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Aim To evaluate whether both bolus insulin injection frequency and smart pen engagement were associated with changes in glycaemic control, using real-world data from adults with type 1 diabetes (T1D). Materials and Methods Adults using a smart pen (NovoPen 6) to administer bolus insulin (fast-acting insulin aspart or insulin aspart) alongside continuous glucose monitoring were eligible for inclusion. Smart pen engagement was characterized by number of days with pen data uploads over the previous 14 days. Glycaemic control was evaluated by analysing glucose metrics. Results Overall, data from 1194 individuals were analysed. The number of daily bolus injections was significantly associated with time in range (TIR; 3.9-10.0 mmol/L [70-180 mg/dL]; P < 0.0001). Individuals administering, on average, three daily bolus insulin injections had an estimated 11% chance of achieving >70% TIR. The probability of achieving >70% TIR increased with the mean number of daily bolus injections. However, the percentage of TIR was lower on days when individuals administered higher-than-average numbers of injections. The observed mean number of daily bolus injections administered across the study population was lower than the optimal number required to reach glycaemic targets (4.8 injections vs. 6-8 injections). Smart pen engagement was significantly associated with improved TIR. Conclusions Glycaemic control was associated with daily bolus insulin injection frequency and smart pen engagement. A treatment regimen combining an optimal bolus injection strategy, and effective smart pen engagement, may improve glycaemic control among adults with T1D.

AIMS: The study aims were to determine autoantibodies associated with type 1 diabetes (T1D), celiac disease (CD) and autoimmune thyroid disease (AITD) in individuals living with type 2 diabetes (T2D) compared to T1D and matched controls. METHODS: Individuals with T1D and T2D were randomly identified in health-care registers. Blood was collected through home-capillary sampling and autoantibodies associated with either T1D against glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A), CD against tissue transglutaminase (tTGA) or AITD against thyroid peroxidase (TPOA) were determined in an automated, multiplex Antibody Detection by Agglutination-PCR (ADAP) assay. RESULTS: GADA were detected in 46 % (88/191) of T1D and increased to 6.2 % (23/372) in T2D compared to 2.6 % (7/259) of controls (p = 0.0367). tTGA was low (1.1-2.6 %) and not different in between the study cohorts, nonetheless, in T1D tTGA was associated to islet autoantibodies. TPOA was more frequent in T1D, 27.1 % (53/191), compared to either T2D, 14.8 % (55/372; p = 0.0002) or controls, 14.3 % (37/259) (p = 0.0004). Overall, TPOA was more frequent in GADA positive (34.8 %; 8/23) than negative (13.5 %; 47/349; p = 0.0053) T2D individuals. CONCLUSION: It's suggested that analyzing GADA and TPOA may refine the autoimmune landscape in individuals clinically classified as T2D.

Aims: The objective was to compare anxiety, depression, and quality of life (QoL) in individuals living with type 1 (T1D) and type 2 (T2D) diabetes with matched controls during the second wave of the COVID-19 pandemic. Methods: Via randomization, individuals living with diabetes T1D (n = 203) and T2D (n = 413), were identified during February-July 2021 through health-care registers. Population controls (n = 282) were matched for age, gender, and residential area. Questionnaires included self-assessment of anxiety, depression, QoL, and demographics in relation to SARS-CoV-2 exposure. Blood was collected through home-capillary sampling, and SARS-CoV-2 Nucleocapsid (NCP) and Spike antibodies (SC2_S1) were determined by multiplex Antibody Detection by Agglutination-PCR (ADAP) assays. Results: Younger age and health issues were related to anxiety, depression, and QoL, with no differences between the study groups. Female gender was associated with anxiety, while obesity was associated with lower QoL. The SARS-CoV-2 NCP seroprevalence was higher in T1D (8.9 %) compared to T2D (3.9 %) and controls (4.0 %), while the SARS-CoV-2 SC2_S1 seroprevalence was higher for controls (25.5 %) compared to T1D (16.8 %) and T2D (14.0 %). Conclusions: A higher SARS-CoV-2 infection rate in T1D may be explained by younger age and higher employment rate, and the associated increased risk for viral exposure., This work was supported by NIH SBIR 2R44DK110005-02, Strategic Research Area Exodiab Dnr 2009-1039, and the Swedish Foundation for Strategic Research Dnr IRC15-0067.

BACKGROUND: The accuracy of continuous glucose monitoring (CGM) systems is crucial for the management of glucose levels in individuals with diabetes mellitus. However, the discussion of CGM accuracy is challenged by an abundance of parameters and assessment methods. The aim of this article is to introduce the Continuous Glucose Deviation Interval and Variability Analysis (CG-DIVA), a new approach for a comprehensive characterization of CGM point accuracy which is based on the U.S. Food and Drug Administration requirements for "integrated" CGM systems. METHODS: The statistical concept of tolerance intervals and data from two approved CGM systems was used to illustrate the CG-DIVA. RESULTS: The CG-DIVA characterizes the expected range of deviations of the CGM system from a comparison method in different glucose concentration ranges and the variability of accuracy within and between sensors. The results of the CG-DIVA are visualized in an intuitive and straightforward graphical presentation. Compared with conventional accuracy characterizations, the CG-DIVA infers the expected accuracy of a CGM system and highlights important differences between CGM systems. Furthermore, it provides information on the incidence of large errors which are of particular clinical relevance. A software implementation of the CG-DIVA is freely available (https://github.com/IfDTUlm/CGM_Performance_Assessment). CONCLUSIONS: We argue that the CG-DIVA can simplify the discussion and comparison of CGM accuracy and could replace the high number of conventional approaches. Future adaptations of the approach could thus become a putative standard for the accuracy characterization of CGM systems and serve as the basis for the definition of future CGM performance requirements., This study was supported by Diabetes Center Berne, Switzerland.

BACKGROUND: The use of insulin pumps (continuous subcutaneous insulin infusion [CSII]) in individuals living with type 1 diabetes (T1D) improves disease control. However, adverse skin reactions may hamper compliance. We aimed to assess the relationship of insulin pumps, particularly that of infusion set therapy, used in children and adults with T1D and dermatitis including allergic contact dermatitis (ACD). METHODS: A systematic search of PubMed, and EMBASE, of full-text studies reporting dermatitis in persons with diabetes using a CSII was conducted from 2020 to 2023. The Newcastle-Ottawa Scale was used to assess study quality. The inventory performed at the Department of Occupational and Environmental Dermatology, Malmö, Sweden (YMDA) was also performed highlighting the diagnostic process. RESULTS: Among the 391 screened abstracts, 21 studies fulfilled the inclusion criteria. Seven studies included data on children only, four studies were on adults, and nine studies reported data on both children and adults. Participants were exposed to a broad range of pumps. Dermatitis was rarely specified. Up to 60% of those referred to a university hospital due to skin reactions possibly related to insulin pumps had an ACD. CONCLUSIONS: The review and our findings indicate that there is not sufficient focus on contact allergy in the primary toxicological evaluations of substances used also for insulin pump therapy products and that possible adverse skin reactions are not correctly followed up in the clinical setting.

BACKGROUND: There are few studies providing a more comprehensive picture of advanced hybrid closed-loop (AHCL) systems in clinical practice. The aim was to evaluate the effects of the AHCL systems, Tandem® t: slim X2™ with Control IQ™, and MiniMed™ 780G, on glucose control, safety, treatment satisfaction, and practical barriers for individuals with type 1 diabetes. METHOD: One hundred forty-two randomly selected adults with type 1 diabetes at six diabetes outpatient clinics in Sweden at any time treated with either the Tandem Control IQ (TCIQ) or the MiniMed 780G system were included. Glycated hemoglobin A1c (HbA1c) and glucose metrics were evaluated. Treatment satisfaction and practical barriers were examined via questionnaires. RESULTS: Mean age was 42 years, median follow-up was 1.7 years, 58 (40.8%) were females, 65% used the TCIQ system. Glycated hemoglobin A1c was reduced by 0.6% (6.8 mmol/mol; 95% confidence interval [CI] = 0.5-0.8% [5.3-8.2 mmol/mol]; P < .001), from 7.3% to 6.7% (57-50 mmol/mol). Time in range (TIR) increased with 14.5% from 57.0% to 71.5% (95% CI = 12.2%-16.9%; P < .001). Time below range (TBR) (<70 mg/dL, <3.9 mmol/L) decreased from 3.8% to 1.6% (P < .001). The standard deviation of glucose values was reduced from 61 to 51 mg/dL (3.4-2.9 mmol/L, P < .001) and the coefficient of variation from 35% to 33% (P < .001). Treatment satisfaction increased, score 14.8 on the Diabetes Treatment Satisfaction Questionnaire (DTSQ) (change version ranging from -18 to 18, P < .001). Four severe hypoglycemia events were detected and no cases of ketoacidosis. Skin problems were experienced by 32.4% of the study population. CONCLUSIONS: Advanced hybrid closed-loop systems improve glucose control with a reasonable safety profile and high treatment satisfaction. Skin problems are common adverse events., This study was financed by grants from the Swedish state under the agreement between the Swedish government and the country councils, the ALF agreement, and the Region of Västra Götaland.

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 clini

Background: Advanced hybrid closed-loop (AHCL) automated insulin delivery systems are the most effective therapy in terms of assisting people with type 1 diabetes (T1D) to achieve glycemic targets; however, the cost can represent a barrier to uptake. Here, a cost-utility analysis of the MiniMedTM 780G AHCL system (MM780G) versus intermittently-scanned continuous glucose monitoring (is-CGM) plus multiple daily insulin injections (MDI) in people with T1D not achieving glycemic goals was performed across six European countries. Methods: Clinical input data were sourced from the ADAPT trial. Assuming a baseline HbA1c of 9.04%, HbA1c reductions of 1.54% for AHCL and 0.2% for is-CGM+MDI were assumed. The analyses were performed from a payer perspective over a time horizon of 40 years and an annual discount rate of 3% was applied. Results: Across all countries, the use of AHCL was projected to result in an incremental gain in quality-adjusted life expectancy of >2 quality-adjusted life years (QALYs) versus is-CGM+MDI. Lifetime direct costs were higher with AHCL resulting in incremental cost-utility ratios for AHCL versus is-CGM+MDI ranging from EUR 11,765 per QALY gained in Austria to EUR 43,963 per QALY gained in Italy. Conclusions: For people with T1D managed with is-CGM+MDI not achieving glycemic targets, initiation of the MM780G system was projected to improve long-term clinical outcomes; however, due to differences in healthcare costs between countries, the health economic outcomes differ. In the countries included here, AHCL is likely to be cost-effective relative to is-CGM+MDI for people not achieving glycemic goals with is-CGM+MDI. The ADAPT trial is registered with ClinicalTrials.gov, NCT04235504.

BACKGROUND: Diabetes is a chronic disease with several long-term complications. Several glucose-lowering drugs are used to treat type 2 diabetes mellitus (T2DM), e.g., glimepiride and liraglutide, in which both having different modes of action. Circulating microRNAs (miRNAs) are suggested as potential biomarkers that are associated with the disease development and the effects of the treatment. In the current study we evaluated the effect of glimepiride, liraglutide on the expression of the circulating miRNAs. METHODS: The present study is a post hoc trial from a previously randomized control trial comparing liraglutide versus glimepiride both in combination with metformin in subjects with T2DM, and subclinical heart failure. miRNAs were determined in the subjects' serum samples with next generation sequencing. Expression patterns of the circulating miRNAs were analyzed using bioinformatic univariate and multivariate analyses (clinical trial registration: NCT01425580). RESULTS: Univariate analyses show that treatment with glimepiride altered expression of three miRNAs in patient serum, miR-206, miR-182-5p, and miR-766-3p. Both miR-182-5p and miR-766-3p were also picked up among the top contributing miRNAs with penalized regularised logistic regressions (Lasso). The highest-ranked miRNAs with respect to Lasso coefficients were miR-3960, miR-31-5p, miR-3613-3p, and miR-378a-3p. Liraglutide treatment did not significantly influence levels of circulating miRNAs. CONCLUSION: Present study indicates that glucose-lowering drugs differently affect the expression of circulating miRNAs in serum in individuals with T2DM. More studies are required to investigate possible mechanisms by which glimepiride is affecting the expression of circulating miRNAs.

The use of continuous subcutaneous insulin infusion delivery via insulin pumps is today considered standard of care for type 1 diabetes (T1D). Closed-loop systems combining continuous glucose monitoring (CGM) with automated algorithm-driven insulin delivery have been shown to be safe and efficacious in randomized controlled studies and in real-life studies in both pediatric and adult individuals with T1D. Implementation of hybrid closed-loop (HCL) systems have shown incremental effectiveness with further reduction of hypoglycemia and hyperglycemia. Although less extensively studied in type 2 diabetes (T2D), insulin pumps have demonstrated their effectiveness on glucose control together with the reduction in insulin needs and a neutral effect on weight. Recent studies have also shown promising results with the use of HCL in T2D. Cost-effectiveness studies both in T1D and T2D have shown that pump is cost effective in several countries, leading to improvements in quality adjusted life years. Insulin pumps are currently reimbursed for T1D in many European countries, but only in a few for individuals with T2D. HCL systems are to be evaluated in future trials performed in T2D to compare their incremental efficacy and cost effectiveness in comparison with available intensification tools which include multiple daily insulin injections, metformin, SGLT-2 inhibitors and GLP-1 receptor agonists. There is a need for updated guidelines for the use of CSII and HCL in individuals living with T2D based on the emerging evidence, identifying, and recommending for the people who'd benefit the most, which would eventually form a basis for the reimbursement and health policies.

AIM: To perform a model-based analysis of the short- and long-term health benefits and costs of further increased implementation of empagliflozin for people with type 2 diabetes and established cardiovascular disease (eCVD) in Sweden. MATERIALS AND METHODS: The validated Institute for Health Economics Diabetes Cohort Model (IHE-DCM) was used to estimate health benefits and 3-years' budget impact, and lifetime costs per quality-adjusted life year (QALY) gained of increased implementation of adding empagliflozin to standard of care (SoC) for people with type 2 diabetes and eCVD in a Swedish setting. Scenarios with 100%/75%/50% implementation were explored. Analyses were based on 30 model cohorts with type 2 diabetes and eCVD (n=131,412 at baseline) from national health data registers. Sensitivity analyses explored the robustness of results. RESULTS: Over 3 years, SoC with empagliflozin (100% implementation) vs. SoC before empagliflozin resulted in 7,700 total life years gained and reductions in cumulative incidence of cardiovascular deaths by 30% and heart failures by 28%. Annual costs increased by 6% from higher treatment costs and increased survival. Half of these benefits and costs are not yet reached with current implementation below 50%. SoC with empagliflozin yielded 0.37 QALYs per person, with an incremental cost-effectiveness ratio of €16,000 EUR per QALY vs. SoC before empagliflozin. CONCLUSIONS: Model simulations using real-world data and trial treatment effects indicated that a broader implementation of empagliflozin, in line with current guidelines for treatment of people with type 2 diabetes and eCVD, would lead to further benefits even in a short-term perspective., Funding agency:Boehringer Ingelheim

AIMS: To assess hospital-based care, work absence, associated costs, and mortality in type 2 diabetes with and without established cardiovascular disease (eCVD) compared to matched controls. METHODS: In a population-based cohort study, we analysed individual-level data from national health, social insurance, and socio-economic registers for people with type 2 diabetes diagnosis<70 years and controls (5:1) in Sweden. Regression analysis attributed costs and days absent to eCVD. Mortality was analysed using Cox proportional hazard regression stratified for birthyear and adjusted for sex and education. RESULTS: Thirty percent (n=136 135 of 454 983) of people with type 2 diabetes had ≥1 person-year with eCVD (women 24%; men 34%). The mean annual costs of hospital-based care for diabetes complications were EUR 2 629 (95% confidence interval [CI] 2 601 to 2 657) of which EUR 2 337 (95% CI 2 309 to 2 365) were attributed to eCVD (89%). The highest-costing person-years (10th percentile) were observed in a broad subgroup, 42% of people with type 2 diabetes and eCVD. People with type 2 diabetes had on average 146 days absent (95% CI 145-147) per year of which 68 days (47%; 95% CI 67-70) were attributed to eCVD. Mortality was increased in type 2 diabetes: eCVD hazard rate [HR] 4.63 (95% CI 4.58-4.68), no eCVD HR 1.86 (95% CI 1.84-1.88). CONCLUSIONS: The sizable burden of eCVD, on the individual with type 2 diabetes and the society, calls for efficient management for reducing the risks for those living with eCVD and postponing its onset. This article is protected by copyright. All rights reserved., Funding agency:Boehringer Ingelheim

In an article in the Journal of Diabetes Science and Technology, Arunachalum et al retrospectively analyzed glycemic outcomes, regarding the use of hybrid closed-loop (HCL) systems in individuals with type-1 diabetes (T1D) in the United States in a real-world evidence (RWE) setting. In clinical trials, diabetes technology has shown to improve time in range (TIR) as well as other glucose metrics. In the light of increasing the use of diabetes technology in the T1D population, why do we not see improvement in clinical outcomes? Is it cost-effective to increase the use diabetes technology? Does access to diabetes technology vary in the United States? There is a need for additional clinical studies evaluating the effectiveness of diabetes technology in T1D including health economic aspects.