38 mmol/mol −18·89 to −15·87) than in those receiving glargine (−1·41% −1·55 to −1·27, −15·41 mmol/mol −16·92 to −13·90). The adjusted mean difference versus glargine was −0·22% (95% CI −0·38 to −0·07, −2·40 mmol/mol –4·15 to −0·77; p=0·005) for dulaglutide 1·5 mg and −0·17% (–0·33 to −0·02, −1·86 mmol/mol –3·61 to −0·22; p=0·015) for dulaglutide 0·75 mg. Five (<1%) patients died after randomisation because of septicaemia (n=1 in the dulaglutide 1·5 mg group); pneumonia (n=1 in the dulaglutide 0·75 mg group); cardiogenic shock; ventricular fibrillation; and an unknown cause (n=3 in the glargine group). We recorded serious adverse events in 27 (9%) patients in the dulaglutide 1·5 mg group, 44 (15%) patients in the dulaglutide 0·75 mg group, and 54 (18%) patients in the glargine group. The most frequent adverse events, arising more often with dulaglutide than glargine, were nausea, diarrhoea, and vomiting. Interpretation Dulaglutide in combination with lispro resulted in a significantly greater improvement in glycaemic control than did glargine and represents a new treatment option for patients unable to achieve glycaemic targets with conventional insulin treatment. Funding Eli Lilly and Company.
Insulin degludec (IDeg) is a basal insulin that forms soluble multihexamers after subcutaneous injection, resulting in an ultra-long action profile. We assessed the efficacy and safety of IDeg ...formulations administered once daily in combination with mealtime insulin aspart in people with type 1 diabetes.
In this 16-week, randomized, open-label trial, participants (mean: 45.8 years old, A1C 8.4%, fasting plasma glucose FPG 9.9 mmol/L, BMI 26.9 kg/m(2)) received subcutaneous injections of IDeg(A) (600 μmol/L; n = 59), IDeg(B) (900 μmol/L; n = 60), or insulin glargine (IGlar; n = 59), all given once daily in the evening. Insulin aspart was administered at mealtimes. RESULTS At 16 weeks, mean A1C was comparable for IDeg(A) (7.8 ± 0.8%), IDeg(B) (8.0 ± 1.0%), and IGlar (7.6 ± 0.8%), as was FPG (8.3 ± 4.0, 8.3 ± 2.8, and 8.9 ± 3.5 mmol/L, respectively). Estimated mean rates of confirmed hypoglycemia were 28% lower for IDeg(A) compared with IGlar (rate ratio RR: 0.72 95% CI 0.52-1.00) and 10% lower for IDeg(B) compared with IGlar (RR: 0.90 0.65-1.24); rates of nocturnal hypoglycemia were 58% lower for IDeg(A) (RR: 0.42 0.25-0.69) and 29% lower for IDeg(B) (RR: 0.71 0.44-1.16). Mean total daily insulin dose was similar to baseline. The frequency and pattern of adverse events was similar between insulin treatments.
In this clinical exploratory phase 2 trial in people with type 1 diabetes, IDeg is safe and well tolerated and provides comparable glycemic control to IGlar at similar doses, with reduced rates of hypoglycemia.
A long-term health economic analysis was performed in Sweden to establish the cost-effectiveness of the FreeStyle Libre® system versus SMBG in T2D insulin treated patients not reaching their glycemic ...goals. The analysis used the IQVIA Core Diabetes Model. Baseline patients' characteristics and HbA1c data were sourced from the recent real-world study using the Swedish National Diabetes Registry combined with hypoglycemia rates from the REPLACE trial. Simulations were performed in 2 different populations, those with HbA1c ≥8-9% (64-75 mmol/mol) and those with HbA1c ≥9-12% (75-108 mmol/mol), that went along with different treatment effects for FreeStyle Libre users (-0.41% and -1.30% HbA1c reduction respectively), assuming no treatment effect for those continuing on SMBG. The analysis was performed from the societal perspective over a lifetime time horizon. The Cost-Effectiveness results are presented below. For Sweden-based patients with T2D on insulin not reaching glycemic goals, the FreeStyle Libre system is associated with improvements in clinical outcomes and seems, with the assumptions taken, a cost-effective disease management option relative to SMBG, based on a willingness-to-pay threshold of SEK 300,000 (USD 34,113) per QALY gained. Sensitivity and scenario analyses confirmed the robustness of the analysis.
Prolonged physical exercise (PE) is a challenge in type 1 diabetes with an increased incidence of both hypoglycemia and hyperglycemia.
To evaluate the impact of two consecutive days of carbohydrate ...(CHO) loading, followed by high intermittent CHO-intake during prolonged PE, facilitated by a proactive use of Real-Time Continuous Glucose Monitoring (rtCGM), on glucose control in individuals with type 1 diabetes.
Ten physically active individuals with type 1 diabetes were invited to participate in a 3-day long sports camp with the objective to evaluate CHO-loading and high intermittent CHO-intake during prolonged PE. 1.5 months later the same procedure was evaluated in relation to a 90 km cross-country skiing race (Vasaloppet). Participants were instructed to act proactively using rtCGM with predictive alerts to maintain sensor glucose values within target range, defined as 72-180 mg/dl (4-10 mmol/l).
Mean glucose values during CHO-loading were: day 1; 140.4 ± 45.0 mg/dl (7.8 ± 2.5 mmol/l) and day 2; 120.6 ± 41.4 mg/dl (6.7 ± 2.3 mmol/l). Mean sensor glucose at start of PE was 126.0 ± 25.2 mg/dl (7.0 ± 1.4 mmol/l) and throughout PE 127.8 ± 25.2 mg/dl (7.1 ± 1.4 mmol/l). Percentage of time spent in range (TIR) respective time spent in hypoglycemia was: CHO-loading 74.7/10.4% and during PE 94.3/0.6%.
High intermittent CHO-intake during prolonged PE combined with proactive use of rtCGM is associated with good glycemic control during prolonged exercise in individuals with diabetes type 1. However, the time spent in hypoglycemia during the 2-days of CHO-loading was 10.4% and therefore a lower insulin dose might be suggested to reduce the time spent in hypoglycemia.
www.ClinicalTrials.gov, identifier NCT03722225.
Diving by persons with diabetes has long been conducted, with formal guidelines published in the early 1990s. Subsequent consensus guidelines produced following a 2005 workshop helped to advance the ...recognition of relevant issues and promote discussion. The guidelines were intended as an interim step in guidance, with the expectation that revisions should follow the gathering of additional data and experience. Recent and ongoing developments in pharmacology and technology can further aid in reducing the risk of hypoglycaemia, a critical acute concern of diving with diabetes. Careful and periodic evaluation remains crucial to ensure that participation in diving activity is appropriate. Close self-monitoring, thoughtful adjustments of medications and meals, and careful review of the individual response to diving can assist in optimising control and ensuring safety. Open communication with diving partners, support personnel, and medical monitors is important to ensure that all are prepared to effectively assist in case of need. Ongoing vigilance, best practice, including graduated clearance for diving exposures and adverse event reporting, are all required to ensure the safety of diving with diabetes and to promote community understanding and acceptance.
Introduction
Real-world evidence has demonstrated improved glycemic control and insulin management following introduction of smart insulin pens in a Swedish type 1 diabetes (T1D) population. To ...understand the implications for healthcare costs and expected health outcomes, this analysis evaluated the long-term cost-effectiveness of introducing smart insulin pens to standard-of-care T1D treatment (standard care) from a Swedish societal perspective.
Methods
Clinical outcomes and healthcare costs (in 2018 Swedish krona, SEK) were projected over patients’ lifetimes using the IQVIA CORE Diabetes Model to estimate cost-effectiveness. Clinical data and baseline characteristics for the simulated cohort were informed by population data and a prospective, noninterventional study of a smart insulin pen in a Swedish T1D population. This analysis captured direct and indirect costs, mortality, and the impact of diabetes-related complications on quality of life.
Results
Over patients’ lifetimes, smart insulin pen use was associated with per-patient improvements in mean discounted life expectancy (+ 0.90 years) and quality-adjusted life expectancy (+ 1.15 quality-adjusted life-years), in addition to mean cost savings (direct, SEK 124,270; indirect, SEK 373,725), versus standard care. A lower frequency and delayed onset of complications drove projected improvements in quality-adjusted life expectancy and lower costs with smart insulin pens versus standard care. Overall, smart insulin pens were a dominant treatment option relative to standard care across all base-case and sensitivity analyses.
Conclusions
Use of smart insulin pens was projected to improve clinical outcomes at lower costs relative to standard care in a Swedish T1D population and represents a good use of healthcare resources in Sweden.
Introduction
Screening for diabetic retinopathy (DR) prevents blindness through the early detection of sight-threatening retinal microvascular lesions that respond to timely local treatment. However, ...the provision of easy and regular access to DR screening programs is currently being challenged by the increasing prevalence of diabetes. One proposed solution is to extend the screening interval for patients at low risk for progression of retinopathy. To date, most providers of screening programs have hesitated to implement a strategy of extended intervals due to the lack of data on whether adherence and safety are compromised when retinal examinations occur less frequently. In the study reported here, we investigated adherence to the screening program and progression of retinopathy in patients with type 2 diabetes participating in a DR screening program with extended intervals.
Methods
This was a retrospective study that included 1000 patients with type 2 diabetes mellitus who attended a screening program for DR. The patients were consecutively placed into a low-risk patient cohort with no retinopathy or into an intermediate-risk patient cohort with mild retinopathy (each cohort
n
= 500). Screening intervals were 36 months for the low-risk cohort and 18 months for the intermediate-risk cohort.
Results
The 1000 subjects enrolled in the study had a median age of 68 (interquartile range 12) years and 60.4% were men. At the follow-up screening visit, data on 102 subjects were not included in the analysis of adherence rate due to death, severe systemic illness, other concurrent eye disease or migration. Among the 898 remaining subjects, adherence to the screening program was 93.7% (413/443) in the 36-month group and 98.3% (449/455) in the 18-month group (
p
< 0.0001). Non-adherence decreased with increasing age (odds ratio 0.92, 95% confidence interval 0.888–0.954,
p
= 0.0005). At follow-up, 65 subjects showed progression of retinopathy; none had worse than moderate retinopathy. Risk factors for DR and treatment for hyperglycemia, hypertension and hyperlipidemia were compared among subjects in the low-risk cohort: non-adherent subjects did not differ from their adherent counterparts without progression of DR, but the former had a shorter duration of diabetes and higher diastolic blood pressure than adherent subjects with progression of DR (4.5 vs. 7.5 years,
p
= 0.007; and 80 vs. 75 mmHg,
p
= 0.02, respectively).
Conclusion
The results suggest that screening DR at extended intervals can be achieved with high adherence rates without compromising patient safety. However, younger subjects and those at higher risk of progression may require extra attention.
PDF
