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Background: Lipohypertrophy is a common complication in patients with diabetes receiving insulin therapy. There is a lack of consensus regarding how much lipohypertrophy affects diabetes management. Our study aimed to assess the potential correlation between lipohypertrophy and glycemic control, as well as insulin dosing in patients with diabetes. Methods: We performed a systematic review followed by a meta-analysis to collect data about glycemic control and insulin dosing in diabetic patients with and without lipohypertrophy. To identify relevant studies published in English, we searched medical databases (MEDLINE/PubMed, Embase, and CENTRAL) from 1990 to January 20, 2023. An additional hand-search of references was performed to retrieve publications not indexed in medical databases. Results of meta-analyses were presented either as prevalence odds ratios (pORs) or mean differences (MDs) with 95% confidence intervals (95% CIs). This study was registered on PROSPERO (CRD42023393103). Results: Of the 5540 records and 240 full-text articles screened, 37 studies fulfilled the prespecified inclusion criteria. Performed meta-analyses showed that patients with lipohypertrophy compared with those without lipohypertrophy were more likely to experience unexplained hypoglycemia (pOR [95% CI] = 6.98 [3.30-14.77]), overall hypoglycemia (pOR [95% CI] = 6.65 [1.37-32.36]), and glycemic variability (pOR [95% CI] = 5.24 [2.68-10.23]). Patients with lipohypertrophy also had higher HbA1c (MD [95% CI] = 0.55 [0.23-0.87] %), and increased daily insulin consumption (MD [95% CI] = 7.68 IU [5.31-10.06]). Conclusions: These results suggest that overall glycemic control is worse in patients with lipohypertrophy than in those without this condition.

Objective: To assess the growing use of continuous glucose monitoring (CGM) systems by older adults and explore additional areas integration that could benefit adults with frailty., Background: The use of CGM devices has expanded rapidly in the last decade. This has been supported by substantial data showing significant benefit in glycemic metrics: hemoglobin A1c improvements, less hypoglycemia, and improved quality of life. However, sub-populations, such as older persons, exist where available data are limited. Furthermore, frail older adults represent a heterogeneous population with their own unique challenges to the management of diabetes. This group has some of the poorest outcomes related to the sequela of diabetes. For example, hypoglycemia resulting in significant morbidity and mortality is more frequent in older person with diabetes than in younger persons with diabetes., Method: We present a concise literature review on CGM use in the older adult as well as expand upon glycemic and nonglycemic benefits of CGM for patients, caregivers, and providers. Retrospective analysis of inpatient glycemic data of 16,935 older adults with Type 2 diabetes mellitus at Atrium Health Wake Forest Baptist indicated those with fraility managed with insulin or sulfonylurea had the highest rates of delirium (4.8%), hypoglycemia (3.5%), cardiovascular complications (20.2%) and ED visits/hospitalizatoins (49%). In addition, we address special consideration of specific situations including inpatient, palliative and long term care settings., Conclusion: This review article summarizes the available data for CGM use in older adults, discusses the benefits and obstacles with CGM use in this population, and identifies areas of future research needed for improved delivery of care to older persons with diabetes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Aloi receives research support from Abbott Diabetes. Dr. Callahan receives research support from the National Institute on Aging, K76 AG059986, under the auspices of the National Institutes of Health, and from the Duke Endowment Foundation.

Objective: Antenatal corticosteroid (ACS) administration is standard practice for pregnant individuals delivering in the late preterm period, though no guidelines are in place for those with diabetes. This study aims to characterize the prevalence of neonatal hypoglycemia after ACS administration in pregnant individuals with diabetes delivering in the late preterm period., Study Design: This is a retrospective, single-center, case-control study of individuals with diabetes who delivered between 34 0/7 and 36 6/7 weeks' gestation at a large academic medical center from 2016 to 2021. A total of 169 individuals were included in the analysis; 87 received corticosteroids and 82 did not. The proportion of neonates with hypoglycemia, neonatal intensive care unit (NICU) admission, respiratory distress syndrome, and hyperbilirubinemia were compared between parents who received ACSs versus those who did not., Results: The prevalence of neonatal hypoglycemia (40.2 vs. 23.2%, p  = 0.027), requiring treatment (40.3 vs. 22.4%, p  = 0.041), and hyperbilirubinemia (35.6 vs 18.5%, p  = 0.018) was greater for neonates born to individuals with diabetes who received late preterm ACSs compared with those who did not. There was no difference in NICU admission and respiratory distress between the groups. These results remained unchanged after controlling for confounders including gestational age at delivery and birth weight., Conclusion: This study demonstrates that late preterm corticosteroid administration to pregnant individuals with diabetes increases the risk for neonatal hypoglycemia without changing the rates of respiratory morbidity., Key Points: · Late preterm ACS in diabetic patients resulted in higher rates of neonatal hypoglycemia.. · There are no differences in rates of respiratory distress syndrome and transient tachypnea of the newborn between the ACS group and control group.. · There was no noted difference in rate of NICU admission and length of stay between the two groups.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Preterm infants have a higher rate of hypoglycemia and hyperglycemia, both of which have been associated with increased neonatal morbidities. The aim of this study was to evaluate the incidence of abnormal glucose homeostasis during the first 72 hours of life and study its association with major morbidities in infants admitted to our neonatal intensive care unit (NICU)., Study Design: This was a retrospective single-center study. We extracted demographic, maternal, and patient information and blood glucose levels for the first 72 hours of life for all infants with birth weight ≤1,000 g admitted to the NICU from January 2017 to December 2019. Continuous data were presented as mean ± standard deviation or as median with interquartile range. Categorical data were presented as frequency and percentage. Student's t -tests and Mann-Whitney U test were used to analyze continuous data and chi-squared test or Fisher's exact test were used to analyze categorical data. Logistic regression analysis was performed to study the relation between hyperglycemia and various morbidities after controlling for gestational age (GA). Statistical significance was set at p  < 0.05., Results: Of the 235 infants included in the study, 49% were hypoglycemic at admission to the NICU. Infants that were small for GA and those with history of maternal β-blocker use had a higher incidence of hypoglycemia. Hypoglycemia at admission was not associated with increased mortality or any major morbidities. Seventy-three percent infants who were hypoglycemic or euglycemic at birth developed iatrogenic hyperglycemia during the first 72 hours of life. The incidence of retinopathy of prematurity (ROP) and severe ROP was higher in infants with hyperglycemia on univariate analysis. However, on multivariate analysis, after adjusting for GA, no difference was noted in the incidence of ROP between the two groups. Multivariate analysis could not be performed for severe ROP due to inadequate sample size., Conclusion: Hyperglycemia in the initial 3 days of life is associated with an increased incidence of severe ROP in preterm infants. Neonatologists should aim to maintain euglycemia in these infants to decrease the risk of adverse outcomes., Key Points: · Preterm infants have a high rate of both hypoglycemia and hyperglycemia.. · Majority of infants who were euglycemic or hypoglycemic at birth develop iatrogenic hyperglycemia.. · Hyperglycemia in the initial 3 days of life is associated with an increased incidence of severe ROP in preterm infants.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: This study aimed to ascertain whether the length of time to complete the gestational diabetes mellitus (GDM) screening was associated with adverse neonatal outcomes., Study Design: This was a retrospective cohort study of singleton, nonanomalous individuals who were screened for GDM at ≥24 weeks' gestation at an academic hospital system. We compared outcomes among people who were diagnosed with GDM and completed the 3-hour glucose tolerance test (GTT) ≤14 second versus >14 days from the 1-hour glucose challenge test (GCT). The primary outcome was a composite adverse neonatal outcome of the following: large for gestational age, shoulder dystocia, birth injury, respiratory distress, hypoglycemia, or fetal/neonatal death. The secondary outcomes included several individual neonatal and maternal morbidities. Multivariable Poisson's regression models were used to evaluate the association. Adjusted relative risk (aRR) and 95% confidence intervals (CI) were calculated., Results: Among the 313 individuals who completed the two-step screening for GDM and had an 1-hour GCT ≥ 135 mg/dL; of them, 171 (54.6%) completed the 3-hour GTT ≤14 days, 142 (45.4%) completed the 3-hour GTT > 14 days. Overall rate of the primary outcome was 44.1%. After multivariable adjustment, the risk of the primary outcome was similar between people who completed the two-step method in ≤14 versus >14 days (aRR = 1.11, 95% CI = 0.81-1.52). There was no significant difference in all secondary adverse outcomes between the two groups. Subgroup analyses, limited to people diagnosed with GDM ( N  = 89, 23.4%), also found similar results as the full analyses., Conclusion: Among individuals who completed the two-step screening for GDM, completion of the 3-hour GTT within ≤14 versus ≥ 14 days was not associated with an increase rate of the adverse outcomes., Key Points: · Among pregnant people in an academic practice, 50% of people with abnormal 1-hour GTT completed GDM two-step screening in 14 days.. · Longer length of time to completion of diagnostic testing for GDM was not associated with an increased rate of adverse outcomes.. · Pregnant people that were diagnosed with GDM and completed the two-step method in >14 days did not have worse perinatal outcomes.., Competing Interests: None declared., (Thieme. All rights reserved.)

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

Background: Hypoglycemia is the commonest metabolic abnormality encountered in newborns. Besides, there is a growing body of evidence that links the causes of early neonatal mortality to neonatal hypoglycemia in Tanzania. However exact factors associated with asymptomatic hypoglycemia in preterm newborns are not known., Objective: To assess factors associated with asymptomatic hypoglycemia among preterm newborns., Materials and Methods: A cross sectional, analytical hospital- based study was carried out at Dar es salaam public regional referral hospitals. Preterm newborns with asymptomatic hypoglycemia were the target population. Data on demographic and clinical characteristics of preterm newborns and their mothers were collected and analyzed using Epi-Info™ software version 7.4. Main data analysis was done by applying a multivariable binary logistic regression model with neonatal random glycaemia coded in a binary fashion at a cut-off point of 2.6 mmol/L. An α-level of 5% was used as a limit of type I error., Results: We recruited and analysed 217 preterm newborns within 6-24 hours post-delivery. Male: Female = 1.1:1 (females n = 105, 48.4%). Median glycemic level was 2.6 (IQR; 2.1-3.9) mmol/L. Median gestational age at delivery was 33 (IQR: 30-35) weeks. Breastfeeding within 1st hour post-delivery was a statistically significant factor against glycemic levels associated with hypoglycemia (OR; 0.123, 95%-CI; 0.052-0.287) in a fitted multivariable logistic regression model., Conclusion: About half of all preterm newborns studied had glycemic values in a statistical range associated with hypoglycemia. Exclusive breast feeding within 1st hour post-delivery was associated with glycemic levels protective from risk of asymptomatic neonatal hypoglycemia., Recommendations: Exclusive breastfeeding practices within 1st hour post-delivery may need to be emphasized to all expectant mothers in order to avoid potential risk of asymptomatic hypoglycemia in preterm newborns., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Salum 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.)

Background: Older adults with diabetes are at high risk of severe hypoglycemia (SH). Many machine-learning (ML) models predict short-term hypoglycemia are not specific for older adults and show poor precision-recall. We aimed to develop a multidimensional, electronic health record (EHR)-based ML model to predict one-year risk of SH requiring hospitalization in older adults with diabetes., Methods and Findings: We adopted a case-control design for a retrospective territory-wide cohort of 1,456,618 records from 364,863 unique older adults (age ≥65 years) with diabetes and at least 1 Hong Kong Hospital Authority attendance from 2013 to 2018. We used 258 predictors including demographics, admissions, diagnoses, medications, and routine laboratory tests in a one-year period to predict SH events requiring hospitalization in the following 12 months. The cohort was randomly split into training, testing, and internal validation sets in a 7:2:1 ratio. Six ML algorithms were evaluated including logistic-regression, random forest, gradient boost machine, deep neural network (DNN), XGBoost, and Rulefit. We tested our model in a temporal validation cohort in the Hong Kong Diabetes Register with predictors defined in 2018 and outcome events defined in 2019. Predictive performance was assessed using area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC) statistics, and positive predictive value (PPV). We identified 11,128 SH events requiring hospitalization during the observation periods. The XGBoost model yielded the best performance (AUROC = 0.978 [95% CI 0.972 to 0.984]; AUPRC = 0.670 [95% CI 0.652 to 0.688]; PPV = 0.721 [95% CI 0.703 to 0.739]). This was superior to an 11-variable conventional logistic-regression model comprised of age, sex, history of SH, hypertension, blood glucose, kidney function measurements, and use of oral glucose-lowering drugs (GLDs) (AUROC = 0.906; AUPRC = 0.085; PPV = 0.468). Top impactful predictors included non-use of lipid-regulating drugs, in-patient admission, urgent emergency triage, insulin use, and history of SH. External validation in the HKDR cohort yielded AUROC of 0.856 [95% CI 0.838 to 0.873]. Main limitations of this study included limited transportability of the model and lack of geographically independent validation., Conclusions: Our novel-ML model demonstrated good discrimination and high precision in predicting one-year risk of SH requiring hospitalization. This may be integrated into EHR decision support systems for preemptive intervention in older adults at highest risk., Competing Interests: JCNC has received research grants and/or honoraria for consultancy or giving lectures, from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Eli-Lilly, GlaxoSmithKline, Merck Serono, Merck Sharp & Dohme, Novo-Nordisk, Pfizer and Sanofi. APSK has received honoraria for consultancy or giving lectures from Abbott, Astra Zeneca, Bayer, Boehringer Ingelheim, Dexcom, Eli-Lilly, Kyowa Kirin, Merck Serono, Merck Sharp & Dohme, Nestle, Novo-Nordisk, Pfizer and Sanofi. RCWM has received research grants and/or honoraria for consultancy or giving lectures, from AstraZeneca, Boehringer Ingelheim, Bayer, Kyowa Kirin, Merck, Novo Nordisk, Pfizer, Roche Diagnostics and Tricida Inc. The proceeds have been donated to the Chinese University of Hong Kong, American Diabetes Association and other charity organizations to support diabetes research and education. RCWM is an Academic Editor on PLOS Medicine’s editorial board. Other authors declared no conflict of interests with this work., (Copyright: © 2024 Shi 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.)

Introduction-Aim: Flexible insulin therapy is currently considered the gold standard therapy of type 1 diabetes. We aimed to study the evolution of glycemic control, weight and nutritional intake of a group of patients with type 1 diabetes, three months after the initiation of functional insulin therapy (FIT)., Methods: This was a prospective longitudinal study having included 30 type 1 diabetic patients hospitalized for education to FIT. Each patient underwent an assessment of glycemic control (glycated hemoglobin (A1C) and number of hypoglycemia), weight and nutritional intake before FIT and 3 months after the initiation of this educative approach., Results: The mean age of patients was 21,8 ± 7,9 years and the sex ratio was 0,5. The mean duration of diabetes was 7,2 ± 6 years. Three months after initiation of FIT, we observed a significant lowering of A1C, which went from 9,2 ± 1,6% to 8,3 ± 1,4% (p<0,001) of the number of minor hypoglycemia (p=0,001) and that of severe hypoglycemia (p= 0,021). the average weight went from 64,6 ± 13,1 kg to 65,5 ± 13,5 kg (p = 0,040) with a significant increase in BMI (p = 0,041). Weight gain was observed in 67% of patients. This weight gain contrasted with a significant decrease in caloric (p = 0,040) and in carbohydrates intakes (p = 0,027)., Conclusion: Weight gain, associated with better glycemic control, should encourage the healthcare team to strengthen therapeutic education of patients undergoing FIT in order to limit weight gain.

Aims: To evaluate the clinical features and impact of flash glucose monitoring in older adults with type 1 diabetes (T1D) across age groups defined as young-old, middle-old, and old-old., Materials and Methods: Clinicians were invited to submit anonymized intermittently scanned continuous glucose monitoring (isCGM) user data to a secure web-based tool within the National Health Service secure network. We collected baseline data before isCGM initiation, such as demographics, glycated haemoglobin (HbA1c) values from the previous 12 months, Gold scores and Diabetes Distress Scale (DDS2) scores. For analysis, people with diabetes were classified as young-old (65-75 years), middle-old (>75-85 years) and old-old (>85 years). We compared baseline clinical characteristics across the age categories using a t test. All the analyses were performed in R 4.1.2., Results: The study involved 1171 people with diabetes in the young-old group, 374 in the middle-old group, and 47 in the old-old group. There were no significant differences in baseline HbA1c and DDS2 scores among the young-old, middle-old, and old-old age groups. However, Gold score increased with age (3.20 [±1.91] in the young-old vs. 3.46 [±1.94] in the middle-old vs. 4.05 [±2.28] in the old-old group; p < 0.0001). This study showed reduced uptake of insulin pumps (p = 0.005) and structured education (Dose Adjustment For Normal Eating [DAFNE] course; p = 0.007) in the middle-old and old-old populations compared to the young-old population with T1D. With median isCGM use of 7 months, there was a significant improvement in HbA1c in the young-old (p < 0.001) and old-old groups, but not in the middle-old group. Diabetes-related distress score (measured by the DDS2) improved in all three age groups (p < 0.001) and Gold score improved (p < 0.001) in the young-old and old-old populations but not in the middle-old population. There was also a significant improvement in resource utilization across the three age categories following the use of is CGM., Conclusion: This study demonstrated significant differences in hypoglycaemia awareness and insulin pump use across the older age groups of adults with T1D. The implementation of isCGM demonstrated significant improvements in HbA1c, diabetes-related distress, hypoglycaemia unawareness, and resource utilization in older adults with T1D., (© 2024 John Wiley & Sons Ltd.)

Introduction: Diabetes prevalence is increasing rapidly; estimates from the International Diabetes Federation put the number at 381 million people have diabetes. Hypoglycemia is a commonly encountered complication in diabetic patients, which, in the short-term, can lead to mortality and, in the long-term, precludes maintenance of euglycemic control. Over 65.2 % of patients have reported at least one incidence of severe and nonsevere hypoglycemia when on oral hypoglycemic agents (OHA) at an annual crude incidence density of 35.1 events per year per person. Insulin more commonly causes hypoglycemia than OHA. However, this study was done with the aim of studying the hypoglycemia specifically caused by OHAs-clinical profile of patients, medications causing hypoglycemia, and the outcome., Materials and Methods: This prospective observational study was conducted in the Department of Medicine at a tertiary care hospital in Western Maharashtra. Data was collected over a period of 18 months from Indoor patients on admission having hypoglycemic symptoms with strip blood sugar levels of <70 and on OHAs. Patients on insulin were excluded from the study., Results: There were 60 patients with hypoglycemia with a mean age of 53.65 years and a higher incidence of hypoglycemia in females, 35 (58.3%) compared to males. There was a statistically significant difference between outcome (i.e., discharged or death) and urine protein-creatinine ratio (UPCR), a deranged liver function, that is, serum albumin, serum glutamic oxaloacetic transaminase (SGOT)/aspartate transaminase, and serum glutamic pyruvic transaminase (SGPT)/alanine transaminase ( p < 0.05). However, there was no statistically significant difference between outcome (discharged or death) and mean age, gender, mean duration of diabetes mellitus (DM), GCS scoring, and drug type of study subjects ( p > 0.05)., Conclusion: The risk factors for hypoglycemia were middle-aged patients. Females are at higher risk of hypoglycemia than men. Hypoglycemia due to OHAs is known to have a recurrence of hypoglycemia due to the long half-life of the drug; however, patients who were hospitalized were well monitored and did not have any recurrence of hypoglycemia. Deranged liver function or raised UPCR have high mortality after OHA-induced hypoglycemia., (© Journal of the Association of Physicians of India 2024.)

Objective: There is a relative lack of consensus regarding the optimal management of hyperglycemia in patients receiving continuous enteral nutrition (EN), with or without a diagnosis of diabetes., Methods: This retrospective study examined 475 patients (303 with known diabetes) hospitalized in critical care setting units in 2019 in a single center who received continuous EN. Rates of hypoglycemia, hyperglycemia, and glucose levels within the target range (70-180 mg/dL) were compared between patients with and without diabetes, and among patients treated with intermediate-acting (IA) biphasic neutral protamine Hagedorn 70/30, long-acting (LA) insulin, or rapid-acting insulin only., Results: Among those with type 2 diabetes mellitus, IA and LA insulin regimens were associated with a significantly higher proportion of patient-days in the target glucose range and fewer hyperglycemic days. Level 1 (<70 mg/dL) and level 2 (<54 mg/dL) hypoglycemia occurred rarely, and there were no significant differences in level 2 hypoglycemia frequency across the different insulin regimens., Conclusion: Administration of IA and LA insulin can be safe and effective for those receiving insulin doses for EN-related hyperglycemia., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Aims: We examined severe hospitalised hypoglycaemia (SHH) rates in people with type 1 and type 2 diabetes in Scotland during 2016-2022, stratifying by sociodemographics., Methods: Using the Scottish National diabetes register (SCI-Diabetes), we identified people with type 1 and type 2 diabetes alive anytime during 2016-2022. SHH events were determined through linkage to hospital admission and death registry data. We calculated annual SHH rates overall and by age, sex, and socioeconomic status. Summary estimates of time and stratum effects were obtained by fitting adjusted generalised additive models using R package mgcv., Results: Rates for those under 20 with type 1 diabetes reached their minimum at the 2020-2021 transition, 30% below the study period average. A gradual decline over time also occurred among 20-49-year-olds with type 1 diabetes. Overall, females had 15% higher rates than males with type 2 diabetes (rate ratio 1.15, 95% CI 1.08-1.22). People in the most versus least deprived quintile experienced 2.58 times higher rates (95% CI 2.27-2.93) in type 1 diabetes and 2.33 times higher (95% CI 2.08-2.62) in type 2 diabetes., Conclusions: Despite advances in care, SHH remains a significant problem in diabetes. Future efforts must address the large socioeconomic disparities in SHH risks., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: P.M.M. declares stock ownership in the following: Bayer and Roche Pharmaceuticals. H.M.C. declares grants from Juvenile Diabetes Research Foundation International, Diabetes UK, IQVIA, Chief Scientist Office, Medical Research Council (UK Research and Innovation), and European Union Commission, honoraria from Novo Nordisk, advisory board fees paid through her institution from Novo Nordisk and Bayer, and stock ownership in Bayer and Roche Pharmaceuticals. S.H. declares consulting fees paid through his institution from Vertex Pharma, Zucara Pharmaceuticals, and Zealand Pharma, honoraria from Medtronic and Novo Nordisk, and has served as Chair of DSMB for Eli Lilly development programme and as a Member of Novo Nordisk Independent Advisory Board. R.J.M. declares honoraria from Sanofi and Novo Nordisk for lectures and presentations, travel support from Sanofi, and is a non-executive member of NHS Tayside Health Board. F.W.G. declares advisory board fees from Abbott Diabetes and Insulet, speaker fees from Abbott Diabetes, Insulet, Novo Nordisk, and Lilly, and travel support from Abbott Diabetes and Novo Nordisk. S.P. declares grants from Novo Nordisk, Lilly, and Amgen, travel support from Novo Nordisk, and has participated on an Advisory board for Roche Pharmaceuticals. N.S. has consulted for and/or received speaker honoraria from Abbott Laboratories, Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Menarini-Ricerche, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi; and received grant support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics outside the submitted work. No other potential conflicts of interest relevant to this article were reported., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: Foetal male sex is associated with adverse perinatal outcomes. However, studies evaluating the impact of foetal sex on perinatal outcomes in women with gestational diabetes (GDM) are scarce. We studied whether male new-born sex is associated with neonatal outcomes, in women with GDM., Methods: This is a retrospective study based on the national Portuguese register of GDM. All women with live-born singleton pregnancies between 2012 and 2017 were eligible for study inclusion. Primary endpoints under analysis were neonatal hypoglycaemia, neonatal macrosomia, respiratory distress syndrome (RDS) and neonatal intensive care unit (NICU) admission. We excluded women with missing data on the primary endpoint. Pregnancy data and neonatal outcomes between female and male new-borns were compared. Multivariate logistic regression models were built., Results: We studied 10,768 new-borns in mothers with GDM, 5635 (52.3%) male, 438 (4.1%) had neonatal hypoglycaemia, 406 (3.8%) were macrosomic, 671 (6.2%) had RDS, and 671 (6.2%) needed NICU admission. Male new-borns were more frequently small or large for gestational age. No differences were observed on maternal age, body mass index, glycated haemoglobin, anti-hyperglycaemic treatment, pregnancy complications or gestational age at delivery. In the multivariate regression analysis, male sex was independently associated with neonatal hypoglycaemia [OR 1.26 (IC 95%: 1.04-1.54), p = 0.02], neonatal macrosomia [1.94 (1.56-2.41), p < 0.001], NICU admission [1.29 (1.07-1.56), p = 0.009], and RDS [1.35 (1.05-1.73, p = 0.02]., Conclusions: Male new-borns have an independent 26% higher risk of neonatal hypoglycaemia, 29% higher risk of NICU admission, 35% higher risk of RDS, and almost twofold higher risk of macrosomia, compared to female new-borns., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims/introduction: To develop and validate a simple prediction model for hypoglycemia risk in patients with type 2 diabetes., Materials and Methods: We prospectively analyzed the data of 1,303 subjects in a third-class hospital in Tianjin and followed up their hypoglycemia events at 3 and 6 months. The hypoglycemia risk prediction models for 3 and 6 months were developed and the model performance was evaluated., Results: A total of 340 (28.4%) patients experienced hypoglycemia within 3 months and 462 (37.2%) within 6 months during the follow-up period. Age, central obesity, intensive insulin therapy, frequency of hypoglycemia in the past year, and hypoglycemia prevention education entered both model 3month and model 6month . The area under the receiver operating characteristic curve of model 3month and model 6month were 0.711 and 0.723, respectively. The Youden index was 0.315 and 0.361, while the sensitivities were 0.615 and 0.714, and the specificities were 0.717 and 0.631. The calibration curves showed that the models were similar to reality. The decision curves implied that the clinical net benefit of the model was clear., Conclusions: The study developed 3 and 6 month hypoglycemia risk prediction models for patients with type 2 diabetes. The discrimination and calibration of the two prediction models were good, and might help to improve clinical decision-making and guide patients to more reasonable self-care and hypoglycemia prevention at home., (© 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Aim: To evaluate the effect of age and disease duration on the efficacy and safety of iGlarLixi versus insulin glargine 100 units/ml (iGlar) or lixisenatide (Lixi) alone in Asian people with type 2 diabetes (T2D) uncontrolled on oral antidiabetic drugs (LixiLan-O-AP) or basal insulin ± oral antidiabetic drugs (LixiLan-L-CN)., Materials and Methods: In this post hoc analysis, the glycated haemoglobin (HbA1c) changes were assessed from baseline to week 24 (LixiLan-O-AP) or 30 (LixiLan-L-CN) in subgroups defined by baseline age (<65, ≥65 years) and duration of T2D. The proportion who achieved the composite of HbA1c <7% (<53.0 mmol/mol) without weight gain and without symptomatic hypoglycaemia (plasma glucose ≤3.9 mmol/L) and the incidences of hypoglycaemia and gastrointestinal disorders were also analysed., Results: HbA1c reductions were consistently greater with iGlarLixi versus iGlar or Lixi across all subgroups, including participants aged ≥65 years and those with T2D for ≥15 or ≥20 years. Greater proportions of participants achieved HbA1c <7% (<53.0 mmol/mol) without weight gain or hypoglycaemia with iGlarLixi versus iGlar or Lixi, regardless of age or T2D duration. Hypoglycaemia incidence was similar with iGlarLixi versus iGlar across most subgroups; the incidence of gastrointestinal disorders was lower with iGlarLixi versus Lixi in all subgroups., Conclusions: iGlarLixi showed consistent efficacy and safety across all age and disease duration subgroups in Asian people with uncontrolled T2D, including older individuals and those with longstanding disease., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background and Objectives: Liver cancer poses a significant global health threat, ranking among the top three causes of cancer-related deaths. Patients with hepatocellular carcinoma (HCC) often present with symptoms associated with neoplasms or unusual clinical features such as paraneoplastic syndromes (PNS), including hypoglycemia, hypercholesterolemia, thrombocytosis, and erythrocytosis. Our study aimed to investigate the prevalence, clinical characteristics, and survival outcomes associated with PNS in HCC patients and assess each PNS's impact on patient survival. Materials and Methods: We conducted a retrospective analysis of PNS clinical features and survival among consecutive HCC patients diagnosed at our department over seven years, comparing them with HCC patients without PNS. The study involved a retrospective data evaluation from 378 patients diagnosed with HCC between January 2016 and October 2023. Results: We obtained a PNS prevalence of 25.7%, with paraneoplastic hypercholesterolemia at 10.9%, hypoglycemia at 6.9%, erythrocytosis at 4.5%, and thrombocytosis at 3.4%. Patients with PNS tended to be younger and predominantly male. Multivariate analysis revealed a strong correlation between PNS and levels of alpha-fetoprotein and tumor size, with diabetes also showing a significant statistical association ( p < 0.05). Subgroup analysis based on specific paraneoplastic syndromes demonstrated shorter survival in patients with PNS, albeit without significant statistical differences, except for hypoglycemia ( p < 0.0001). Matched analysis indicated a shorter survival rate for patients with PNS, although no significant statistical differences were observed. Conclusions: PNS are frequently observed in HCC cases and are associated with unfavorable prognoses and decreased survival rates due to their correlation with increased tumor burdens. However, they do not independently predict poor survival. The impact of individual PNS on HCC prognosis varies.

Importance: The circumstances under which neonatal hypoglycemia leads to brain damage remain unclear due to a lack of long-term data on the neurodevelopment of affected children. As a result, diagnostic strategies and treatment recommendations are inconsistent., Objective: To evaluate whether the occurrence of severe transitional neonatal hypoglycemia (defined as having at least 1 blood glucose measurement of 30 mg/dL or below) is associated with adverse neurodevelopment in midchildhood., Design, Setting, and Participants: This cohort study using neurodevelopmental testing of a retrospectively recruited cohort was conducted at a single-center tertiary hospital in Germany between March 2022 and February 2023. Children with neonatal blood glucose screening data were randomly selected from all births between 2010 and 2015. Frequency matching for sex, birth weight, gestational age, socioeconomic status, and primary risk factors for neonatal hypoglycemia was performed. Children with persistent hypoglycemia diseases or any risk factor for adverse neurodevelopment except hypoglycemia were excluded. Data were analyzed between February 2023 and March 2023., Exposure: At least 1 neonatal hypoglycemia measurement with blood glucose measuring 30 mg/dL or below vs all measured blood glucose levels above 30 mg/dL during postnatal blood glucose screening starting on the first day of life., Main Outcomes and Measures: Cognitive function measured by full-scale IQ test. Secondary outcomes included standardized scales of motor, visual, and executive functions, and child behavior, each measured at ages 7 to 11 years., Results: A total of 140 children (mean [SD] age 9.1 [1.3] years; 77 male [55.0%]) participated in the study. Children with severe neonatal hypoglycemia had a 4.8 points lower mean full-scale IQ than controls (107.0 [95% CI, 104.0-109.9] vs 111.8 [95% CI, 108.8-114.8]). They showed a 4.9-fold (95% CI, 1.5-15.5) increased odds of abnormal fine motor function and a 5.3-fold (95% CI, 2.1-13.3) increased odds of abnormal visual-motor integration. Significantly higher T scores for attention problems (58.2 [95% CI, 56.1-60.2] vs 54.6 [95% CI, 52.6-56.6]) and attention-deficit/hyperactivity disorder symptoms (58.2 [95% CI, 56.2-60.2] vs 54.7 [95% CI, 52.8-56.7]) were reported by parents., Conclusions and Relevance: Neonatal hypoglycemia with blood glucose levels of 30 mg/dL or below was associated with an increased risk for suboptimal neurodevelopmental outcomes in midchildhood. These findings imply that treatment strategies should aim to prevent episodes of hypoglycemia at these severely low levels.

Objective: This cross-sectional survey was performed to assess the prevalence, factors, and economic burden of non-severe hypoglycemia among insulin-treated type 2 diabetes (T2D) patients in northern Thailand., Methods: Between April 2021 and August 2022, 600 participants were evaluated via structured questionnaires containing sociodemographic and clinical characteristics, medications, and economic burden. Patients were divided into two groups (having and not having non-severe hypoglycemia). Variables with a p value <.05 in the univariate model were included in the multivariate model., Results: The percentage of non-severe hypoglycemia was 50.3% (302/600). Of all participants, the average age was 61.4 ± 26.0 years, 55.7% were female, 53.5% used premix insulin, and the average duration of diabetes was 16.1 ± 10.0 years. Multivariate logistic regression analysis indicated that age (OR = .96; p  <.001), duration of diabetes (OR = 1.04; p  <.001), BMI (OR = .95; p  = .002), thiazolidinedione (OR = 1.56; p  = .012) and insulin regimens were associated with having non-severe hypoglycemia. Compared to basal insulin, basal bolus (OR = 6.93; p  = .001), basal plus (OR = 3.58; p  <.001), and premix insulin (OR = 1.83; p  =.003) were associated with hypoglycemia. Greater numbers of sick leave were found in the hypoglycemia group (14 vs 4 patients, p  = .029)., Conclusions: These findings help to individuate those patients who are at higher risk of non-severe hypoglycemia in insulin-treated T2D patients. Compared to the non-hypoglycemia group, patients with hypoglycemia were younger, had longer diabetes duration, lower BMI, received thiazolidinedione and insulin regimens such as premix, basal plus, or basal bolus insulins, and more productivity loss.

Aims: To determine the prevalence and associations of impaired awareness of hypoglycemia (IAH) in pediatric type 1 diabetes., Methods: Nationwide, population-based cross-sectional study with 51 % participation. Participants (n = 1329; 53 % males) aged 2-19 years (median 13.3) with type 1 diabetes ≥ 6 months (median 4.6 years) self-assessed hypoglycemia awareness with a validated questionnaire ('Clarke'). Parents responded for children aged < 9 years (n = 235). We estimated associations between IAH and clinical data in the Norwegian Childhood Diabetes Registry., Results: The overall prevalence of IAH was 22 %, but gradually decreased from 53 % in preschoolers to 12 % in adolescents aged ≥ 16 years. IAH was associated (adjusted OR; 95 %CI) with episodes of severe hypoglycemia (6.0; 3.04, 11.8) and diabetic ketoacidosis (3.45; 1.37, 8.68) the preceding year, increased fear of hypoglycemia (highest quartile vs. lowest: 2.27; 1.51, 3.40), female sex (1.41; 1.05, 1.90), and HbA1c ≥ 8.5 % (69 mmol/mol) vs. 7.5-8.4 % (58-68 mmol/mol) (1.48; 1.01, 2.18), but not with disease duration, use of insulin pump or continuous glucose monitoring, or HbA1c < 7.5 % (58 mmol/mol)., Conclusions: IAH is prevalent in pediatric diabetes and more likely reported in young children. IAH is associated with severe hypoglycemia and fear of hypoglycemia, but good metabolic control seems achievable without increased risk of IAH., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To describe changes in glucose-lowering drug (GLD) dispensing by frailty status for people with diabetes following admission for hypoglycaemia or hyperglycaemia., Methods: This study included all people with probable type 2 diabetes in the state of Victoria, Australia, admitted to hospital for hypoglycaemia (n = 2,506 admissions) or hyperglycaemia (n = 1,693) between 1 July 2013 and 29 June 2017. Frailty was defined via the Hospital Frailty Risk Score (HFRS). We examined differences in dispensing of GLDs in the year before and after admission using linear regression models adjusted for age, sex, comorbidities, and socioeconomic status., Results: Dispensing of GLDs decreased following hypoglycaemia admission. Decreased dispensing was strongly associated with frailty status, with a change in mean annual GLD dispensing count of -4.11 (-5.05, -3.17) for an HFRS of 15 vs. -0.99 (-1.47, -0.50) for an HFRS of 0. Changes were greatest for metformin and sulfonylureas. Following hyperglycaemia admission, the mean number of annual GLD dispensings increased, with a smaller increase with increasing frailty: 2.44 (1.32, 3.56) for an HFRS of 0 vs. 1.16 (0.18, 2.14) for an HFRS of 15., Conclusions: Frailty was associated with more conservative diabetes medication management following hypoglycaemia and hyperglycaemia admissions., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aim: To report on the effectiveness and safety of the MiniMed 780G automated insulin delivery system in real-world users during the month of Ramadan., Materials and Methods: CareLink Personal data were extracted from MiniMed 780G system users from the Gulf region. Users were included if they had ≥10 days of sensor glucose data during the month of Ramadan 2022 as well as in the month before and after. For the main analysis, continuous glucose monitoring endpoints were aggregated per month and were reported by time of day (daytime: 05.31-18.00 h, and night-time). Additional analyses were performed to study the pace at which the algorithm adapts., Results: Glycaemic control was well kept in the 449 included users (mean sensor glucose = 152.6 ± 18.7 mg/dl, glucose management indicator = 7.0 ± 0.4%, time in range = 70.7 ± 11.0%, time below 70 mg/dl = 2.3 ± 2.3%). Albeit some metrics differed from the month before (p < .0001 for all), absolute differences were very small and considered clinically irrelevant. During Ramadan, there was no increased risk of hypoglycaemia during daytime (time below 70 mg/dl = 2.3 ± 2.4%), time in range was highest during daytime (80.0 ± 10.7%, night: 60.4 ± 15.3%), while time above 180 mg/dl was highest during night-time (37.3 ± 16.3%, day: 17.7 ± 10.7%). The algorithm adapted immediately upon lifestyle change., Conclusion: The MiniMed 780G automated insulin delivery system is effective, safe and fast in adapting to the substantial changes that occur in the lifestyle of people with type 1 diabetes during Ramadan., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aim: To assess the efficacy and safety of iGlarLixi in older people (≥65 years) with type 2 diabetes (T2D) advancing or switching from oral agents, a glucagon-like peptide-1 receptor agonist (GLP-1RA), or basal insulin., Materials and Methods: The data of participants aged <65 years and ≥65 years from four LixiLan trials (LixiLan-O, LixiLan-G, LixiLan-L, SoliMix) were evaluated over 26 or 30 weeks., Results: Participants aged <65/≥65 years (n = 1039/n = 497) had a mean baseline body mass index of 31.4 and 30.7 kg/m 2 and glycated haemoglobin (HbA1c) concentration of 66 mmol/mol (8.2%) and 65 mmol/mol (8.1%), respectively. Least squares mean HbA1c change from baseline to end of treatment (EOT) was -14.32 mmol/mol (-1.31%) (95% confidence interval [CI] -14.97, -13.77 [-1.37%, -1.26%]) for those aged <65 years and -13.66 mmol/mol (-1.25%) (95% CI -14.54, -12.79 [-1.33%, -1.17%]) for those aged ≥65 years. At EOT, achievement of HbA1c targets was similar between the group aged <65 years and the group aged ≥65 years: <53 mmol/mol (<7%) (59.0% and 56.5%, respectively), <59 mmol/mol (<7.5%) (75.5% and 73.0%, respectively) and <64 mmol/mol (<8%) (83.8% and 84.1%, respectively). The incidence and event rate of American Diabetes Association Level 1 hypoglycaemia during the studies were also comparable between the two groups: 26.7% and 28.2% and 1.7 and 2.1 events per patient-year for the group aged <65 years and the group aged ≥65 years, respectively. A clinically relevant reduction in HbA1c (>1% from baseline for HbA1c ≥64 mmol/mol [≥8%] or ≥0.5% from baseline for HbA1c <64 mmol/mol [<8%]) without hypoglycaemia was attained by 50.0% and 47.6% of participants aged <65 years and ≥65 years, respectively. Adverse events were similar between the two age groups., Conclusions: iGlarLixi is a simple, well-tolerated, once-daily alternative for treatment advancement in older people with T2D that provides significant improvements in glycaemic control without increasing hypoglycaemia risk, thus reducing the treatment burden., (© 2023 Sanofi and The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To investigate differences in maternal and foetal outcomes in pregnancy, where patients developed hypoglycaemia following the 2-hour 75g oral glucose tolerance test (OGTT)., Method: A retrospective cohort study of 200 pregnancies attending the Antenatal Clinic at Tameside General Hospital between 2018 and 2022. Outcomes were compared between 4 groups: normal OGTT [G1; (n = 39, 20%), diagnosis of gestational diabetes mellitus (GDM) based on OGTT [G2; BG ≥ 5.6 mmol/L or 2-h OGTT ≥7.8 (n = 41, 21%)], hypoglycaemia [G3; 2 h OGTT 3.0-3.9 mmol/L (n = 93, 47%)], or clinically significant hypoglycaemia [G4; 2 h OGTT <3.0 mmol/L (n = 27, 14%)]. Maternal BMI, foetal birth weight (FBW), neonatal complications, neo-natal intensive care unit (NICU) stay and conversion to GDM were assessed., Results: Maternal BMI was lower in G3 and G4 (27.3 kg/m 2 and 28.1 kg/m 2 respectively) compared to G1 (30.4 kg/m 2 ) (p = 0.02). NICU stay was more frequent in G3 (12%, n = 11) and G4 (8%, n = 2) compared to G1 (5%, n = 2). Foetal complications occurred in 27% of G3 (n = 25) and 33% of G4 (n = 9) compared to 23% in G1 (n = 9) and 17% in G2 (n = 7). FBW was similar in G1 when compared to G3 and G4 (p = 0.34). Of the 120 patients in G3 and G4, 25 patients self-monitored blood glucose for two weeks; 28% (n = 7) subsequently developed GDM., Conclusion: Higher rates of NICU stay and foetal complications were seen in both hypoglycaemic groups. In patients with hypoglycaemia following OGTT there is evidence to support self-monitoring blood glucose as 28% were later diagnosed with GDM., 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., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Aims: Studies suggested a higher prevalence of Attention-deficit/hyperactivity disorder (ADHD) in individuals with Type 1 Diabetes Mellitus (T1D). However, it is unclear how ADHD impacts glycemia and diabetes-related complications. This systematic review and meta-analysis aimed to investigate the effect of ADHD and ADHD medications on HbA1c and acute complications in T1D., Methods: A literature search was conducted in PubMed, EMBASE, CINAHL, Scopus, PsycINFO, CENTRAL, and Web of Science collections up to November 22, 2023. Seventeen studies were selected for the systematic review by independent reviewers, with twelve included in the meta-analysis., Results: Mean HbA1c levels were significantly higher in T1D individuals with ADHD compared to those without ADHD (MD = 0.60; 95 % CI: 0.41, 0.79; I 2  = 90.1 %; p-value < 0.001). The rates of suboptimal HbA1c levels, hospitalization, diabetic ketoacidosis, and hypoglycemia were all substantially higher in T1D individuals with ADHD than those without ADHD. No difference was found in mean HbA1c between those who received ADHD treatment and those who did not (mean difference = -0.52; 95 % confidence interval: -1.16, 0.13; I 2  = 78.6 %; p-value = 0.12)., Conclusions: ADHD is associated with higher HbA1c and increased acute diabetes-related complications. More research is needed to assess the effects of ADHD treatments on T1D management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: To explore the relationship between preconception severe hypoglycemia (PSH) and pregnancy outcomes in pregnancies complicated with type 1 diabetes mellitus (T1DM)., Materials and Methods: In this multicenter prospective cohort study, women with pregestational T1DM were stratified by episodes of severe hypoglycemia within 1 year before conception: No PSH, sporadic PSH (1-6 times/year), and recurrent PSH (>6 times/year). We analysed the predictive ability of PSH for maternal and neonatal outcomes using log-binomial regression models and receiver operating characteristic (ROC) curve., Results: Of the 124 women studied, 37.1% experienced at least one episode of severe hypoglycemia preconception. In the multiple adjusted regression models, recurrent PSH was significantly associated with increased incidence of preeclampsia (RR 17.59, 95% CI: 2.89-150.62, p for trend = 0.007), preterm birth (RR 6.34, 95% CI: 1.22-40.63, p for trend = 0.027), neonatal hypoglycemia (RR 4.52, 95% CI: 1.14-17.16, p for trend = 0.017), neonatal hyperbilirubinemia (RR 4.12, 95% CI: 1.11-15.56, p for trend = 0.004), and composite neonatal outcome (RR 3.85, 95% CI: 1.01-19.61, p for trend = 0.003). In the ROC analysis, PSH predicted preeclampsia, preterm birth, neonatal hypoglycemia, neonatal hyperbilirubinemia, and composite neonatal outcome with areas under the ROC curve all ≥0.6., Conclusions: Recurrent preconception severe hypoglycemia is associated with increased risks of adverse outcomes in pregnant women with T1DM., (© 2023 John Wiley & Sons Ltd.)

Purpose: People with pediatric and early adulthood type 1 diabetes (T1D) might have a higher fracture risk at several sites compared to the general population. Therefore, we assessed the hazard ratios (HR) of various fracture sites and determined the risk factors associated with fractures among people with newly diagnosed childhood and adolescence T1D., Methods: All people from the UK Clinical Practice Research Datalink GOLD (1987-2017), below 20 years of age with a T1D diagnosis code (n = 3100) and a new insulin prescription, were included and matched 1:1 by sex, age, and practice to a control without diabetes. Cox regression was used to estimate HRs of any, major osteoporotic fractures (MOFs) and peripheral fractures (lower-arm and lower-legs) for people with T1D compared to controls. The analyses were adjusted for sex, age, diabetic complications, medication (glucocorticoids, anti-depressants, anxiolytics, bone medication, anti-convulsive), Charlson-comorbidity-index (CCI), hypoglycemia, falls and alcohol. T1D was further stratified by diabetes duration, presence of diabetic microvascular complications (retinopathy, nephropathy, and neuropathy) and boys versus girls., Results: The crude HRs for any fracture (HR: 1.30, CI95%: 1.11-1.51), lower-arm (HR: 1.22, CI95%: 1.00-1.48), and lower-leg fractures (HR: 1.54, CI95%: 1.11-2.13) were statistically significant increase in T1D compared to controls, but the effect disappeared in the adjusted analyses. For MOFs, no significant differences were seen. Risk factors in the T1D cohort were few, but the most predominantly one was a previous fracture (any fracture: HR: 2.00, CI95%: 1.70-2.36; MOFs: HR: 1.89, CI95%: 1.44-2.48, lower- arm fractures: HR: 2.08, CI95%: 1.53-2.82 and lower-leg fractures: HR: 2.08, CI95%: 1.34-3.25). Others were a previous fall (any fracture: HR: 1.54, CI95%: 1.20-1.97), hypoglycemia (Any fracture: HR: 1.46, CI95%: 1.21-1.77 and lower-leg fractures: HR: 2.34, CI95%: 1.47-3.75), and anxiolytic medication (Any fracture: HR: 1.52, CI95%: 1.10-2.11). Whereas girls had a lower risk compared to boys (Any fracture: HR: 0.78, CI95%: 0.67-0.90 and lower-arm fractures; HR: 0.51, CI95%: 0.38-0.68). The risk of any fracture in T1D did not increase with longer diabetes duration compared to controls (0-4 years: HR: 1.20, CI95%: 1.00-1.44; 5-9 years: HR: 1.17, CI95%: 0.91-1.50; <10 years: HR: 0.83, CI95%: 0.54-1.27). Similar patterns were observed for other fracture sites. Furthermore, one complication compared to none in T1D correlated with a higher fracture risk (1 complication: HR: 1.42, CI95%: 1.04-1.95)., Conclusion: The overall fracture risk was not increased in pediatric and early adulthood T1D; instead, it was associated with familiar risk factors and specific diabetes-related ones., Competing Interests: Declaration of competing interest Peter Vestergaard is head of research in the Steno Diabetes Center North Denmark sponsored by the Novo Nordisk Foundation. Joop van den Bergh: unrestricted research grant and lecture fee from Amgen and UCB, is consultant for PoroUS. Nicklas H. Rasmussen holds shares in Novo Nordisk, has lecture fees from Boehringer Ingelheim and travel expenses from UCB. The other authors Johanna Driessen, Patrick Souverein and Annika Kvist declare that they have no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim: This work aims to characterize the clinical profile of individuals with frailty syndrome, diabetes mellitus (DM), and hyperglycemia during hospitalization in regard to glycemic control and treatment regimen., Methods: This cross-sectional multicentric study included patients with DM or hyperglycemia at admission. Demographic data, blood glucose values, treatment administered during hospitalization, and treatment indicated at discharge were analyzed. The sample was divided into three groups according to score on a frailty questionnaire. Generalized additive models were used to describe the relationship between either glycemic variability (GV) or minimum capillary blood glucose and hypoglycemia. Models were adjusted for age, comorbidity, and sarcopenia., Results: A total of 1,137 patients were analyzed. Patients with frailty syndrome had more comorbidity and sarcopenia, worse renal function, and lower albumin and lymphocyte levels. A GV between 21% and 60% was related to a higher probability of hypoglycemia, especially in patients with frailty. Regarding minimum capillary blood glucose, patients with frailty had the highest probability of hypoglycemia. This probability remained significant even in the group with frailty in which, with a reference value of 200 mg/dl, the adjusted odds ratio of a minimum capillary blood glucose of 151 mg/dL was 1.08 (95% confidence interval (1.12-1.05)). Baseline treatments showed a significant predominance of insulin use in the frailest groups., Conclusions: Patients with frailty had more sarcopenia and undernourishment. These patients were managed in a similar manner during hospitalization to patients without frailty, despite their higher risk of hypoglycemia according to GV or minimum capillary blood glucose levels., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Aim: To investigate safety and effectiveness of iGlarLixi in adults with type 2 diabetes mellitus (T2DM) observing fast during Ramadan from Gulf countries., Methods: This planned subgroup analysis of the SoliRam - a multinational, prospective, non-interventional, real-world, observational study - focused on participants from Gulf countries. Primary endpoint was proportion of participants experiencing ≥1 episode of severe and/or symptomatic documented (<70 mg/dL [<3.9 mmol/L]) hypoglycemia., Results: A total of 241 individuals with T2DM (mean age: 58.1 years; male: 54.4%; mean duration of diabetes: 13.3 years) were included. All 234 eligible participants followed during Ramadan were able to fast for ≥25 days and no participants broke fast due to hypoglycemia. Primary endpoint was reported in one participant (0.5%) during fasting hours during Ramadan. Improvements (mean ± SD change) in HbA1c (-1.0 ± 1.0% [-11 ± 10 mmol/mol]), FPG (-22.5 ± 29.7 mg/dL), and body weight (-1.5 ± 2.0 kg) were observed from pre-Ramadan to post-Ramadan. Three participants (1.2 %) reported an adverse event (AE) of any cause and one (0.4%) reported a gastrointestinal AE., Conclusions: iGlarLixi is an effective and well-tolerated treatment in people with T2DM from Gulf countries, including during Ramadan fasting, and is associated with low risk of hypoglycemia., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mohamed Hassanein reports administrative support, article publishing charges, equipment, drugs, or supplies, statistical analysis, and writing assistance were provided by Sanofi. Adel El Naggar reports administrative support, article publishing charges, equipment, drugs, or supplies, statistical analysis, and writing assistance were provided by Sanofi. Abdulrahman Al Sheikh reports administrative support, article publishing charges, equipment, drugs, or supplies, statistical analysis, and writing assistance were provided by Sanofi. Lydie Melas-Melt reports administrative support, article publishing charges, and writing assistance were provided by Sanofi. Saud AlSifri reports administrative support, article publishing charges, equipment, drugs, or supplies, statistical analysis, and writing assistance were provided by Sanofi. Mohamed Hassanein reports a relationship with Sanofi, Boehringer Ingelheim, and Novo Nordisk that includes: board membership. Mohamed Hassanein reports a relationship with Sanofi, Novo Nordisk, Eli Lilly and Company, Merck Sharp and Dohme, Janssen, and LifeScan that includes: speaking and lecture fees. Adel El Naggar reports a relationship with Sanofi, Novo Nordisk, and Merck & Co that includes: board membership. Adel El Naggar reports a relationship with Sanofi, Novo Nordisk, AstraZeneca, MSD, Organon & Co., Boehringer Ingelheim, Eli Lilly and Company, and Novartis that includes: speaking and lecture fees. Khier Djaballah reports a relationship with Sanofi that includes: employment and equity or stocks. Mohamed Saeed reports a relationship with Sanofi that includes: employment. Lydie Melas-Melt reports a relationship with IVIDATA Life Sciences that includes: employment. Saud AlSifri reports a relationship with Sanofi that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

High rates of academic underachievement at 9-10 years have been identified in children born at risk of neonatal hypoglycaemia. This study investigated the stability of behaviour from early to mid-childhood and how this relates to academic outcomes in children born with at least one risk factor of neonatal hypoglycaemia in Aotearoa, New Zealand. Behaviour data was collected using the Bayley Scales of Infant and Toddler Development, Child Behaviour Checklist 1.5-5, and the Strengths and Difficulties Questionnaire for 466 children (52 % male; 27 % Māori, 60 % New Zealand European, 2 % Pacific, 11 % Other) at multiple timepoints between ages 2 and 10 years. Academic data was collected at 9-10 years using the e-asTTle online learning and assessment tool. Findings revealed a link between early childhood behaviour and academic outcomes could be detected as early as age 2, suggesting that identifying and addressing early behavioural issues in children at risk of neonatal hypoglycaemia could aid in targeted interventions., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Once-weekly basal insulin icodec has been tested in clinical trials for efficacy and safety over currently available glargine-100 and degludec in different clinical settings for type 2 diabetes. We performed this meta-analysis to evaluate its overall safety and efficacy as compared to glargine-100 and degludec (nonicodec), from all available randomized controlled trials., Methods: Seven trials comparing once-daily basal insulin analogs to once-weekly basal insulin icodec were included. Based on available information, outcomes in terms of HbA1c, fasting plasma glucose reduction, and increase in time in range (TIR) were compared. Side-effects were compared for overall hypoglycemia, severe hypoglycemia, and weight gain. The pooled effect size for continuously distributed data was measured as a reduction in "estimated differences in mean (with 95% CI)." For categorical data, the pooled effect size was measured as the Mantel-Haenszel risk ratio (with 95% CI)., Results: Analyzing against the nonicodec comparators together, the "estimated mean changes" in HbA1c and fasting plasma glucose favoring icodec were -0.22% (-0.35, -0.10) and -1.59 mg% (-9.26, 6.08) respectively. The "estimated mean increment" in weight for icodec was 0.64 kg (0.61, 0.67). The "estimated mean percentage" increment in TIR for icodec was 4.24% (2.99, 5.49). The Mantel-Haenszel risk ratios for all hypoglycemic events and severe hypoglycemia for icodec were 1.24 (1.02, 1.50) (P = .03) and 0.81 (0.31, 2.08) (P is not significant), respectively, suggesting a 24% increased incidence of all hypoglycemia with icodec., Conclusion: Once-weekly basal insulin icodec as compared to once-daily basal insulin analogs had a slight increase in the risk of overall hypoglycemia and weight gain, without any difference in severe hypoglycemia, with similar glycemic control (in terms of fasting plasma glucose, HbA1c, and TIR)., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2023 AACE. Published by Elsevier Inc. All rights reserved.)

Aims: Automated insulin delivery systems improve blood glucose control in patients with type 1 diabetes (T1D). However, optimizing their performance requires patient's proper compliance to meal insulin bolus administration. We explored real-life prevalence of delayed prandial boluses (DBs) in adults with T1D on advanced technologies, and their association with glycemic control and fear of hypoglycemia (FH)., Methods: In the last two-week web-based reports of 152 adults with T1D on Hybrid Closed Loop Systems (HCLS) or Sensor Augmented Pump (SAP), DBs were identified when a steep increase in blood glucose occurred at CGM before the prandial bolus, and CGM metrics were evaluated. All participants completed an online questionnaire on FH., Results: Mean DBs over two weeks were 10.2 ± 4.7 (M ± SD, range 1-23) and more frequent in women than men (11.0 ± 4.6 vs. 9.4 ± 4.7, p = 0.036). Participants with more DBs (>12) showed significantly lower Time-In-Range (62.4 ± 13.8 vs. 76.6 ± 9.0 %) than those with less DBs (<7.7), along with higher Time-Above-Range, GMI, and Coefficient-of-Variation (ANOVA, p < 0.001 for all). Participants with higher FH score showed more DBs (11.6 ± 5.0) than those in lower tertiles (9.57 ± 4.59 and 9.47 ± 4.45, ANOVA p = 0.045)., Conclusions: In patients on advanced technologies, delayed boluses are extremely common, and associate with significantly worse glycemic control. Utmost attention is needed to bolus timing, mainly tackling fear of hypoglycemia., Competing Interests: Declaration of competing interest No potential conflicts of interest relevant to this article were reported., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Previous studies have reported an association between hypoglycemia and cardiovascular (CV) events in people with type 2 diabetes (T2D), but it is unclear if this association is causal or identifies a high-risk patient phenotype., Objective: To evaluate the associations between hypoglycemia and CV outcomes., Design, Setting, and Participants: This secondary analysis was a post hoc assessment of the multinational, double-blind CARMELINA (Cardiovascular and Renal Microvascular Outcome Study With Linagliptin; 2013-2016) and CAROLINA (Cardiovascular Outcome Trial of Linagliptin vs Glimepiride in Type 2 Diabetes; 2010-2018) randomized clinical trials of the antihyperglycemic drug, linagliptin, a dipeptidyl peptidase 4 inhibitor. Participants were adults with T2D at high CV risk with or without high kidney risk. By design, participants in the CARMELINA trial had longer duration of T2D and had a higher CV risk than participants in the CAROLINA trial. Data analyses were conducted between June 2021 and June 2023., Intervention: Linagliptin or placebo in the CARMELINA trial, and linagliptin or glimepiride in the CAROLINA trial., Main Outcomes and Measures: The primary outcome for both trials was CV death, myocardial infarction (MI), or stroke (3-point major adverse CV events [3P-MACE]). For the present analyses, hospitalization for heart failure (HF) was added. Hypoglycemia was defined as plasma glucose less than 54 mg/dL or severe hypoglycemia (episodes requiring the assistance of another person). Associations between the first hypoglycemic episode and subsequent CV events and between nonfatal CV events (MI, stroke, hospitalization for HF) and subsequent hypoglycemic episodes were assessed using multivariable Cox proportional hazards regression models. Sensitivity analyses explored the risk of CV events within 60 days after each hypoglycemic episode., Results: In the CARMELINA trial (6979 patients; 4390 males [62.9%]; mean [SD] age, 65.9 [9.1] years), there was an association between hypoglycemia and subsequent 3P-MACE plus hospitalization for HF (hazard ratio [HR], 1.23; 95% CI, 1.04-1.46) as well as between nonfatal CV events and subsequent hypoglycemia (HR, 1.39; 95% CI, 1.06-1.83). In the CAROLINA trial (6033 patients; 3619 males (60.0%); mean [SD] age, 64.0 [9.5] years), there was no association between hypoglycemia and subsequent 3P-MACE plus hospitalization for HF (HR, 1.00; 95% CI, 0.76-1.32) and between nonfatal CV events and subsequent hypoglycemia (HR, 1.44; 95% CI, 0.96-2.16). In analyses of CV events occurring within 60 days after hypoglycemia, there was either no association or too few events to analyze., Conclusions and Relevance: This study found bidirectional associations between hypoglycemia and CV outcomes in the CARMELINA trial but no associations in either direction in the CAROLINA trial, challenging the notion that hypoglycemia causes adverse CV events. The findings from the CARMELINA trial suggest that both hypoglycemia and CV events more likely identify patients at high risk for both., Trial Registration: ClinicalTrials.gov Identifier: NCT01897532 (CARMELINA) and NCT01243424 (CAROLINA).

Introduction: Impaired awareness of hypoglycemia (IAH) refers to a diminished capacity to detect hypoglycemia. IAH can result in severe and even life-threatening outcomes for individuals with diabetes, especially those in advanced stages of the disease. This study aimed to assess the prevalence of IAH in people with diabetes on hemodialysis., Research Design and Methods: We conducted a single-center audit to assess the prevalence of IAH using the Clarke questionnaire. Simultaneously, we measured fear of hypoglycemia with an adapted version of the Hypoglycemia Survey and recorded the incidence of severe hypoglycemia. Data were presented as mean±SD or counts/percentages. Logistic regression was then employed to analyze the association between IAH and various sociodemographic and clinical factors., Results: We included 56 participants with diabetes on hemodialysis, with a mean age of 67.2 years (±12.9), of whom 51.8% were male. The ethnic distribution was 23.2% white, 23.2% black, 19.6% Asian, and 33.9% unspecified. The mean HbA1c was 52 mmol/mol (±18.6). The majority (91.1%) had a diagnosis of type 2 diabetes, and 55.4% of those were treated with insulin. The use of diabetes technology was low, with 2.8% of the participants using a continuous glucose monitor. IAH prevalence was 23.2%, and among the 57 participants, 23.6% had a history of severe hypoglycemia, and 60.6% reported fear of hypoglycemia. There were no significant differences in sociodemographic and clinical characteristics between those with IAH and normal hypoglycemia awareness., Conclusions: We observed that 23.2% of individuals with diabetes undergoing hemodialysis had IAH. IAH was more prevalent in people who reported a fear of hypoglycemia and had a history of severe hypoglycemia episode. The study highlights the unmet needs and disparities in access to diabetes technology within this population., Competing Interests: Competing interests: HHH-A received speaker honoraria from AstraZeneca and Bayer. MR received speaker honoraria from AstraZeneca. DCW has an ongoing consultancy contract with AstraZeneca. He has received payments for consultancy working and/or speaking activities from Amgen, Astellas, Bayer, Boehringer Ingelheim, Eledon, GSK, Galderma, Gilead, Janssen, Mundipharma, Menarini, MSD, Novo Nordisk, Pharmacosmos, Tricida and Vifor., (© 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.)

Objective: To measure the association between ambient heat and hypoglycemia-related emergency department visit or hospitalization in insulin users., Research Design and Methods: We identified cases of serious hypoglycemia among adults using insulin aged ≥65 in the U.S. (via Medicare Part A/B/D-eligible beneficiaries) and Taiwan (via National Health Insurance Database) from June to September, 2016-2019. We then estimated odds of hypoglycemia by heat index (HI) percentile categories using conditional logistic regression with a time-stratified case-crossover design., Results: Among ∼2 million insulin users in the U.S. (32,461 hypoglycemia case subjects), odds ratios of hypoglycemia for HI >99th, 95-98th, 85-94th, and 75-84th percentiles compared with the 25-74th percentile were 1.38 (95% CI, 1.28-1.48), 1.14 (1.08-1.20), 1.12 (1.08-1.17), and 1.09 (1.04-1.13) respectively. Overall patterns of associations were similar for insulin users in the Taiwan sample (∼283,000 insulin users, 10,162 hypoglycemia case subjects)., Conclusions: In two national samples of older insulin users, higher ambient temperature was associated with increased hypoglycemia risk., (© 2024 by the American Diabetes Association.)

Backgruound: No recent meta-analysis has holistically analyzed and summarized the efficacy and safety of omarigliptin in type 2 diabetes mellitus (T2DM). We conducted a meta-analysis to address this knowledge gap., Methods: Electronic databases were searched to identify randomized controlled trials (RCTs) that included patients with T2DM who received omarigliptin in the intervention arm. The control arm consisted of either a placebo (passive control group [PCG]) or an active comparator (active control group [ACG]). The primary outcome assessed was changes in hemoglobin A1c (HbA1c), while secondary outcomes included variations in glucose levels, achievement of glycemic targets, adverse events (AEs), and hypoglycemic events., Results: From 332 initially screened articles, data from 16 RCTs involving 8,804 subjects were analyzed. Omarigliptin demonstrated superiority over placebo in reducing HbA1c levels (mean difference, -0.58%; 95% confidence interval, -0.75 to -0.40; P<0.00001; I2=91%). Additionally, omarigliptin outperformed placebo in lowering fasting plasma glucose, 2-hour postprandial glucose, and in the percentage of participants achieving HbA1c levels below 7.0% and 6.5%. The glycemic efficacy of omarigliptin was similar to that of the ACG across all measures. Although the omarigliptin group experienced a higher incidence of hypoglycemic events compared to the PCG, the overall AEs, serious AEs, hypoglycemia, and severe hypoglycemia were comparable between the omarigliptin and control groups (PCG and ACG)., Conclusion: Omarigliptin has a favorable glycemic efficacy and safety profile for managing T2DM.

Aims: Bespoke glycaemic control strategies following antenatal corticosteroids for women with diabetes in pregnancy (DIP) may mitigate hyperglycaemia. This study aims to identify predictive factors for the glycaemic response to betamethasone in a large cohort of women with DIP., Methods: Evaluation of a prospective cohort study of 347 consecutive DIP pregnancies receiving two doses of 11.4 mg betamethasone 24 h apart between 2017 and 2021 and treated with the Pregnancy-IVI intravenous insulin protocol. Regression modelling identified factors associated with maternal glycaemic time-in-range (TIR) and maternal insulin requirements following betamethasone. Factors associated with neonatal hypoglycaemia (glucose <2.6 mmol/L) in infants born within 48 h of betamethasone administration (n = 144) were investigated., Results: The mean maternal age was 31.9 ± 5.8 years, with gestational age at betamethasone of 33.5 ± 3.4 weeks. Gestational diabetes was present in 81% (12% type 1; 7% type 2). Pre-admission subcutaneous insulin was prescribed for 63%. On-infusion maternal glucose TIR (4.0-7.8 mmol/L) was 83% [IQR 77%-90%] and mean on-IVI glucose was 6.6 ± 0.5 mmol/L. Maternal hypoglycaemia (<3.8 mmol/L) was uncommon (0.47 h/100 on-IVI woman hours). Maternal glucose TIR was negatively associated with indicators of insulin resistance (type 2 diabetes, polycystic ovary syndrome), late-pregnancy complications (pre-eclampsia, chorioamnionitis) and the 1-h OGTT result. Intravenous insulin requirements were associated with type of diabetes, pre-eclampsia and intrauterine infection, the 1-h OGTT result and the timing of betamethasone administration. Neonatal hypoglycaemia was associated with pre-existing diabetes but not with measures of glycaemic control., Conclusion: An intravenous infusion protocol effectively controls maternal glucose after betamethasone. A risk-factor-based approach may allow individualisation of therapy., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Purpose: Adverse drug reactions (ADRs) are a major cause of morbidity and mortality, especially in older people. Older people with diabetes mellitus may be at especially high risk of ADRs but this risk has not been well studied. This study aimed to compare severity and type of ADRs in hospitalised, multimorbid older people with and without diabetes and secondly to assess the impact of ADRs on mortality, rehospitalisation and length of stay., Methods: Participants in the SENATOR (Software Engine for the Assessment and optimization of drug and non-drug Therapy in Older peRsons) trial were assessed for 12 common and 'other' prevalent and incident adverse drug reactions using a blinded end-point adjudication process. Descriptive analyses, logistic regression and mediation analyses were undertaken., Results: Of 1537 people in the SENATOR trial, 540 (35.1%) had diabetes mellitus (mean age 77.4 ± 7.3 years, 58.5% male). In the total population, 773 prevalent and 828 incident ADRs were reported. Both prevalent and incident symptomatic hypoglycaemia and incident acute kidney injury (AKI) were significantly more common in people with diabetes (p < 0.05). Patients with diabetes had higher all-cause mortality at 12 weeks than those without (9.1% vs 6.3%, p = 0.04). Mediation analysis revealed that mortality was significantly higher (OR = 1.43, Sobel test p = 0.048) in people with diabetes and ADRs causing AKI., Conclusions: Older multimorbid people with diabetes presenting to hospital with acute illness have significantly more ADRs than those without, and a significantly higher mortality that is mediated by medication-associated AKI and poorer renal function., (© 2023. The Author(s).)

Aim: Hypoglycaemia is common in neonates born to mothers with gestational diabetes mellitus (GDM). We aimed to determine predictors of hypoglycaemia among neonates of women with GDM and association with short-term outcomes., Methods: We conducted a secondary cohort analysis of data from a multi-centre randomised trial (the TARGET trial) conducted across ten maternity hospitals in New Zealand between May 2015 and November 2017. Data were analysed using univariate analysis and multivariable forward stepwise logistic regression., Results: Among 1085 neonates, those born to Asian mothers had reduced odds of hypoglycaemia (OR [95% CI]: 0.54 [0.38, 0.75], p = 0.001), as did those born at higher gestational ages (0.76 [0.68, 0.85], p < 0.001). Neonates born to Pacific mothers had increased odds of hypoglycaemia (OR [95% CI]: 1.57 [1.04, 2.39], p = 0.034). Neonates who experienced hypoglycaemia were more likely to experience neonatal intensive care unit admission (8.3% vs. 2.1%; p ≤ 0.001), hyperbilirubinaemia (8.6% vs. 3.3%; p ≤ 0.001) and receive respiratory support (11.4% vs. 4.8%; p ≤ 0.001) and less likely to be breastfed at discharge (92.4% vs. 96.2%; p = 0.009)., Conclusion: Among neonates of women with GDM, maternal ethnicity and gestation at birth are independent predictors of hypoglycaemia, and hypoglycaemia is associated with short-term comorbidities. Additional surveillance may be appropriate for neonates in these high-risk groups., (© 2023 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Aim: Many Muslims with Type II diabetes (T2DM) fast during Ramadan, which can put them at increased risk of hypoglycemia. This sub-analysis of the global DIA-RAMADAN study assessed the effectiveness and safety of gliclazide modified release (MR) 60 mg in the Bangladeshi cohort. Materials & methods: DIA-RAMADAN was an international, prospective, observational study conducted in adult T2DM patients intending to fast and receiving gliclazide MR 60 mg once daily for ≥90 days before Ramadan. Dosing was switched from morning to evening at the start of Ramadan. The primary outcome was the proportion of patients with ≥1 symptomatic hypoglycemic event. Secondary outcomes included changes between inclusion (V0) and end of study visit (V1) in glycated hemoglobin (HbA1c), body weight and fasting plasma glucose (FPG). Results: Among the 98 Bangladeshi patients, 80 (81.6%) were at moderate/low-risk (category 3) for fasting and 18 (18.4%) were high-risk (category 2), as per International Diabetes Federation and Diabetes and Ramadan International Alliance (IDF-DAR) guidelines. Gliclazide MR was being prescribed as monotherapy to 59 (60.2%) patients and in combination with metformin to 39 (39.8%). There was no incidence of severe hypoglycemic events. Mean (±SD) HbA1c change from V0 was -0.1 ± 0.8% (p = 0.159). Mean (±SD) changes in FPG and body weight were -0.8 ± 39.7 mg/dl (p = 0.876) and -0.0 ± 1.5 kg (p = 0.810), respectively. Conclusion: In a real-world setting, this sub-analysis in Bangladeshi patients shows that patients with T2DM treated with gliclazide MR 60 mg can fast safely during Ramadan with a very low risk of hypoglycemia, while maintaining glycemic control and body weight.

Almost 90% of patients with type 2 diabetes mellitus (DM2) are obese. Obesity increases the risk of developing DM2 several times. The calculation of anthropometric indices is used to diagnose the severity of obesity, as well as to assess the risk associated with obesity. The aim of the study is to study the relationship between Body Mass Index (BMI), waist circumference to hip circumference ratio (waist-to-hip ratio, WC/HR), Body Roundness Index (BRI) and Visceral Adiposity Index (VAI) with the risk of hypoglycemia in elderly and senile patients with DM2. The study included 122 elderly and senile patients (mean age 71±6,18 years) with DM2. The study participants were divided into 2 groups: patients with cases of hypoglycemia (n=65) and patients without a history of hypoglycemia (n=57). We have found that lower BMI, WC/HR, BRI, and VAI values are significantly associated with an increased risk of hypoglycemia in patients with DM2 of older age groups.

Introduction Affordability of insulin products has become a concern in the past several years as the average price of various insulin products has increased. While awaiting legislation at the federal level that would address issues leading to high insulin costs, providers may have shifted prescribing practices to prescribe the lowest-priced insulin products to achieve patients' treatment goals. Objective To compare the prevalence of hypoglycemic events between patients receiving lower-cost neutral protamine Hagedorn (NPH)-containing human insulins and higher-cost long-acting insulin analogs in Medicare Part D enrollees within a management services organization, as well as assessing glycemic control and changes in body mass index. Methods This was a multicenter, retrospective study conducted at three primary care clinics. The co-primary outcomes were percent difference of documented mild and severe hypoglycemic events between individuals receiving NPH-containing human insulin and long-acting insulin. Results A total of 72 patients met inclusion criteria and were receiving NPH-containing human insulins or the long-acting insulin analogs, 15 and 57 patients, respectively. Severe hypoglycemic events occurred in 3.5% vs 0% of the long-acting insulin analog and NPH-containing human insulin group, respectively ( P = 0.999). Mild hypoglycemic episodes were experienced by 31.6% versus 33.3% of long-acting insulin analog and NPH, respectively ( P = 0.539). For secondary outcomes, no difference was observed in glycemic control outcomes across insulin groups. Conclusion Among Medicare Part D patients with type 2 diabetes mellitus, the use of NPH-containing human insulins was not associated with an increased risk of mild or severe hypoglycemia-related episodes or reduced glycemic control compared with long-acting insulin. Study findings suggest that lower-cost, NPH-containing human insulins may be an alternative to higher-cost, long-acting insulin analogs.

Background: Hypoglycemia is an acute episode that can lead to death in patients with diabetes mellitus (DM). This condition is preventable with patient education, and identifying factors influencing their occurrence is essential to creating effective and efficient education. It also leads to prevention and control by re-organizing the service system and diabetes policies. This study aimed to determine factors contributing to hypoglycemic episodes in type 2 DM outpatients covered by the state-provided Jaminan Kesehatan Nasional (JKN) health insurance., Methods: The study used a cross-sectional design and collected data from five regional general hospitals in Jakarta, Indonesia. The outpatients were sampled consecutively from two hospitals in September-November 2021, one in January-March 2022, and two others in April-June 2023. Interviews produced primary data related to experienced hypoglycemic episodes, and medical records provided secondary data on patients' clinical characteristics and treatments. Binary logistic regression analysis was employed to process the contributing factors statistically., Results: From 501 patients who met the inclusion and exclusion criteria, it was found that the prevalence of hypoglycemia was 53.3%. Factors that significantly increased hypoglycemic risk (p < 0.05) were high HbA1c levels (OR 1.9; 95% CI 1.2-2.9), comorbidities (OR 1.6; 95% CI 1.1-2.4), insulin/sulfonylurea therapy (OR 2; 95% CI 1-4), non-smoking habit (OR 2.2; 95% CI 1.3-3.6) and physically active lifestyle (OR 1.8; 95% CI 1.2-2.6)., Conclusion: The prevalence of hypoglycemia in type 2 diabetes mellitus (DM) outpatients with the state-provided health insurance Jaminan Kesehatan Nasional (JKN) at general hospitals in Jakarta is high. The diabetes self-management education (DSME) services provided by health professionals for these outpatients must be further improved.

Objective: Severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) remain significant risks with intensive insulin therapy. While these adverse event (AE) rates are generally very low in advanced hybrid closed-loop (AHCL) clinical studies, prospectively collected real-world AE rates are lacking. Research Design and Methods: The Control-IQ Observational (CLIO) study was a single-arm, prospective, longitudinal, postmarket surveillance study of individuals with type 1 diabetes (T1D) age 6 years and older who began the use of t:slim X2 insulin pump with Control-IQ technology in the real-world outpatient setting. AEs were reported monthly over 12 months and were compared to historical data from the T1D Exchange. Patient-reported outcomes were assessed quarterly. All study visits were virtual. Results: Three thousand one hundred fifty-seven participants enrolled from August 2020 through March 2022. Two thousand nine hundred ninety-eight participants completed through 12 months. SH rates were significantly lower than historic rates for children (9.31 vs. 19.31 events/100 patient years, d  = 0.29, P  < 0.01) and adults (9.77 vs. 29.49 events/100 patient years, d  = 0.53, P  < 0.01). DKA rates were also significantly lower in both groups. Lower observed rates of AEs occurred independent of baseline hemoglobin A1c or prior insulin delivery method. Time in range 70-180 mg/dL was 70.1% (61.0-78.8) for adults, 61.2% (52.4-70.5) for age 6-13, 60.9% (50.1-71.8) for age 14-17, and 67.3% (57.4-76.9) overall. Reduction in diabetes burden was consistently reported. Conclusions: SH and DKA rates were lower for users of t:slim X2 with Control-IQ technology compared to historical data for both adults and children. Real-world use of this AHCL system proved safe and effective in this virtual study design. The study was registered at clinicaltrials.gov (NCT04503174).

Objectives: The management for improving maternal and neonatal outcomes of women with gestational diabetes mellitus (GDM) arriving at the delivery ward with pre-labour rupture of membranes (PROM) has not been elucidated. We tested the hypothesis that prolonged PROM in women with GDM would result in higher rates of neonatal hypoglycemia., Methods: We retrospectively enrolled women with diet or insulin-controlled GDM who presented with spontaneous clear PROM. Each woman was allocated into one of two groups based on the PROM-delivery time: <18 hours (group 1) and ≥18 hours (group 2). The primary outcome was the incidence of neonatal hypoglycemia, defined as glucose <40 mg/dL (2.2 mmol/L) within 24 hours of birth., Results: We ultimately analyzed 631 cases of GDM (6.7%), 371 with PROM-delivery <18 hours, and 260 with PROM-delivery ≥18 hours. The incidence of neonatal hypoglycemia did not differ between the two groups, reaching 7.3%. Women in group 2 were at increased risk of both cesarean delivery (20% vs. 12.4%, P < 0.01) and maternal chorioamnionitis morbidity (6.5% vs. 1.3%, P < 0.001)., Conclusions: In a sub-group of women with GDM, a PROM-delivery time ≥18 hours is not associated with higher rates of neonatal hypoglycemia, but higher rates of chorioamnionitis and cesarean delivery were noted. Therefore, we suggest consideration for early delivery when managing women with GDM and PROM., (Copyright © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Aim: This non-interventional observational study aimed to describe the clinical outcomes of patients with T2DM treated with Gla-300 during the period of Ramadan., Background: Type 2 diabetes mellitus (T2DM) patients who decide to fast during the holy month of Ramadan face several challenges in achieving glycemic control without increasing the risk of hypoglycemia. Insulin glargine-300 (Gla-300) has well-established safety and efficacy in improving glycemic control in multiple randomized clinical trials (RCTs). However, limited evidence is available regarding its safety and effectiveness during fasting., Objective: The objective of this study was to assess the safety and clinical outcomes of insulin glargine-300 (Gla-300) in T2DM patients before, during, and after Ramadan., Methods: We conducted a prospective, observational, non-comparative, multicenter study on patients with T2DM currently treated with Gla-300 who planned to fast and continue on Gla-300 during Ramadan in four countries (Egypt, Jordan, Lebanon, and Turkey). The study outcomes included the change in glycemic parameters and incidence of hypoglycemia before, during, and after Ramadan., Results: One hundred and forty T2DM patients were included. Nearly 61% of the included patients had a duration of diabetes of <10 years. The mean Gla-300 daily doses during the pre-Ramadan, Ramadan, and post-Ramadan periods were 22.2 ±7.4, 20.4 ±7.5, and 22.5 ±4.7 IU, respectively. The mean change values from pre-Ramadan to Ramadan and post-Ramadan were -1.7 ±6.9 IU and 0.5 ±4.7 IU, respectively, among the included patients. The mean HbA1c decreased during the study period initiating from 7.9% ±1.4% pre-Ramadan to 6.9% ±0.4% post-Ramadan. The overall HBA1c target value was 6.9% ±0.4%, while the HbA1c target was achieved by 29 patients (21.9%). The mean fasting blood glucose (FPG) showed a reduction from baseline value in the post-Ramadan period by -0.9 ±2.3 mmol/L. Five patients (3.57%) had symptomatic documented hypoglycemia during Ramadan, and none was considered to have severe hypoglycemia., Conclusion: Our study showed that insulin Gla-300 maintained the glycemic control of T2DM patients who decided to fast during the holy month of Ramadan without increasing the risk of hypoglycemia. Regular self-monitoring of blood glucose levels during Ramadan is highly recommended to avoid possible complications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aims: This study examined the association between hypoglycemia and mild cognitive impairment (MCI) among patients with type 2 diabetes mellitus (T2DM) and identified risk factors for MCI in patients with hypoglycemia., Methods: In this retrospective study, 328 patients with T2DM were screened in 2019 and followed up in 2022. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA). The diagnosis of MCI was based on established criteria. Risk ratio (RR) with 95 % confidence intervals (CI) was calculated to estimate the risk of MCI. Univariate and multivariate logistic regression analyses were conducted to identify risk factors for MCI in those with hypoglycemia., Results: Patients with hypoglycemia had lower cognitive performance 3 years later. The RR of MCI was 2.221 (95 % CI 1.269-3.885). Multivariate logistic analysis showed that low grip strength, existing diabetic retinopathy (DR), and multiple hypoglycemia episodes were associated with higher odds of MCI in patients with hypoglycemia (adjusted odds ratio [OR] 0.909 [95 % CI 0.859-0.963]), 3.078 [95 % CI 1.158-12.358], and 4.642 [95 % CI 1.284-16.776], respectively, all P < 0.05)., Conclusions: Hypoglycemia increased MCI risk among patients with T2DM. Low grip strength, DR, and multiple hypoglycemia episodes may be potential risk factors for hypoglycemia-associated MCI., 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 © 2023. Published by Elsevier B.V.)

Aim: Frequent hypoglycaemia results in disruption to usual hypoglycaemic autonomic responses leading to impaired awareness of hypoglycaemia, which is associated with an increased risk of severe hypoglycaemia requiring third-party assistance (SH). The UK Driving and Vehicle Licensing Agency (DVLA) does not permit car driving if they have either a complete loss of hypoglycaemia awareness or more than one SH event a year., Methods: The FreeStyle Libre (FSL) Association of British Clinical Diabetologists (ABCD) Nationwide Audit consists of data collected by clinicians during routine clinical work, submitted into a secure web-based tool held within the National Health Service (NHS) N3 network. Analysis of paired baseline and follow-up data for people with type 1 diabetes who also held a driving licence was undertaken., Results: The study consisted of 6304 people who had data recorded about driving status from 102 UK specialist diabetes centres, of which 4218 held a driving licence: 4178 a group 1, standard licence, 33 a group 2, large lorries and buses, seven a taxi licence; 1819 did not drive. Paired baseline and follow-up data were available for a sub-cohort of 1606/4218. At a mean follow-up of 6.9 months [95% CI (6.8, 7.1)], the Gold score had improved (2.3 ± 1.5 vs. 2.0 ± 1.3 p < .001), and the number of people who experienced an SH episode was also significantly lower (12.1% vs. 2.7%, p < .001)., Conclusion: This study suggests that intermittently scanned continuous glucose monitoring may improve impaired awareness of hypoglycaemia and reduce the number of people with type 1 diabetes with a driving licence experiencing a severe hypoglycaemic episode., (© 2023 John Wiley & Sons Ltd.)

Background: With evolving diabetes technology, continuous glucose monitoring (CGM) and time in range have been advanced as critical measurements to assess complications. They have shown improvement in A1C levels and decreased episodes of blood glucose extrusion., Aims: This study aimed to assess the awareness and utilization of blood glucose time in range and its effectiveness in reducing the risk of blood glucose extrusion and improving blood glucose metrics among patients with type 1 diabetes mellitus., Methods: A retrospective study included 342 patients who met the inclusion criteria and were using the CGM, aiming for a TIR of 70% daily. Glycemic control was followed using TIR data, blood glucose extrusion frequency (including hyperglycemia and hypoglycemia events), active sensor time, average blood glucose, and glucose management indicator (GMI) levels., Results: A total of 342 individuals participated in this study, the majority of whom were below 18 years of age (62.3%). The hypoglycemic frequency was significantly increased compared to the baseline, and most participants experienced hypoglycemia events (p = 0.0001). The incidences increased over time, with 90.9% and 93% having hypoglycemia at 60 and 90 days (p = 0.0001), respectively. The active scan and sensor time were not followed, which led to the blood glucose target not being achieved, with no improvement throughout the study. Consequently, no improvement occurred in glycemic control., Conclusion: CGM technology has been promising and proven effective in improving glycemic. However, our study did not show these benefits as expected, which could be explained by the underutilization and improper use of the CGM., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aims: To determine the frequency, severity, burden, and utility of hypoglycaemia symptoms among adults with type 1 diabetes (T1D) and impaired awareness of hypoglycaemia (IAH) at baseline and week 24 following the HypoCOMPaSS awareness restoration intervention., Methods: Adults (N = 96) with T1D (duration: 29 ± 12 years; 64% women) and IAH completed the Hypoglycaemia Burden Questionnaire (HypoB-Q), assessing experience of 20 pre-specified hypoglycaemia symptoms, at baseline and week 24., Results: At baseline, 93 (97%) participants experienced at least one symptom (mean ± SD 10.6 ± 4.6 symptoms). The proportion recognising each specific symptom ranged from 15% to 83%. At 24 weeks, symptom severity and burden appear reduced, and utility increased., Conclusions: Adults with T1D and IAH experience a range of hypoglycaemia symptoms. Perceptions of symptom burden or utility are malleable. Although larger scale studies are needed to confirm, these findings suggest that changing the salience of the symptomatic response may be more important in recovering protection from hypoglycaemia through regained awareness than intensifying symptom frequency or severity., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)