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Introduction: Automated insulin delivery (AID) systems have improved glycemic control in individuals with type 1 diabetes (T1D) but overweight and increased cardiovascular risk remain a challenge. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with improved cardiometabolic profile but are currently not approved for the treatment of T1D., Material and Methods: Individuals with T1D at Steno Diabetes Center Copenhagen, Denmark, treated with AID and off-label GLP-1 RA for at least six months between January 2017 and May 2024 were included in a retrospective chart review study., Results: Nineteen individuals with (median [range]) age 42 (24-60) years were included. At GLP-1 RA initiation, hemoglobin A1c (HbA1c) was 7.3% (6.1%-8.7%), HbA1c 56 (43-72) mmol/mol, body weight 91.5 (78.0-115.0) kg, and body mass index 35.4 (27.0-42.0) kg/m 2 . Time in range was 74% (29%-82%), time above range 25% (18%-71%) while time below range was 1% (0%-5%). After six months of treatment, body weight changed -11% (-22% to -3%; P = .001) and total daily insulin dose changed -15.1 (-32.5 to -8.2) IU ( P = .004). There were no significant changes in HbA1c or other glucose measures. One person developed ketoacidosis caused by infusion set failure, but none reported severe hypoglycemia., Conclusion: Glucagon-like peptide-1 receptor agonist as add-on therapy for six months in individuals with obesity and AID-treated T1D led to considerable weight loss and a reduction in insulin dose., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: PH and MBC have no conflicts of interest. KN received funding to her institution for participating in advisory boards from Medtronic, Novo Nordisk, and Convatec and for lecturing from Sanofi, Novo Nordisk, Medtronic, and Dexcom. Her institution received funding for studies she performed from Zealand Pharma, RSP Systems, Novo Nordisk, Medtronic, and Dexcom. SS has received speaker’s fee from Novo Nordisk and Nordic Infucare and had been employed with Novo Nordisk.

Introduction: Two phase 3 randomized controlled studies (ADJUNCT ONE (Clinicaltrials.gov: NCT01836523), ADJUNCT TWO (Clinicaltrials.gov: NCT02098395)) evaluated liraglutide (1.8, 1.2 or 0.6 mg) vs placebo in participants with type 1 diabetes (T1D) as an adjunct to insulin therapy. This paper aims to improve our understanding of the potential mechanisms leading to premature discontinuation of this treatment regimen., Methods: Post hoc comparisons were conducted on baseline characteristics and adverse event (AE) rates of participants completing and not completing the ADJUNCT studies due to AEs/lack of tolerance using summary tables and variance analysis., Results: Non-completers (liraglutide and placebo combined) had lower baseline body mass index (BMI) (ADJUNCT ONE: 27.8 kg/m 2 vs 29.8 kg/m 2 , P < .0001; ADJUNCT TWO: 26.3 kg/m 2 vs 29.2 kg/m 2 , P < .0001), longer duration of T1D (25.8 years vs 21.0 years, P < .0001; 24.1 years vs 21.0 years, P = .04), lower daily insulin doses by continuous infusion (46.4 U vs 57.3 U, P = .01; 40.9 U vs 57.4 U, P = .12) or multiple injections (58.4 U vs 68.5 U, P = .006; 56.0 U vs 65.8 U, P =.03) and a higher proportion of participants with undetectable C-peptide (91.5% vs 81.3%; 87.0% vs 84.9%) compared to completers. When analyzed by treatment group, only duration of T1D and C-peptide differed between completers and non-completers among liraglutide (and not placebo) participants. The AE rates were higher for non-completers., Conclusion: Individuals with longer-standing T1D and low levels of C-peptide at baseline were more likely to discontinue adjunctive liraglutide treatment due to AEs/lack of tolerance than individuals with residual insulin production. Lower BMI predicted a greater likelihood of non-completion for the included participants, regardless of treatment. These new findings may be relevant for clinical practice., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors disclose the following competing interests: Rikke M. Agesen, Lars Bardtrum, and Erik Christiansen are all employees and shareholders of Novo Nordisk A/S. Jennifer Snaith and Jerry R. Greenfield have received semaglutide and matched placebo from Novo Nordisk A/S for an investigator-initiated study in T1D. Jennifer Snaith is supported by JDRF Australia (Grant# 3-SRA-2023-1296-M-N), the recipient of the Commonwealth of Australia grant for Accelerated Research under the Medical Research Future Fund. Jerry R. Greenfield has received honorarium from the following companies for delivering talks to health professionals over the last 10 years: Novartis, Novo Nordisk A/S, Amgen, Allergan, Boehringer Inglheim, Lilly and Abbott. Viral N. Shah’s institution has received research funding from Alexion, Enable Bioscience, JDRF (Breakthrough T1D), and NIH (NIDDK). Viral N. Shah’s institution has received drug support for an investigator-initiated trial of semaglutide in adults with T1D from Novo Nordisk A/S. Viral N. Shah has received honoraria for consulting, advising, or speaking from Dexcom, Insulet, Tandem Diabetes Care, Sanofi, Eli Lilly, Novo Nordisk A/S, Embecta, and Ascensia Diabetes Care, unrelated to this submitted work.

Background: Nocturnal hypoglycemia (NH) remains a major burden for people with type 1 diabetes (T1D). Daytime physical activity (PA) increases the risk of NH. This pilot study tested whether cumulative daytime PA measured using a smartphone-based step tracker was associated with NH., Methods: Adults with T1D for ≥ 5 years (y) on multiple daily insulin or continuous insulin infusion, not using continuous glucose monitoring and HbA1c 6 to 10% wore blinded Freestyle Libre Pro sensors and recorded total daily carbohydrate (TDC) and total daily dose (TDD) of insulin. During this time, daily step count (DSC) was tracked using the smartphone-based Fitbit MobileTrack application. Mixed effects logistic regression was used to estimate the effect of DSC on NH (sensor glucose <70, <54 mg/dl for ≥15 minutes), while adjusting for TDC and TDD of insulin, and treating participants as a random effect., Results: Twenty-six adults, with 65.4% females, median age 27 years (interquartile range: 26-32) mean body mass index 23.9 kg/m 2 , median HbA1c 7.6% (7.1-8.1) and mean Gold Score 2.1 (standard deviation 1.0) formed the study population. The median DSC for the whole group was 2867 (1820-4807). There was a significant effect of DSC on NH episodes <70 mg/dl. (odds ratio 1.11 [95% CI: 1.01-1.23, P = .04]. There was no significant effect on NH <54 mg/dl., Conclusion: Daily PA measured by a smartphone-based step tracker was associated with the risk of NH in people with type 1 diabetes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Treatment-induced neuropathy of diabetes (TIND) is an under-recognised complication that arises after rapid glycaemic control in diabetic patients. It presents with acute autonomic dysfunction and/or neuropathic pain resulting from small fibre nerve damage. This case involves a woman in her 50s with type 2 diabetes who transitioned from oral hypoglycaemic agents to insulin therapy, leading to a significant drop in HbA1c from 10% to 7.2% within the last 3 months. She presented with painful sensations, orthostatic hypotension and syncope. A diagnostic workup revealed peripheral nerve and autonomic dysfunction. Symptomatic treatment, including pregabalin and intravenous fluids, led to symptom resolution. This case highlights the importance of recognising TIND in patients with rapid glycaemic control to prevent unnecessary interventions. Awareness and appropriate management, including gradual glycaemic correction, can significantly improve patient outcomes., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Gestational diabetes is one of the most prevalent diseases in pregnancy, with an incidence of 5 to 18% in Brazil, and is associated with high morbidity rates. The first-line treatment is insulin, although some recent studies have indicated that metformin might also be effective. Metformin is safe in pregnancy and appears to produce better results than insulin, including reduced gestational weight gain (GWG) and smaller gestational-age newborns. Few studies have been conducted on this topic in low- and middle-income countries., Methods: We designed an open randomized controlled trial comparing two treatments for pregnant women with type II diabetes mellitus (DM) and gestational diabetes (DMG): the metformin group (intervention) and the insulin group (as a routine service). The primary outcome is glycemic control. The secondary outcomes are GWG, the occurrence of hypertensive syndromes, macrosomia, and neonatal hypoglycemia. The sample will comprise 92 pregnant women, 46 per group. The inclusion criteria will be GDM or type II DM requiring medication for glycemic control, singleton pregnancy, and gestational age under 34 weeks. The exclusion criteria will be current treatment with any medication for glycemic control, type I DM, and intolerance to the study medications (metformin or insulin). Women will be routinely followed during antenatal care, childbirth, and the postpartum period. Statistical analyses will include the intention-to-treat approach and a comparison between the two groups., Discussion: Considering the Brazilian socioeconomic reality and the safety of metformin demonstrated in previous trials, we expect that the MevIP study will demonstrate that metformin is an adequate and appropriate medication for GDM treatment in the Brazilian population, representing an alternative to insulin for GDM., Trial Registration: This protocol has been registered prospectively in ReBEC under the ID RBR-3j3cktx in August 11, 2023., Competing Interests: Declarations. Ethics approval and consent to participate {24}: This research protocol has been approved by the National Ethical Committee of Research in Health, CONEP (CAAE: 32868920.9.0000.5404.) and registered in the government platform of clinical trials, ReBEC (RBR-3j3cktx). Consent for publication {32}: This item is not applicable, as no personal information will be published or presented in the trial results. Competing interests {28}: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Background: Self-monitoring of blood glucose (SMBG) using web-based diabetes management platforms has demonstrated promise in managing type 2 diabetes (T2D). However, the effectiveness of such systems incorporating algorithm-guided insulin titration has not been extensively studied in Asian populations., Objective: This study evaluates the efficacy and safety of the ALRT telehealth solution-a US Food and Drug Administration-cleared, web-based platform that integrates SMBG with algorithm-driven insulin dose adjustments-in improving glycemia in insulin-treated T2D., Methods: This 24-week, pre-post intervention study enrolled 25 adults with T2D (mean age 58.9, SD 7.0 y; n=14, 56% male) on twice-daily premixed insulin. Inclusion criteria included a baseline hemoglobin A1c (HbA1c) level between 7.5% to 9.9% (58-86 mmol/mol), a BMI ≤40 kg/m², and experience with SMBG. Participants uploaded twice-daily SMBG data weekly via a mobile app, which generated insulin titration recommendations based on a predefined algorithm. Physicians reviewed and approved the recommendations, which were then communicated back to participants via the app. The primary outcome was the change in HbA1c level from baseline to 24 weeks. Secondary outcomes included changes in fasting plasma glucose, insulin dose, hypoglycemia incidence, and SMBG adherence., Results: Participants achieved significant reductions in HbA1c level from 8.6% (70 mmol/mol) at baseline to 7.4% (57 mmol/mol) at 24 weeks (P<.001), with reductions of 0.8% and 0.4% in the first and second 12 weeks, respectively. Fasting plasma glucose decreased from 8.7 (SD 2.0) mmol/L to 7.1 (SD 1.4) mmol/L (P<.001). Mean total daily insulin dose increased modestly from 0.73 (SD 0.31) units/kg/day to 0.79 (SD 0.34) units/kg/day (P=.007). Participants demonstrated high adherence, completing 97.3% (327/336) of prescribed SMBG measurements. During the study, 48% (12/25) of participants experienced at least 1 hypoglycemia episode, predominantly mild hypoglycemia (85/96, 88.5%; glucose 3.0-3.9 mmol/L). Hypoglycemia episodes increased from 24 during weeks 0-12 to 72 during weeks 13-24. There were no episodes of severe hypoglycemia requiring external assistance. BMI increased slightly from 29.0 (SD 3.6) kg/m² to 29.5 (SD 3.6) kg/m² (P=.03), reflecting a modest weight gain associated with improved glycemia., Conclusions: In conclusion, patients with insulin-treated T2D initiated on a web-based glucose monitoring system with algorithm-guided dosing recommendations showed significant improvement in glycemic control compared to baseline. High adherence rates underscore the feasibility of integrating algorithm-guided insulin titration into routine care. While hypoglycemia incidence rose slightly, episodes were predominantly mild, and no severe events occurred. This intervention shows promise for broader adoption in T2D management, particularly in resource-constrained settings., (© Nishanth Thiagarajan, Hong Chang Tan, Suresh Rama Chandran, Phong Ching Lee, Yun Ann Chin, Wanling Zeng, Emily Tse Lin Ho, David Carmody, Su-Yen Goh, Yong Mong Bee. Originally published in JMIR Formative Research (https://formative.jmir.org).)

Objective To describe a successful pharmacist-led intervention to effectively and safely provide education and pharmacotherapy management for an older patient with uncontrolled type 2 diabetes mellitus (T2DM) who failed to remove the needle shield on insulin pens for injection. Setting: Family medicine residency clinic. Practice Description: The clinic, part of a major urban health system, consists of 27 medical residents, 15 attending physicians, and 1 ambulatory care pharmacist managing chronic diseases collaboratively. It primarily serves low-income patients in a Midwest city. Practice Innovation: A 93-year-old White female with T2DM, receiving insulin therapy, was referred to the ambulatory care pharmacist by her physician for diabetes management. The patient had been hospitalized recently for hyperosmolar hyperglycemic state with a hemoglobin A1c of 15.9%. The pharmacist identified a failure to remove the needle shield on the insulin pen resulting in ineffective insulin administration, which caused persistent hyperglycemia and subsequent hospitalizations. This also posed a safety concern for severe hypoglycemia if proper administration resumed without adjusting the inflated dosing. The pharmacist used demonstration devices and the teach-back method to provide education and implement pharmacotherapy adjustments, resulting in effective and safe insulin administration. Main Outcome Measurements: Change in diabetes medication regimen, home blood glucose readings including continuous glucose monitor data, hemoglobin A1c results, frequency of hypoglycemic episodes, and number of hospitalizations for T2DM. Results: Over seven months, dose adjustments to basal insulin, combined with proper administration technique and the addition of empagliflozin, resulted in a hemoglobin A1c below 7%, with no severe hypoglycemia or diabetes-related hospitalizations. Conclusion: Medication errors, including insulin administration errors, highlight the need for thorough education in insulin therapy management. Education and monitoring empower older patients to self-manage diabetes safely and effectively, aligning with guidelines. Further research is required to identify optimal strategies for educating older patients on self-managing T2DM with insulin therapy.

Background: During calendar years 2021 through 2023, our health system admitted 200,837 persons 18 years and older with diabetes, of which 61% (n = 123,393) were 65 years and older with orders for insulin administration. The incidence of diabetes among hospitalized persons 65 and older continues to increase in the United States, with 24 million adults 65 and older with diabetes reported in 2020. Insulin, a high-risk medication, has the potential for adverse drug events, which can cause significant harm to patients, potentially resulting in death. With the 2023 initiation of voluntary electronic clinical quality measures reporting for severe glycemic harm events from the Centers for Medicare Services, the study team saw an opportunity to evaluate and standardize insulin-related practices across the system., Methods: We implemented an Insulin Safety Campaign (ISC), to review, evaluate, and standardize insulin-related processes across our health system. The primary goal was to reduce severe glycemic harm events system-wide. Insulin-related practices were reviewed for best practice alignment and standardized. Outcomes were measured according to the Centers for Medicare and Medicaid Services' electronic clinical quality measures reporting guidelines., Results: Comparing pre-and post-implementation results, all five medical centers achieved statistically significant reductions in sever hyper- and hypoglycemic harm events., Conclusions: Through a collaborative effort, we were able to identify, address, and reduce insulin-related process variabilities through standardization, reducing the percentage of severe glycemic harm events and improving blood glucose management in our hospitalized persons 65 and older., (© 2024 The American Geriatrics Society.)

Background: The effect of closed-loop insulin delivery on the risk of acute diabetes complications in people with type 1 diabetes is unclear. We investigated whether the rates of severe hypoglycaemia and diabetic ketoacidosis are lower with hybrid closed-loop insulin therapy compared with sensor-augmented (open-loop) pump therapy in a large cohort of young people., Methods: In this population-based cohort study, we evaluated young people with type 1 diabetes from 250 diabetes centres in Germany, Austria, Switzerland, and Luxembourg participating in the Diabetes Prospective Follow-up (DPV) initiative. Included participants were aged 2-20 years, with diabetes duration of more than 1 year, and were treated between Jan 1, 2021, and Dec 31, 2023. The primary outcomes were the rates of severe hypoglycaemia and ketoacidosis in people using closed-loop therapy versus open-loop therapy. Key secondary outcomes were differences in HbA 1c levels, percentage of time in glucose range of 3·9-10·0 mmol/L, and glycaemic variability. To account for relevant confounders, we applied propensity score inverse probability of treatment weighting considering several baseline characteristics., Findings: 13 922 young people (median age 13·2 years [IQR 10·0 to 16·0]; 51% male) in the DPV database met inclusion criteria and were included in the analysis. 7088 used closed-loop therapy and 6834 used open-loop therapy, with a median observation time of 1·6 years [IQR 1·1 to 2·4]. Individuals using closed-loop therapy had a higher rate of ketoacidosis (1·74 per 100 patient-years) than those using open-loop therapy (0·96 per 100 patient-years; incidence rate ratio 1·81 [1·37 to 2·40], p<0·0001) and there was no significant difference between groups in the rate of severe hypoglycaemia (5·59 per 100 patient-years vs 6·63 per 100 patient-years; incidence rate ratio 0·84 [95% CI 0·69 to 1·03], p=0·089). Individuals using closed-loop therapy had a lower rate of hypoglycaemic coma (0·62 per 100 patient-years) compared with individuals using open-loop therapy (0·91 per 100 patient-years; incidence rate ratio 0·68 [95% CI 0·48 to 0·97], p=0·034). Those in the closed-loop therapy group also had a lower HbA 1c level (7·34% vs 7·50%; difference -0·16% [95% CI -0·20 to -0·13], p=0·0007), higher percentage of time in target glucose range of 3·9-10·0 mmol/L (64% vs 52%, difference 12% [10 to 14], p<0·0001), and less glycaemic variability (coefficient of variation 35·4% vs 38·3%; difference -2·9% [-3·3 to -2·5], p<0·0001) than those in the open-loop therapy group. The rate of ketoacidosis was particularly high in young people with HbA 1c of 8·5% or higher in the closed-loop therapy group (5·25 per 100 patient-years) compared with the open-loop therapy group (1·53 per 100 patient-years; incidence rate ratio 3·43 [95% CI 1·69 to 6·97], p<0·0001)., Interpretation: Hybrid closed-loop insulin delivery has no significant effect on the rate of severe hypoglycaemia, and is associated with an increased risk of diabetic ketoacidosis, but is associated with a reduced risk of hypoglycaemic coma and improved glycaemia. These findings indicate the need for additional educational measures for the use of closed-loop insulin delivery., Funding: German Center for Diabetes Research, German Diabetes Society, and Robert Koch Institute., Competing Interests: Declaration of interests The institution of TB received grants and services from Ypsomed and Dexcom, and grants from Vitalaire for clinical trials. TB received consulting fees from Ypsomed, honoraria for lectures from Insulet, Dexcom, Ypsomed, Vitalaire, and Abbott, and participated in advisory boards for Dexcom, Insulet, Medtronic, and Ypsomed. MT received consulting fees from Sanofi and Abbott Diabetes Care, honoraria for lectures from Eli Lilly, Medtronic, and Ypsomed, and his institution received support for attending meetings from Eli Lilly. AG and TB are members and TB is Treasurer of the Executive Board of the German Society of Paediatric and Adolescent Endocrinology and Diabetology (DGPAED). BK is member of the Executive Board of the German Diabetes Society (DDG). All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Aims: In 2022, the Centers for Medicare & Medicaid Services released proposed changes to Medicare's continuous glucose monitoring (CGM) coverage policy, making individuals with a history of problematic hypoglycaemia eligible for CGM coverage, irrespective of insulin use. This study estimated the burden of hypoglycaemia in Medicare Advantage beneficiaries with noninsulin-treated type 2 diabetes (T2D)., Materials and Methods: We retrospectively analysed US healthcare claims data using Optum's deidentified Clinformatics® database. Noninsulin-treated beneficiaries were identified in the 16 years from January 2007 to March 2023. Hypoglycaemia-related encounters (HREs) were those accompanied by a hypoglycaemia-specific ICD-9/10 diagnosis code in any position on the claim or the first or second position. HREs following the first claim related to T2D were reported by setting (ambulatory or inpatient/emergency department [ED])., Results: HREs were identified in 689,853 (21.4%) of 3,229,695 noninsulin-treated Medicare Advantage beneficiaries, of whom 82.9% (n = 571,581) had ≥1 HRE in an ambulatory location and 26.8% (n = 184,833) in an ED/inpatient location. Use of sulfonylurea (odds ratio [OR]: 4.33 confidence interval [CI: 4.27-4.38]), evidence of end-stage kidney disease (OR: 2.87 [CI: 2.79-2.94]), hypertension (OR: 3.09 [CI: 3.04-3.15]) and retinopathy (OR: 2.94 [CI: 2.82-3.07]) were the strongest predictors of an HRE (p < 0.001)., Conclusions: These findings show that HREs are prevalent in noninsulin-treated diabetes and identify a large number of patients who may benefit from CGM. Because >80% of HREs occur in the ambulatory setting and >70% occur in patients not taking sulfonylureas, primary care providers should be aware of the latest eligibility criteria for Medicare's coverage of CGM and not restrict this technology to their sulfonylurea-treated patients., (© 2024 John Wiley & Sons Ltd.)

Objective: To assess the accuracy of "diabetes overtreatment" proxy definitions in predicting hypoglycemia in older adults with type 2 diabetes (T2D)., Research Design and Methods: Inclusion of patients from HYPOAGE cohort with insulin-treated T2D, aged ≥75 years, and using a continuous glycemic monitoring (CGM) device for 28 days. "Diabetes overtreatment" was defined as HbA1c <7.0% (fixed proxy definition) or as HbA1c <7.0%, 7.5%, and 8.0% according to patient's health status (individualized proxy definition). The primary outcome was time below range (TBR) ≥1%., Results: Of the 134 patients included (81.6 ± 5.4 years, 59% male), 25 (19%) and 53 (40%) were overtreated, based on fixed and individualized proxy definitions, respectively. CGM data showed TBR >1% in nearly all patients regardless of overtreatment status. Both proxy definitions had low sensitivity (20% [14; 29] and 41% [32; 50]) and accuracy (27% [20; 35] and 44% [35; 53]) in predicting hypoglycemia., Conclusions: A revised definition of diabetes overtreatment is needed to better manage older insulin-treated patients and protect them from hypoglycemia., (© 2024 by the American Diabetes Association.)

With increasing prevalence of obesity and cardiovascular diseases, there is a growing interest in the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) as an adjunct therapy in type 1 diabetes (T1D). The GLP-1RAs are currently not approved by the US Food and Drug Administration for the treatment of T1D in the absence of randomized controlled trials documenting efficacy and safety of these agents in this population. The Diabetes Technology Society convened a series of three consensus meetings of clinicians and researchers with expertise in diabetes technology, GLP-1RA therapy, and T1D management. The project was aimed at synthesizing current literature and providing conclusions on the use of GLP-1RA therapy as an adjunct to automated insulin delivery (AID) systems in adults with T1D. The expert panel members met virtually three times on January 17, 2024, and April 24, 2024, and August 14, 2024, to discuss topics ranging from physiology and outcomes of GLP-1RAs in T1D to limitations of current sensors, algorithms, and insulin for AID systems. The panelists also identified research gaps and future directions for research. The panelists voted to in favor of 31 recommendations. This report presents the consensus opinions of the participants that, in adults with T1D using AID systems, GLP-1RAs have the potential to (1) provide effective adjunct therapy and (2) improve glycemic and metabolic outcomes without increasing the risk of severe hypoglycemia or diabetic ketoacidosis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: VNS received research support from Novo Nordisk, Insulet, and Tandem Diabetes Care and received honoraria from LifeScan for advisory board attendance and from Dexcom, Embecta, and Insulet for speaking arrangements. ALP is on the advisory board of Medscape, Vertex, and Lilly; has received research support from Insulin and Abbott; and reports stock options from Omada Health. GEU has received research support (to Emory University) from Abbott, Bayer, Dexcom, and Sanofi. HKA received research support through University of Colorado from Dexcom, Tandem Diabetes, Senseonics, Medtronic, Eli Lilly, REMD Biotherapeutics, IM Therapeutics, and IAFMS and received honoraria through University of Colorado from Senseonics and Mannkind for advisory board attendance. GA has received research support to her institution Northwestern University from Fractyl Health, MannKind, Insulet, Tandem Diabetes, and Welldoc. GA has received consulting fees from Dexcom and Insulet. LB reports having participated in advisory boards of Eli Lilly, Novo Nordisk, Oviva, Roche Diabetes Care, Sanofi, and Ypsomed and received speaker fees from Dexcom, Ypsomed and Oviva. EC is an advisory board member and consultant for Novo Nordisk, Eli Lilly, Adocia, MannKind, Lexicon, Arecor, PortalInsulin, and Proventionbio. EC was also a speaker for Novo Nordisk. KD discloses research support from Dexcom, Sanofi, Viacyte, Abbott, and Insulet; consulting with Eli Lilly, Insulet, Oppenheimer, Dexcom; and honorarium from UptoDate, Medscape, Med Learning Group, Impact Education, and Elsevier. CF receives royalties from Dexcom and Novo Nordisk managed through her institution. PGJ reports receiving grants from the National Institutes of Health, The Leona M. and Harry B. Charitable Trust, the Juvenile Diabetes Research Foundation, Dexcom, and the Oregon Health & Science University Foundation; consultancy fees from CDISC; US patents 62/352,939, 63/269,094, 62/944,287, 8810388, 9,480,418, 8,317,700, 61/570382, 8,810,388, 7,976,466, and 6,558,321; and reports stock options from Pacific Diabetes Technologies, outside submitted work. RAL reports consulting fees from Abbott Diabetes Care, Biolinq, Capillary Biomedical, Deep Valley Labs, Gluroo, PhysioLogic Devices, ProventionBio, and Tidepool. JKM is a member of the advisory board of Abbott Diabetes Care, Becton-Dickinson, Boehringer Ingelheim, Eli Lilly, Embecta, Medtronic, Novo Nordisk A/S, Prediktor A/S, Roche Diabetes Care, Sanofi-Aventis, and Viatris and received speaker honoraria from Abbott Diabetes Care, AstraZeneca, Boehringer Ingelheim, Dexcom, Eli Lilly, Menarini, MSD, Novo Nordisk A/S, Roche Diabetes Care, Sanofi, Servier, and Ypsomed. JLS has conducted clinical trials for Eli Lilly, Insulet, and Medtronic and has received in-kind support for research studies from Dexcom and Medtronic. She has consulted for Eli Lilly, Lexicon, Medtronic, and Sanofi. She has been a member of advisory boards for Bigfoot Biomedical, Cecelia Health, Eli Lilly, Insulet, the T1D Fund, and Vertex. DCK is a consultant for Afon, Better Therapeutics, Integrity, Lifecare, Nevro, Novo, Samsung, and Thirdwayv. AC, UM, PP, SS, EZ, CNH, ATA, TT, and REA have nothing to disclose.

Globally, health care workers (HCWs) are at a high risk of occupational exposure to needlestick injuries (NSIs). Needlestick injuries not only are associated with an increased risk of infections caused by bloodborne pathogens but are also a primary source of emotional distress and job burnout for HCWs and patients. Insulin injection-related NSIs are common among HCWs working in hospitals in the Asia-Pacific (APAC) region and impose a significant burden. Insulin pen needles have a high risk of transmitting infections (at both the patient-end and cartridge end of the sharp) after use. Recapping a needle after administering an insulin injection poses a major risk to HCWs. Currently, several safety-engineered needle devices (SENDs) are available with active or passive safety mechanisms. Passive insulin safety pen needles with dual-ended protection and automatic recapping capabilities have resulted in a significant drop in accidental punctures to HCWs while administering insulin to patients with diabetes. In this article, we have reviewed the burden and common causes of NSIs with insulin injections among HCWs in the APAC region. We have discussed current approaches to address the issues associated with NSIs and the benefits of introducing SENDs in health care settings, including long-term care facilities, nursing homes, and home care settings where patients may require assisted insulin injections. This review also summarizes key strategies/recommendations to prevent NSIs in HCWs and patients with diabetes in the APAC region., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Shailendra Bajpai and Kevin Friedman are employees and stockholders of BD/embecta (formerly BD Diabetes Care), manufacturer of a range of safety-engineered devices. No other potential conflict of interest relevant to this article was reported by the rest of the authors.

Background: One of the biggest challenges for people with type 1 diabetes (T1D) using multiple daily injections (MDIs) is nocturnal hypoglycemia (NH). Recurrent NH can lead to serious complications; hence, prevention is of high importance. In this work, we develop and externally validate, device-agnostic Machine Learning (ML) models to provide bedtime decision support to people with T1D and minimize the risk of NH., Methods: We present the design and development of binary classifiers to predict NH (blood glucose levels occurring below 70 mg/dL). Using data collected from a 6-month study of 37 adult participants with T1D under free-living conditions, we extract daytime features from continuous glucose monitor (CGM) sensors, administered insulin, meal, and physical activity information. We use these features to train and test the performance of two ML algorithms: Random Forests (RF) and Support Vector Machines (SVMs). We further evaluate our model in an external population of 20 adults with T1D using MDI insulin therapy and wearing CGM and flash glucose monitoring sensors for two periods of eight weeks each., Results: At population-level, SVM outperforms RF algorithm with a receiver operating characteristic-area under curve (ROC-AUC) of 79.36% (95% CI: 76.86%, 81.86%). The proposed SVM model generalizes well in an unseen population (ROC-AUC = 77.06%), as well as between the two different glucose sensors (ROC-AUC = 77.74%)., Conclusions: Our model shows state-of-the-art performance, generalizability, and robustness in sensor devices from different manufacturers. We believe it is a potential viable approach to inform people with T1D about their risk of NH before it occurs., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Immunotherapy, including the use of immune checkpoint inhibitors such as nivolumab, is increasingly common in cancer treatment and can lead to various immune-related adverse effects, including rare cases of diabetic ketoacidosis. This case report highlights an unique instance of nivolumab-induced diabetic ketoacidosis in a patient without prior history of diabetes, emphasizing the importance of careful monitoring even in those without traditional risk factors., Case Presentation: We report a case of a 70-year-old Caucasian male with metastatic esophageal adenocarcinoma who developed diabetic ketoacidosis 3 weeks after stopping nivolumab therapy. The patient had no previous history of diabetes, nor had he used sodium-glucose transport protein 2 inhibitors or corticosteroids. Diagnostic tests confirmed diabetic ketoacidosis, and while he was initially treated following the institutional protocol, he continued to require insulin therapy indefinitely., Conclusions: This case report underscores the risk of diabetic ketoacidosis linked to nivolumab, even in patients without predisposing factors, emphasizing the need for increased vigilance among both oncologists and physicians. It highlights the importance of monitoring for new-onset diabetes and diabetic ketoacidosis, whether immunotherapy is active or discontinued, and ensuring comprehensive care including hospitalization, insulin management, and diabetes education if diabetic ketoacidosis is diagnosed., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Written informed consent was obtained from the patient for publication of this case report. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests: The authors declare no financial interest and potential competing interests., (© 2024. The Author(s).)

Objective: Hyperglycemia in preterm infants is usually treated with adjustment of glucose intake and, if persistent, with continuous insulin infusion. However, hypoglycemia is a well-known complication of intravenous (iv) insulin treatment. The aim of this study was to evaluate the feasibility of continuous subcutaneous insulin infusion (CSII) in extremely preterm infants., Methods: Clinical data from extremely premature infants (<28 weeks of gestation) undergoing CSII treatment for severe hyperglycemia in the neonatal intensive care unit were included. Blood glucose levels during CSII, as well as the nutritional intake and insulin intake were recorded. Data were analyzed and compared to a control group of very preterm infants receiving iv insulin therapy., Results: Normoglycemia rates were best in the iv insulin-cohort (n=22, 50.3%) compared to the CSII group (n=15, 15.6%). Hypoglycemia was very rare in both groups (0.4% vs. 0.0%). CSII therapy appears to require higher insulin doses compared to continuous iv therapy to achieve a similar effect. Subcutaneous Insulin therapy in extremely preterm infants is feasible, at least for prevention of hypoglycemia. However, dose control needs to be improved., Conclusion: The results justify further model validation and clinical trial research to explore a model-based protocol and the use of CSII in this population., Competing Interests: Conflict of interest: None declared., (©Copyright 2024 by Turkish Society for Pediatric Endocrinology and Diabetes / The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)

Aims: To describe the development of a culturally adapted, evidence-based, and theory-driven diabetes self-management programme for Chinese adults with type 2 diabetes receiving insulin injection therapy and to assess the feasibility, acceptability, and preliminary effects of the newly developed intervention., Methods: The Medical Research Council framework was adopted to guide the intervention development and a feasibility study. A prospective, two-arm, parallel-group, assessor-blinded randomised controlled trial was conducted. Participants were randomly allocated to receive either the newly developed intervention or parallel attention control contact from community nurses. Between-group differences in changes in outcome variables were analysed using the Mann-Whitney U test., Results: The newly developed intervention consists of one individual interview session, three group-based education sessions, and two telephone-based maintenance sessions. A total of 24 participants were recruited with the recruitment rate and overall retention rate of 77.4 % and 95.8 %, respectively. The results indicated that the intervention participants reported significantly greater improvements in self-efficacy (Hedge's g = 1.69) and self-management behaviours (Hedge's g = 3.24), and reductions in diabetes-related distress (Hedge's g = 1.49) compared with those in the control group (all p< 0.05)., Conclusion: The diabetes self-management programme was feasible and acceptable. The intervention showed promising patient-centred benefits. A future large-scale randomised controlled trial is warranted., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Insulin autoimmune syndrome (IAS) is characterized by hyperinsulinemic hypoglycemia and elevated anti-insulin antibodies. While thiol-containing drugs commonly induce IAS, cases induced by proton pump inhibitors are rare. We report a case of IAS induced by omeprazole in a 27-year-old Chinese man with the HLA-DRB1*0406 subtype. This patient presented with Whipple's triad after taking omeprazole without concurrent insulin use. The mixed-meal tolerance test (MMTT) and insulin-C-peptide release tests revealed a rapid surge in insulin levels within one hour, with a non-significant increase in C-peptide and a significant rise in insulin after precipitation. Further examination revealed high-titer positive insulin autoantibodies, leading to a diagnosis of insulin autoimmune syndrome (IAS). Symptoms resolved upon discontinuation of omeprazole and adherence to dietary recommendations, with insulin autoantibody levels decreasing after a 6-month follow-up. This case highlights omeprazole's potential to induce IAS, underscoring the need for vigilance due to widespread use of proton pump inhibitor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: Atrial fibrillation (AF) and diabetes mellitus (DM) are both associated with adverse clinical events, but the associations have not been fully elucidated, particularly with concomitant insulin use. This study aimed to analyse the associations between adverse events and DM, as well as adverse events and sole insulin use., Materials and Methods: Our analysis included individuals with AF from the prospective Global Registry on Long-Term Oral Anti-Thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry with 3-year follow-up. Outcomes included all-cause death, major bleeding, cardiovascular (CV) death, myocardial infarction (MI), stroke, thromboembolism and major adverse cardiovascular events (MACE)., Results: A total of 15 861 AF individuals were included (age 70.0 ± 10.2 years; 55% male, 20% Asian), of whom, 3666 had DM (age 70.0 ± 9.5 years ; 59% male, 21% Asian). After adjustment, those with DM had higher risks of all-cause death (hazard ratio [HR]: 1.46, 95% confidence interval [CI]: 1.28-1.66), CV death (HR: 1.53 95% CI: 1.27-1.86), major bleeding (HR: 1.23, 95% CI: 1.01-1.48), MI (HR: 1.50, 95% CI: 1.17-1.94) and MACE (HR: 1.42, 95% CI: 1.23-1.63). Compared to individuals with DM receiving oral hypoglycaemic agents, those receiving insulin alone were associated with increased risks of all-cause death (HR: 2.16, 95% CI: 1.61-2.91), CV death (HR: 2.24, 95% CI: 1.45-3.47), major bleeding (HR: 1.89, 95% CI: 1. 21-2.95), MI (HR: 2.24, 95% CI: 1.31-3.82) and MACE (HR: 2.11, 95% CI: 1.54-2.88)., Conclusions: DM was independently associated with higher risks of all-cause death, CV death, MI, major bleeding and MACE in AF individuals. Individuals receiving insulin alone were associated with higher risks of all-cause death, CV death, MI, major bleeding and MACE., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Cholesterol-lowering medications, blood pressure medication, insulin, and exogenous hormones (including hormone replacement therapy, oral contraceptives, and minipills) are commonly utilized in clinical practice. Recent studies indicate that the use of these medications may significantly influence the occurrence and progression of cerebral infarction. This study aims to investigate the relationship between these medications and cerebral infarction using Mendelian randomization (MR) analysis, with the goal of offering valuable insights for the clinical management of cerebral infarction., Methods: To explore the correlation between cholesterol-lowering medication, blood pressure medication, insulin, exogenous hormones, and cerebral infarction, relevant single nucleotide polymorphisms (SNPs) were extracted from the genome-wide association study (GWAS) database. Methods for univariate MR analysis include inverse variance weighting (IVW), the weighted median method, and the MR-Egger method, with IVW being the predominant approach. Subsequently, multivariable Mendelian randomization (MVMR) was conducted on the positive results obtained from the IVW analysis to verify the independent effect of each positive exposure, with IVW still predominating. The causal relationship between this class of drugs and cerebral infarction was evaluated using odds ratio (OR) and 95% confidence interval (CI). MR-PRESSO was used to test for pleiotropy. The robustness of the findings was assessed through leave-one-out analysis, Cochran's Q test, and funnel plot., Results: Univariate MR results indicated that the use of blood pressure medication, insulin, and cholesterol-lowering medication was significantly associated with the occurrence of cerebral infarction (all p < 0.05). However, due to the stringent inclusion criteria for SNPs, the number of available SNPs is insufficient to elucidate the association between exogenous hormone drugs, contraceptives, and cerebral infarction. Furthermore, the MVMR analysis, which builds upon univariate MR, only identified significant causal associations between blood pressure medication, insulin, and cerebral infarction (p < 0.05). The association between cholesterol-lowering medication and cerebral infarction was confounded by other positive exposures and did not demonstrate a significant causal relationship when only its independent effects were considered. After integrating the findings from both univariate and MVMR and controlling for confounding variables to the greatest extent possible, the available evidence supports only a potential causal relationship between blood pressure medication, insulin, and cerebral infarction., Conclusion: This study suggests that the misuse of blood pressure medications and insulin is a risk factor for the occurrence and progression of cerebral infarction., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Introduction: Diabetic Ketoacidosis (DKA) is commonly treated with intravenous (IV) regular insulin. However, patients with less severe DKA may benefit from a subcutaneous (SC) scheme., Methods: We systematically searched PubMed, Cochrane, and Embase for randomized controlled trials (RCTs) comparing SC rapid-acting insulin analogue (RAIAs) with IV regular insulin. Risk ratios (RR) were used to compare treatment effects for binary outcomes and mean differences (MD) for continuous data with the corresponding 95 % confidence intervals (CI). P values <0.05 were considered statistically significant. We used the R version 4.3.2 for statistical analyses., Results: Our meta-analysis included eight RCTs encompassing 415 patients. No statistically significant differences were found between RAIAs and IV regular insulin in the treatment of mild to moderate DKA in the pediatric and adult population in the primary outcome of time until DKA resolution (MD 0.00 h; 95 % CI -1.27 to 1.28; P = 1.00). Both treatments showed comparable results in the secondary outcomes total insulin usage (P = 0.65), time until hyperglycemia resolution (P = 0.22), length of hospital stay (P = 0.11), the incidence of hypoglycemia (P = 0.15) and DKA recurrence (P = Not estimable). There were no reports of death, cerebral edema, or venous thrombosis in the studies., Conclusion: In this meta-analysis of eight RCTs we found that SC RAIAs and regular IV insulin are comparable in resolving mild to moderate DKA in children and adults. PROSPERO registration: CRD42023485032., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: Studies evaluating the cardiovascular safety of pioglitazone show inconsistent results and ischemic heart disease (IHD) risks associated with different anti-diabetic drugs added to metformin uncontrolled type 2 diabetes mellitus (T2DM) are not assessed. This study aimed to evaluate IHD risk associated with pioglitazone and/or insulin added to patients with metformin uncontrolled T2DM., Methods: Data were extracted from the National Health Insurance Research Database of Taiwan. A total of 19,952 patients with T2DM uncontrolled on metformin received pioglitazone and/or insulin added to metformin were included., Results: Compared to those who never received pioglitazone and/or insulin, patients receiving both insulin and pioglitazone had higher cumulative risk of IHD (adjusted HR [aHR] = 1.911, 95 % confidence interval [CI]: 1.506-2.351), pioglitazone alone (aHR = 1.446, 95 % CI: 1.111-1.775), and insulin alone (aHR = 1.351, 95 % CI: 1.1052-1.684) (all, p < 0.05). Patients who received both pioglitazone and insulin had a higher cumulative risk of IHD than those who received insulin or pioglitazone as well as a similar result in the cumulative defined daily dose (cDDD) of the drugs., Conclusion: Administering pioglitazone plus insulin to patients with T2DM uncontrolled on metformin may increase the risk of IHD, suggesting that other second-line anti-diabetes drugs may be a better choice for patients with T2DM uncontrolled on metformin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: This meta-analysis was performed to obtain a comprehensive overview of the differences between once-weekly basal insulin (including icodec and basal insulin Fc) and once-daily basal insulin (including glargine and degludec) in patients with type 1 and type 2 diabetes mellitus., Methods: PubMed, EMBASE, and Cochrane Library were systematically searched for eligible studies up to 2 January 2024., Results: A total of 12 studies were included, comprising 5,895 patients, with 3,104 (52.7%) using once-weekly insulin and 2,791 (47.3%) using once-daily insulin. In the pooled data, glycated hemoglobin (HbA1c) change from baseline [mean difference (MD) -0.11%; 95% confidence interval (CI) -0.20 to -0.01%] and the odds of achieving an end-of-trial HbA1c <7% (OR 1.41, 95% CI 1.13, 1.77) demonstrated a significantly good glycemic control in the once-weekly insulin group, especially in insulin-naïve type 2 diabetics or patients using icodec. Body weight increase for once-weekly insulin was 0.43 kg compared to controls (95% CI 0.09 to 0.76 kg). In addition, once-weekly insulin was correlated with a higher risk of level 1 hypoglycemia (OR 1.42, 95% CI 1.26 to 1.6). There was no significant difference in fasting plasma glucose (MD 2.46 mg/dL; 95% CI -2.60 to 7.52 mg/dL), time in range (MD 2.03%; 95% CI -0.50 to 4.56%), and level 2 or 3 hypoglycemic events (OR 1.19; 95% CI 0.93 to 1.53)., Conclusions: Once-weekly basal insulin is safe and effective in modestly reducing HbA1c with similar level 2 or 3 hypoglycemic events compared to once-daily insulin, although the risk of level 1 hypoglycemia and weight gain was slightly increased., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, Identifier CRD42024496812., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xue, Shen, Tang, Deng and Dai.)

Background: Continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusions (CSIIs) are the current standard treatment devices for type 1 diabetes (T1D) management. With a high prevalence of T1D beginning in pediatrics and carrying into adulthood, insufficient glycemic control leads to poor patient outcomes. Dermatologic complications such as contact dermatitis, lipodystrophies, and inflammatory lesions are among those associated with CGM and CSII, which reduce glycemic control and patient compliance., Objective: This systematic review aims to explore the current literature surrounding dermatologic complications of CGM and CSII as well as the impact on patient outcomes., Methods: A systematic review of the literature was carried out using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines using 5 online databases. Included articles were those containing primary data relevant to human participants and adverse reactions to CGM and CSII devices in pediatric populations, of which greater than 50% of the sample size were aged 0-21 years. Qualitative analysis was chosen due to the heterogeneity of outcomes., Results: Following the application of exclusion criteria, 25 studies were analyzed and discussed. An additional 5 studies were identified after the initial search and inclusion. The most common complication covered is contact dermatitis, with 13 identified studies. Further, 7 studies concerned lipodystrophies, 5 covered nonspecific cutaneous changes, 3 covered unique cutaneous findings such as granulomatous reactions and panniculitis, and 2 discussed user acceptability., Conclusions: The dermatologic complications of CGM and CSII pose a potential risk to long-term glycemic control in T1D, especially in young patients where skin lesions can lead to discontinuation. Increased manufacturer transparency is critical and further studies are needed to expand upon the current preventative measures such as device site rotation and steroid creams, which lack consistent effectiveness., (© Alicia Podwojniak, Joseph Flemming, Isabella J Tan, Hira Ghani, Zachary Neubauer, Anne Jones. Originally published in JMIR Dermatology (http://derma.jmir.org).)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Cecilia Svedman participates in the IDEA project sponsored by the International Fragrance Association (IFRA).

Introduction: Automatic insulin delivery (AID) systems improve glycemic control and quality of life in individuals with type 1 diabetes (T1D). Our aim was to assess the feasibility, effectiveness, and safety of switching from a sensor-augmented pump (SAP) to AID in T1D subjects at high risk of hypoglycemia., Materials and Methods: A manufacturer-led program consisting of three sessions was implemented. Over three days, all patients completed the first session in-person, in groups of 6-12 people, to receive device training. Subsequently, the automatic mode was activated virtually (session 2), followed by online data download (session 3). Glucometric outcomes were evaluated after one month, along with serious adverse events (SAEs), technical incidents, and perceived satisfaction., Results: The switch was performed in 125 patients, 56.8% of whom were women, with a mean age of 44.1 ± 14.9 years. 99.2% (n = 124) initialized auto-mode. There was an increase in time in range 70-180 mg/dL (64.3 ± 11.3 vs. 74.7 ± 11.2; p < 0.001) and a decrease in time below 70 mg/dL (4.1 ± 3.9 vs. 2.0 ± 1.8; p < 0.001) (N = 97). Forty-one related calls were received, with 10 requiring in-person visits. Medtronic technical service handled 92 related calls (0.74 per patient), from 47 different users (37.6%). One event of severe hypoglycemia was recorded as an SAE. Perceived security and satisfaction with the switch process were high in 91% and 92% of patients, respectively., Conclusions: Massive switch from SAP to AID in T1D patients at high risk of hypoglycemia is feasible and safe through a hybrid program conducted in collaboration with the manufacturer., Competing Interests: Declaration of competing interest O.M. and J.C. are employees of Medtronic. The remaining authors declared no conflicts of interest regarding the drafting of this article., (Copyright © 2024 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Control-IQ technology version 1.5 allows for a wider range of weight and total daily insulin (TDI) entry, in addition to other changes to enhance performance for users with high basal rates. This study evaluated the safety and performance of the updated Control-IQ system for users with basal rates >3 units/h and high TDI in a multicenter, single arm, prospective study., Methods: Adults with type 1 diabetes (T1D) using continuous subcutaneous insulin infusion (CSII) and at least one basal rate over 3 units/h (N = 34, mean age = 39.9 years, 41.2% female, diabetes duration = 21.8 years) used the t:slim X2 insulin pump with Control-IQ technology version 1.5 for 13 weeks. Primary outcome was safety events (severe hypoglycemia and diabetic ketoacidosis (DKA)). Central laboratory hemoglobin A 1c (HbA 1c ) was measured at system initiation and 13 weeks. Participants continued using glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose transport protein 2 (SGLT-2) inhibitors, or other medications for glycemic control and/or weight loss if on a stable dose., Results: All 34 participants completed the study. Fifteen participants used a basal rate >3 units/h for all 24 hours of the day. Nine participants used >300 units TDI on at least one day during the study. There were no severe hypoglycemia or DKA events. Time in range 70-180 mg/dL was 64.8% over the 13 weeks, with 1.0% time <70 mg/dL. Hemoglobin A 1c decreased from 7.69% at baseline to 6.87% at 13 weeks (-0.82%, P < .001)., Conclusions: Control-IQ technology version 1.5, with wider range of weight and TDI input and enhancements for users with high insulin requirements, was safe in individuals with T1D in this study., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.L.C.’s employer, International Diabetes Center, has received research support and/or consulting fees from Eli Lilly, Novo Nordisk, Sanofi, Medtronic, Tandem, Insulet, Dexcom, Abbott Diabetes, and MannKind. T.E.G.’s employer, Diabetes & Endocrine Treatment Specialists, has received research support/and or consulting fees from Novo Nordisk, Eli Lilly, Sanofi, Provention Bio, Novartis, Tandem, Insulet, Ascendis Pharma, and Progenitor Life Sciences. H.K.A. has received research grants through University of Colorado from Tandem Diabetes Care, Medtronic, Dexcom, Eli Lilly, and MannKind and has received consulting fees through University of Colorado from Tandem Diabetes Care, Medtronic, and Dexcom. D.R.L. has received funding for clinical research from Abbott Diabetes Care, Biolinq, Senseonics, Dexcom, Diasome, Sanvita, Medtronic, Tandem, Provention, Eyenuk, TrialNet, and JAEB Center for Clinical Research. R.M.B. has received research support, has acted as a consultant, or has been on the scientific advisory board for Abbott Diabetes Care, Ascensia, Bigfoot Biomedical, Inc, CeQur, Dexcom, Eli Lilly, Embecta, Hygieia, Insulet, Medtronic, Novo Nordisk, Onduo, Roche Diabetes Care, Tandem Diabetes Care, Sanofi, United Healthcare, Vertex Pharmaceuticals, and Zealand Pharma. R.M.B.’s employer, non-profit HealthPartners Institute, contracts for his services, and he receives no personal income from these activities. B.S. has received payments from Medtronic, Insulet, and Tandem as a certified pump trainer, consulting fees from Eli Lilly, honorariums from Medtronic, the Academy of Nutrition & Dietetics, the Association of Diabetes Care & Education Specialists, and the American Diabetes Association. V.N.S. has received research grants through University of Colorado from Tandem Diabetes Care, Insulet, Novo Nordisk, Alexion, JDRF, and NIH and consulting fees through University of Colorado from Dexcom, Insulet, Tandem Diabetes Care, Embecta, Novo Nordisk, and Medscape. M.S. has received consulting fees from Sanvita. P.Z., P.B., R.S.-K., and J.E.P. are employees of Tandem Diabetes Care, Inc.

Background: Optimization of automated insulin delivery (AID) settings is required to achieve desirable glycemic outcomes. We evaluated safety and efficacy of a computerized system to initialize and adjust insulin delivery settings for the t:slim X2 insulin pump with Control-IQ technology in adults with type 1 diabetes (T1D)., Methods: After a 2-week continuous glucose monitoring (CGM) run-in period, adults with T1D using multiple daily injections (MDI) (N = 33, mean age 36.1 years, 57.6% female, diabetes duration 19.7 years) were transitioned to 13 weeks of Control-IQ technology usage. A computerized algorithm generated recommendations for initial pump settings (basal rate, insulin-to-carbohydrate ratio, and correction factor) and weekly follow-up settings to optimize glycemic outcomes. Physicians could override the automated settings changes for safety concerns., Results: Time in range 70 to 180 mg/dL improved from 45.7% during run-in to 69.1% during the last 30 days of Control-IQ use, a median improvement of 18.8% (95% confidence interval [CI]: 13.6-23.9, P < .001). This improvement was evident early in the study and was sustained over 13 weeks. Time <70 mg/dL showed a gradual decreasing trend over time. Percentage of participants achieving HbA1c <7% went from zero at baseline to 55% at study end ( P < .001). Only six of the 318 automated settings adaptations (1.9%) were overridden by study investigators., Conclusions: Computerized initiation and adaptation of Control-IQ technology settings from baseline MDI therapy was safe in adults with T1D. The use of this simplified system for onboarding and optimizing Control-IQ technology may be useful to increase uptake of AID and reduce staff and patient burden in clinical care., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: VNS has received research grants through University of Colorado from Tandem Diabetes Care, Insulet, NovoNordisk, Alexion, JDRF and NIH. He has received fees through University of Colorado for speaking or consulting work for Dexcom, Insulet, Tandem Diabetes Care, Embecta, NovoNordisk and Medscape. HKA has received research grants through University of Colorado from Tandem Diabetes Care, Medtronic, Dexcom, Eli Lilly, Mannkind. He has received consulting fees through University of Colorado from Tandem Diabetes Care, Medtronic and Dexcom. AT, NP, AW, ES, KC, LM, KW, LF, RSK, LM, SH, AC, and JEP are employees of Tandem Diabetes Care, Inc.

Introduction: Insulin pump therapy can be adversely affected by interruption of insulin flow, leading to a rise in blood glucose (BG) and subsequently of blood beta-hydroxybutyrate (BHB) ketone levels., Methods: We performed a PubMed search for English language reports (January 1982 to July 2024) estimating the rate of rise in BG and/or BHB after ≥ 60 minutes of interruption of continuous subcutaneous insulin infusion (CSII) in persons with type 1 diabetes (PwT1D). We also simulated the rise in BG in a virtual population of 100 adults with T1D following suspension of continuous subcutaneous insulin infusion., Results: We identified eight relevant studies where BG and BHB (seven of these eight studies) were measured following suspension of CSII as a model for occlusion. After 60 minutes post-suspension, the mean extracted rates of rise averaged 0.62 mg/dL/min (37 mg/dL/h) for BG and 0.0038 mmol/L/min (0.20 mmol/L/h) for BHB. Mean estimated time to moderately/severely elevated BG (300/400 mg/dL) or BHB (1.6/3.0 mmol/L) was, respectively, 5.8/8.5 and 8.0/14.2 hours. The simulation model predicted moderately/severely elevated BG (300/400 mg/dL) after 9.25/12, 6.75/8.75, and 4.75/5.75 hours in the virtual subjects post-interruption with small (5th percentile), medium (50th percentile), and large (95th percentile) hyperglycemic changes., Discussion: Clinical studies and a simulation model similarly predicted that, following CSII interruption, moderate/severe hyperglycemia can occur within 5-9/6-14 hours, and clinical studies predicted that moderate/severe ketonemia can occur within 7-12/13-21 hours. Patients and clinicians should be aware of this timing when considering the risks of developing metabolic complications after insulin pump occlusion., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: D.C.K. is a consultant for Afon, Embecta, GlucoTrack, Lifecare, Novo, Samsung, and Thirdwayv. C. N. H. has nothing to disclose. A.T.A. has nothing to disclose. C.F. reports receiving research support from Novo Nordisk A/S and Dexcom, Inc handled by the University of Virginia, and patent royalties from Novo Nordisk A/S and Dexcom, Inc handled by the University of Virginia’s Licensing and Ventures Group. M.F.V.-T. reports receiving patent royalties from Dexcom, Inc handled by the University of Virginia’s Licensing and Ventures Group. E.A. has nothing to disclose. E.C. has served on the scientific advisory board of Novo Nordisk, Eli Lilly, MannKind, Arecor, Portal Insulin, Provention Bio, Tandem, and Ypsomed. L.E. receives salary support from NIDDK; has received research support from JDRF, Medtronic, MannKind, and Abbot and has served on the advisory board of Diabetes Center Berne, Sequel, and Medtronic. She has received consulting fees from Jaeb, Tandem Diabetes Care, and Ypsomed and has received honorarium fees from Medtronic and Insulet. J.C.W. has received research support from Dexcom, Inc and Tandem Diabetes Care. L.H. is a shareholder of the Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany, Science Consulting in Diabetes GmbH Düsseldorf, and diateam GmbH, Bad Mergentheim, and Düsseldorf. L.H. is a consultant for several companies that are developing novel diagnostic and therapeutic options for diabetes treatment. M.A.K. has nothing to disclose.

Background: Immune checkpoint inhibitors (ICIs) are becoming more frequently used in the treatment of many types of malignant cancers by disinhibiting T-cell activation, which promotes the destruction of cancer cells. This disinhibition can also result in autoimmune conditions, like endocrinopathies., Case: We report a case of a 78-year-old male patient with malignant mesothelioma treated with combination ICI therapy who presented with diabetic ketoacidosis (DKA) with no history of diabetes mellitus or hyperglycemia. The patient was admitted to the intensive care unit and treated with intravenous (IV) fluid repletion and IV insulin for DKA. The patient was diagnosed with new-onset type 1 diabetes mellitus (T1DM) induced by ICI therapy., Discussion: Approximately 75% of patients diagnosed with ICI-induced T1DM initially present with DKA. This, along with the rapid onset of hyperglycemia in this patient, suggests current guidelines for monitoring blood glucose are inadequate. Current guidelines recommend monitoring blood glucose at the following times: baseline, at the initiation of each cycle for 12 weeks, and then every 3-6 weeks thereafter. We propose the following schedule for monitoring blood glucose in patients receiving ICI therapy: baseline, twice weekly for the first six cycles, and then once weekly thereafter. This proposed update is supported by our patient's rapid onset of hyperglycemia and other case reports and reviews showing that most patients with this diagnosis have an initial presentation of DKA. Detecting hyperglycemia and starting treatment early is important in the prevention of acute complications from uncontrolled T1DM, like DKA., Conclusion: This case adds to the existing body of literature and provides support for more frequent monitoring of blood glucose in patients receiving ICI therapy. Blood glucose monitoring is a simple, reliable, low risk, and inexpensive laboratory test that should be used in patients receiving ICI therapy to ensure prompt diagnosis and treatment of T1DM., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Background: This study assessed changes in actigraphy-estimated sleep and glycemic outcomes after initiating automated insulin delivery (AID)., Methods: Ten adults with long-standing type 1 diabetes and impaired awareness of hypoglycemia (IAH) participated in an 18-month clinical trial assessing an AID intervention on hypoglycemia and counter-regulatory mechanisms. Data from eight participants (median age = 58 years) with concurrent wrist actigraph and continuous glucose monitoring (CGM) data were used in the present analyses. Actigraphs and CGM measured sleep and glycemic control at baseline (one week) and months 3, 6, 9, 12, 15, and 18 (three weeks) following AID initiation. HypoCount software integrated actigraphy with CGM data to separate wake and sleep-associated glycemic measures. Paired sample t -tests and Cohen's d effect sizes modeled changes and their magnitude in sleep, glycemic control, IAH (Clarke score), hypoglycemia severity (HYPO score), hypoglycemia exposure (CGM), and glycemic variability (lability index [LI]; CGM coefficient-of-variation [CV]) from baseline to 18 months., Results: Sleep improved from baseline to 18 months (shorter sleep latency [ P < .05, d = 1.74], later sleep offset [ P < .05, d = 0.90], less wake after sleep onset [ P < .01, d = 1.43]). Later sleep onset ( d = 0.74) and sleep midpoint ( d = 0.77) showed medium effect sizes. Sleep improvements were evident from 12 to 15 months after AID initiation and were preceded by improved hypoglycemia awareness (Clarke score [ d = 1.18]), reduced hypoglycemia severity (HYPO score [ d = 2.13]), reduced sleep-associated hypoglycemia (percent time glucose was < 54 mg/dL, < 60 mg/dL,< 70 mg/dL; d = 0.66-0.81), and reduced glucose variability (LI, d = 0.86; CV, d = 0.62)., Conclusion: AID improved sleep initiation and maintenance. Improved awareness of hypoglycemia, reduced hypoglycemia severity, hypoglycemia exposure, and glucose variability preceded sleep improvements.This trial is registered with ClinicalTrials.gov NCT03215914 https://clinicaltrials.gov/ct2/show/NCT03215914., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Severe hypoglycemia is a serious adverse drug event associated with hypoglycemia-prone medications; older patients with diabetes are particularly at high risk. Economic food insecurity (food insecurity due to financial limitations) is a known risk factor for hypoglycemia; however, less is known about physical food insecurity (due to difficulty cooking or shopping for food), which may increase with age, and its association with hypoglycemia., Objective: Study associations between food insecurity and severe hypoglycemia., Design: Survey based cross-sectional study., Participants: Survey responses were collected in 2019 from 1,164 older (≥ 65 years) patients with type 2 diabetes treated with insulin or sulfonylureas., Main Measures: Risk ratios (RR) for economic and physical food insecurity associated with self-reported severe hypoglycemia (low blood glucose requiring assistance) adjusted for age, financial strain, HbA1c, Charlson comorbidity score and frailty. Self-reported reasons for hypoglycemia endorsed by respondents., Key Results: Food insecurity was reported by 12.3% of the respondents; of whom 38.4% reported economic food insecurity only, 21.1% physical food insecurity only and 40.5% both. Economic food insecurity and physical food insecurity were strongly associated with severe hypoglycemia (RR = 4.3; p = 0.02 and RR = 4.4; p = 0.002, respectively). Missed meals ("skipped meals, not eating enough or waiting too long to eat") was the dominant reason (77.5%) given for hypoglycemia., Conclusions: Hypoglycemia prevention efforts among older patients with diabetes using hypoglycemia-prone medications should address food insecurity. Standard food insecurity questions, which are used to identify economic food insecurity, will fail to identify patients who have physical food insecurity only., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Objective: Automated insulin delivery (AID) systems are a rapidly growing component in the area of continuous subcutaneous insulin infusion (CSII) therapy. As more patients use these systems in the outpatient setting, it is important to assess safety if their use is allowed to continue in the inpatient setting., Methods: Analysis was conducted of the records of patients using AID technology upon admission to our hospital between June 2020 and December 2022. Adverse events and glycemic control of AID users were compared with patients using non-AID systems and with patients who had CSII discontinued., Results: There were 185 patients analyzed: 64 on AID, 86 on non-AID, and 35 who had CSII discontinued. The number of patients on AID increased over the course of the observation period, whereas non-AID users decreased. Pairwise comparisons indicated that patient-stay mean glucose levels and percentage of hypoglycemic events were similar between all groups, but the percentage of patient hyperglycemic measurements was significantly lower in the AID cohort. No adverse events (diabetic ketoacidosis, pump site complications, equipment malfunction) were reported in any either CSII cohort., Conclusion: The type of CSII technology encountered in the hospital is shifting from non-AID toward AID technologies. This analysis supports earlier findings that outpatient AID systems can be successfully transitioned into the inpatient setting. Further study is needed to define if AID systems offer any advantage in glycemic control., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Background: Automated insulin delivery is the treatment of choice in adults with type 1 diabetes. Data are needed on the efficacy and safety of automated insulin delivery for children and youth with diabetes and elevated glycated hemoglobin levels., Methods: In this multicenter, open-label randomized controlled trial, we assigned patients with type 1 diabetes in a 1:1 ratio either to use an automated insulin delivery system (MiniMed 780G) or to receive usual diabetes care of multiple daily injections or non--automated pump therapy (control). The patients were children and youth (defined as 7 to 25 years of age) with elevated glycemia (glycated hemoglobin ≥8.5% with no upper limit). The primary outcome was the baseline-adjusted between-group difference in glycated hemoglobin at 13 weeks., Results: A total of 80 patients underwent randomization (37 to automated insulin delivery and 43 to control) and all patients completed the trial. At 13 weeks, the mean (±SD) glycated hemoglobin decreased from 10.5±1.9% to 8.1±1.8% in the automated insulin delivery group but remained relatively consistent in the control group, changing from 10.4±1.6% to 10.6±1.8% (baseline-adjusted between-group difference, -2.5 percentage points; 95% confidence interval [CI], -3.1 to -1.8; P<0.001). Patients in the automated insulin delivery group spent on average 8.4 hours more in the target glucose range of 70 to 180 mg/dl than those in the control group. One severe hypoglycemia event and two diabetic ketoacidosis events occurred in the control group, with no such events in the automated insulin delivery group., Conclusions: In this trial of 80 children and youth with elevated glycated hemoglobin, automated insulin delivery significantly reduced glycated hemoglobin compared with usual diabetes care, without resulting in severe hypoglycemia or diabetic ketoacidosis events. (Funded by Lions Clubs New Zealand District 202F and others; Australian New Zealand Clinical Trials Registry number, ACTRN12622001454763.).

Background: The conventional dose of 10 units of intravenous (IV) regular insulin to treat hyperkalemia has been associated with hypoglycemia. There have been retrospective studies evaluating weight-based dose vs conventional dose of IV regular insulin but the comparative efficacy and safety is not well established. Objective : Evaluate the difference in weight-based dosing of IV regular insulin between patients who experienced hypoglycemia vs. patients who did not experience hypoglycemia after the administration of IV regular insulin. Methods: This was a retrospective, electronic chart review at a single academic medical center which included patients ≥18 years of age with an emergency department or inpatient encounter who were administered IV regular insulin within 6 hours of a pre-treatment potassium of ≥5 mmol/L. Results: There was no significant difference in the weight-based insulin dose between patients who experienced a hypoglycemic event and patients who did not experience a hypoglycemic event (.14 vs .22 units/kg; P = .44). The potassium-lowering effect was similar between the two groups (1.02 vs .96 mmol/L; P = .56). A regression analysis revealed that female sex, low baseline blood glucose (glucose <140 mg/dL), and those who received a repeat dose of IV regular insulin were independent risk factors for development of hypoglycemia. Conclusion: This study found no difference in hypoglycemic events and potassium lowering based on IV weight-based regular insulin dosing, however other risk factors may predict hypoglycemia., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To predict hypoglycemia and hyperglycemia risk during and after activity for adolescents with type 1 diabetes (T1D) using real-world data from the Type 1 Diabetes Exercise Initiative Pediatric (T1DEXIP) study. Methods: Adolescents with T1D ( n = 225; [mean ± SD] age = 14 ± 2 years; HbA1c = 7.1 ± 1.3%; T1D duration = 5 ± 4 years; 56% using hybrid closed loop), wearing continuous glucose monitors (CGMs), logged 3738 total activities over 10 days. Repeated Measures Random Forest (RMRF) and Repeated Measures Logistic Regression (RMLR) models were used to predict a composite risk of hypoglycemia (<70 mg/dL) and hyperglycemia (>250 mg/dL) within 2 h after starting exercise. Results: RMRF achieved high precision predicting composite risk and was more accurate than RMLR Area under the receiver operating characteristic curve (AUROC 0.737 vs. 0.661; P < 0.001). Activities with minimal composite risk had a starting glucose between 132 and 160 mg/dL and a glucose rate of change at activity start between -0.4 and -1.9 mg/dL/min. Time <70 mg/dL and time >250 mg/dL during the prior 24 h, HbA1c level, and insulin on board at activity start were also predictive. Separate models explored factors at the end of activity; activities with glucose between 128 and 133 mg/dL and glucose rate of change between 0.4 and -0.6 mg/dL/min had minimal composite risk. Conclusions: Physically active adolescents with T1D should aim to start exercise with an interstitial glucose between 130 and 160 mg/dL with a flat or slightly decreasing CGM trend to minimize risk for developing dysglycemia. Incorporating factors such as historical glucose and insulin can improve prediction modeling for the acute glucose responses to exercise.

Aims: To conduct a systematic review and meta-analysis, within the Coordinating Research and Evidence for Medical Devices (CORE-MD) project, evaluating CE-marked high-risk devices for glucose management., Materials and Methods: We identified interventional and observational studies evaluating the efficacy and safety of eight automated insulin delivery (AID) systems, two implantable insulin pumps, and three implantable continuous glucose monitoring (CGM) devices. We meta-analysed randomized controlled trials (RCTs) comparing AID systems with other treatments., Results: A total of 182 studies published between 2009 and 2024 were included, comprising 166 studies on AID systems, six on insulin pumps, and 10 on CGM devices; 26% reported industry funding; 18% were pre-market; 37% had a comparator group. Of the studies identified, 29% were RCTs, 24% were non-randomized trials, and 47% were observational studies. The median (interquartile range) sample size was 48 (28-102), age 34.8 (14-44.2) years, and study duration 17.5 (12-26) weeks. AID systems lowered glycated haemoglobin by 0.5 percentage points (absolute mean difference [MD] = -0.5; 21 RCTs; I 2  = 86%) and increased time in target range for sensor glucose level by 13.4 percentage points (MD = 13.4; 14 RCTs; I 2  = 90%). At least one safety outcome was assessed in 71% of studies., Conclusions: High-risk devices for glucose monitoring or insulin dosing, in particular AID systems, improve glucose control safely, but evidence on diabetes-related end-organ damage is lacking due to short study durations. Methodological heterogeneity highlights the need for developing standards for future pre- and post-market investigations of diabetes-specific high-risk medical devices., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objective: Use of continuous glucose monitoring (CGM) has led to greater detection of hypoglycemia; the clinical significance of this is not fully understood. The Hypoglycaemia-Measurement, Thresholds and Impacts (Hypo-METRICS) study was designed to investigate the rates and duration of sensor-detected hypoglycemia (SDH) and their relationship with person-reported hypoglycemia (PRH) in people living with type 1 diabetes (T1D) and insulin-treated type 2 diabetes (T2D) with prior experience of hypoglycemia., Research Design and Methods: We recruited 276 participants with T1D and 321 with T2D who wore a blinded CGM and recorded PRH in the Hypo-METRICS app over 10 weeks. Rates of SDH <70 mg/dL, SDH <54 mg/dL, and PRH were expressed as median episodes per week. Episodes of SDH were matched to episodes of PRH that occurred within 1 h., Results: Median [interquartile range] rates of hypoglycemia were significantly higher in T1D versus T2D; for SDH <70 mg/dL (6.5 [3.8-10.4] vs. 2.1 [0.8-4.0]), SDH <54 mg/dL (1.2 [0.4-2.5] vs. 0.2 [0.0-0.5]), and PRH (3.9 [2.4-5.9] vs. 1.1 [0.5-2.0]). Overall, 65% of SDH <70 mg/dL was not associated with PRH, and 43% of PRH had no associated SDH. The median proportion of SDH associated with PRH in T1D was higher for SDH <70 mg/dL (40% vs. 22%) and SDH <54 mg/dL (47% vs. 25%) than in T2D., Conclusions: The novel findings are that at least half of CGM hypoglycemia is asymptomatic, even below 54 mg/dL, and many reported symptomatic hypoglycemia episodes happen above 70 mg/dL. In the clinical and research setting, these episodes cannot be used interchangeably, and both need to be recorded and addressed., (© 2024 by the American Diabetes Association.)

Aims: The safety and efficacy of insulin analogue insulin aspart (IAsp) have been demonstrated in a randomised clinical trial in pregnant women with Type 1 diabetes (T1D), and IAsp is widely used during pregnancy. The aim of this study was to assess glycaemic control and safety of IAsp versus other bolus insulins in Type 1 diabetic pregnancy in a real-world setting., Methods: This was a post hoc analysis of a prospective cohort study of 1840 pregnant women with T1D, treated with IAsp (n = 1434) or other bolus insulins (n = 406) in the Diabetes Pregnancy Registry. The primary (composite) outcome was the proportion of pregnancies resulting in major congenital malformations or perinatal or neonatal death. Secondary outcomes included all HbA 1c values measured immediately before and during pregnancy and major hypoglycaemia, as well as abortion, pre-eclampsia, pre-term delivery, large for gestational age at birth, stillbirth and fetal malformations., Results: There were no significant differences found in any of the pregnancy outcomes between treatment with IAsp and other bolus insulins in either the crude or propensity score-adjusted analyses. However, maternal HbA 1c was lower in the IAsp group at the end of the third trimester (adjusted difference, -0.16% point [95% CI -0.28;-0.05]; -1.8 mmol/mol [95% CI -3.1;-0.6]; p = 0.0046)., Conclusions: No significant differences in safety or pregnancy outcomes were demonstrated when comparing treatment with IAsp versus other bolus insulins in women with T1D during pregnancy. The observed improvement in HbA 1c with IAsp in late pregnancy should be confirmed in other studies., (© 2024 The Author(s). Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Rationale: Glucagon-like peptide-1 is an endogenous incretin that plays an active role in weight loss and hypoglycemia. Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), which has been approved for the treatment of patients with type 2 diabetes (T2D). GLP-1RAs can increase insulin secretion and inhibit glucagon release, thereby leading to a decrease in blood glucose levels within the body. Specifically, GLP-1RAs control postprandial blood glucose levels by inhibiting hepatic glucose production and delaying gastric emptying. However, attention should be given to gastrointestinal adverse reactions. There are currently a few cases of GLP-1RA causing diabetic ketoacidosis (DKA)., Patient Concerns: The following report details the case of a 50-year-old Chinese female who has been living with diabetes for 12 years. Initially diagnosed with T2D, she was subsequently identified as a patient with latent autoimmune diabetes in adults (LADA) following treatment. The patient presented severe nausea, vomiting, and fatigue 1 day after injecting dulaglutide 1 time and discontinuing insulin therapy. She was diagnosed with severe DKA in the emergency department., Diagnoses: LADA and DKA., Interventions: Changed from dulaglutide to insulin therapy., Outcomes: After discontinuing dulaglutide and switching to insulin for blood glucose reduction, the patient's DKA was corrected, and blood glucose levels returned to normal., Lessons: This case suggests that clinicians should be alert to patients with severe DKA in cases of severe gastrointestinal adverse reactions after the use of GLP-1RAs. In addition, in most countries, GLP-1RAs are administered to patients with T2D, but we should consider the use of GLP-1RAs in patients with type 1 diabetes and LADA., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Nocturnal hypoglycemia is a common acute complication of people with diabetes on insulin therapy. In particular, the inability to control glucose levels during sleep, the impact of external factors such as exercise, or alcohol and the influence of hormones are the main causes. Nocturnal hypoglycemia has several negative somatic, psychological, and social effects for people with diabetes, which are summarized in this article. With the advent of continuous glucose monitoring (CGM), it has been shown that the number of nocturnal hypoglycemic events was significantly underestimated when traditional blood glucose monitoring was used. The CGM can reduce the number of nocturnal hypoglycemia episodes with the help of alarms, trend arrows, and evaluation routines. In combination with CGM with an insulin pump and an algorithm, automatic glucose adjustment (AID) systems have their particular strength in nocturnal glucose regulation and the prevention of nocturnal hypoglycemia. Nevertheless, the problem of nocturnal hypoglycemia has not yet been solved completely with the technologies currently available. The CGM systems that use predictive models to warn of hypoglycemia, improved AID systems that recognize hypoglycemia patterns even better, and the increasing integration of artificial intelligence methods are promising approaches in the future to significantly minimize the risk of a side effect of insulin therapy that is burdensome for people with diabetes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: BK is head of the research institute of the diabetes academy Bad Mergentheim (FIDAM). BK has received speakers’ honoraria or consulting fees form Abbott, Bayer, Berlin Chemie, Dexcom, Embecta, Emperra, Lilly, Novo Nordisk, Roche, Sanofi, and Ypsomed. GF is general manager and medical director of the Institute for Diabetes Technology (Institut für Diabetes-Technologie Forschungs- und Entwicklungsgesellschaft mbH an der Universität Ulm, Ulm, Germany IfDT), I, which carries out clinical studies, eg, with medical devices for diabetes therapy on its own initiative and on behalf of various companies. GF/IfDT have received research support, speakers’ honoraria, or consulting fees in the last three years from Abbott, Ascensia, Berlin Chemie, Boydsense, Dexcom, Lilly Deutschland, Novo Nordisk, Perfood, PharmaSens, Roche, Sinocare, Terumo, and Ypsomed. RZ has received speakers’ honoraria or consulting fees in the last three years from Abbott, Dexcom, Lilly, Medtronic, mySugr, Novo Nordisk, Roche Diabetes Care, Sanofi, Vertex, VitalAire/Tandem, and Ypsomed. LH is a shareholder of the Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany and a consultant for several companies that are developing novel diagnostic and therapeutic options for diabetes treatment. OS is general manager and founder of Sciarc GmbH. He is consultant to several companies that are developing products for metabolic, cardiovascular, and kidney diseases.

Aim: To compare the efficacy and safety profiles of recent innovations in type 2 diabetes mellitus (T2DM), which include once-weekly formulations such as tirzepatide, a dual glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptor agonist, and once-weekly insulin options such as icodec and basal insulin Fc., Methods: A systematic search of the PubMed, Scopus, Cochrane, and Web of Science databases was conducted. The network meta-analysis protocol was registered at OSF registries (https://osf.io/gd67x). The primary outcome of interest was change in glycated haemoglobin (HbA1c), with change in fasting plasma glucose (FPG), body weight, incidence of hypoglycaemia, and treatment discontinuation as secondary outcomes., Results: Tirzepatide exhibited superior efficacy in reducing HbA1c levels compared with insulin therapies, with the 15-mg dose showing the most significant reduction (mean difference [MD] -1.27, 95% confidence interval [CI] -1.49; -1.0). In terms of FPG reduction, tirzepatide 15 mg ranked highest (MD -0.70, 95% CI -1.05; -0.34), followed by tirzepatide 10 mg and 5 mg. Additionally, tirzepatide led to substantial weight loss, with the 15-mg dose exhibiting the most pronounced effect (MD -12.13, 95% CI -13.98; -10.27). However, a higher incidence of adverse events (AEs) and treatment discontinuation were associated with tirzepatide, particularly at higher doses., Conclusion: Tirzepatide, particularly at higher doses, demonstrates superior efficacy in lowering HbA1c and reducing hypoglycaemia risk compared with weekly insulin. However, its use is also associated with a higher incidence of AEs and treatment discontinuation., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Nocturnal hypoglycaemia is a burden for people with diabetes, particularly when treated with multiple daily injections (MDI) therapy. However, the characteristics of nocturnal hypoglycaemic events in this patient group are only poorly described in the literature., Method: Continuous glucose monitoring (CGM) data from 185 study participants with type 1 diabetes using MDI therapy were collected under everyday conditions for up to 13 weeks. Hypoglycaemic events were identified as episodes of consecutive CGM readings <70 mg/dl or <54 mg/dl for at least 15 minutes. Subsequently, the time <54 mg/dl (TB54), time below range (TBR), time in range (TIR), time above range (TAR), glucose coefficient of variation (CV), and incidence of hypoglycaemic events were calculated for diurnal and nocturnal periods. Furthermore, the effect of nocturnal hypoglycaemic events on glucose levels the following day was assessed., Results: The incidence of hypoglycaemic events <70 mg/dl was significantly lower during the night compared to the day, with 0.8 and 3.8 events per week, respectively, while the TBR, TB54, and incidence of events with CGM readings <54 mg/dl was not significantly different. Nocturnal hypoglycaemic events <70 mg/dl were significantly longer (60 vs 35 minutes) and enveloped by less rapidly changing glucose levels. On days following nights containing hypoglycaemic events, there was a decrease in TAR, mean CGM glucose level and morning glucose levels and an increase in TB54, TBR, and CV., Conclusions: The results showed that nocturnal hypoglycaemic events are a common occurrence in persons with type 1 diabetes using MDI with significant differences between the characteristics of nocturnal and diurnal events., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: GF is the general manager and medical director of the Institute for Diabetes Technology (Institut für Diabetes-Technologie Forschungs- und Entwicklungsgesellschaft mbH an der Universität Ulm, Ulm, Germany), which carries out clinical studies, for example, with medical devices for diabetes therapy on its own initiative and on behalf of various companies. GF/IfDT have received research support, speakers’ honoraria or consulting fees in the last 3 years from Abbott, Ascensia, Berlin Chemie, Boydsense, Dexcom, Lilly Deutschland, Novo Nordisk, Perfood, Pharmasens, Roche, Sinocare, Terumo, and Ypsomed. ME, DW, and SÖ are employees of IfDT. LH is a shareholder of the Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany. LH is a consultant for several companies that are developing novel diagnostic and therapeutic options for diabetes treatment. RZ has received speakers’ honoraria or consulting fees in the last 3 years from Abbott, Dexcom, Lilly, Medtronic, mySugr, Novo Nordisk, Roche Diabetes Care, VitalAire, and Ypsomed. BK has received speakers’ honoraria or consulting fees from Abbott, Bayer, Berlin Chemie, Dexcom, Embecta, Emperra, Lilly, Novo Nordisk, Roche, Sanofi, Ypsomed. OS is the founder and general manager of Sciarc GmbH, Baierbrunn, Germany. OS is a consultant for several companies that are developing diagnostic and therapeutic options for the management of cardiovascular diseases, chronic kidney diseases, obesity, and metabolic diseases. TG is an employee and stockholder of Roche Diabetes Care GmbH, Mannheim, Germany.

Introduction: Lipodystrophy can cause poor glycemic control in addition to cosmetic problems in children and adolescents with type 1 diabetes mellitus. However, data on its prevalence and associated factors is scarce among children and adolescents who live in developing countries like Ethiopia., Objective: To determine the prevalence and identify associated factors of lipodystrophy in children and adolescents with type 1 diabetes mellitus who visited the endocrinology clinic of Ayder Comprehensive Specialized Hospital between May 1 and July 31, 2020., Method: This was an institution-based cross-sectional study conducted on 57 children and 65 adolescents with type 1 diabetes mellitus who had been taking insulin injections for a year or more. The dependent variable was lipodystrophy. A pretested, structured questionnaire was used to collect data related to lipodystrophy and other characteristics. The principal investigator oversaw the data collection, which was done by pediatric and child health specialty residents with training. Data was subjected to descriptive statistics, and predictors of lipodystrophy were identified by fitting a multivariable logistic regression model. Statistical significance was declared at p < 0.05., Results: More than half (53.3%) of patients were in the age range of 13 to 17. The male-to-female ratio was almost 1:1. Educational status for 63.1% of patients was primary school. Four-fifths of patients were residing in urban areas. Of the 122 participants, 60 (49.2%) had lipodystrophy (48.3% lipohypertrophy and 0.8% lipoatrophy), with grade II lipohypertrophy being the most common type at 81.7%. The thigh was the most common site of lipodystrophy. In multivariable regression analysis, the long duration of insulin injection (AOR = 3.6, 95% CI, 1.5 to 9.0, p = 0.005) and inappropriate rotation of the injection site (AOR = 9.0, 95% CI, 2.2 to 37.0, p = 0.002) were significantly associated with lipodystrophy. HbA1c testing was conducted for 70 patients, and poor glycemic control (HbA1c ≥ 7%) was found in 43 (61.4%) of them. Patients with lipodystrophy were more likely to have poor glycemic control (75%) than those without lipodystrophy (47.1%) (p = 0.016)., Conclusion: The prevalence of lipodystrophy was comparable with other studies. Long duration of insulin injection and improper rotation of the injection site are associated with an increased risk of lipodystrophy. Patients with lipodystrophy were more likely to have poor glycemic control, defined by higher HgA1c, than those without lipodystrophy. Proper education of patients and their parents must include correct injection techniques, rotating injection sites, and changing injection sites intermittently to lessen the risk of developing lipodystrophy., (© 2024. The Author(s).)

Background: Antidiabetic drugs are widely used in clinical practice as essential drugs for the treatment of diabetes. The effect of hypoglycemic drugs on erectile dysfunction has not been fully proven due to the presence of multiple confounding factors., Methods: Two-sample Mendelian randomization (TSMR) was used to examine the causal effect of antidiabetic drugs (including metformin, insulin and gliclazide) on erectile dysfunction. We used five robust analytic methods, of which the inverse variance weighting (IVW) method was the primary method, and also assessed factors such as sensitivity, pleiotropy, and heterogeneity. Effect statistics for exposures and outcomes were downloaded from publicly available data sets, including open Genome-Wide Association Studies (GWAS) and the UK Biobank (UKB)., Results: In some of the hypoglycemic drug use, there was a significant causal relationship between metformin use and erectile dysfunction [Beta: 4.9386; OR:1.396E+02 (95% CI:9.13-2135); p-value: 0.0004), suggesting that metformin increased the risk of erectile dysfunction development. Also, we saw that gliclazide use also increased the risk of erectile dysfunction [Beta: 11.7187; OR:0.0125 (95% CI:12.44-1.21E+09); P value: 0.0125). There was no significant causal relationship between insulin use and erectile dysfunction [Beta: 3.0730; OR:21.6071 (95% CI:0.24-1942.38); p-value: 0.1806).Leave-one-out, MR-Egger, and MR-PRESSO analyses produced consistent results., Conclusion: The use of metformin and gliclazide have the potential to increase the risk of erectile dysfunction. There is no causal relationship between the use of insulin and erectile dysfunction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Feng, Jinhua, Shulin, Jiangping, Zhongxiang and Xiaohong.)

Background: Inpatient use of insulin pump therapy has been increasing due to greater availability of this technology, however there is a paucity of research that investigates glycemic control of inpatient insulin pump users., Objective: To compare the glycemic control of hospitalized patients with type 1 diabetes (T1D) who used insulin pump vs. multiple daily injections (MDI)., Design: Retrospective chart review., Participants: Patients with T1D who were hospitalized between January 1, 2017, and December 31, 2019, in an academic medical center in the New York metropolitan area., Main Measures: Patients were categorized into three groups based on their method of insulin administration: "pump only" group used insulin pump exclusively, "MDI only" group used MDI only, and "intermittent pump" group used a combination of both methods. The primary endpoints are mean blood glucose, rates of hypoglycemic events (blood glucose < 70 mg/dL), and rates of hyperglycemic events (blood glucose > 250 mg/dL). Separate multivariable Poisson regressions were performed to determine the association between the type of insulin administration and rate outcomes (i.e., rate of hypoglycemic events and rate of hyperglycemic events)., Results: The study included 78 patients with a mean age of 51, who were mostly male (54%), and white (72%). The average proportion of glucose measurements that were hyperglycemic for the "pump only", "MDI only", and "intermittent pump" groups were 0.11 (SD = 0.11), 0.25 (SD = 0.19), and 0.24 (SD = 0.25), respectively. The "pump only" group has a significantly lower proportion of hyperglycemic events as compared to the "MDI only" group (p = 0.0227)., Conclusions: In this sample, patients who exclusively used their insulin pump while inpatient had a lower rate of hyperglycemic events than patients who used MDI only; suggesting that select patients can safely continue their insulin pump therapy in the inpatient setting., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Aim: Experimental hypoglycaemia blunts the counterregulatory hormone and symptom responses to a subsequent episode of hypoglycaemia. In this study, we aimed to assess the associations between antecedent exposure and continuous glucose monitoring (CGM)-recorded hypoglycaemia during a 1-week period and the counterregulatory responses to subsequent experimental hypoglycaemia in people with type 1 diabetes., Materials and Methods: Forty-two people with type 1 diabetes (20 females, mean ± SD glycated haemoglobin 7.8% ± 1.0%, diabetes duration median (interquartile range) 22.0 (10.5-34.9) years, 29 CGM users, and 19 with impaired awareness of hypoglycaemia) wore an open intermittently scanned CGM for 1 week to detect hypoglycaemic exposure before a standardized hyperinsulinaemic-hypoglycaemic [2.8 ± 0.1 mmol/L (50.2 ± 2.3 mg/dl)] glucose clamp. Symptom responses and counterregulatory hormones were measured during the clamp. The study is part of the HypoRESOLVE project., Results: CGM-recorded hypoglycaemia in the week before the clamp was negatively associated with adrenaline response [β -0.09, 95% CI (-0.16, -0.02) nmol/L, p = .014], after adjusting for CGM use, awareness of hypoglycaemia, glycated haemoglobin and total daily insulin dose. This was driven by level 2 hypoglycaemia [<3.0 mmol/L (54 mg/dl)] [β -0.21, 95% CI (-0.41, -0.01) nmol/L, p = .034]. CGM-recorded hypoglycaemia was negatively associated with total, autonomic, and neuroglycopenic symptom responses, but these associations were lost after adjusting for potential confounders., Conclusions: Recent exposure to CGM-detected hypoglycaemia was independently associated with an attenuated adrenaline response to experimental hypoglycaemia in people with type 1 diabetes., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)