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Aim: This study is aimed at assessing the prevalence of poor glycemic control using different metrics and its association with in-hospital adverse outcomes. Methods: This cross-sectional study was conducted in diabetic patients admitted to a third-level hospital in Colombia between January and July 2022. Poor glycemic control was determined using capillary glucose metrics, including mean glucose values outside the target range, derived time in range (dTIR) (100-180 mg/dL) < 70%, coefficient of variation (CV > 36%), and hypoglycemia (<70 mg/dL). Multiple regression models were adjusted for hospital outcomes based on glycemic control, as well as other sociodemographic and clinical covariates. Results: A total of 330 Hispanic patients were included. A total of 27.6% had mean glucose measurements outside the target range, 33% had a high CV, 64.8% had low dTIR, and 28.8% experienced hypoglycemia. The in-hospital mortality rate was 8.8%. An admission HbA1c level greater than 7% was linked to an increased mortality risk ( p = 0.016), as well as a higher average of glucometer readings (186 mg/dL vs. 143 mg/dL; p < 0.001). A lower average of dTIR (41.0% vs. 60.0%; p < 0.001) was also associated with a higher mortality risk. Glycemic variability was correlated with an increased risk of mortality, hypoglycemia, delirium, and length of hospital stay (LOS). Conclusion: A significant number of hospitalized diabetic patients exhibit poor glycemic control, which has been found to be associated with adverse outcomes, including increased mortality. Metrics like dTIR and glycemic variability should be considered as targets for glycemic control, highlighting the need for enhanced management strategies., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Edwin Mora Garzón et al.)

Introduction: there is a lack of research evaluating the impact of therapeutic switching from human insulin to analogues, particularly in paediatric populations from low- and middle-income countries., Aim: The study aimed to retrospectively assess the effectiveness and safety of transitioning from human insulin to insulin analogs in Tunisian children with diabetes., Methods: This retrospective descriptive study included children with type 1 diabetes who changed their insulin therapy protocol after at least one year of treatment with human insulin. Clinical, therapeutic, and glycaemic homeostasis parameters were assessed following the transition from human insulin (NPH + rapid-acting insulin) to the Basal-Bolus insulin analog- protocol., Results: The study included 60 patients. Following the switch, all patients showed a significant reduction in mean fasting blood glucose levels (11.11 mmol/l vs. 8.62 mmol/l; p=0.024). Glycated haemoglobin A1C levels decreased notably in children who adhered to their diet (from 9.93% to 8.38%; p=0.06) and/or engaged in regular physical activity (from 10.40% to 8.61%; p=0.043). The average number of hypoglycemic events per year decreased from 4.03 events/year to 2.36 events/year (p=0.006), along with a decrease in the rate of patients hospitalized for acid-ketotic decompensation (from 27% to 10%; p=0.001). Financial constraints led to 82% of patients reusing microfine needles ≥2 times per day, and 12% were compelled to revert to the initial insulin therapy protocol due to a lack of access to self-financed microfine needles or discontinued social coverage., Conclusions: Although insulin analogues offer clear benefits, their use poses challenges as a therapeutic choice for children with diabetes in low- to middle-income countries. These challenges hinder the achievement of optimal glycemic control goals.

Background: In the United States, approximately 1% of pregnancies are complicated by pregestational diabetes. Individuals with type 1 diabetes have an increased risk of adverse maternal and neonatal outcomes. While continuous glucose monitoring has demonstrated benefits for patients with type 1 diabetes, its cost is higher than traditional intermittent fingerstick monitoring, particularly if used only during pregnancy., Objective: To develop an economic analysis model to compare in silico the cost of continuous glucose monitoring and self-monitoring of blood glucose in a cohort of pregnant individuals with type 1 diabetes mellitus., Study Design: We developed an economic analysis model to compare two glucose monitoring strategies in pregnant individuals with type 1 diabetes: continuous glucose monitoring and self-monitoring. The model considered hypertensive disorders of pregnancy, large for gestational age, cesarean delivery, neonatal intensive care unit (NICU) admission, and neonatal hypoglycemia. The primary outcome was the total cost per strategy in 2022 USD from a health system perspective, with self-monitoring as the reference group. Probabilities, relative risks, and costs were extracted from the literature, and the costs were adjusted to 2022 US dollars. Sensitivity analyses were conducted by varying parameters based on the probability, relative risk, and cost distributions. The robustness of the results was tested through 1000 Monte Carlo simulations., Results: In the base-case analysis, the cost of pregnancy using continuous glucose monitoring was $26,837 compared to $29,039 for self-monitoring, resulting in a cost reduction of $2,202 per individual. The parameters with the greatest effect on the incremental cost included the relative risk of NICU admission, cost of NICU admission, continuous glucose monitoring costs, and usual care costs. Monte Carlo simulations indicated that continuous glucose monitoring was the optimal strategy 98.7% of the time. One-way sensitivity analysis showed that continuous glucose monitoring was more economical if the relative risk of NICU admission with continuous glucose monitoring vs. self-monitoring was below 1.15., Conclusion: Compared to self-monitoring, continuous glucose monitoring is an economical strategy for pregnant individuals with type 1 diabetes mellitus., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: Therapeutic inertia, hypoglycaemia and poor treatment persistence can lead to glycaemic fluctuation and poor outcomes in type 2 diabetes (T2D). We compared glycated haemoglobin (HbA1c) variability, insulin initiation, severe hypoglycaemia and clinical events in patients with T2D initiated dipeptidyl peptidase-4 inhibitors (DPP4is) at low versus high HbA1c thresholds., Methods: Using territory-wide electronic medical records in Hong Kong, we curated a propensity score-matched cohort of patients initiated DPP4i at HbA1c <7.5% versus ≥7.5% in 2007-2019. We expressed the HbA1c variability score (HVS) as a proportion of HbA1c varied by ≥0.5% compared with preceding values. We used the Cox model to compare the risks of insulin initiation and clinical outcomes, adjusted for time-varying variables between the two groups. Mediation analysis estimated the effects of HbA1c variability on outcomes., Results: Among 6874 insulin-naïve patients who initiated DPP4i, 88.7% were treated with metformin and 79.6% with sulphonylureas at baseline (54.9% men; mean age 65.2 ± 11.4 years). After a median follow-up of 4.6 years, compared with the high-threshold plus high-HVS group (≥50%), the low-threshold plus low-HVS (<50%) group had reduced hazard ratios (95% confidence interval) of insulin initiation (0.35, 0.31-0.40), severe hypoglycaemia (0.38, 0.34-0.44), major adverse cardiovascular endpoints (0.76, 0.66-0.88), heart failure (0.42, 0.36-0.49), end-stage kidney disease (0.65, 0.36-0.49) and mortality (0.45, 0.35-0.57). Reduced HbA1c variability explained 31.1%-81.2% of the effect size of DPP4i initiation at HbA1c <7.5% versus ≥7.5% on outcomes., Conclusions: In Chinese patients with T2D, avoiding therapeutic inertia with intensified glycaemic control at HbA1c <7.5% using drugs with low risk of hypoglycaemia and good tolerability, such as DPP4i, delayed insulin treatment, reduced HbA1c variability and improved clinical events., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To assess whether adults with diabetes on oral hypoglycaemic agents undergoing general endotracheal anaesthesia during nine common surgical procedures who are glucagon-like peptide-1 receptor agonist (GLP1-RA) users, compared with non-users, are at increased risk of six peri- and post-procedure complications., Materials and Methods: A retrospective observational cohort analysis of over 130 million deidentified US adults with diabetes (defined as being on oral hypoglycaemic agents) from a nationally representative electronic health dataset between 1 January 2015 and 1 April 2023 was analysed. Cohorts were matched by high-dimensionality propensity scoring. We compared the odds of six peri- and postoperative complications in GLP1-RA users and non-users. A sensitivity analysis compared these odds in GLP1-RA users to non-users with diabetes and obesity. We measured the odds of (a) a composite outcome of postoperative decelerated gastric emptying, including antiemetic use, ileus within 7 days post-procedure, gastroparesis diagnosis, gastric emptying study; (b) postoperative aspiration or pneumonitis; (c) severe respiratory failure; (d) postoperative hypoglycaemia; (e) inpatient mortality; and (f) 30-day mortality., Results: Among 13 361 adults with diabetes, 16.5% were treated with a GLP1-RA. In the high-dimensionality propensity score-matched cohort, GLP1-RA users had a lower risk of peri- and postoperative complications for decelerated gastric emptying and antiemetic use compared with non-users. The risk of ileus within 7 days, aspiration/pneumonitis, hypoglycaemia and 30-day mortality were not different. A sensitivity analysis showed similar findings in patients with diabetes and obesity., Conclusion: No increased risk of peri- and postoperative complications in GLP1-RA users undergoing surgery with general endotracheal anaesthesia was identified., (© 2024 John Wiley & Sons Ltd.)

Aims: In-hospital dysglycemia is associated with adverse outcomes. Identifying patients at risk of in-hospital dysglycemia early on admission may improve patient outcomes., Methods: We analysed 117 inpatients admitted with pneumonia and type 2 diabetes monitored by continuous glucose monitoring. We assessed potential risk factors for in-hospital dysglycemia and adverse clinical outcomes., Results: Time in range (3.9-10.0 mmol/l) decreased by 2.9 %-points [95 % CI 0.7-5.0] per 5 mmol/mol [2.6 %] increase in admission haemoglobin A1c, 16.2 %-points if admission diabetes therapy included insulin therapy [95 % CI 2.9-29.5], and 2.4 %-points [95 % CI 0.3-4.6] per increase in the Charlson Comorbidity Index (CCI) (integer, as a measure of severity and amount of comorbidities). Thirty-day readmission rate increased with an IRR of 1.24 [95 % CI 1.06-1.45] per increase in CCI. In-hospital mortality risk increased with an OR of 1.41 [95 % CI 1.07-1.87] per increase in Early Warning Score (EWS) (integer, as a measure of acute illness) at admission., Conclusions: Dysglycemia among hospitalised patients with pneumonia and type 2 diabetes was associated with high haemoglobin A1c, insulin treatment before admission, and the amount and severity of comorbidities (i.e., CCI). Thirty-day readmission rate increased with high CCI. The risk of in-hospital mortality increased with the degree of acute illness (i.e., high EWS) at admission. Clinical outcomes were independent of chronic glycemic status, i.e. HbA1c, and in-hospital glycemic status., Competing Interests: Declaration of competing interest MTO, CKK, and KBH have nothing to disclose. UPB has served on advisory boards and received lecture fees from Novo Nordisk and Sanofi. PLK has received speaker fees from Sanofi, Boehringer Ingelheim, Novo Nordisk, and AstraZeneca., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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.)

Aims: Hospitalized patients can have inconsistent nutritional intake due to acute illness, changing diet, or unpredictable meal delivery. The aim of this study was to evaluate whether implementation of a hospital-wide policy shifting nutritional insulin administration from pre-meal to post-meal was associated with changes in glycemic control or length of stay (LOS)., Methods: This retrospective study performed at a community hospital evaluated adult inpatients receiving nutritional insulin across three time periods. pre-intervention, immediate post-intervention, and distant post-intervention. Outcomes included rates of hypoglycemia (glucose ≤ 70 mg/dL), moderate hypoglycemia (< 54 mg/dL), severe hypoglycemia (≤ 40 mg/dL), severe hyperglycemia (≥ 300 mg/dL), daily mean glucose level, and LOS., Results: The number of patient-days analyzed across the cohorts were 1948, 1751, and 3244, respectively. After multivariate adjustment, risk of developing any hypoglycemia and severe hypoglycemia significantly decreased over time (p = 0.001 and p = 0.009, respectively). Daily mean glucose increased over time (194.6 ± 62.5 vs 196.8 ± 65.5 vs 199.3 ± 61.5 mg/dL; p = 0.003), but there were no significant differences among rates of severe hyperglycemia (p = 0.10) or LOS (p = 0.74)., Conclusions: Implementing a hospital-wide shift to postprandial nutritional insulin administration significantly reduced hypoglycemia rates without increasing severe hyperglycemia. This suggests a promising strategy for improving patient safety, but further prospective randomized controlled trials are warranted to confirm these findings., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.P.D. has received grant funding from DexCom, Inc for an unrelated outpatient study in patients with T1D. M.Z. discloses consulting for DexCom, Inc. and EMD Serono. All other authors have no declarations of interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: Gestational diabetes (GD) is a global health concern with significant implications for maternal and neonatal outcomes. This study investigates the association between early GD (eGD) diagnosis (<24 weeks), pharmacotherapy requirements and adverse neonatal outcomes., Materials and Methods: A cohort of 369 pregnant women underwent a 75-g oral glucose tolerance test. Maternal variables, pharmacotherapy prescriptions and neonatal outcomes were analysed employing t-tests, χ 2 tests, and logistic regression. A p < .05 was considered significant., Results: Early GD increased the odds of neonatal hypoglycaemia [odds ratio (OR): 18.57, p = .013] and respiratory distress syndrome (OR: 4.75, p = .034). Nutritional therapy prescription by an accredited nutritionist was the most common treatment in women diagnosed after 24 weeks, but those with eGD required more frequently specialized nutritional consulting + metformin to achieve glycaemic control (p = .027). eGD was associated with a higher requirement of nutritional therapy prescription + metformin (OR: 2.26, 95% confidence interval: 1.25-4.09, p = .007) and with maternal hyperglycaemia during the post-partum period at 2 h of the oral glucose tolerance test (OR: 1.03, 95% confidence interval: 1.02-1.13, p = .024)., Conclusion: Timely diagnosis and personalized treatment of GD are desirable because an earlier presentation is related to a higher risk of adverse neonatal and maternal outcomes., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To assess the efficacy and safety of dulaglutide 1.5 mg versus dulaglutide 0.75 mg in Japanese participants with type 2 diabetes (T2D)., Materials and Methods: A Phase 3, multicentre, randomized, double-blind, parallel-group study was conducted in Japanese participants aged ≥20 years, with T2D for ≥6 months and inadequate glycaemic control, while on a single oral antihyperglycaemic medication (NCT04809220). The primary objective was to evaluate superiority of dulaglutide 1.5 mg versus dulaglutide 0.75 mg measured by mean change in glycated haemoglobin (HbA1c) from baseline to 26 weeks. Other efficacy and safety endpoints were evaluated at 26 and 52 weeks. All statistical analyses were conducted using the intention-to-treat population., Results: Overall, 591 participants were randomized to once-weekly dulaglutide 1.5 mg or 0.75 mg. At Week 26, dulaglutide 1.5 mg was superior to dulaglutide 0.75 mg in HbA1c reduction from baseline (least squares mean [LSM] difference -0.29% [95% confidence interval {CI} -0.43, -0.14]). At Week 52, the dulaglutide 1.5-mg arm had a significantly greater proportion of participants who achieved HbA1c <7.0% (46.3% vs. 38.5%; p = 0.03) and showed significantly greater reduction in fasting serum glucose (LSM difference -9.4 mg/dL [95% CI -14.4, -4.3]; p < 0.001) versus the dulaglutide 0.75-mg arm. No statistically significant change in body weight was observed in either treatment arm. Overall, 442 participants (75.4%) experienced treatment emergent adverse events (TEAEs). Constipation (11.3%), diarrhoea (9.6%) and pyrexia (9.0%) were the most commonly reported TEAEs., Conclusions: Dulaglutide 1.5 mg once weekly demonstrated superior glycaemic control versus dulaglutide 0.75 mg once weekly, with comparable safety and tolerability, in Japanese people with T2D., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: Fluoroquinolone-related hypoglycaemia is rare but may become clinically relevant in individuals at high baseline hypoglycaemic risk, such as patients with diabetes using sulphonylureas. Our population-based cohort study assessed whether fluoroquinolones are associated with an increased risk of severe hypoglycaemia compared with amoxicillin among patients treated with sulphonylureas., Materials and Methods: Using the UK's Clinical Practice Research Datalink Aurum linked to hospitalization and vital statistics data, we assembled a base cohort of patients who initiated second-generation sulphonylureas (1998-2020). The study cohort included patients initiating either fluoroquinolones or amoxicillin while on sulphonylureas. Using an intent-to-treat exposure definition, we assessed the 30-day risk of severe hypoglycaemia (hospitalization with or death because of hypoglycaemia) associated with fluoroquinolones compared with amoxicillin. Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of severe hypoglycaemia after 1:5 matching on previous sulphonylurea use and propensity scores. Secondary analyses were stratified by demographics and glycated haemoglobin., Results: Overall, 143 417 patients initiated fluoroquinolones (n = 13 123) or amoxicillin (n = 130 294) while on sulphonylureas. Compared with amoxicillin, fluoroquinolones were not associated with the risk of severe hypoglycaemia (HR, 1.17; 95% CI, 0.91-1.50). Fluoroquinolones were associated with an increased risk in patients <65 years (HR, 2.90; 95% CI, 1.41-5.97) but not in those ≥65 years (HR, 1.03; 95% CI, 0.79-1.35) in stratified analyses. There was no evidence of effect modification by sex or glycated haemoglobin., Conclusions: In patients using second-generation sulphonylureas, fluoroquinolones were not associated with an increased risk of severe hypoglycaemia compared with amoxicillin. An increased risk among younger adults is possible., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To identify risk factors for nocturnal/morning hypo- and hyperglycaemia in type 1 diabetes., Methods: Data on self-management practices were obtained from 3-day records. We studied the associations between self-management practices on the first recording day and the self-reported blood glucose (BG) concentrations on the subsequent night/morning., Results: Of the 1025 participants (39 % men, median age 45 years), 4.4 % reported nocturnal hypoglycaemia (<3.9 mmol/l), 9.8 % morning hypoglycaemia, 51.5 % morning euglycaemia, and 34.3 % morning hyperglycaemia (≥8.9 mmol/l). Within hypoglycaemic range, insulin pump use was associated with higher nocturnal BG concentration (B=0.486 [95 % Confidence Interval=0.121-0.852], p=0.009). HbA 1c was positively (0.046 [0.028-0.065], p<0.001), while antecedent fibre intake (-0.327 [-0.543 - -0.111], p=0.003) and physical activity (PA) (-0.042 [-0.075 - -0.010], p=0.010) were inversely associated with morning BG concentration. The odds of morning hypoglycaemia were increased by previous day hypoglycaemia (OR=2.058, p=0.002) and alcohol intake (1.031, p=0.001). Previous day PA (0.977, p=0.031) and fibre intake (0.848, p=0.017) were inversely, while HbA 1c (1.027, p<0.001) was positively associated with the risk of morning hyperglycaemia., Conclusions: Alcohol avoidance may prevent nocturnal hypoglycaemia, while PA and fibre intake may reduce hyperglycaemia risk. Avoidance of daytime hypoglycaemia and keeping HbA 1c in control may help maintain normoglycaemia also at night-time., Competing Interests: Declaration of Competing Interest Professor Per-Henrik Groop has received investigator-initiated grants from Eli Lilly and Roche, is an advisory board member for AbbVie, Astellas, Astra Zeneca, Bayer, Boehringer-Ingelheim, Eli Lilly, Janssen, Medscape, MSD, Mundipharma, Nestlé, Novartis, Novo Nordisk, and Sanofi. He has received lecture honoraria from Astellas, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Elo Water, Genzyme, Medscape, MSD, Mundipharma, Novartis, Novo Nordisk, PeerVoice, Sanofi and Sciarc. Erika Parente has received lecture honoraria from Eli Lilly, Abbott, Astra Zeneca, Sanofi, and Boehringer Ingelheim. The other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: Studies examining the safety and effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT2is) versus glucagon-like peptide-1 receptor agonists (GLP-1RAs) among community-dwelling adults may not generalize to nursing home (NH) residents, who are typically older and more multimorbid. We compared the safety and cardiovascular effectiveness of SGLT2is and GLP-1RAs among US NH residents., Materials and Methods: Eligible individuals were aged ≥66 years with type 2 diabetes mellitus and initiated an SGLT2i or GLP-1RA in an NH between 2013 and 2018. Safety outcomes included fall-related injuries, hypoglycaemia, diabetic ketoacidosis (DKA), urinary tract infection or genital infection, and acute kidney injury in the year following treatment initiation. Cardiovascular effectiveness outcomes included death, major adverse cardiovascular events and hospitalization for heart failure. Per-protocol adjusted hazard ratios (HR) were calculated using stabilized inverse probability of treatment and censoring weighted cause-specific hazard regression models accounting for 127 covariates., Results: The study population included 7710 residents (31.08% SGLT2i, 68.92% GLP-1RA). Compared with GLP-1RA initiators, SGLT2i initiators had higher rates of DKA (HR 1.95, 95% confidence limits 1.27, 2.99) and death (HR 1.18, 95% confidence limits 1.02, 1.36). Rates of urinary tract infection or genital infection, acute kidney injury, major adverse cardiovascular events, and heart failure were also elevated, while rates of fall-related injuries and hypoglycaemia were reduced, but all estimates were imprecise and highly compatible with no difference., Conclusions: SGLT2is do not have superior, and may have inferior, effectiveness compared with GLP-1RAs for cardiovascular and mortality outcomes in NH residents. Residents initiating SGLT2is should be monitored closely for DKA., (© 2024 John Wiley & Sons Ltd.)

Background: Ebola virus disease (EVD) is associated with multisystem organ failure and high mortality. Severe hypoglycaemia is common, life-threatening, and correctable in critically ill patients, but glucose monitoring may be limited in EVD treatment units., Methods: We conducted a retrospective review of patients admitted to EVD treatment units in Butembo and Katwa, Eastern DRC. Glucose measurements were done using a handheld glucometer at the bedside or using the Piccolo xpress Chemistry Analyzer on venous samples., Findings: 384 patients (median age 30 years (interquartile range, IQR, 20-45), 57% female) and 6422 glucose measurements (median 11 per patient, IQR 4-22) were included in the analysis. Severe hypoglycaemia (≤2.2 mmol/L) and hyperglycaemia (>10 mmol/L) were recorded at least once during the ETU admission in 97 (25%) and 225 (59%) patients, respectively. A total of 2004 infusions of glucose-containing intravenous solutions were administered to 302 patients (79%) with a median cumulative dose of 175g (IQR 100-411). The overall case fatality rate was 157/384 (41%) and was 2.2-fold higher (95% CI 1.3-3.8) in patients with severe hypoglycaemia than those without hypoglycaemia (p = 0.0042). In a multivariable Cox proportional hazards model, periods of severe hypoglycaemia (adjusted hazard ratio (aHR) 6.2, 95% CI 3.2-12, p < 0.0001) and moderate hypoglycaemia (aHR 3.0, 95% CI 1.9-4.8, p < 0.0001) were associated with elevated mortality., Interpretation: Hypoglycaemia is common in EVD, requires repeated correction with intravenous dextrose solutions, and is associated with mortality., Funding: This study was not supported by any specific funding., Competing Interests: Declaration of interests SM is employed by Ridgeback Biotherapeutics, and is listed as inventor on the patent application for mAb 114, US Application No.62/087, 087 (PCT Application No. PCT/US2015/060,733) related to anti-Ebola virus antibodies and their use. SM receives royalties paid by the NIH Office of Financial Management (OFM)., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Hypoglycemia is an adverse event (AE) that cannot be ignored in clinical practice. This study aimed to identify the most common and top drugs associated with the risk of hypoglycemia based on the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database., Research Design and Methods: We used OpenVigil 2.1 pharmacovigilance analytics platform to query FAERS database and data from 2004 to 2023 were retrieved. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify hypoglycemia cases, and DrugBank database was used to determine drug generic names., Results: A total of 11,155,106 AEs reports were identified, of which 28,443 (0.25%) were related to hypoglycemia. Metformin (6926 cases) was associated with most cases of hypoglycemia. According to the disproportionality analysis, the top five drugs with the highest ROR and PRR were penamecillin, nikethamide, sotagliflozin, norethandrolone, glimepiride/pioglitazone. Nineteen of the top 50 drugs did not have hypoglycemia indicated in the package insert., Conclusions: By analyzing the FAERS database, we listed drugs with a strong hypoglycemic signal for which the label does not provide a reminder. Notably, the potential hypoglycemia risks are of great importance and should be closely monitored in medical practice.

Objectives: The Hypoglycemia During Hospitalization (HyDHo) score predicts hypoglycemia in a population of Canadian inpatients by assigning various weightings to 5 key clinical criteria known at the time of admission, in particular age, recent presentation to an emergency department, insulin use, use of oral hypoglycemic agents, and chronic kidney disease. Our aim in this study was to externally validate the HyDHo score by applying this risk calculator to an Australian population of inpatients with diabetes., Methods: This study was a retrospective data analysis of a subset of the Diabetes IN-hospital: Glucose & Outcomes (DINGO) cohort. The HyDHo score was applied based on clinical information known at the time of admission to stratify risk of inpatient hypoglycemia., Results: The HyDHo score was applied to 1,015 patients, generating a receiver-operating characteristic c-statistic of 0.607. A threshold of ≥9, as per the original study, generated a sensitivity of 83% and a specificity of 20%. A threshold of ≥10, to better suit this Australian population, generated a sensitivity of 90% and a specificity of 34%. The HyDHo score has been externally valid in a geographically different population; in fact, it outperformed the original study after accounting for local hypoglycemia rates., Conclusions: Our findings support the external validity of the HyDHo score in a geographically different population. Application of this simple and accessible tool can serve as an adjunct to predict an inpatient's risk of hypoglycemia and guide more appropriate glucose monitoring and diabetes management., (Copyright © 2024 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Purpose: The target glycemic control for nondiabetic patients in the postanesthesia care unit (PACU) after hysteroscopic surgery remains unclear. Our goal is to determine the optimal level of glycemic control by finding the relationship between blood glucose level (BGL) leaving the PACU and postoperative hypoglycemia in nondiabetic patients., Design: This retrospective cohort study was conducted at a comprehensive tertiary hospital in Chongqing, China between June 2018 and December 2020., Methods: The target independent and dependent variables were BGL leaving the PACU and postoperative hypoglycemia, respectively. The primary outcome was the incidence of hypoglycemia. Logistic regression was used to explore the association between discharge BGL and hypoglycemia. The optimal glycemic control range was determined by using the receiver operating characteristic (ROC) curve., Findings: Prior to insulin use, BGL in the insulin-using subgroup might be as high as 20 mmol/L. Hypoglycemia was related to the BGL while leaving the PACU (odds ratio (OR) 0.37 [95% confidence interval (CI) 0.22 to 0.65]). The best cut-off value (12.95 mmol/L) was determined by fitting the ROC curve., Conclusions: If severe hyperglycemia develops during hysteroscopic surgery in individuals with 5% glucose as the mediator of uterine distention, the recommendation is to maintain blood glucose above 12.95 mmol/L when treated with insulin., Competing Interests: Declaration of Competing Interest None to report., (Copyright © 2024 The American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

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.)

Introduction: Reporting of hypoglycaemia and its impact in clinical studies is often retrospective and subject to recall bias. We developed the Hypo-METRICS app to measure the daily physical, psychological, and social impact of hypoglycaemia in adults with type 1 and insulin-treated type 2 diabetes in real-time using ecological momentary assessment (EMA). To help assess its utility, we aimed to determine Hypo-METRICS app completion rates and factors associated with completion., Methods: Adults with diabetes recruited into the Hypo-METRICS study were given validated patient-reported outcome measures (PROMs) at baseline. Over 10 weeks, they wore a blinded continuous glucose monitor (CGM), and were asked to complete three daily EMAs about hypoglycaemia and aspects of daily functioning, and two weekly sleep and productivity PROMs on the bespoke Hypo-METRICS app. We conducted linear regression to determine factors associated with app engagement, assessed by EMA and PROM completion rates and CGM metrics., Results: In 602 participants (55% men; 54% type 2 diabetes; median(IQR) age 56 (45-66) years; diabetes duration 19 (11-27) years; HbA1c 57 (51-65) mmol/mol), median(IQR) overall app completion rate was 91 (84-96)%, ranging from 90 (81-96)%, 89 (80-94)% and 94(87-97)% for morning, afternoon and evening check-ins, respectively. Older age, routine CGM use, greater time below 3.0 mmol/L, and active sensor time were positively associated with app completion., Discussion: High app completion across all app domains and participant characteristics indicates the Hypo-METRICS app is an acceptable research tool for collecting detailed data on hypoglycaemia frequency and impact in real-time., (© 2024 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Purpose: We undertook a study to investigate the relationship between duration of medication use and prevalence of impaired awareness of hypoglycemia (IAH) among patients with insulin-treated or sulfonylurea-treated type 2 diabetes in Taiwan., Methods: A total of 898 patients (41.0% insulin users, 65.1% sulfonylurea users; mean [SD] age = 59.9 [12.3] years, 50.7% female) were enrolled in pharmacies, clinics, and health bureaus of Tainan City, Taiwan. Presence of IAH was determined with Chinese versions of the Gold questionnaire (Gold-TW) and Clarke questionnaire (Clarke-TW). Sociodemographics, disease and treatment histories, diabetes-related medical care, and health status were collected. We used multiple logistic regression models to assess the relationship between duration of medication use and IAH., Results: Overall IAH prevalence was 41.0% (Gold-TW) and 28.2% (Clarke-TW) among insulin users, and 65.3% (Gold-TW) and 51.3% (Clarke-TW) among sulfonylurea users. Prevalence increased with the duration of sulfonylurea use, whereas it decreased with the duration of insulin use. After controlling for potential confounders, 5 or more years of sulfonylurea use was significantly associated with 3.50-fold (95% CI, 2.39-5.13) and 3.06-fold (95% CI, 2.11-4.44) increases in the odds of IAH based on the Gold-TW and Clarke-TW criteria, respectively. On the other hand, regular blood glucose testing and retinal examinations were associated with reduced odds in both insulin users and sulfonylurea users., Conclusions: The prevalence of IAH was high among patients using sulfonylureas long term, but the odds of this complication were attenuated for those who received regular diabetes-related medical care. Our study suggests that long-term sulfonylurea use and irregular follow-up increase risk for IAH. Further prospective studies are needed to confirm the observed associations. Annals Early Access article., (© 2024 Annals of Family Medicine, Inc.)

Introduction: Glucagon-like peptide-1 receptor agonist use has increased over the last decade for glycemic control in type 2 diabetes mellitus, cardiovascular risk reduction, and weight loss. Clinical trials indicate that gastrointestinal adverse effects are commonly experienced and severe hypoglycemia is rare; however, there is little data regarding glucagon-like peptide-1 receptor agonist in overdose., Methods: We performed a retrospective chart review evaluating and characterizing glucagon-like peptide-1 receptor agonist exposures reported to a single poison center between 2006 and 2023. Patient demographics, circumstances of exposure, clinical effects, and outcomes were abstracted from charts. Descriptive statistics were utilized to summarize demographic information and clinical factor data., Results: A total of 152 charts met inclusion criteria. Therapeutic errors accounted for 91% of exposures. Most patients (67%) reported no symptoms, although not all patients were followed to a definitive outcome. Nausea, vomiting, generalized weakness, and abdominal pain were the predominant symptoms reported. Most patients (62%) were monitored and closely followed in the home setting. Hypoglycemia was rare but occurred in the setting of a single agent glucagon-like peptide-1 receptor agonist exposure in two patients. Two additional patients who developed hypoglycemia involved co-administration of insulin. 21% of the exposures were related to errors on initial use of the pen., Conclusion: Exposures to glucagon-like peptide-1 receptor agonist have increased substantially over the years. Effects from an exposure tended to be mild and primarily involve gastrointestinal symptoms. Hypoglycemia was rare. Therapeutic and administration errors were common. Education on pen administration may help to reduce errors., (© 2024. The Author(s).)

Objectives: Detecting and treating severe hypoglycemia promptly after birth is crucial due to its association with adverse long-term neurodevelopmental outcomes. However, limited data are available on the optimal timing of glucose screening in asymptomatic high-risk neonates prone to hypoglycemia. Risk factors associated with asymptomatic high-risk neonates include late prematurity ≥35 and <37 weeks gestation (LPT), small-for-gestational-age (SGA), large-for-gestational-age (LGA), and infant-of-a-diabetic mother (IDM). This study aims to determine the incidence and the impact of individual risk factors on early hypoglycemia (defined as blood glucose ≤25 mg/dL in the initial hour after birth) in asymptomatic high-risk neonates., Methods: All asymptomatic high-risk neonates ≥35 weeks gestation underwent early blood glucose screening within the first hour after birth (n=1,690). A 2-year retrospective analysis was conducted to assess the incidence of early neonatal hypoglycemia in this cohort and its association with hypoglycemia risk factors., Results: Out of the 9,919 births, 1,690 neonates (17 %) had risk factors for neonatal hypoglycemia, prompting screening within the first hour after birth. Incidence rates for blood glucose ≤25 mg/dL and ≤15 mg/dL were 3.1 and 0.89 %, respectively. Of concern, approximately 0.5 % of all asymptomatic at-risk neonates had a blood glucose value of ≤10 mg/dL. LPT and LGA were the risk factors significantly associated with early neonatal hypoglycemia., Conclusions: Asymptomatic high-risk neonates, particularly LPT and LGA neonates, may develop early severe neonatal hypoglycemia identified by blood glucose screening in the first hour of life. Additional investigation is necessary to establish protocols for screening and managing asymptomatic high-risk neonates., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Aim: To assess the impact of insulin glargine (100 U/mL) and lixisenatide (iGlarLixi) fixed-ratio combination therapy on the overall management of glycaemia in patients with type 2 diabetes (T2D), previously inadequately controlled with oral antidiabetic drugs ± basal insulin or glucagon-like peptide-1 receptor agonists (GLP-1 RAs)., Materials and Methods: This 12-month, international, multicentre, prospective, observational study included patients (age ≥ 18 years) with T2D who had initiated iGlarLixi within 1 month prior to study inclusion. Data were collected at study inclusion, month 3, month 6 and month 12 from patient diaries, self-measured plasma glucose, and questionnaires. The primary endpoint was change in HbA1c from baseline to month 6., Results: Of the 737 eligible participants (mean age: 57.8 [standard deviation: 11.2] years; male: 49%), 685 had baseline and post-baseline HbA1c data available. The least squares mean change in HbA1c from baseline to month 6 was -1.4% (standard error [95% confidence interval (CI)]: 0.05 [-1.5, -1.3]). The absolute change from baseline at month 12 was -1.7% ± 1.9% (95% CI: -1.9, -1.5). There were 72 hypoglycaemia events reported during the study period, with a very low incidence of severe hypoglycaemia (two participants [rate: 0.003 events per patient-year])., Conclusions: This real-world observational study shows that initiation of iGlarLixi in people with T2D inadequately controlled on oral antidiabetic drugs ± basal insulin or GLP-1 RAs improves glycaemic control with a low incidence of hypoglycaemia., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

The older population is increasing worldwide and up to 30% of older adults have diabetes. Older adults with diabetes are at risk of glucose-related acute and chronic complications. Recently, mostly in type 1 diabetes (T1D), continuous glucose monitoring (CGM) devices have proven beneficial in improving time in range (TIR glucose, 70-180 mg/dL or glucose 3.9-10 mmol/L), glycated hemoglobin (HbA1c), and in lowering hypoglycemia (time below range [TBR] glucose <70 mg/dL or glucose <3.9 mmol/L). The international consensus group formulated CGM glycemic targets relating to older adults with diabetes based on very limited data. Their recommendations, based on expert opinion, were aimed at mitigating hypoglycemia in all older adults. However, older adults with diabetes are a heterogeneous group, ranging from healthy to very complex frail individuals based on chronological, biological, and functional aging. Recent clinical trial and real-world data, mostly from healthy older adults with T1D, demonstrated that older adults often achieve CGM targets, including TIR recommended for non-vulnerable groups, but less often meet the recommended TBR <1%. Existing data also support that hypoglycemia avoidance may be more strongly related to minimization of glucose variability (coefficient of variation [CV]) rather than lower TIR. Very limited data are available for glucose goals in older adults adjusted for the complexity of their health status. Herein, we review the bidirectional associations between glucose and health status in older adults with diabetes; use of diabetes technologies, and their impact on glucose control; discuss current guidelines; and propose a new set of CGM targets for older adults with insulin-treated diabetes that are individualized for health and living status., 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: ET is a consultant for Vertex/Sequel. DON has received research support from Medtronic, Insulet, Dexcom, Roche, GlySens, BioCapillary, and Endogenex. He is on the advisory boards for Medtronic, Insulet, Abbott, Ypsomed, Novo Nordisk, and Sanofi. He has also received honoraria for lectures from Medtronic, Insulet, Abbott, Novo Nordisk, and Sanofi. MM is a consultant for Sanofi. AJ has no conflicts of interest.

Background: Continuous glucose monitoring has facilitated the evaluation of dynamic changes in glucose throughout the day and their effect on fetal growth abnormalities in pregnancy. However, studies of multiple continuous glucose monitoring metrics combined and their association with other adverse pregnancy outcomes are limited., Objective: This study aimed to (1) use machine learning techniques to identify discrete glucose profiles based on weekly continuous glucose monitoring metrics in pregnant individuals with pregestational diabetes mellitus and (2) investigate their association with adverse pregnancy outcomes., Study Design: This study analyzed data from a retrospective cohort study of pregnant patients with type 1 or 2 diabetes mellitus who used Dexcom G6 continuous glucose monitoring and delivered a nonanomalous, singleton pregnancy at a tertiary center between 2019 and 2023. Continuous glucose monitoring data were collapsed into 39 weekly glycemic measures related to centrality, spread, excursions, and circadian cycle patterns. Principal component analysis and k-means clustering were used to identify 4 discrete groups, and patients were assigned to the group that best represented their continuous glucose monitoring patterns during pregnancy. Finally, the association between glucose profile groups and outcomes (preterm birth, cesarean delivery, preeclampsia, large-for-gestational-age neonate, neonatal hypoglycemia, and neonatal intensive care unit admission) was estimated using multivariate logistic regression adjusted for diabetes mellitus type, maternal age, insurance, continuous glucose monitoring use before pregnancy, and parity., Results: Of 177 included patients, 90 (50.8%) had type 1 diabetes mellitus, and 85 (48.3%) had type 2 diabetes mellitus. This study identified 4 glucose profiles: (1) well controlled; (2) suboptimally controlled with high variability, fasting hypoglycemia, and daytime hyperglycemia; (3) suboptimally controlled with minimal circadian variation; and (4) poorly controlled with peak hyperglycemia overnight. Compared with the well-controlled profile, the suboptimally controlled profile with high variability had higher odds of a large-for-gestational-age neonate (adjusted odds ratio, 3.34; 95% confidence interval, 1.15-9.89). The suboptimally controlled with minimal circadian variation profile had higher odds of preterm birth (adjusted odds ratio, 2.59; 95% confidence interval, 1.10-6.24), cesarean delivery (adjusted odds ratio, 2.76; 95% confidence interval, 1.09-7.46), and neonatal intensive care unit admission (adjusted odds ratio, 4.08; 95% confidence interval, 1.58-11.40). The poorly controlled profile with peak hyperglycemia overnight had higher odds of preeclampsia (adjusted odds ratio, 2.54; 95% confidence interval, 1.02-6.52), large-for-gestational-age neonate (adjusted odds ratio, 3.72; 95% confidence interval, 1.37-10.4), neonatal hypoglycemia (adjusted odds ratio, 3.53; 95% confidence interval, 1.37-9.71), and neonatal intensive care unit admission (adjusted odds ratio, 3.15; 95% confidence interval, 1.20-9.09)., Conclusion: Discrete glucose profiles of pregnant individuals with pregestational diabetes mellitus were identified through joint consideration of multiple continuous glucose monitoring metrics. Prolonged exposure to maternal hyperglycemia may be associated with a higher risk of adverse pregnancy outcomes than suboptimal glycemic control characterized by high glucose variability and intermittent hyperglycemia., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To examine the relationship between gestational glucose intolerance (GGI) and neonatal hypoglycemia., Research Design and Methods: This was a secondary analysis of 8,262 mother-infant dyads, with delivery at two hospitals between 2014 and 2023. We categorized maternal glycemic status as normal glucose tolerance (NGT), GGI, or gestational diabetes mellitus (GDM). We defined NGT according to a normal glucose load test result, GGI according to an abnormal glucose load test result with zero (GGI-0) or one (GGI-1) abnormal value on the 100-g oral glucose tolerance test, and GDM according to an abnormal glucose load test result with two or more abnormal values on the glucose tolerance test. Neonatal hypoglycemia was defined according to blood glucose <45 mg/dL or ICD-9 or ICD-10 diagnosis of neonatal hypoglycemia. We used logistic regression analysis to determine associations between maternal glucose tolerance category and neonatal hypoglycemia and conducted a sensitivity analysis using Δ-adjusted multiple imputation, assuming for unscreened infants a rate of neonatal hypoglycemia as high as 33%., Results: Of infants, 12% had neonatal hypoglycemia. In adjusted models, infants born to mothers with GGI-0 had 1.28 (95% 1.12, 1.65), GGI-1 1.58 (95% CI 1.11, 2.25), and GDM 4.90 (95% CI 3.81, 6.29) times higher odds of neonatal hypoglycemia in comparison with infants born to mothers with NGT. Associations in sensitivity analyses were consistent with the primary analysis., Conclusions: GGI is associated with increased risk of neonatal hypoglycemia. Future research should include examination of these associations in a cohort with more complete neonatal blood glucose ascertainment and determination of the clinical significance of these findings on long-term child health., (© 2024 by the American Diabetes Association.)

Objective: Up to one-third of older adults with type 1 diabetes experience impaired awareness of hypoglycemia (IAH), yet the factors associated with IAH remain underexplored in older adults., Research Design and Methods: This post hoc analysis evaluated the clinical and glycemic correlates of IAH in adults ≥60 years old with type 1 diabetes in the WISDM study. IAH and normal awareness of hypoglycemia (NAH) were defined by a Clarke score of ≥4 or <4, respectively. Demographic, clinical, and glycemic metrics were compared in those with IAH and NAH at baseline and in whom IAH did or did not improve over 26 weeks, using descriptive statistics and a multiple logistic regression variable selection procedure., Results: Of the 199 participants (age 68.1 ± 5.7 years, 52% female), 30.6% had IAH. At baseline, participants with IAH had a longer diabetes duration and greater daytime hypoglycemia and glycemic variability, and more participants had nondetectable C-peptide levels than those with NAH. Logistic regression associated longer diabetes duration (odds ratio [OR] 1.03, 95% CI 1.01-1.05; P = 0.008) and greater daytime hypoglycemia (OR 1.31, 95% CI, 1.15-1.51; P < 0.0001) with a greater odds of IAH. A similar modeling procedure identified less daytime hypoglycemia (OR per additional percentage point 0.55, 95% CI 0.32-0.94; P = 0.029) and shorter diabetes duration (OR per additional year 0.96, 95% CI 0.91-1.004; P = 0.07) as predictors of restored awareness at 26 weeks, although the effect size for diabetes duration was not statistically significant., Conclusions: In older adults with type 1 diabetes, longer diabetes duration and greater daytime hypoglycemia are drivers of IAH. Dedicated research can personalize IAH management., (© 2024 by the American Diabetes Association.)

Background: Glycemia risk index (GRI) is a novel composite metric assessing overall glycemic risk, accounting for both hypoglycemia and hyperglycemia and weighted toward extremes. Data assessing GRI as an outcome measure in closed-loop studies and its relation with conventional key continuous glucose monitoring (CGM) metrics are limited., Methods: A post hoc analysis was performed to evaluate the sensitivity of GRI in assessing glycemic quality in adults with type 1 diabetes randomized to 26 weeks hybrid closed-loop (HCL) or manual insulin delivery (control). The primary outcome was GRI comparing HCL with control. Comparisons were made with changes in other CGM metrics including time in range (TIR), time above range (TAR), time below range (TBR), and glycemic variability (standard deviation [SD] and coefficient of variation [CV])., Results: GRI with HCL (N = 61) compared with control (N = 59) was significantly lower (mean [SD] 33.5 [11.7] vs 56.1 [14.4], respectively; mean difference -22.8 [-27.2, -18.3], P = .001). The mean increase in TIR was +14.8 (11.0, 18.5)%. GRI negatively correlated with TIR for combined arms ( r = -.954; P = .001), and positively with TAR >250 mg/dL ( r = .901; P = .001), TBR < 54 mg/dL ( r = .416; P = .001), and glycemic variability (SD [ r = .916] and CV [ r = .732]; P = .001 for both)., Conclusions: Twenty-six weeks of HCL improved GRI, in addition to other CGM metrics, compared with standard insulin therapy. The improvement in GRI was proportionally greater than the change in TIR, and GRI correlated with all CGM metrics. We suggest that GRI may be an appropriate primary outcome for closed-loop trials., 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: MHL has received speaker honoraria from Medtronic. DNO. has served on advisory boards for Abbott Laboratories, Medtronic, Merck Sharp & Dohme, Novo Nordisk, Roche, and Sanofi; received research support from Medtronic, Novo Nordisk, Roche, Eli Lilly and Company, and Sanofi; and received travel support from Novo Nordisk and Merck Sharp & Dohme. SV and TWJ have nothing to disclose.

Aims: To capture the types and content of healthcare encounters following severe hypoglycemia requiring emergency medical services (EMS) and to correlate their features with subsequent risk of severe hypoglycemia., Methods: A retrospective cohort was obtained by linking data from a multi-state health system and an advanced life support ambulance service. This identified 1977 EMS calls by 1028 adults with diabetes experiencing hypoglycemia between 1/1/2013-12/31/2019. We evaluated the healthcare engagement over the following 7 days to identify rates of discussion of hypoglycemia, change of diabetes medications, glucagon prescribing, and referral for diabetes., Results: Rates of hypoglycemia discussion increased with escalating levels of care, from 11.5 % after EMS calls without emergency department (ED) transport or outpatient clinical encounters to 98 % among hospitalized patients with outpatient follow-up. EMS transport and outpatient follow-up were associated with significantly higher odds of discussion of hypoglycemia (OR 60 and OR 22.1, respectively). Interventions were not impacted by previous severe hypoglycemia within 30 days. Prescription of glucagon was rare among all patients., Conclusions: Interventions to prevent recurrent hypoglycemia increase with escalating levels of care but remain inadequate and inconsistent with clinical guidelines. Greater attention is needed to ensure timely diabetes-related follow-up and treatment modification for patients experiencing severe hypoglycemia., 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.)

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.)

Aims: To describe trends in risk factor control and serious hypoglycaemia in people with type 1 diabetes and to assess the effect of starting continuous glucose monitoring (CGM) in the real-world setting., Methods: Two cross-sectional surveys including 5746 individuals in 2012 and 18,984 individuals in 2020 based on data recorded in the Norwegian Diabetes Register for Adults (NDR-A) and an analysis of a longitudinal cohort of 2057 individuals where data on CGM and HbA1c were available in the NDR-A in 2012 and 2020., Results: In the cross-sectional surveys mean HbA1c decreased from 66 mmol/mol (99% CI 65, 66) (8.2%) in 2012 to 61 mmol/mol (99% CI 61, 61) (7.7%) in 2020 (p < 0.0001). The proportion reporting serious hypoglycaemia decreased from 16.9 to 6.2% in 2020 (p < 0.0001). Mean LDL-cholesterol decreased from 2.80 (99% CI 2.78, 2.83) to 2.63 (99% CI 2.61, 2.65) mmol/l in 2020 (p < 0.0001). Mean blood pressure increased slightly. In the CGM cohort, we found a 3 mmol/mol (0.3%) greater improvement in mean HbA1c and a greater reduction in serious hypoglycaemia (-12.3% vs. -6.2%) among individuals that had started using CGM between 2013 and 2020 when compared with individuals that had not started using CGM., Conclusions: Between 2012 and 2020, we found marked improvements in glycaemic control and a considerable decrease in the proportion of individuals reporting serious hypoglycaemia. The proportion of individuals using CGM increased substantially and individuals that had started using CGM by 2020 showed greater improvement in glycaemic control and less serious hypoglycaemia., (© 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.

This systematic review aimed to compare the influence of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on the efficacy and safety of elderly patients with type 2 diabetes and younger individuals. A comprehensive search of PubMed, Embase, and Web of Science databases was conducted up to September 2022. The summary standard means difference and odds ratios were calculated. Thirteen articles were included in the analysis. The incidence of adverse events (AEs) leading to discontinuation was higher in elderly patients (OR = 0.67, 95% CI 0.47 to 0.96, p = 0.028). However, no significant differences were observed in weight loss (SMD = 0.03, 95% CI -0.12 to 0.19, p = 0.686), HbA1c% (SMD = -0.02, 95% CI -0.11 to 0.08, p = 0.715), FBG levels (SMD = -0.03, 95% CI -0.11 to 0.06, p = 0.537), and the incidence of overall AEs (OR = 0.85, 95% CI 0.71 to 1.01, p = 0.072), serious AEs (OR = 0.68, 95% CI 0.45 to 1.04, p = 0.077), nausea (OR = 0.91, 95% CI 0.81 to 1.03, p = 0.140), vomiting (OR = 0.95, 95% CI 0.79 to 1.13, p = 0.532), diarrhea (OR = 0.86, 95% CI 0.72 to 1.02, p = 0.081), and hypoglycemia (OR = 1.22, 95% CI 0.90 to 1.65, p = 0.193). In conclusion, while certain AEs leading to discontinuation may be more prevalent in older patients, GLP-1RAs are effective for weight loss and lead to decreased glucose concentrations with a low rate of complications in elderly patients.

Objective: Impaired awareness of hypoglycaemia (IAH) is a risk factor for severe hypoglycaemia (SH) in type 1 diabetes (T1D). Much of the IAH prevalence data comes from older studies where participants did not have the benefit of the latest insulins and technologies. This study surveyed the prevalence of IAH and SH in a tertiary adult clinic population and investigated the associated factors., Methods: Adults (≥18 years) attending a tertiary T1D clinic completed a questionnaire, including a Gold and Clarke score. Background information was collected from health records., Results: 189 people (56.1% female) with T1D (median [IQR] disease duration 19.3 [11.5, 29.1] years and age of 41.0 [29.0, 52.0] years) participated. 17.5% had IAH and 16.0% reported ≥1 episode of SH in the previous 12 months. Those with IAH were more likely to report SH (37.5% versus 11.7%, p = 0.001) a greater number of SH episodes per person (median [IQR] 0 [0,2] versus 0 [0,0] P<0.001) and be female (72.7% versus 52.6%, p = 0.036). Socio-economic deprivation was associated with IAH (p = 0.032) and SH (p = 0.005). Use of technology was the same between IAH vs aware groups, however, participants reporting SH were more likely to use multiple daily injections (p = 0.026). Higher detectable C-peptide concentrations were associated with a reduced risk of SH (p = 0.04)., Conclusion: Insulin pump and continuous glucose monitor use was comparable in IAH versus aware groups. Despite this, IAH remains a risk factor for SH and is prevalent in females and in older people. Socioeconomic deprivation was associated with IAH and SH, making this an important population to target for interventions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Baxter et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: Continuous glucose monitoring (CGM) metrics can assist diabetes management. Consensus statements recommend > 70 % time in range (TIR) and ≤ 36 % glucose coefficient of variation (CV). However, how these targets perform in clinical practice is unknown. This retrospective, longitudinal cohort study analyzed relationships between TIR, CV, glycated hemoglobin (HbA1c), and hypoglycemia in a real-world setting., Methods: Data of 542 adults with type 1 diabetes who used CGM (January 2014-July 2020) were analyzed. Associations between TIR and HbA1c at the same and subsequent visits, incidence rate ratios (IRRs) for hypoglycemia at different CVs, and number of hypoglycemic events at cross-sections of HbA1c and CV were estimated by regression., Results: TIR was inversely related to HbA1c; for every 10 % increase in TIR, HbA1c was significantly reduced by 0.34 % (4 mmol/mol) and 0.20 % (2 mmol/mol) at the same and subsequent visits, respectively. Level 2 hypoglycemia was significantly reduced at CV < 30 %, 30-33 %, 33.1-36 %, and 36.1-40 %: adjusted IRRs vs CV ≥ 40.1 % of 0.14, 0.28, 0.32, and 0.50, respectively. Hypoglycemic events were reduced at lower CV across HbA1c levels and at higher HbA1c across CV levels., Conclusion: This study quantifies HbA1c improvements with increased TIR and hypoglycemia reductions with improved CV in clinical practice., Competing Interests: Declaration of competing interest M.P.-N., L.F., E.R.H., and Y.Y are employees of, and shareholders in, Eli Lilly and Company. R.J. was an Executive Director of Diabetes Global Medical Affairs at Eli Lilly and Company when he contributed to this article, and is currently a Senior Director, Clinical Development Strategy, at Novo Nordisk Inc., which provided no review of, or other support for, this article. R.B.M., S.L.E., and G.T.A. have no additional conflicts of interest to declare. V.N.S. has received honoraria from NovoNordisk, Medscape, Embecta, Insulet, Tandem Diabetes Care, Ascensia, and Dexcom for speaking, consulting or being on advisory boards, and his institution, University of Colorado, has received research support from NovoNordisk, Tandem Diabetes Care, Insulet, Alexion, Eli Lilly and Company, JDRF, and NIH (NIDDK & NIAMS)., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: To evaluate the long-term safety and efficacy of enavogliflozin 0.3 mg/day added to metformin in patients with type 2 diabetes mellitus., Materials and Methods: After 24 weeks of a randomized, double-blind treatment period with enavogliflozin 0.3 mg/day (n = 101) or dapagliflozin 10 mg/day (n = 99) added to metformin, all patients received enavogliflozin 0.3 mg/day plus metformin for an additional 28 weeks during the open-label extension period., Results: Eighty-two patients continued enavogliflozin (maintenance group), and 77 were switched from dapagliflozin to enavogliflozin (switch group). All adverse drug reactions (ADR) were mild in severity. In the maintenance group, ADRs (cystitis and vaginal infection) were reported in two patients (2.44%) during 52 weeks. In the switch group, ADR (hypoglycaemia) was reported in one patient (1.30%) during a 28-week open-label extension period. At week 52, glycated haemoglobin and fasting plasma glucose were significantly lower than at the baseline, by 0.85% and 29.08 mg/dl, respectively, in the maintenance group (p < .0001 for both), and by 0.81% and 32.77 mg/dl, respectively, in the switch group (p < .0001 for both). At week 52, 68.92% of patients from the maintenance group and 64.29% from the switch group achieved glycated haemoglobin <7%. A significant increase in the urine glucose-creatinine ratio was observed at week 52, by 58.81 g/g and 63.77 g/g in the maintenance and switch groups, respectively (p < .0001)., Conclusions: Enavogliflozin added to metformin was tolerated well for up to 52 weeks and provided continual glycaemic control in type 2 diabetes mellitus, along with a significant increase in the urine glucose-creatinine ratio., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objective: To determine how diabetes technologies, including continuous glucose monitoring (CGM) and automated insulin delivery (AID) systems, impact glycemic metrics, prevalence of severe hypoglycemic events (SHEs), and impaired awareness of hypoglycemia (IAH) in people with type 1 diabetes in a real-world setting within the U.S., Research Design and Methods: In this retrospective, observational study with cross-sectional elements, participants aged ≥18 years were enrolled from the T1D Exchange Registry/online community. Participants completed a one-time online survey describing glycemic metrics, SHEs, and IAH. The primary objective was to determine the proportions of participants who reported achieving glycemic targets (assessed according to self-reported hemoglobin A1c) and had SHEs and/or IAH. We performed additional subgroup analyses focusing on the impact of CGM and insulin delivery modality., Results: A total of 2,074 individuals with type 1 diabetes were enrolled (mean ± SD age 43.0 ± 15.6 years and duration of type 1 diabetes 26.3 ± 15.3 years). The majority of participants (91.7%) were using CGM, with one-half (50.8%) incorporating AID. Despite high use of diabetes technologies, only 57.7% reported achieving glycemic targets (hemoglobin A1c <7%). SHEs and IAH still occurred, with ∼20% of respondents experiencing at least one SHE within the prior 12 months and 30.7% (95% CI 28.7, 32.7) reporting IAH, regardless of CGM or AID use., Conclusions: Despite use of advanced diabetes technologies, a high proportion of people with type 1 diabetes do not achieve glycemic targets and continue to experience SHEs and IAH, suggesting an ongoing need for improved treatment strategies., (© 2024 by the American Diabetes Association.)

Aims: To examine, among youth and young adults (YYA) with type 1 diabetes (T1D), the association of household food insecurity (HFI) with: 1) HbA 1c and 2) episodes of diabetic ketoacidosis (DKA) and severe hypoglycemia., Methods: HFI was assessed using the U.S. Household Food Security Survey Module in SEARCH for Diabetes in Youth participants with T1D between 2016 and 2019. Linear and logistic regression models adjusted for age, diabetes duration, sex, race, ethnicity, clinic site, parent/participant education, household income, health insurance, and diabetes technology use., Results: Of 1830 participants (mean age 20.8 ± 5.0 years, 70.0 % non-Hispanic White), HbA 1c was collected for 1060 individuals (mean HbA1c 9.2 % ± 2.0 %). The prevalence of HFI was 16.4 %. In the past 12 months, 18.2 % and 9.9 % reported an episode of DKA or severe hypoglycemia, respectively. Compared to participants who were food secure, HFI was associated with a 0.33 % (95 % CI 0.003, 0.657) higher HbA 1c level. Those with HFI had 1.58 (95 % CI 1.13, 2.21) times the adjusted odds of an episode of DKA and 1.53 (95 % CI 0.99, 2.37) times the adjusted odds of an episode of severe hypoglycemia as those without HFI., Conclusions: HFI is associated with higher HbA 1c levels and increased odds of DKA in YYA with T1D., 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.)

Hajj is an obligatory duty for all healthy adult Muslims once in the lifetime subjected to the ability. Considering the 10.5 % global prevalence of diabetes coupled with the numbers of Muslims performing the Hajj, ∼ 1.8 million in 2023, it is estimated that Muslims with diabetes performing Hajj may exceed 340,000 this year. During Hajj the pattern and amount of their meal, fluid intake and physical activity are markedly altered. Many people with diabetes insist on doing the Hajj duty, thereby creating a medical challenge for themselves and their health care providers. It is therefore important that medical professionals be aware of the potential risks that may be associated with Hajj. People with diabetes may face many health hazards during Hajj including but not limited to the killer triad which might occur during Hajj: Hypoglycemia, Foot injury and Infections. Many precautions should be taken to prevent and treat these potentially serious complications. Risk stratification, medication adjustments, proper clinical assessment, and education before doing Hajj are crucial., 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.)

Objective: To examine trends in incidence of acute diabetes complications in individuals with type 1 or type 2 diabetes with and without severe mental illness (SMI) in Denmark by age and calendar year., Research Design and Methods: We conducted a cohort study using nationwide registers from 1996 to 2020 to identify individuals with diabetes, ascertain SMI status (namely, schizophrenia, bipolar disorder, or major depression) and identify the outcomes: hospitalization for hypoglycemia and diabetic ketoacidosis (DKA). We used Poisson regression to estimate incidence rates (IRs) and incidence rate ratios (IRRs) of recurrent hypoglycemia and DKA events by SMI, age, and calendar year, accounting for sex, diabetes duration, education, and country of origin., Results: Among 433,609 individuals with diabetes, 8% had SMI. Risk of (first and subsequent) hypoglycemia events was higher for individuals with SMI than for those without SMI (for first hypoglycemia event, IRR: type 1 diabetes, 1.77 [95% CI 1.56-2.00]; type 2 diabetes, 1.64 [95% CI 1.55-1.74]). Individuals with schizophrenia were particularly at risk for recurrent hypoglycemia events. The risk of first DKA event was higher in individuals with SMI (for first DKA event, IRR: type 1 diabetes, 1.78 [95% CI 1.50-2.11]; type 2 diabetes, 1.85 [95% CI 1.64-2.09]). Except for DKA in the type 2 diabetes group, IR differences between individuals with and without SMI were highest in younger individuals (<50 years old) but stable across the calendar year., Conclusions: SMI is an important risk factor for acute diabetes complication and effective prevention is needed in this population, especially among the younger population and those with schizophrenia., (© 2024 by the American Diabetes Association.)

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: Diabetes mellitus (DM) is the most common metabolic disorder in pregnancy. Women with Type 2 DM seems to have no better perinatal outcomes than those with Type 1 DM., Methods: Single-center prospective cohort observational study. Pregnant women with diabetes (141 with Type 1 DM and 124 with Type 2 DM) that were followed in the university hospital between 2009 and 2021 were included in this study. Clinical data and obstetric and perinatal outcomes were collected., Results: As expected, women with Type 1 DM were younger and had a longer duration of diabetes than women with Type 2 DM. Obesity and chronic hypertension were higher in the group of women with Type 2 DM and their value of HbA1c in the second and third trimesters were lower than in Type 1 DM. No differences in prematurity were found, but more extreme prematurity was observed in Type 2 DM, as well as a higher rate of congenital malformations. The frequency of hypoglycemia and the weight of the newborn was higher in Type 1 DM. The maternal independent factors related to the weight of the newborn were: the glycemic control at the third trimester, the weight gain during pregnancy, and pregestational BMI., Conclusions: Newborns born to mothers with Type 1 DM were larger and had a higher frequency of hypoglycemia, while congenital malformations and precocious preterm was more associated to Type 2 DM. Metabolic control, weight gain and pregestational weight were important determinants of both obstetric and neonatal complications., (© 2024. The Author(s).)

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.

Objective: This was a systematic review and meta-analysis comparing maternal and neonatal outcomes of patients screened with the 1-step or 2-step screening method for gestational diabetes mellitus., Data Sources: PubMed, Scopus, Cochrane, ClinicalTrials.gov, and LILACS were searched from inception up to September 2022., Study Eligibility Criteria: Only randomized controlled trials were included. Studies that had overlapping populations were excluded (International Prospective Register of Systematic Review registration number: CRD42022358903)., Methods: Risk ratios were computed with 95% confidence intervals by 2 authors. Unpublished data were requested. Large for gestational age was the primary outcome., Results: The search yielded 394 citations. Moreover, 7 randomized controlled trials met the inclusion criteria. A total of 54,650 participants were screened for gestational diabetes mellitus by either the 1-step screening method (n=27,163) or the 2-step screening method (n=27,487). For large for gestational age, there was no significant difference found between the groups (risk ratio, 0.99; 95% confidence interval, 0.93-1.05; I 2 =0%). Newborns of patients who underwent 1-step screening had higher rates of neonatal hypoglycemia (risk ratio, 1.24; 95% confidence interval, 1.14-1.34; I 2 =0%) and neonatal intensive care unit admissions (risk ratio, 1.13; 95% confidence interval, 1.04-1.21; I 2 =0%) than newborns of patients who underwent 2-step screening. Patients in the 1-step screening method group were more likely to be diagnosed with gestational diabetes mellitus (risk ratio, 1.73; 95% confidence interval, 1.44-2.09; I 2 =80%) than patients in the 2-step screening method group. In addition, among trials that tested all patients before randomization and excluded patients with pregestational diabetes mellitus, newborns were more likely to have macrosomia (risk ratio, 1.27; 95% confidence interval, 1.21-1.34; I 2 =0%). Overall risk of bias assessment was of low concern., Conclusion: Large for gestational age did not differ between patients screened using the 1-step screening method and those screened using the 2-step screening method. However, patients randomized to the 1-step screening method had higher rates of neonatal hypoglycemia and neonatal intensive care unit admission and maternal gestational diabetes mellitus diagnosis than the patients randomized to the 2-step screening method., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To determine the risk factors for hypoglycaemia in patients with diabetes on general hospital wards based on a systematic review of the literature since 2013 and meta-analysis., Methods: Systematic review of the literature focused on the conceptual and methodological aspects of the PRISMA Declaration. The search carried out in Pub Med, Web of Science, Medline, Scielo, Lilacs, OVID, grey literature and Google Academic focused on risk factors for hypoglycaemia in patients with diabetes on general hospital wards. The CASPe (Critical Appraisal Skills Programme Spanish) tool was applied for quality control., Results: From 805 references, 70 potentially eligible articles were identified for review of abstracts and full text. Finally, according to inclusion and exclusion criteria, seven studies with 554,601 patients of Asian, European and North American ethnicity were selected. A meta-analysis performed using the random effects model found an association between the presence of hypoglycaemia and: the use of insulin (OR 2.89 [95% CI: 1.8-4.5]); the use of long-acting insulin (OR 2.27 [95% CI: 1.8-2.8]) or fast-acting insulin (OR 1.4 [95% CI: 1.18-1.85]); nasogastric tube feeding (OR 1.75 [95% CI: 1.33-2.3]); chronic kidney disease (OR 1.65 [95% CI: 1.14-2.38]); congestive heart failure (OR 1.36 [95% CI: 1.10-1.68]); and elevated levels of glycosylated haemoglobin (OR 1.59 [95% CI: 1.32-1.91])., Conclusion: The factors associated with the risk of hypoglycaemia in non-critically ill hospitalised patients with type 2 diabetes were: use of any insulin; nasogastric tube feeding; elevated glycosylated haemoglobin levels; history of congestive heart failure; and chronic kidney disease., (Copyright © 2024 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: This study aimed to evaluate whether transient fetal growth restriction (FGR) that resolves prior to delivery confers a similar risk of neonatal morbidity as uncomplicated FGR that persists at term., Study Design: This is a secondary analysis of a medical record abstraction study of singleton live-born pregnancies delivered at a tertiary care center between 2002 and 2013. Patients with fetuses that had either persistent or transient FGR and delivered at 38 weeks or later were included. Patients with abnormal umbilical artery Doppler studies were excluded. Persistent FGR was defined as estimated fetal weight (EFW) <10th percentile by gestational age from diagnosis through delivery. Transient FGR was defined as EFW <10th percentile on at least one ultrasound, but not on the last ultrasound prior to delivery. The primary outcome was a composite of neonatal morbidity: neonatal intensive care unit admission, Apgar's score <7 at 5 minutes, neonatal resuscitation, arterial cord pH <7.1, respiratory distress syndrome, transient tachypnea of the newborn, hypoglycemia, sepsis, or death. Baseline characteristics and obstetric and neonatal outcomes were compared using Wilcoxon's rank-sum and Fisher's exact test. Log binomial regression was used to adjust for confounders., Results: Of 777 patients studied, 686 (88%) had persistent FGR and 91 (12%) had transient FGR. Patients with transient FGR were more likely to have a higher body mass index, gestational diabetes, diagnosed with FGR earlier in pregnancy, have spontaneous labor, and deliver at later gestational ages. There was no difference in the composite neonatal outcome (relative risk = 1.03, 95% confidence interval [CI] 0.72, 1.47) for transient versus persistent FGR after adjusting for confounders (adjusted relative risk = 0.79, 95% CI 0.54, 1.17). There were no differences in cesarean delivery or delivery complications between groups., Conclusion: Neonates born at term after transient FGR do not appear to have differences in composite morbidity compared with those where uncomplicated FGR persists at term., Key Points: · No differences in neonatal outcomes in uncomplicated persistent versus transient FGR at term.. · Transient FGR pregnancies more likely to deliver at later gestational ages.. · No differences in mode of delivery or obstetric complications in persistent versus transient FGR at term.., Competing Interests: None declared., (Thieme. All rights reserved.)

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.)

Objective: Newborn hypothermia has been implicated in neonatal morbidity without randomized evidence that it compromises the infant. Our objective was to determine if a difference in operating room temperature at cesarean birth impacts neonatal morbidity., Study Design: Women undergoing cesarean delivery of a liveborn infant without major malformations were included. The institutional preexisting operating room temperature of 20°C (67°F) was compared with an experimental group of 24°C (75°F) by cluster randomization assigned on a weekly basis. Newborn hypothermia was defined as axillary temperature on arrival to the nursery of less than 36.5°C (<97.7°F). The primary outcome was a composite of neonatal morbidity including respiratory support, sepsis, hypoglycemia, and neonatal death., Results: Between November 2016 and May 2018, 5,221 women had cesarean deliveries at Parkland Hospital with 2,817 randomized to the standard care group and 2,404 to the experimental group. The rate of neonatal composite morbidity did not differ between the groups: standard care 398 (14%) versus experimental 378 (16%), p  = 0.11. This was despite a significant decrease in the rate of neonatal hypothermia: standard care 1,195 (43%) versus experimental 414 (18%), p  < 0.001. There was no difference in the composite outcome for preterm infants (<37 wk) between the groups: standard care 194 (49%) versus experimental 185 (54%), p  = 0.25., Conclusion: An 8°F increase in operating room temperature was significantly associated with a reduced rate of neonatal hypothermia, although this decrease was not associated with a significant improvement in neonatal morbidity. However, the increase in operating room temperature was met with resistance from obstetricians and operating room personnel. This trial is registered (registration no.: NCT03008577)., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: Neonatal hypoglycemia is a common complication associated with gestational diabetes and therefore relevant to consider in evaluations of maternal treatment. We aimed to investigate the risk of neonatal hypoglycemia in offspring exposed to metformin treatment alone (MT) or combined with insulin (MIT) in comparison with nutrition therapy alone (NT), and insulin treatment alone (IT). In addition, we investigated MT in comparison with MIT. Secondary outcomes included neonatal anthropometrics, respiratory morbidity, hyperbilirubinemia, 5-min Apgar score, and preterm birth., Material and Methods: This Swedish population-based cohort included 16 181 women diagnosed with gestational diabetes, and their singleton offspring born in 2019-2021. We estimated risk as adjusted odds ratio (aOR) with 95% confidence interval (CI), using individual-level, linkage register-data in multivariable logistic regression models., Results: In the main analysis, MT was associated with a lower risk of neonatal hypoglycemia vs NT (aOR 0.85, 95% CI: 0.74-0.96), vs MIT (0.74 [0.64-0.87]), and vs IT (0.47 [0.40-0.55]), whereas MIT was associated with a similar risk of neonatal hypoglycemia vs NT (1.14 [0.99-1.30]) and with lower risk vs IT (0.63 [0.53-0.75]). However, supplemental feeding rates were lower for NT vs pharmacological treatments (p < 0.001). In post hoc subgroup analyses including only exclusively breastfed offspring, the risk of neonatal hypoglycemia was modified and similar among MT and NT, and higher in MIT vs NT. Insulin exposure, alone or combined with metformin, was associated with increased risk of being large for gestational age. Compared with NT, exposure to any pharmacological treatment was associated with significantly lower risk of 5-min Apgar score < 4. All other secondary outcomes were comparable among the treatment categories., Conclusions: The risk of neonatal hypoglycemia appears to be comparable among offspring exposed to single metformin treatment and nutrition therapy alone, and the lower risk that we observed in favor of metformin is probably explained by a difference in supplemental feeding practices rather than metformin per se. By contrast, the lower risk favoring metformin exposure over insulin exposure was not explained by supplemental feeding. However, further investigations are required to determine whether the difference is an effect of metformin per se or mediated by other external factors., (© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: Hypoglycemia is a frequent occurrence in chronic kidney disease patients due to alterations in glucose and insulin metabolism. However, there are sparse data examining the predictors and clinical implications of hypoglycemia including mortality risk among incident hemodialysis patients., Design and Methods: Among 58,304 incident hemodialysis patients receiving care from a large national dialysis organization over 2007-2011, we examined clinical characteristics associated with risk of hypoglycemia, defined as a blood glucose concentration <70 mg/dL, in the first year of dialysis using expanded case-mix + laboratory logistic regression models. We then examined the association between hypoglycemia during the first year of dialysis with all-cause mortality using expanded case-mix + laboratory Cox models., Results: In the first year of dialysis, hypoglycemia was observed among 16.8% of diabetic and 6.9% of nondiabetic incident hemodialysis patients. In adjusted logistic regression models, clinical characteristics associated with hypoglycemia included younger age, female sex, African-American race, presence of a central venous catheter, lower residual renal function, and longer dialysis session length. In the overall cohort, patients who experienced hypoglycemia had a higher risk of all-cause mortality risk (reference: absence of hypoglycemia): adjusted hazard ratio (95% confidence interval) 1.08 (1.04, 1.13). In stratified analyses, hypoglycemia was also associated with higher mortality risk in the diabetic and nondiabetic subgroups: adjusted hazard ratios (95% confidence interval's) 1.08 (1.04-1.13), and 1.17 (0.94-1.45), respectively., Conclusions: Hypoglycemia was a frequent occurrence among both diabetic and nondiabetic hemodialysis patients and was associated with a higher mortality risk. Further studies are needed to identify approaches that reduce hypoglycemia risk in the hemodialysis population., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)