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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: 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).

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: 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.

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.).

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.)

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: 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.)

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: 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.)

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.)

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.

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.)

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.

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.)

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.)

Insulin autoimmune syndrome (IAS) is a rare condition triggered by exposure to various drugs containing sulfhydryl compounds, proton pump inhibitors, supplements, plasma proteins, viral infections like measles, influenza, hepatitis C, and autoimmune conditions like Graves' disease and systemic lupus erythematosus. 1,3 We report two patients with recurrent episodes of hypoglycemia who were then diagnosed with IAS due to the consumption of α-lipoic acid (ALA) present in a multivitamin supplement. Eating small, frequent meals containing complex carbohydrates and steroids helps normalize blood glucose levels and reduce the insulin autoantibodies (IAA) to undetectable levels. 3 ., (© Journal of the Association of Physicians of India 2024.)

Aim: To assess the differential association of risk factors with severe and non-severe hypoglycaemia., Materials and Methods: The Hypoglycaemia Assessment Tool study evaluated the risk of hypoglycaemia over a 4-week period in patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) on insulin in 24 countries. Negative binomial regressions were applied to examine the associations of several risk factors with severe and non-severe hypoglycaemia., Results: The median age was 41 years in 5949 patients with T1D and 62 years in 12 914 patients with T2D. The 4-week rates of non-severe hypoglycaemic were 5.57 and 1.40 episodes per person in T1D and T2D, respectively; the corresponding rates for severe hypoglycaemia were 0.94 and 0.30. The excess risk was 42% higher for severe than non-severe hypoglycaemia in females versus males with T2D; 27% higher in patients with T2D with versus without a continuous glucose monitoring (CGM); and 47% lower in patients with T1D with versus without an insulin pump. The excess risk also differed across geographical areas and was marginally lower for severe than non-severe hypoglycaemia for higher values of HbA1c in patients with T2D. Associations with severity of hypoglycaemia were not different for age, diabetes and insulin therapy duration, previous hypoglycaemic episodes and insulin regimen., Conclusions: The risk of severe versus non-severe hypoglycaemia differs in patients with T1D and T2D; sex, the use of a CGM and insulin pump, and geographical areas were differently associated with one type of hypoglycaemia than the other., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Introduction: This study examined associations between hypoglycemia awareness status and hypoglycemia symptoms reported in real-time using the novel Hypoglycaemia-MEasurement, ThResholds and ImpaCtS (Hypo-METRICS) smartphone application (app) among adults with insulin-treated type 1 (T1D) or type 2 diabetes (T2D). Methods: Adults who experienced at least one hypoglycemic episode in the previous 3 months were recruited to the Hypo-METRICS study. They prospectively reported hypoglycemia episodes using the app for 10 weeks. Any of eight hypoglycemia symptoms were considered present if intensity was rated between "A little bit" to "Very much" and absent if rated "Not at all." Associations between hypoglycemia awareness (as defined by Gold score) and hypoglycemia symptoms were modeled using mixed-effects binary logistic regression, adjusting for glucose monitoring method and diabetes duration. Results: Of 531 participants (48% T1D, 52% T2D), 45% were women, 91% white, and 59% used Flash or continuous glucose monitoring. Impaired awareness of hypoglycemia (IAH) was associated with lower odds of reporting autonomic symptoms than normal awareness of hypoglycemia (NAH) (T1D odds ratio [OR] 0.43 [95% confidence interval {CI} 0.25-0.73], P  = 0.002); T2D OR 0.51 [95% CI 0.26-0.99], P  = 0.048), with no differences in neuroglycopenic symptoms. In T1D, relative to NAH, IAH was associated with higher odds of reporting autonomic symptoms at a glucose concentration <54 than >70 mg/dL (OR 2.18 [95% CI 1.21-3.94], P  = 0.010). Conclusion: The Hypo-METRICS app is sensitive to differences in hypoglycemia symptoms according to hypoglycemia awareness in both diabetes types. Given its high ecological validity and low recall bias, the app may be a useful tool in research and clinical settings. The clinical trial registration number is NCT04304963.

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.)

Background: Metformin is a first-line pharmacotherapy for type 2 diabetes, but there is limited evidence about its safety in early pregnancy., Objective: To evaluate the teratogenicity of metformin use in the first trimester of pregnancy., Design: In an observational cohort of pregnant women with pregestational type 2 diabetes receiving metformin monotherapy before the last menstrual period (LMP), a target trial with 2 treatment strategies was emulated: insulin monotherapy (discontinue metformin treatment and initiate insulin within 90 days of LMP) or insulin plus metformin (continue metformin and initiate insulin within 90 days of LMP)., Setting: U.S. Medicaid health care administration database (2000 to 2018)., Participants: 12 489 pregnant women who met the eligibility criteria., Measurements: The risk and risk ratio of nonlive births, live births with congenital malformations, and congenital malformations among live births were estimated using standardization to adjust for covariates., Results: A total of 850 women were in the insulin monotherapy group and 1557 in the insulin plus metformin group. The estimated risk for nonlive birth was 32.7% under insulin monotherapy (reference) and 34.3% under insulin plus metformin (risk ratio, 1.02 [95% CI, 1.01 to 1.04]). The estimated risk for live birth with congenital malformations was 8.0% (CI, 5.7% to 10.2%) under insulin monotherapy and 5.7% (CI, 4.5% to 7.3%) under insulin plus metformin (risk ratio, 0.72 [CI, 0.51 to 1.09])., Limitation: Possible residual confounding by glycemic control and body mass index., Conclusion: Compared with switching to insulin monotherapy, continuing metformin and adding insulin in early pregnancy resulted in little to no increased risk for nonlive birth among women receiving metformin before pregnancy. Under conventional statistical criteria, anything between a 49% decrease and a 9% increase in risk for congenital malformations was highly compatible with our data., Primary Funding Source: National Institutes of Health., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-2038.

Aim: To provide updated efficacy and safety information for teplizumab in the treatment of Stage 3 type 1 diabetes mellitus (T1DM)., Materials and Methods: The PubMed, Embase and Cochrane databases were searched for randomized controlled trials (RCTs) comparing teplizumab to placebo for T1DM that reported any of the following outcomes: (1) C-peptide area under the curve (AUC); (2) glycated haemoglobin (HbA1c) levels; (3) insulin requirements; and (4) adverse events. Heterogeneity was examined with I 2 statistics. p values <0.05 were taken to indicate statistical significance. The continuous endpoints were compared through the pooled mean difference (MD) and binary endpoints were assessed using risk ratios, both with 95% confidence intervals (CIs). Statistical analyses were performed using Review Manager Web software., Results: Eight RCTs with 1052 patients (754 receiving teplizumab) were included. Teplizumab significantly increased the AUC of C-peptide levels at 6 (MD 0.10 nmol/L, 95% CI 0.05, 0.16), 12 (MD 0.13 nmol/L, 95% CI 0.06, 0.20), 18 (MD 0.18 nmol/L, 95% CI 0.09, 0.27) and 24 months (MD 0.16 nmol/L, 95% CI 0.02, 0.31), significantly reduced HbA1c levels at 6 (MD -0.57%, 95% CI -1.07, -0.08) and 12 months (MD -0.31%, 95% CI -0.59, -0.02), and significantly reduced insulin requirements at 6 (MD -0.12 U/kg, 95% CI -0.16, -0.08), 12 (MD -0.11 U/kg, 95% CI -0.15, -0.07), 18 (MD -0.17 U/kg, 95% CI -0.26, -0.09) and 24 months (MD -0.11 U/kg, 95% CI -0.22, -0.01)., Conclusion: Teplizumab increases AUC of C-peptide levels and decreases HbA1c levels and insulin use, without raising serious adverse event risk., (© 2024 John Wiley & Sons Ltd.)

Inpatient treatment of hyperkalaemia with insulin and dextrose can be complicated by iatrogenic hypoglycaemia. We sought to assess the incidence of hypoglycaemia in hospitalised patients with renal disease and assess the impact of the introduction of a local guideline incorporating the use of sodium zirconium cyclosilicate (SZC) for patients with moderate hyperkalaemia. After establishing a significant burden of hypoglycaemia in the initial observation period, a requirement for hourly capillary blood glucose monitoring (for up to 6 h) following the administration of insulin for hyperkalaemia was incorporated into the guidelines. The two-fold introduction of SZC alongside changes in patient care after the administration of insulin/dextrose resulted in more appropriate use of insulin/dextrose, as well as a significant (73%) reduction in the iatrogenic burden of hypoglycaemia (P = 0.04)., Competing Interests: Declaration of competing interest None of the authors have any conflict of interest or relationships with industry that could have influenced this manuscript., (Copyright © 2024. Published by Elsevier Ltd.)

Aims/hypothesis: A protective role of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1 receptor agonists (GLP1-ra) in the development of diabetic retinopathy and diabetic macular oedema has been described in some recent studies, which may extend beyond glycaemic control. We aimed to review the clinical impact of SGLT2i and GLP1-ra therapy on the risk of diabetic retinopathy and diabetic macular oedema in individuals with type 2 diabetes taking insulin., Methods: This is a retrospective cohort analysis of approximately two million people with type 2 diabetes receiving insulin across 97 healthcare organisations using a global federated health research network (TriNetX, Cambridge, USA). Two intervention cohorts (SGLT2i + insulin, n=176,409; GLP1-ra + insulin, n=207,034) were compared against a control cohort (insulin with no SGLT2i/GLP1-ra, n=1,922,312). Kaplan-Meier survival analysis was performed and estimated HRs were reported for each outcome. Propensity score was used to 1:1 match for age, sex, ischaemic heart disease, hypertension, microvascular complications, chronic kidney disease, HbA 1c , BMI and use of pioglitazone, lipid modifying agents, antilipemic agents, ACE inhibitors, angiotensin II inhibitors and metformin. A sub-analysis comparing the two intervention cohorts was also performed., Results: SGLT2i with insulin was associated with a reduced HR (95% CI) for diabetic macular oedema compared with the control cohort (0.835; 0.780, 0.893), while GLP1-ra with insulin demonstrated a lack of signal with no statistical significance to the HR (1.013; 0.960, 1.069). SGLT2i with insulin was not associated with a clinically significant increase in the risk of developing diabetic retinopathy (1.076; 1.027, 1.127), while GLP1-ra with insulin increased diabetic retinopathy risk (1.308; 1.261, 1.357). Compared with SGLT2i with insulin, GLP1-ra with insulin was associated with higher risk of diabetic retinopathy (1.205; 1.153, 1.259) and diabetic macular oedema (1.130; 1.056, 1.208)., Conclusions/interpretation: Our study suggests that the combination of SGLT2i and insulin is associated with lower risk of developing diabetic macular oedema. However, the use of GLP1-ra was associated with an increased risk of diabetic retinopathy in individuals with type 2 diabetes also taking insulin. A comparative analysis showed favourable outcomes with SGLT2i and insulin in the development of diabetic macular oedema and diabetic retinopathy. RCTs using dedicated  retinal imaging are required to determine the causal relationship with these therapies., (© 2024. The Author(s).)

Introduction: Insulin-derived amyloidosis (AIns), a skin complication in patients with diabetes, causes impaired insulin absorption. This systematic review aims to get a better understanding of this overlooked condition., Methods: Comprehensive literature searches were performed in Scopus, PubMed, EMBASE, and Web of Science databases until June 17, 2023. From 19,343 publications, duplicate and irrelevant records were eliminated by title, and the full texts of the remaining studies were examined for validity. Clinical, pathological, and therapeutic findings were extracted from 44 papers., Results: Forty-four articles were studied that covered 127 insulin-treated patients with diabetes. From the 62 patients with reported age and sex, males had a mean age of 58 years, and females 68.5 years. While AIns were twice as likely to develop in men (66.13 %) as in women (33.87 %), the administered insulin dose was significantly higher in males (p = 0.017). The most common insulin injection site was the abdominal wall (77.63 %). Histological findings showed the presence of amorphous material with the occasional presence of lymphocytes, plasma cells, macrophages, adipocytes, histocytes, and giant cells. The mean HbA1c level was 8.8 % and the need for receiving insulin was increased in AIns. Changing the site of insulin injections and/or surgically removing the nodules were the most common treatments to obtain better insulin uptake and controlled serum glucose levels., Conclusion: This study highlights the importance of AIns, proper rotation of insulin injection site, and post-treatment patient follow-up to recognize and prevent the development of amyloid nodules., 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 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved.)

Aim: To summarise, in a narrative review, published data on hypoglycaemia occurrence with basal insulin therapy in adults with type 1 diabetes treated with basal-bolus insulin regimens in treat-to-target randomised controlled trials., Methods: Data were included from 21 eligible trials, which mainly used self-measured blood glucose or plasma glucose to detect hypoglycaemia., Results: All-day self-measured blood glucose or plasma glucose level 2 (glucose threshold of 3.1 or 3.0 mmol/L) and level 3 (severe, requiring assistance) hypoglycaemic events were reported, respectively, by a range of 69.0%-97.5% and 0%-13.4% adults when receiving basal-bolus insulin therapy, with rates of 10.6-68.1 and 0.0-0.4 events per patient-year of exposure, respectively. Hypoglycaemia rates measured using continuous glucose monitoring (three studies) were numerically, yet consistently, higher than with either other method, except when limiting to symptomatic events. Nocturnal hypoglycaemia rates were generally less than 30% of the equivalent all-day rates., Conclusions: Differences across the studies in design (e.g., titration targets) and participant characteristics hindered comparison of hypoglycaemia rates by insulin formulation. Consequently, few trends were identified by insulin formulation, study methodology or individuals' characteristics, suggesting that further research is required to identify treatment strategies that facilitate development of individualised recommendations to lower hypoglycaemia risk. These findings are useful to understand hypoglycaemia risk with available basal insulin therapies when used in a multiple daily injection regimen, as well as to provide context for the results of ongoing and future clinical trials, including those for two once-weekly basal insulins, insulin icodec and basal insulin Fc., (© 2024 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Objective: Many hybrid closed-loop (HCL) systems struggle to manage unusually high glucose levels as experienced with intercurrent illness or pre-menstrually. Manual correction boluses may be needed, increasing hypoglycemia risk with overcorrection. The Cambridge HCL system includes a user-initiated algorithm intensification mode ("Boost"), activation of which increases automated insulin delivery by approximately 35%, while remaining glucose-responsive. In this analysis, we assessed the safety of "Boost" mode., Methods: We retrospectively analyzed data from closed-loop studies involving young children (1-7 years, n = 24), children and adolescents (10-17 years, n = 19), adults (≥24 years, n = 13), and older adults (≥60 years, n = 20) with type 1 diabetes. Outcomes were calculated per participant for days with ≥30 minutes of "Boost" use versus days with no "Boost" use. Participants with <10 "Boost" days were excluded. The main outcome was time spent in hypoglycemia <70 and <54 mg/dL., Results: Eight weeks of data for 76 participants were analyzed. There was no difference in time spent <70 and <54 mg/dL between "Boost" days and "non-Boost" days; mean difference: -0.10% (95% confidence interval [CI] -0.28 to 0.07; P = .249) time <70 mg/dL, and 0.03 (-0.04 to 0.09; P = .416) time < 54 mg/dL. Time in significant hyperglycemia >300 mg/dL was 1.39 percentage points (1.01 to 1.77; P < .001) higher on "Boost" days, with higher mean glucose and lower time in target range ( P < .001)., Conclusions: Use of an algorithm intensification mode in HCL therapy is safe across all age groups with type 1 diabetes. The higher time in hyperglycemia observed on "Boost" days suggests that users are more likely to use algorithm intensification on days with extreme hyperglycemic excursions., 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: RH reports having received speaker honoraria from Eli Lilly, Dexcom, and Novo Nordisk; receiving license fees from BBraun; patents related to closed-loop; and being director at CamDiab. JW reports receiving speaker honoraria from Ypsomed. YR is a consultant at CamDiab. MEW is a consultant at CamDiab and reports patents related to closed-loop. CKB reports receiving consultancy fees from CamDiab and speaker honoraria from Ypsomed. SH reports speaker and advisory board fees from Dexcom, Medtronic, Sanofi, and Ypsomed; being director at ASK Diabetes Ltd; and receiving consulting/training fees from CamDiab. LB reports receiving research support from Dexcom and CamDiab. REJB reports receiving speaking honoraria from Eli Lilly and Springer Healthcare, and sitting as a voluntary unpaid member of the NovoNordisk UK Foundation Research Selection committee. FMC reports receiving speaker honoraria from Eli Lilly, Dexcom, and Novo Nordisk and Insulet, and consultancy fees from Abbott Diabetes Care. EF-R reports having received speaker honoraria from Eli Lilly and Novo Nordisk, serving on advisory boards for Eli Lilly and Sanofi. MLE is a clinical triallist with or has served on advisory boards or received speakers or writers fees from Medtronic, Dexcom, Abbott Diabetes Care, Roche, AstraZeneca, Novo Nordisk, Eli Lilly, Zucara, Pila Pharma, and Imcyse Pharma. SEH has received speaker honoraria by Eli Lilly, Vertex, Minimed Medtronic, Insulet, Ypsomed, and Sanofi. TMK reports having received speaker honoraria from Eli Lilly and Novo. LL has received personal fees from Abbott Diabetes Care, Dexcom, Insulet, Medtronic, Novo Nordisk, Sanofi, and Diabetes Care. JKM is a member on the advisory board of Boehringer Ingelheim, Becton-Dickinson, Eli Lilly, Medtronic, Prediktor A/S, Roche Diabetes Care, and Sanofi-Aventis, and received speaker honoraria from Abbott Diabetes Care, AstraZeneca, Becton-Dickinson, Dexcom, Eli Lilly, Mercke Sharp & Dohme, NovoNordisk, Roche Diabetes Care, Sanofi, Servier, and Ypsomed. TR reports receiving speaker honoraria from Novo Nordisk and consultancy fees from Abbott Diabetes Care. HT reports receiving research support from Dexcom and speaker honoraria from Eli Lilly. MT reports having received speaker honoraria from Eli Lilly, Novo Nordisk, and Medtronic and advisory board fees from Abbott Diabetes Care. BR-M has received speaker honoraria from Abbott Diabetes Care, Eli Lilly, Medtronic, Novo Nordisk, Roche Diabetes Care, Sanofi, and Menarini and has been on the advisory boards of Eli Lilly, Roche Diabetes Care, and Abbott Diabetes Care. CdB has received speaker honoraria from Minimed Medtronic, and has been member of their European Psychology and e-learning Advisory Board. JMA reports training fees from CamDiab. DE, WMM, PN, TP, AG, AT, KD, and NT have no disclosures.

Objective: To investigate causal associations between diabetes, insulin treatment and osteoporosis using LDSC analysis with a 2-way Mendelian randomization study., Methods: LDSC analysis was used to estimate the likelihood-scale heritability of the genome-wide association study used with genetic correlation between the 2 genome-wide association study used. Then a 2-sample Mendelian randomization study was performed using 3 methods including inverse variance weighted, MR Egger, and weighted median., Results: The genetic correlation between diabetes, insulin treatment (h2&#95;Z = 3.70, P = 2.16e-4), osteoporosis (h2&#95;Z = 4.93, h2&#95;p = 8.13e-7) and genes was significant. There was a significant genetic correlation (rg = 0.122, P = 0.0211). There was a causal association between diabetes, insulin treatment and osteoporosis [P = 0.003754, OR (95%CI) = 0.998876 (0.998116-0.999636)], while no causal association existed between osteoporosis and insulin use (P = 0.998116-0.999636) causal association existed (P = 0.333244)., Conclusion: There was a strong genetic correlation between diabetes, insulin treatment and osteoporosis, a causal association between diabetes, insulin treatment and osteoporosis, and no causal association between osteoporosis and diabetes, insulin treatment., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The infusion of glucose-insulin-potassium (GIK) has yielded conflicting results in terms of cardioprotective effects. We conducted a meta-analysis to examine the impact of perioperative GIK infusion in early outcome after cardiac surgery. Randomized controlled trials (RCTs) were eligible if they examined the efficacy of GIK infusion in adults undergoing cardiac surgery. The main study endpoint was postoperative myocardial infarction (MI) and secondary outcomes were hemodynamics, any complications and hospital resources utilization. Subgroup analyses explored the impact of the type of surgery, GIK composition and timing of administration. Odds ratio (OR) or mean difference (MD) with 95% confidence interval (CI) were calculated with a random-effects model. Fifty-three studies (n=6129) met the inclusion criteria. Perioperative GIK infusion was effective in reducing MI (k=32 OR 0.66[0.48, 0.89] P=0.0069), acute kidney injury (k=7 OR 0.57[0.4, 0.82] P=0.0023) and hospital length of stay (k=19 MD -0.89[-1.63, -0.16] days P=0.0175). Postoperatively, the GIK-treated group presented higher cardiac index (k=14 MD 0.43[0.29, 0.57] L/min P<0.0001) and lesser hyperglycemia (k=20 MD -30[-47, -13] mg/dL P=0.0005) than in the usual care group. The GIK-associated protection for MI was effective when insulin infusion rate exceeded 2 mUI/kg/min and after coronary artery bypass surgery. Certainty of evidence was low given imprecision of the effect estimate, heterogeneity in outcome definition and risk of bias. Perioperative GIK infusion is associated with improved early outcome and reduced hospital resource utilization after cardiac surgery. Supporting evidence is heterogenous and further research is needed to standardize the optimal timing and composition of GIK solutions., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: To document the prevalence of skin problems associated with insulin pump use and identify contributing factors among children with type 1 diabetes mellitus in China., Methods: In total, 461 children were recruited from an online community (i.e., a Wechat group) of pediatric patients with T1DM. A self-developed questionnaire was filled in by parents, collecting the information on social demographics, disease, and insulin pump therapy related characteristics and skin problems. We applied the Mann-Whitney U test, Chi square test and logistic regression analysis to identify the factors associated with skin problems., Results: Of the 461 responders, 308 (66.8 %) children were reported to have skin problems. More specifically, 38.8 % had pigmentation changes, 22.3 % allergy/dermatitis, 20.2 % scaring, 11.5 % pain, 10.8 % infection, 10.6 % subcutaneous lipohypertrophy, and 6.1 % lipoatrophy. Logistic regression analysis showed that independent associated factors of skin problems were the caregiver's educational level as college or above, patient having skin allergies, and using the Brand 2 insulin pump (p values < 0.05)., Conclusions: The present study documents the prevalence of skin problems and identifies associated factors, such as caregiver's education, patients skin allergies, and using a specific brand of pump. Health education should address these factors in addition to the traditionally emphasized factors., 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.)

The objective of this review was to comprehensively present and summarize trends in reported rates of hypoglycemia with one or two times per day basal insulin analogs in individuals with type 2 diabetes to help address and contextualize the emerging theoretical concern of increased hypoglycemic risk with once-weekly basal insulins.Hypoglycemia data were extracted from treat-to-target randomized clinical trials conducted during 2000-2022. Published articles were identified on PubMed or within the US Food and Drug Administration submission documents. Overall, 57 articles were identified: 44 assessed hypoglycemic outcomes in participants receiving basal-only therapy (33 in insulin-naive participants; 11 in insulin-experienced participants), 4 in a mixed population (insulin-naive and insulin-experienced participants) and 9 in participants receiving basal-bolus therapy. For the analysis, emphasis was placed on level 2 (blood glucose <3.0 mmol/L (<54 mg/dL)) and level 3 (or severe) hypoglycemia.Overall, event rates for level 2 or level 3 hypoglycemia across most studies ranged from 0.06 to 7.10 events/person-year of exposure (PYE) for participants receiving a basal-only insulin regimen; the rate for basal-bolus regimens ranged from 2.4 to 13.6 events/PYE. Rates were generally lower with second-generation basal insulins (insulin degludec or insulin glargine U300) than with neutral protamine Hagedorn insulin or first-generation basal insulins (insulin detemir or insulin glargine U100). Subgroup categorization by sulfonylurea usage, end-of-treatment insulin dose or glycated hemoglobin reduction did not show consistent trends on overall hypoglycemia rates. Hypoglycemia rates reported so far for once-weekly basal insulins are consistent with or lower than those reported for daily-administered basal insulin analogs., Competing Interests: Competing interests: JR has served on advisory panels for Applied Therapeutics, Biomea Fusion, Boehringer Ingelheim, Eli Lilly, Endogenex, Hanmi, Novo Nordisk, Oramed, Regor, Sanofi, Scholar Rock, Structure Therapeutics, Terns Pharmaceuticals and Zealand Pharma; and has received research support, consulting fees or honoraria from Applied Therapeutics, AstraZeneca, Biomea Fusion, Boehringer Ingelheim, Eli Lilly, Endogenex, Hanmi, Novo Nordisk, Oramed, Regor, Sanofi, Scholar Rock, Structure Therapeutics, Terns Pharmaceuticals and Zealand Pharma. HSB reports trial fees paid to his institution by Amgen, AstraZeneca, Boehringer Ingelheim, Ceapro, Eli Lilly, Gilead, Janssen, Kowa Pharmaceuticals, Madrigal Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, Ionis and Tricida. IL reports receiving grants, personal fees, or non-financial support from Sanofi, Lilly, Boehringer Ingelheim, Merck/Pfizer, Mylan, AstraZeneca, Johnson & Johnson, Intercept, Target Pharma, Zealand, Shionogi, Carmot, Structure, Bayer, Mediflix, WebMD, GI Dynamics, Intarcia Therapeutics, Mannkind, Novartis, Novo Nordisk, Structure Therapeutics and Valeritas. SRH reports consultancy with Eli Lilly, Zealand Pharma and Zucara Pharma; has participated in speaker panels for AstraZeneca, Medtronic and Novo Nordisk; and receives grant support from Dexcom., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hyperglycemia occurs in 22% to 46% of hospitalized patients, negatively affecting patient outcomes, including mortality, inpatient complications, length of stay, and hospital costs. Achieving inpatient glycemic control is challenging due to inconsistent caloric intake, changes from home medications, a catabolic state in the setting of acute illness, consequences of acute inflammation, intercurrent infection, and limitations in labor-intensive glucose monitoring and insulin administration., Method: We conducted a retrospective cross-sectional analysis at the University of California San Francisco hospitals between September 3, 2020 and September 2, 2021, comparing point-of-care glucose measurements in patients on nil per os (NPO), continuous total parenteral nutrition, or continuous tube feeding assigned to our novel automated self-adjusting subcutaneous insulin algorithm (SQIA) or conventional, physician-driven insulin dosing. We also evaluated physician efficiency by tracking the number of insulin orders placed or modified., Results: The proportion of glucose in range (70-180 mg/dL) was higher in the SQIA group than in the conventional group (71.0% vs 69.0%, P = .153). The SQIA led to a lower proportion of severe hyperglycemia (>250 mg/dL; 5.8% vs 7.2%, P = .017), hypoglycemia (54-69 mg/dL; 0.8% vs 1.2%, P = .029), and severe hypoglycemia (<54 mg/dL; 0.3% vs 0.5%, P = .076) events. The number of orders a physician had to place while a patient was on the SQIA was reduced by a factor of more than 12, when compared with while a patient was on conventional insulin dosing., Conclusions: The SQIA reduced severe hyperglycemia, hypoglycemia, and severe hypoglycemia compared with conventional insulin dosing. It also improved physician efficiency by reducing the number of order modifications a physician had to place., 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/aims: Exogenous insulin therapy increases systemic exposure to insulin which may promote the development of colorectal neoplasia. We sought to evaluate the association between exogenous insulin therapy and the incidence of advanced adenoma in type 2 diabetes mellitus., Methods: A retrospective cohort study was conducted from January 1, 2007, to January 1, 2018, in a regional health system serving the United States Philadelphia metropolitan area, Central New Jersey, and South Central Pennsylvania. Study patients consisted of a random sample of patients with type 2 diabetes mellitus aged 40-80 years who had undergone two rounds of colonoscopy examinations. The exposure was cumulative duration of insulin therapy (i.e., no use, 1-365 days and > 365 days). The outcome was time to incident advanced adenoma., Results: Of the 975 eligible patients, 184 patients accumulated > 365 days of insulin therapy before the follow-up colonoscopy. The mean (standard deviation) duration between the two rounds of colonoscopy examination was 5.1 (2.9) years among the insulin users and 5.3 (3.9) years among non-users. Compared to no insulin exposure, receiving > 365 days of insulin therapy was associated with an increased incidence of advanced adenoma (adjusted hazard ratio [aHR] 4.84, 95% confidence interval [CI] 2.82-8.30), right-sided advanced adenoma (aHR 5.48, 95% CI 2.90-10.35), and 3 or more adenomas (aHR 2.61, 95% CI 1.46-4.69) at the follow-up colonoscopy examination., Conclusion: Insulin therapy is associated with an increased risk of advanced adenoma and may serve as a novel risk-stratification factor to enhance the efficiency of existing colorectal cancer screening and surveillance programs., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background and Aims: Hypoglycemia may lead to anxiety, poor adherence, and hypoglycemia unawareness and is especially a threat during the night in patients with insulin-treated type 2 diabetes (T2D). It would therefore be beneficial to warn patients at risk of hypoglycemia at bedtime so they can react accordingly and avoid the episode. Hence, the aim of the present study was to develop a model for predicting nocturnal hypoglycemia., Methods: Continuous glucose monitoring (CGM), mealtime, and insulin data were collected from 67 insulin-treated patients with T2D (NCT01819129). Data were structured into 24-hour periods and labeled as nocturnal hypoglycemia or not depending on whether 15 consecutive minutes were spent below 3.0 mmol/L (54 mg/dL) during the following night. Each period was divided into "last night," "morning," "day," and "evening" for feature extraction purposes, and 72 potential features were extracted for every period. A five-fold cross-validation was used to select features by forward selection and for training and validating a model based on logistic regression., Results: The prediction model was based on 30 patients with 60/496 periods resulting in nocturnal hypoglycemia. Forward selection revealed that the best features were based on CGM and involved the last value and mean value during the evening, as well as the relative difference in maximum value during the day between the present period and previous periods. The model obtained a mean area under the receiver operating characteristics curve (AUC) of 0.82 with an accuracy of 0.79., Conclusions: The model was able to predict nocturnal hypoglycemia with an acceptable accuracy and could therefore prevent such cases., 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.

Purpose: While intravenous (IV) insulin is often administered at a fixed dose of 10 units for acute hyperkalemia, optimal dosing for minimizing hypoglycemia while effectively reversing hyperkalemia has not been established. The purpose of this analysis was to evaluate the effect of insulin dosing strategies on hypoglycemia in patients with hyperkalemia., Methods: Adult patients presenting to an academic medical center who received IV insulin for hyperkalemia between 2016 and 2020 were retrospectively identified. Patients treated with 10 units of insulin (fixed) were compared to those who received < 10 units (reduced). The primary outcome was the incidence of hypoglycemia (blood glucose < 70 mg/dL) within 12 hours of insulin administration. Secondary outcomes included the incidence of severe hypoglycemia (blood glucose < 40 mg/dL) and change in potassium. Multivariable analyses were used to assess for risk factors for hypoglycemia and severe hypoglycemia., Findings: Of the 2576 patients included, 305 (11.8%) received reduced dosing and 2271 (88.2%) received fixed dosing. Hypoglycemia occurred in 16.7% of the reduced group and 15.9% of the fixed group (P = 0.70). Severe hypoglycemia occurred in 2.3% of the reduced group and 2.5% of the fixed group (P = 0.86). Median potassium reduction from baseline to first check post-insulin was less with reduced dosing (-0.6 mEq/L vs -0.8 mEq/L, P < 0.001). On multivariable regression analysis, greater weight-based insulin dose and ED location were significant predictors for hypoglycemia and severe hypoglycemia. Location in the intensive care unit was associated with a decreased risk of hypoglycemia. Higher pre-insulin glucose was protective for hypoglycemia and severe hypoglycemia., Implications: The incidence of hypoglycemia was similar among both groups. Greater weight-based insulin dose was a significant risk factor for hypoglycemia, while higher baseline glucose levels were associated with a decreased risk, indicating that patient-specific insulin dosing for hyperkalemia may be warranted., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jeremy DeGrado reports a relationship with Pfizer Inc that includes: consulting or advisory. Jeremy DeGrado reports a relationship with Eli Lilly and Company that includes: consulting or advisory. Jeremy DeGrado reports a relationship with Marinus Pharmaceuticals Inc that includes: consulting or advisory. If there are other authors, they 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.)

Objective: While there are some recommendations about early insulin therapy in newly diagnosed Type 2 Diabetes Mellitus (T2DM) patients, there is not sufficient evidence on this strategy's cost-effectiveness. This study compared early insulin therapy versus oral anti-diabetic drugs (OADs) for managing T2DMusing a cost-effectiveness analysis approach in Iran., Methods: In this economic evaluation, a decision analytic model was designed. The target population was newly diagnosed type 2 diabetic patients, and the study was carried out from the perspective of Iran's healthcare system with a one-year time horizon. Basal insulin, Dipeptidyl peptidase-4 (DPP-4) inhibitors, and Thiazolidinediones (TZDs) were compared in this evaluation. The main outcome for assessing the effectiveness of each intervention was the reduction in the occurrence of diabetes complications. Strategies were compared using the incremental cost-effectiveness ratio (ICER), and deterministic and probabilistic sensitivity analyses were carried out., Results: The DPP-4 inhibitors strategy was the dominant strategy with the highest effectiveness and the lowest cost. Early insulin therapy was dominated (ICER: $-53,703.18), meaning that it was not cost-effective. The sensitivity analyses consistently affirmed the robustness of the base case findings. The probabilistic sensitivity analysis indicated probabilities of 77%, 22%, and 1% for DPP-4 inhibitors, TZDs strategies, and early insulin therapy, respectively, in terms of being cost-effective., Conclusion: In terms of cost-effectiveness, early insulin therapy was not cost-effective compared to OADs for managing newly diagnosed T2DM patients. Future studies in this regard, utilizing more comprehensive evidence, can yield more accurate results.

Aims: To compare the efficacy and safety of basal-plus (BP) insulin regimen with or without sitagliptin in non-critically ill patients with type 2 diabetes (T2D)., Methods: This open-label, randomized clinical trial included inpatients with a previous diagnosis of T2D and blood glucose (BG) between 180 and 400 mg/dL. Participants received basal and correctional insulin doses (BP regimen) either with or without sitagliptin. The primary outcome was the difference in the mean daily BG among the groups., Results: Seventy-six patients (mean age 60 years, 64 % men) were randomized. Compared with BP insulin therapy alone, the sitagliptin-BP combination led to a lower mean daily BG (158.8 vs 175.0 mg/dL, P = 0.014), a higher percentage of readings within a BG range of 70-180 mg/dL (75.9 % vs 64.7 %, P < 0.001), and a lower number of BG readings >180 mg/dL (P < 0.001). Sitagliptin-BP resulted in fewer basal and supplementary insulin doses (P = 0.024 and P = 0.017, respectively) and lower daily insulin injections (P = 0.023) than those with insulin alone. The proportion of patients with hypoglycemia was similar in the two groups., Conclusions: For inpatients with T2D and hyperglycemia, the sitagliptin and BP regimen combination is safe and more effective than insulin therapy alone., Clinicaltrials: gov identifier: NCT05579119., 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: Lipohypertrophy is a common complication in patients with diabetes receiving insulin therapy. There is a lack of consensus regarding how much lipohypertrophy affects diabetes management. Our study aimed to assess the potential correlation between lipohypertrophy and glycemic control, as well as insulin dosing in patients with diabetes. Methods: We performed a systematic review followed by a meta-analysis to collect data about glycemic control and insulin dosing in diabetic patients with and without lipohypertrophy. To identify relevant studies published in English, we searched medical databases (MEDLINE/PubMed, Embase, and CENTRAL) from 1990 to January 20, 2023. An additional hand-search of references was performed to retrieve publications not indexed in medical databases. Results of meta-analyses were presented either as prevalence odds ratios (pORs) or mean differences (MDs) with 95% confidence intervals (95% CIs). This study was registered on PROSPERO (CRD42023393103). Results: Of the 5540 records and 240 full-text articles screened, 37 studies fulfilled the prespecified inclusion criteria. Performed meta-analyses showed that patients with lipohypertrophy compared with those without lipohypertrophy were more likely to experience unexplained hypoglycemia (pOR [95% CI] = 6.98 [3.30-14.77]), overall hypoglycemia (pOR [95% CI] = 6.65 [1.37-32.36]), and glycemic variability (pOR [95% CI] = 5.24 [2.68-10.23]). Patients with lipohypertrophy also had higher HbA1c (MD [95% CI] = 0.55 [0.23-0.87] %), and increased daily insulin consumption (MD [95% CI] = 7.68 IU [5.31-10.06]). Conclusions: These results suggest that overall glycemic control is worse in patients with lipohypertrophy than in those without this condition.

ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review insulin, which has at least one plausible mechanism for slowing ALS progression. However, pre-clinical studies are limited and there have been no trials in PALS yet. Insulin use in patients without a metabolic need may cause very serious and potentially lethal side effects. While further studies to evaluate potential benefits may be warranted, at this time we cannot endorse insulin treatment to slow ALS progression.

Objective: Determine whether continuous glucose monitor (CGM) metrics can provide actionable advance warning of an emergency department (ED) visit or hospitalization for hypoglycemic or hyperglycemic (dysglycemic) events. Research Design and Methods: Two nested case-control studies were conducted among insulin-treated diabetes patients at Kaiser Permanente, who shared their CGM data with their providers. Cases included dysglycemic events identified from ED and hospital records (2016-2021). Controls were selected using incidence density sampling. Multiple CGM metrics were calculated among patients using CGM >70% of the time, using CGM data from two lookback periods (0-7 and 8-14 days) before each event. Generalized estimating equations were specified to estimate odds ratios and C-statistics. Results: Among 3626 CGM users, 108 patients had 154 hypoglycemic events and 165 patients had 335 hyperglycemic events. Approximately 25% of patients had no CGM data during either lookback; these patients had >2 × the odds of a hypoglycemic event and 3-4 × the odds of a hyperglycemic event. While several metrics were strongly associated with a dysglycemic event, none had good discrimination. Conclusion: Several CGM metrics were strongly associated with risk of dysglycemic events, and these can be used to identify higher risk patients. Also, patients who are not using their CGM device may be at elevated risk of adverse outcomes. However, no CGM metric or absence of CGM data had adequate discrimination to reliably provide actionable advance warning of an event and thus justify a rapid intervention.