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Background: Postbariatric hypoglycemia (PBH) is a challenging condition affecting quality of life of patients after bariatric surgery. However, its incidence and predictive factors remain debated., Objectives: To determine the incidence of PBH, identify predictors of PBH and assess its association with weight trajectory after bariatric surgery., Setting: University Hospital., Methods: Prospective observational cohort study including 222 nondiabetic patients who underwent Roux-en-Y gastric bypass between 2014 and 2021, had an oral glucose tolerance test (OGTT) and/or A1C (glycated hemoglobin) measurement prior to surgery and were followed for at least 12 months. Diagnosis of PBH was made when symptoms of hypoglycemia were accompanied by a postprandial plasma glucose level < 3.9 mmol/l or a glycemia < 3.9 mmol/l during continuous glucose monitoring, with resolution of symptomatology after carbohydrate consumption. Univariable and multivariable logistic regression analyses were performed to identify factors associated with PBH., Results: Out of 222 patients, 71 (32%) were diagnosed with PBH. The highest incidence rate was observed at 2 years postbariatric surgery with a cumulative incidence of 26.5%. Predictive factors for higher risk of PBH were younger age at surgery (OR = .97; 95% CI: .94-.99; P = .049) and early dumping syndrome (OR = 3.05; 95% CI: 1.62-6.04; P = .0008). In multivariable logistic regression, higher glycemia at 2 hours during preoperative OGTT was associated with lower risk of PBH (OR = .8; 95% CI: .63-.98; P = .04). PBH was not associated with weight trajectory after surgery in our cohort., Conclusions: Younger age at time of surgery and lower blood glucose at 120 minute during preoperative OGTT are risk factors for PBH. Early dumping syndrome is significantly associated with PBH and could be used as a red flag to help identify patients at risk of PBH., (Copyright © 2024 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Gestational diabetes is associated with increased risk of hypertensive disorders of pregnancy, but there are limited data on fetal growth and neonatal outcomes when both conditions are present., Objective: We evaluated the risk of abnormal fetal growth and neonatal morbidity in pregnancies with co-occurrence of gestational diabetes and hypertensive disorders of pregnancy., Study Design: In a retrospective study of 47,093 singleton pregnancies, we compared the incidence of appropriate for gestational age birthweight in pregnancies affected by gestational diabetes alone, hypertensive disorders of pregnancy alone, or both gestational diabetes and hypertensive disorders of pregnancy with that in pregnancies affected by neither disorder using generalized estimating equations (covariates: maternal age, nulliparity, body mass index, insurance type, race, marital status, and prenatal care site). Secondary outcomes were large for gestational age birthweight, small for gestational age birthweight, and a neonatal morbidity composite outcome (stillbirth, hypoglycemia, hyperbilirubinemia, respiratory distress, encephalopathy, preterm delivery, neonatal death, and neonatal intensive care unit admission)., Results: The median (interquartile range) birthweight percentile in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy (50 [24.0-78.0]; N=179) was similar to that of unaffected pregnancies (50 [27.0-73.0]; N=35,833). However, the absolute rate of appropriate for gestational age birthweight was lower for gestational diabetes/hypertensive disorders of pregnancy co-occurrence (78.2% vs 84.9% for unaffected pregnancies). Adjusted analyses showed decreased odds of appropriate for gestational age birthweight in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy compared with unaffected pregnancies (adjusted odds ratio, 0.72 [95% confidence interval, 0.52-1.00]; P=.049), and in pregnancies complicated by gestational diabetes alone (adjusted odds ratio, 0.78 [0.68-0.89]; P<.001) or hypertensive disorders of pregnancy alone (adjusted odds ratio, 0.73 [0.66-0.81]; P<.001). The absolute risk of large for gestational age birthweight was greater in pregnancies with both gestational diabetes and hypertensive disorders of pregnancy (14.5%) than in unaffected pregnancies (8.2%), without apparent difference in the risk of small for gestational age birthweight (7.3% vs 6.9%). However, in adjusted models comparing pregnancies with gestational diabetes/hypertensive disorders of pregnancy co-occurrence with unaffected pregnancies, neither an association with large for gestational age birthweight (adjusted odds ratio, 1.33 [0.88-2.00]; P=.171) nor small for gestational age birthweight (adjusted odds ratio, 1.32 [0.80-2.19]; P=.293) reached statistical significance. Gestational diabetes/hypertensive disorders of pregnancy co-occurrence carried an increased risk of neonatal morbidity that was greater than that observed with either condition alone (gestational diabetes/hypertensive disorders of pregnancy: adjusted odds ratio, 3.13 [2.35-4.17]; P<.001; gestational diabetes alone: adjusted odds ratio, 2.01 [1.78-2.27]; P<.001; hypertensive disorders of pregnancy alone: adjusted odds ratio, 1.38 [1.26-1.50]; P<.001)., Conclusion: Although pregnancies with both gestational diabetes and hypertensive disorders of pregnancy have a similar median birthweight percentile to those affected by neither condition, pregnancies concurrently affected by both conditions have a higher risk of abnormal fetal growth and neonatal morbidity., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The standard of care for burned patients experiencing hyperglycemia associated with the hypermetabolic response is insulin therapy. Insulin treatment predisposes burn patients to hypoglycemia, which increases morbidity and mortality. Metformin has been suggested as an alternative to insulin therapy for glycemic control in burn patients given its safety profile, but further research is warranted. This study investigated whether metformin use in burn patients is associated with improved glycemic control and morbidity/mortality outcomes compared to insulin use alone., Materials and Methods: Using the TriNetX database, we conducted a retrospective study of burned patients who were administered insulin, metformin, or both within one week of injury. Demographic, comorbidity, and burn severity information were collected. Patients were categorized by treatment type, propensity score-matched, and compared for the following outcomes within 3 months: hyperglycemia, hypoglycemia, sepsis, lactic acidosis, and death. Statistical significance was set a priori at p ≤ 0.05., Results: The insulin cohort was at increased risk for all outcomes (all p < 0.0001) compared to the metformin cohort, and an increased risk for sepsis, lactic acidosis, and death (all p ≤ 0.0002) compared to the insulin/metformin combination cohort. When compared to the metformin cohort, the combination cohort was at increased risk for all outcomes (all p ≤ 0.0107) except death., Conclusions: Treatment with metformin after burn is associated with a reduced risk of morbidity and mortality compared to insulin. The combination of insulin and metformin is no more effective in reducing the risk of hyperglycemia and hypoglycemia than insulin alone but is less effective than metformin alone., Competing Interests: Declaration of Competing Interest The authors do not have any financial disclosures or other conflicts of interest to report other than that SEW is the editor of this journal., (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

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

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

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.)

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.)

Objectives: We aimed to assess how patients value the importance of type 2 diabetes mellitus (T2DM) related outcomes., Methods: Overview of systematic reviews (SRs) reporting patients' utilities or disutilities for T2DM outcomes. We searched 3 databases from inception until June 2021. Study selection and data extraction were conducted in pairs. We evaluated the quality of SRs with the Joanna Briggs Institute Checklist, and the overlap with the corrected covered area. We estimated descriptive statistics, and, when possible, conducted metanalysis., Results: We identified 11 SRs, including 119 studies and 70 outcomes. Most reviews were high-quality SRs. The outcomes with the lowest utilities were hypoglycemia with very severe symptoms (acute complications), stroke (macrovascular complications), diabetic peripheral neuropathy with severe pain (microvascular complications), extreme obesity (comorbidities), and insulin only or combined (management of diabetes). Good/excellent glucose control and noninsulin injectable showed higher values than T2DM without complications. The outcomes with the highest disutilities were amputation, depression, major hypoglycemia, stroke, and management using only insulin., Conclusions: We provide standardized, reliable utility values (or associated disutilities) for T2DM, acute, microvascular and macrovascular complications, related comorbidities and treatments that may support judgments when making clinical recommendations, designing decision support tools, and developing interventions and economic analysis., Competing Interests: Author Disclosures The authors reported no conflicts of interest., (Copyright © 2023 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The detection and management of blood glucose abnormalities in high-risk neonates are crucial for clinical care. The objective of the study was to investigate the continuous glucose profile of hypoxic-ischemic encephalopathy (HIE) patients in the whole-process of therapeutic hypothermia (TH) and its association with clinical and neurological outcomes., Method: In this single-center retrospective study, HIE patients who received both TH and continuous glucose monitoring (CGM) were recruited from March 2016 to September 2021., Results: Of 47 neonates recruited, 24 had unfavorable outcome. Dysglycemia was most prevalent in the first 24 h of TH, among which hyperglycemia occurred more frequently. CGM showed that the duration, episodes and area under curve (AUC) of hypoglycemia were statistically different in neonates with different outcomes. The occurrence, longer duration, greater AUC of hypoglycemia and an early high coefficient of variation (CV%, CV = SD/mean) were associated with unfavorable outcomes (aOR 26.55 [2.02-348.5], aOR 2.11 [1.08-4.14], aOR 1.80 [1.11-2.91] and aOR respectively), while hyperglycemia was not., Conclusion: During the whole process of TH, hypoglycemia and early unstable glycemic variability were strongly associated with unfavorable outcomes. CGM can instantly detect dysglycemia and facilitate precise glucose management in HIE neonates., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The care of elderly diabetic patients has now become a real public health issue due to the increase in the number of patients. In this population, complications are more serious and are intertwined with more specifically gerontological issues. Treatment goals should be individualized based on the patient's clinical presentation. New therapeutic drug classes are particularly interesting because of their effectiveness in terms of cardiovascular and renal protection, but the risk/benefit ratio needs to be well assessed on an individual basis. Insulin therapy is often necessary, either in case of failure of oral antidiabetics or because of comorbidities, particularly in the event of renal failure. Educating the patient and family early in the course of the disease is one of the keys to effective and safe treatment. The management of elderly diabetic patients must avoid both too much laxity in those who have successfully aged and unreasonable activism in fragile subjects because of the risk of hypoglycemia., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: ONWARDS 6 compared the efficacy and safety of once-weekly subcutaneous insulin icodec (icodec) and once-daily insulin degludec (degludec) in adults with type 1 diabetes., Methods: This 52-week (26-week main phase plus a 26-week safety extension), randomised, open-label, treat-to-target, phase 3a trial was done at 99 sites across 12 countries. Adults with type 1 diabetes (glycated haemoglobin [HbA 1c ] <10·0% [86 mmol/mol]) were randomly assigned (1:1) to once-weekly icodec or once-daily degludec, both in combination with insulin aspart (two or more daily injections). The primary endpoint was change in HbA 1c from baseline to week 26, tested for non-inferiority (0·3 percentage point margin) in all randomly assigned participants. This trial is registered with ClinicalTrials.gov, NCT04848480, and is now complete., Findings: Between April 30 and Oct 15, 2021, of 655 participants screened, 582 participants were randomly assigned to icodec (n=290) or degludec (n=292). At week 26, from baseline values of 7·59% (icodec) and 7·63% (degludec), estimated mean changes in HbA 1c were -0·47 percentage points and -0·51 percentage points, respectively (estimated treatment difference 0·05 percentage points [95% CI -0·13 to 0·23]), confirming non-inferiority of icodec to degludec (p=0·0065). Overall rate of combined clinically significant or severe hypoglycaemia (baseline to week 26) was statistically significantly higher with icodec than degludec (19·9 vs 10·4 events per patient-year of exposure; estimated rate ratio 1·9 [95% CI 1·5 to 2·3]; p<0·0001). The rate was also statistically significantly higher with icodec than degludec when evaluated over 57 weeks (52 weeks plus a 5-week follow-up period). 39 serious adverse events were reported in 24 (8%) participants receiving icodec, and 25 serious adverse events were reported in 20 (7%) participants receiving degludec. One participant in the icodec group died; this was judged unlikely to be due to the trial product., Interpretation: In adults with type 1 diabetes, once-weekly icodec showed non-inferiority to once-daily degludec in HbA 1c reduction at week 26, with statistically significantly higher rates of combined clinically significant or severe hypoglycaemia. For icodec, time below 3·0 mmol/L (<54 mg/dL) was at the threshold of the internationally recommended target (<1%) during weeks 22-26 and below target during weeks 48-52., Funding: Novo Nordisk., Competing Interests: Declaration of interests DR-J reports research income or advisory board honoraria from AstraZeneca, Dexcom, Lilly, Medtronic, Novartis, Novo Nordisk, and Sanofi. TB has received research grants from Abbott, Daiichi Sancho, Eli Lilly, Ono Pharmaceuticals, Terumo, Novartis, Sanwa Kagaku Kenkyusho, and Boehringer Ingelheim and has received honoraria or consulting fees from Tanabe-Mitsubishi, Sumitomo Farma, Eli Lilly, and Novo Nordisk. RC, SE, and MISK are employees of Novo Nordisk and hold stock in Novo Nordisk. CI provided advisory board services for Abbott, Ascensia, Menarini, Novo Nordisk, Roche Diabetes Care Italy, and Senseonics, and received speaker fees from Abbott, Ascensia, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. CM serves or has served on the advisory panel for ActoBio Therapeutics, AstraZeneca, Avotres, Boehringer Ingelheim, Eli Lilly, Imcyse, Insulet, MannKind, Medtronic, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Roche, Sandoz, Sanofi, Vertex, and Zealand Pharma; financial compensation for these activities has been received by KU Leuven (Leuven, Belgium). KU Leuven reports research support for CM from ActoBio Therapeutics, Imcyse, Medtronic, Novo Nordisk, and Sanofi. CM serves or has served on the speakers' bureau for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novartis, Novo Nordisk, and Sanofi; financial compensation for these activities has been received by KU Leuven. JR has served on scientific advisory boards and received honorarium or consulting fees from Applied Therapeutics, Biomea Fusion, Boehringer Ingelheim, Eli Lilly, Hanmi, Intarcia, Novo Nordisk, Oramed, Sanofi, Scholar Rock, Structure Therapeutics, Terns Pharmaceuticals, and Zealand, and has received research support from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi, Novartis, Merck, Novo Nordisk, Oramed, Pfizer, and Sanofi. VW has acted as a consultant for Novo Nordisk and received speaker fees from Novo Nordisk. DCK has acted as a consultant for Better Therapeutics, EOFlow, Integrity, Lifecare, Nevro, Novo Nordisk, Sanofi, and Thirdwayv., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Among guidelines on gestational diabetes mellitus, there is an incongruity about the threshold of maternal hyperglycemia to diagnose gestational diabetes mellitus., Objective: This study aimed to ascertain the association between continuous glucose monitoring metrics and adverse outcomes among individuals undergoing gestational diabetes mellitus screening., Study Design: This was a prospective study (from June 2020 to January 2022) of individuals who underwent 2-step gestational diabetes mellitus screening at ≤30 weeks of gestation. The participants wore a blinded continuous glucose monitoring device (Dexcom G6 Pro; Dexcom, Inc, San Diego, CA) for 10 days starting when they took the 50-g glucose challenge test. The primary outcome was a composite of adverse neonatal outcomes (large for gestational age, shoulder dystocia or neonatal injury, respiratory distress, need for intravenous glucose treatment for hypoglycemia, or fetal or neonatal death). The secondary neonatal outcomes included preterm birth, neonatal intensive care unit admission, hypoglycemia, mechanical ventilation or continuous positive airway pressure, hyperbilirubinemia, and hospital length of stay. The secondary maternal outcomes included weight gain during pregnancy, hypertensive disorders of pregnancy, induction of labor, cesarean delivery, and postpartum complications. Time within the target range (63-140 mg/dL), time above the target range (>140 mg/dL) expressed as a percentage of all continuous glucose monitoring readings, and mean glucose level were analyzed. The Youden index was used to choose the threshold of ≥10% for the time above the target range and association with adverse outcomes., Results: Of 136 participants recruited, data were available from 92 individuals (67.6%). The 2-step method diagnosed gestational diabetes mellitus in 2 individuals (2.2%). Continuous glucose monitoring indicated that 17 individuals (18.5%) had time above the target range of ≥10%. Individuals with time above the target range of ≥10% had a significantly higher likelihood of composite adverse neonatal outcomes than individuals with time above the target range of <10% (63% vs 18%; P=.001). Furthermore, compared with neonates born to individuals with time above the target range of <10%, neonates born to individuals with time above the target range of ≥10% had an increased likelihood for hypoglycemia (14.5% vs 47%; P=.009) and had a longer length of stay (2 vs 4 days; P=.03). No difference in maternal outcomes was noted between the groups., Conclusion: In this prospective study of individuals undergoing gestational diabetes mellitus screening, a cutoff of the time above the target range of ≥10% using continuous glucose monitoring was associated with a higher rate of neonatal adverse outcomes. A randomized trial of continuous glucose monitoring vs 2-step screening for gestational diabetes mellitus to lower the rate of adverse outcomes is underway (identification number: NCT05430204)., (Published by Elsevier Inc.)

Objectives: To study the potential association between increases in daily mean air temperature and time below range (TBR <54 mg/dl) and time above range (TAR >250 mg/dl) in children and adolescents with type 1 diabetes., Research Design and Methods: Individuals with type 1 diabetes <21 years with information on daily glucose profiles from the diabetes prospective follow-up study (DPV) were included (n = 2582). Further inclusion criteria were age at least 6 months at diabetes onset, diabetes duration for at least one year and treatment years 2020-2021. Mean daily air temperature and other meteorological parameters from 78 measurement stations in Germany were linked to the individual glucose sensor profile via the five-digit postcode areas of residency. We used multivariable repeated measures fractional logistic regression models with a compound symmetry covariance structure to study the association between a 1 °C increase in daily mean temperature and time in specific glucose ranges., Results: A 1 °C increase in daily mean temperature was associated with an acute (Odds Ratio (OR) 1.009 (95%-CI 1.007, 1.011)) and up to 7 days delayed (OR 1.003 (1.001, 1.005)) increase in TBR <54 mg/dl. Moreover, an acute decrease in TAR >250 mg/dl (OR 0.997 (0.996, 0.997)) was found., Conclusions: Results of the DPV registry showed small, but statistically significant changes in TBR and TAR in association with a short-term temperature increase. Higher blood flow and faster insulin absorption might be one possible mechanism. In times of increasing temperature fluctuations meteorological impacts on time in range could become even more relevant., 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 Elsevier Inc. All rights reserved.)

Background: Neonatal hypoglycemia is a common metabolic occurrence among small for gestational age (SGA) neonates. This study aims to determine the incidence of early neonatal hypoglycemia and confirms the potential risk factors among term and late preterm SGA neonates in a well-baby newborn nursery of a tertiary medical center in Southern Taiwan., Methods: We performed a retrospective medical record review of term and late preterm SGA (birth weight <10 percentile) neonates, born between January 1, 2012 and December 31, 2020, in the well-baby newborn nursery, of a tertiary medical center in Southern Taiwan. Blood glucose monitoring was routinely performed at 0.5, 1, 2, and 4 h of life. Antenatal and postnatal risk factors were recorded. Mean blood glucose level, age of occurrence, symptomatic hypoglycemia, and need for intravenous glucose treatment of early hypoglycemia in SGA neonates were documented., Results: 690 SGA neonates in the nursery met the criteria and were retrospectively enrolled in the study, 358 of whom (51.80%) were male and 332 (48.10%) female. Of 690 enrolled SGA neonates, 134(19.42%) SGA neonates developed hypoglycemia during a well-baby nursery stay. Among these neonates, 97% of early hypoglycemic episodes occur during the first 2 h of life. The lowest blood glucose level was 46.78 ± 11.13 mg/dL, recorded in the first hour of life. Among the hypoglycemic 134 neonates, 26 (19.40%) neonates had to be transferred from the nursery to the neonatal ward and they required intravenous glucose treatment to achieve euglycemia. 14 (10.40%) neonates had symptomatic hypoglycemia. A multivariate logistic regression analysis revealed that cesarean delivery, small head circumference, small chest circumference, and low 1-min Apgar score were significant risk factors for early hypoglycemia in these neonates., Conclusion: Periodic routine blood glucose level monitoring within the first 4 h of life in term and late preterm SGA neonates is required, especially those with cesarean delivery and low Apgar score., Competing Interests: Declaration of competing interest The author declares that they have no conflicts of interest., (Copyright © 2023 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background: Birth asphyxia causes hypoxia or inadequate perfusion to the organs of newborns, leading to metabolism dysfunctions including blood glucose disorders., Methods: Neonates with and without birth asphyxia were retrospectively recruited from 53 hospitals in Hubei Province from January 1 to December 31, 2018. In summary, 875, 1139, and 180 cases in the control group, the mild asphyxia group, and the severe asphyxia group were recruited, respectively. Neonatal blood glucose values at postnatal 1, 2, 6, and 12 h (time error within 0.5 h was allowed) were gathered from the medical records., Results: The incidence rates of hyperglycemia in the control group, the mild asphyxia group and the severe asphyxia group were 2.97%, 7.90%, and 23.33%, respectively (p < 0.001). Additionally, the incidence rates of hypoglycemia in the three groups above were 3.66%, 4.13%, and 7.78%, respectively (p = 0.042). The blood glucose values of neonates with hypoglycemia in the asphyxia group were lower than in the control group (p = 0.003). Furthermore, the blood glucose values of neonates with hyperglycemia were highest in the severe asphyxia group (p < 0.001). There were 778 and 117 cases with blood glucose records at four predefined time points in the mild and severe asphyxia group, respectively. The incidence of blood glucose disorders in the mild asphyxia group significantly decreased from postnatal 6 h (p＜0.05). However, we found no obvious changes of the incidence of glucose disorders within postnatal 12 h in the severe asphyxia group (p = 0.589)., Conclusion: Birth asphyxia is likely to cause neonatal blood glucose disorders, both hypoglycemia and hyperglycemia, during the early postnatal life. The neonates with severe asphyxia have higher incidence, worse severity and longer duration of blood glucose disorders than neonates with mild asphyxia., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Aims: To assess if switching to or adding sulfonylureas increases major adverse cardiovascular events (MACE) or severe hypoglycemia versus remaining on metformin alone., Materials and Methods: This was a retrospective, longitudinal cohort utilizing United States Veterans Health Administration and Medicare data. Veterans with type 2 diabetes on metformin monotherapy between 2004 and 2006 were identified. Follow-up occurred through 2016. Those treated with either metformin plus a second-generation sulfonylurea (N = 45,305) or converted from metformin to a second-generation sulfonylurea (N = 2813) were compared to those receiving metformin monotherapy (N = 65,550). Hazard ratios (HR) and 95%CI from longitudinal competing risk Cox models were used to measure the association between sulfonylureas and outcomes., Results: Switching to or adding a sulfonylurea to metformin was associated with 3 times the risk of severe hypoglycemia versus metformin monotherapy (HR:3.44, 95% CI: 3.06,3.85 and HR: 3.08, 95% CI: 2.77,3.42, respectively). Switching to or adding a sulfonylurea to metformin was associated with a 7-19% higher risk of MACE versus metformin monotherapy (HR: 1.07, 95% CI: 1.00,1.14 and HR: 1.19, 95% CI: 1.13,1.25, respectively)., Conclusions: Switching to and adding second-generation sulfonylureas was associated an increase in severe hypoglycemia and MACE versus remaining on metformin alone. In an era where guidelines recommend diabetes therapies based on compelling indications, safety outcomes should be a key consideration when selecting therapy., Competing Interests: Declaration of Competing Interest D Taber has received grants from Merck, Veloxis, CareDx and is on an advisory board for Veloxis and Eurofins. None of these relationships are relevant to this manuscript. This work represents the views of the authors and not those of the Medical University of South Carolina (MUSC) or Veteran Health Administration (VHA)., (Published by Elsevier Ltd.)

Aims: To assess insulin glargine 100 U/mL (IGlar-100) treatment outcomes according to newly-defined subgroups of type 2 diabetes mellitus (T2DM)., Methods: Insulin-naïve T2DM participants (n = 2684) from nine randomised clinical trials initiating IGlar-100 were pooled and assigned to subgroups "Mild Age-Related Diabetes (MARD)", "Mild Obesity Diabetes (MOD)", "Severe Insulin Resistant Diabetes (SIRD)", and "Severe Insulin Deficient Diabetes (SIDD)", according to age at onset of diabetes, baseline HbA1c, BMI, and fasting C-peptide using sex-specific nearest centroid approach. HbA1c, FPG, hypoglycemia, insulin dose, and body weight were analysed at baseline and 24 weeks., Results: Subgroup distribution was MARD 15.3 % (n = 411), MOD 39.8 % (n = 1067), SIRD 10.5 % (n = 283), SIDD 34.4 % (n = 923). From baseline HbA1c 8.0-9.6% adjusted least square mean reductions after 24 weeks were similar between subgroups (1.4-1.5 %). SIDD was less likely to achieve HbA1c < 7.0 % (OR: 0.40 [0.29, 0.55]) than MARD. While the final IGlar-100 dose (0.36 U/kg) in MARD was lower than in other subgroups (0.46-0.50 U/kg), it had the highest hypoglycemia risk. SIRD had lowest hypoglycemia risk and SIDD exhibited greatest body weight gain., Conclusions: IGlar-100 lowered hyperglycemia similarly in all T2DM subgroups, but level of glycemic control, insulin dose, and hypoglycemia risk differed between subgroups., Competing Interests: Declaration of Competing Interest W.L. is an employee of Sanofi, Germany, and Sanofi shareholder. G.B. is an IVIDATA employee, contracted to Sanofi. B.M.F. has served on advisory panels for Eli Lilly and Zucara Therapeutics, and on the speakers’ bureau for Eli Lilly, Novo Nordisk, Sanofi, and Abbott. G.B.B. is a consultant for Eli Lilly and Sanofi; has received research support from Sanofi; and is on the speakers’ bureau for Eli Lilly, Menarini, and Sanofi. D.R.O. has received honoraria for lecturing and consulting from Boehringer Ingelheim, Eli Lilly, Roche Diagnostics, Sanofi, and Takeda., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Emotional problems including anxiety, depression and fear of hypoglycemia (FOH) are common in patients with type 1 diabetes mellitus (T1DM). The aim of this study was to determine the prevalence of depressive and anxiety symptoms among patients with T1DM and their relation to glycemic control, diabetes complications and to FOH., Methods: This study included 325 patients with T1DM. Anxiety and depressive symptoms were assessed by Hospital Anxiety and Depression Scale (HADS) and FOH was assessed by Hypoglycemia Fear Survey II (HFS-II). Glycemic control was assessed by both fasting plasma glucose and HbA1c. A subsample of 75 patients was screened for diabetes complications., Results: The prevalence of anxiety symptoms, depressive symptoms and FOH was 76.3%, 61.8% and 20% respectively. Female sex was related to depressive symptoms but not to anxiety symptoms. Logistic regression analysis showed that both HbA1c and HFS-II total score were independently correlated with both anxiety symptoms and depressive symptoms. Age showed independent correlation with both HFS-II (total score) and with Hypoglycemia Fear Survey-worry (HFS-W) while HbA1c showed independent correlation with Hypoglycemia Fear Survey-behavior (HFS-B). Both anxiety and depressive symptoms were positively correlated to HFS-B score, HFS-W score and HFS-II total score., Conclusions: FOH is not uncommon among Egyptian patients with T1DM and it seems to be one of the factors contributing to the increased prevalence of anxiety and depressive symptoms among those individuals. Addressing and managing the different psychological aspects of diabetes should be integrated within the routine diabetes care services for people with T1DM., (Copyright © 2023 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Introduction: To prevent hypoglycemic episodes, the management of insulin therapy against post-transplant diabetes mellitus (PTDM) is important. We compared glargine (long-acting insulin) versus NPH isophane (intermediate-acting insulin) as an armamentarium against PTDM. Indeed, the study evaluated PTDM patients with hypoglycemic episodes treated with isophane or glargine., Material and Methods: We evaluated a total number of 231 living-donor renal transplant recipients with PTDM of age ≥ 18 years admitted to the hospital between January 2017 and September 2021. However, patients taking hypoglycemic agents before transplantation were excluded from this study. Out of 231 patients, 52 (22.15%) suffered from PTDM out of whom 26 were treated with glargine or isophane., Results: After applying exclusion criteria, out of 52 PTDM patients 23 were included in the study: 13 PTDM patients were treated with glargine, whereas 10 PTDM patients with isophane. Our analysis revealed 12 episodes of hypoglycemia in glargine-treated PTDM patients compared to 3 in isophane-treated PTDM patients (p = 0.056). Clinically, 9 out of 15 hypoglycemic episodes were nocturnal (60%). Furthermore, no other risk factors were observed in our study population. Detailed analysis showed that both groups had equivalent doses of immunosuppressants and oral hypoglycemic agents. The odds ratio for hypoglycemia in the group treated with isophane compared to that treated with glargine was 0.224 (95% CI, 0.032-1.559). Glargine users recorded significantly lower blood sugar levels before lunch, dinner and at bedtime with p-values of 0.001, 0.009 and 0.001 respectively. A better hemoglobin A1c (HbA1c) level was seen in the glargine vs. isophane group (6.98 ± 0.52 vs. 7.45 ± 0.49, p-value 0.03)., Conclusion: The study shows better blood sugar control with long-acting insulin analog, glargine, than with intermediate-actin analog, isophane. Overall, a higher number of hypoglycemic episodes was nocturnal. Long term safety of long-acting insulin analogs needs to be further studied., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: The purpose of the present study was to investigate the fear of hypoglycemia (FoH) and its predictors among diabetic pregnant women., Study Design: Cross-sectional conducted between January to August 2022., Methods: In the present study, 250 diabetic pregnant women from Qazvin province participated. Demographic and fertility characteristics, FoH, adherence to treatment, self-efficacy, anxiety and depression were assessed. Data were analyzed using univariable and multivariable linear regression models., Results: The participants' mean age was 31.02 years (SD=4.72). The FoH mean score was 32.88 (out of 72). Based on the multivariable linear regression model, having a history of hypoglycemia (β = 0.44, p < 0.001), lower education (β = 0.17, p = 0.001), being treated with insulin (β = 0.22, p < 0.001), being treated with both insulin and diet (β = 0.16 p = 0.003), being of younger age (β = -0.13, p = 0.008), and depression (β = 0.16, p = 0.002) were independent predictors of FoH among pregnant women., Conclusion: Diabetic pregnant women experience FoH, particularly those with a history of hypoglycemia. Therefore, providing education and counseling concerning hypoglycemia, complications, and necessary measures for this group of diabetic pregnant women are needed along with those who are younger, less educated, and have comorbid mental health conditions., 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 © 2022 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background: Neonatal hypoglycemia is a common metabolic disorder in newborns, which may present with non-specific symptoms or even be asymptomatic. Current guidelines recommend screening for hypoglycemia in at-risk babies (late preterm, small for gestational age, large for gestational age, and infants of diabetic mothers). Past studies have suggested other potential risk factors, such as maternal obesity, gestational hypertension, cesarean section, etc. In this study, we aim to identify additional prenatal and perinatal maternal/fetal characteristics associated with early asymptomatic hypoglycemia in term and late preterm babies., Methods: We performed a retrospective review on medical charts of all newborns, born between January, 2017 and December, 2020, in the well-baby newborn nursery of a tertiary medical center. We identified newborns who had received blood glucose concentration monitor after birth. Detailed prenatal and perinatal maternal/newborn information were collected for analysis., Results: In the study period, 841 newborns had received blood glucose screening after birth. After matching by sex and indication for postnatal blood glucose screen (SGA, LGA, and GDM), 148 newborns were included in the "hypoglycemia group" and 296 newborns were included in the "euglycemia group". In the univariate analysis, parity, insulin treatment for gestational diabetes mellitus (GDM), and cesarean section were associated with an increased risk for neonatal hypoglycemia. Factors associated with decreased risk included higher gestational age, longer duration of skin-to-skin contact, neonatal hyperthermia, higher maternal labor pain score, and epidural anesthesia administration. By multivariable analysis, insulin treatment for GDM was identified as an independent factor associated with increased risk for neonatal hypoglycemia., Conclusion: Our study showed insulin treatment for GDM to be independently associated with neonatal hypoglycemia. Other risk factors noted in the univariate analysis, such as decreased skin-to-skin contact duration, hypothermia, Cesarean section, and preterm delivery, would require further investigation to confirm the findings., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background and Aims: To face the rapid spread of SARS-CoV2 coronavirus pandemic, home lockdown in Spain was decreed on 15th March 2020. The main objective of this study is to evaluate the impact of this constraint on glycemic control in children and adolescents with type 1 diabetes mellitus (T1D)., Patients and Methods: Observational, retrospective study in children and adolescents with T1D users of interstitial glucose monitoring systems. The following information corresponding to the last 2 weeks of lockdown was collected for subsequent comparison with data of 2 weeks prior to quarantine: daily insulin needs, mean interstitial glucose, estimated HbA1c, coefficient of variation (CV), time in range (70-180mg/dl), hypoglycemia (<70 and <54mg/dl) and hyperglycemia (>180 and> 250mg/dl), sensor use and number of blood glucose measurements. Data about meal routines, physical exercise, need for adjustments in therapy, acute complications and lockdown of caregivers were assessed via a survey., Results: 80 patients were studied (mean age 12.61±3.32 years, mean time of evolution of the disease 5.85±3.92 years), 66.2% treated with an insulin pump, users of following glucose monitoring systems: Guardian 3 (65%), FreeStyle Libre (18.8%) and Dexcom G6 (16.2%). Time in range in the cohort increased significantly during confinement (72.1±10.5 vs 74.8±10.5%; P=0.011) with lower time in hypoglycemia both <70mg/dl (4.6±3.2 vs 3.2±2.7%; P<0.001) and <54mg/dl (1.2±1.6 vs 0.7±1.2%; P<0.001) and hyperglycemia >250mg/dl (4.6±3.9 vs 3.7±3.7%; P=0.038). CV also decreased (35.8±6.3 vs 33.1±6.1%; P<0.001). Patients treated with multiple doses of insulin and poorer baseline glycemic control experienced greatest improvement. Daily insulin requirements remained stable. Regular practice of physical exercise and caregivers' confinement did not have a significant impact., Conclusions: Glycemic control in children and adolescents with T1D improved during quarantine, particularly in those with worse baseline control., (Copyright © 2022 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: This study to assess the incidence rates and risk factors of hypoglycemia in a wide real-life sample of patients with insulin-treated type 2 diabetes mellitus., Methods: In a prospective epidemiological study, data from 817 subjects were collected from medical records and via interviews. Over a 3-month period, hypoglycemic episodes were recorded via self-measurement of glucose levels at least twice daily. Cox proportional and negative binomial multivariable models were applied to estimate adjusted and unadjusted hazard ratios and incidence rate ratios of hypoglycemic events., Results: Of the 817 patients, 52.9% experienced hypoglycemia, 38.1% had only nonsevere episodes, and 14.8% had at least 1 severe episode. Total events per patient-year were estimated at 13.3 (±24.8), with 11.8 (±21.6) and 1.4 (±4.7) being nonsevere and severe, respectively. History of hypoglycemia and severe hypoglycemia were consistent risk factors of hypoglycemia. Intensification of therapy was associated with higher incidence rates, whereas the effect on the hazard rates was more moderate. Longer duration of insulin therapy and the presence of congestive heart failure were associated with a higher risk of developing and frequency of hypoglycemia. Hypoglycemia awareness was found to independently affect only mild hypoglycemia., Conclusions: Hypoglycemia is a common complication in patients with insulin-treated type 2 diabetes mellitus. The risk factors of developing hypoglycemia are to some extent different from those of the frequency of hypoglycemic episodes. Particular attention is required for patients with recurrent hypoglycemic events and on intensive antidiabetic therapy., (Copyright © 2021 ISPOR--The professional society for health economics and outcomes research. Published by Elsevier Inc. All rights reserved.)

Objectives: To estimate the direct medical cost of type 2 diabetes mellitus (T2DM) and its complications in the Indonesian population from a payer perspective using a prevalence-based approach., Methods: The direct medical costs in 2016 were estimated using the database of Indonesia's National Health Insurance, known as Jaminan Kesehatan Nasional, which included diagnosis-related group costs and unbundled costs for patients accessing advanced care. The study population included people aged 30 years or older having a diagnosis of T2DM. T2DM and its related complications were identified using the International Classification of Diseases, 10th Revision, code. Hypoglycemia and all complications listed in the Diabetes Severity Complications Index were included. Descriptive analysis was conducted. Costs were converted to 2016 US dollar equivalent., Results: Of the 18.9 million Jaminan Kesehatan Nasional members who accessed secondary and tertiary care, 812 204 (4%) were identified with T2DM, of which 57% had complications. The most common complication was cardiovascular diseases (24%). The total direct medical cost was US $576 million, with 56% spent on hospitalization, 38% on specialist visits, 4% on unbundled non-diabetes-related medication, and 2% on unbundled anti-hyperglycemic medications. Approximately 74% of the total costs was used for the management of people with complications. People with complications (US $930/person/year ± US $1480/person/year) incurred twice the cost of those without complications (US $421/person/year ± US $745/person/year)., Conclusion: The direct medical cost for management of people with T2DM in Indonesia was high. Early diagnosis and optimal management of T2DM to prevent complications may reduce the costly sequelae and have a possibility of cost savings., (Copyright © 2021. Published by Elsevier Inc.)

Background: Beta-blocker (BB) intoxications are common in both childhood and adulthood. In the case of poisoning, bradycardia, hypotension, ventricular dysrhythmias, mental status changes, seizures, hypoglycemia, and bronchospasm may occur. Effects on the cardiovascular system are commonly seen, but hypoglycemia is not frequently observed in clinical practice. In this study, we aimed to answer the question, "Is hypoglycemia more commonly observed in BB intoxications than in other intoxications?", Method: This was a case-control study conducted in a pediatric emergency department of a university hospital. The case group (Group 1) consisted of cases with BB poisonings and the control group (Group 2) consisted of cases with selective serotonin receptor inhibitor (SSRI) poisonings. Data were obtained from patient files. We recorded the blood glucose levels (BGLs) of all patients on admission to the emergency department and at the 1-, 6-, and 24-h follow-up. The amounts of BBs received by the cases were compared with the specific toxic doses of each drug. The data obtained were analyzed using the Statistical Package for the Social Sciences 22 (SPSS.22) program. Mean and standard deviation for numerical values and frequency for categorical data are reported; at test, chi-square test, and ANOVA tests were used for the analysis., Results: The study comprised 40 patients (Group 1) and 40 controls (Group 2). The mean serum BGLs of patients in Group 1 at admission and at the 1-, 6-, and 24-h follow-up were 107.2 ± 46.3 mg/dl, 86.3 ± 20.1 mg/dl, 88.6 ± 28.4 mg/dl, and 86.5 ± 23.7 mg/dl, respectively. The mean values of Group 2 cases were 100 ± 39.5 mg/dl, 92.1 ± 30 mg/dl, 91±28 mg/dl, and 127.8 ± 60.7 mg/dl, respectively, at admission and at the 1-, 6-, and 24-h follow-up (p = 0.4, p < 0.001, p = 0.7, and p < 0.001, respectively). The mean BGLs of patients who were exposed to propranolol at admission and at the 1-, 6-, and 24-h follow-up were significantly lower than those of the patients who had taken different BBs in Group 1. No linear correlation was found between the percentage of exposure to BB toxic doses and BGLs., Conclusion: Our study showed that the BGLs of patients receiving BBs could be lower, but they were not at a level that would have serious consequences. Nevertheless, the BGLs of all cases of intoxication should be monitored closely., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Background: Evidence for the metabolic impact of long-term exposure to air pollution on diabetes is lacking. We investigated the association of particulate matter <10 μm (PM 10 ) and <2.5 μm (PM 2.5 ) with yearly averages of HbA1c, daily insulin dose (IU/kg) and rates of severe hypoglycaemia in type 1 diabetes (T1D)., Methods: We studied data of 44,383 individuals with T1D < 21 years which were documented in 377 German centres within the diabetes prospective follow-up registry (DPV) between 2009 and 2018. Outcomes were aggregated by year and by patient. PM 10 -and PM 2.5 -yearly averages prior to the respective treatment year were linked to individuals via the five-digit postcode areas of residency. Repeated measures linear and negative binomial regression were used to study the association between PM-quartiles (Q1 lowest, Q4 highest concentration) and yearly averages of HbA1c, daily insulin dose and rates of severe hypoglycaemia (confounders: sex, time-dependent age, age at diabetes onset, time-dependent type of treatment, migratory background, degree of urbanisation and socioeconomic index of deprivation)., Results: Adjusted mean HbA1c increased with PM 10 (Q1: 7.96% [95%-CI: 7.95-7.98], Q4: 8.03% [8.02-8.05], p-value<0.001) and with PM 2.5 (Q1: 7.97% [7.95-7.99], Q4: 8.02% [8.01-8.04], p < 0.001). Changes in daily insulin dose were inversely related to PM (PM 10 and PM 2.5 : Q1 0.85 IU/kg [0.84-0.85], Q4: 0.83 IU/kg [0.82-0.83], p < 0.001). Adjusted rates of severe hypoglycaemia increased with PM-quartile groups (PM 10 Q1:11.2 events/100 PY [10.9-11.5], PM 10 Q4: 15.3 [14.9-15.7], p < 0.001; PM 2.5 Q1: 9.9 events/100 PY [9.6-10.2], PM 2.5 Q4: 14.2 [13.9-14.6], p < 0.001)., Discussion: Air pollution was associated with higher HbA1c levels and increased risk of severe hypoglycaemia in people with T1D, consequently indicating a higher risk of diabetes complications. Further studies are needed to explore causal pathways of the observed associations., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Gestational diabetes that is not properly controlled with diet has been commonly treated with insulin. In recent years, several studies have published that metformin can lead to, at least, similar obstetrical and perinatal outcomes as insulin. Nevertheless, not all clinical guidelines endorse its use, and clinical practice is heterogeneous., Objective: This study aimed to test whether metformin could achieve the same glycemic control as insulin and similar obstetrical and perinatal results, with a good safety profile, in women with gestational diabetes that is not properly controlled with lifestyle changes., Study Design: The metformin for gestational diabetes study was a multicenter, open-label, parallel arms, randomized clinical trial performed at 2 hospitals in Málaga (Spain), enrolling women with gestational diabetes who needed pharmacologic treatment. Women at the age of 18 to 45 years, in the second or third trimesters of pregnancy, were randomized to receive metformin or insulin (detemir or aspart). The main outcomes were (1) glycemic control (mean glycemia, preprandial and postprandial) and hypoglycemic episodes and (2) obstetrical and perinatal outcomes and complications (hypertensive disorders, type of labor, prematurity, macrosomia, large for gestational age, neonatal care unit admissions, respiratory distress syndrome, hypoglycemia, jaundice). Outcomes were analyzed on an intention-to-treat basis., Results: Between October 2016 and June 2019, 200 women were randomized, 100 to the insulin-treated group and 100 to the metformin-treated group. Mean fasting and postprandial glycemia did not differ between groups, but postprandial glycemia was significantly better after lunch or dinner in the metformin-treated-group. Hypoglycemic episodes were significantly more common in the insulin-treated group (55.9% vs 17.7% on metformin; odds ratio, 6.118; 95% confidence interval, 3.134-11.944; P=.000). Women treated with metformin gained less weight from the enrollment to the prepartum visit (36-37 gestational weeks) (1.35±3.21 vs 3.87±3.50 kg; P=.000). Labor inductions (45.7% [metformin] vs 62.5% [insulin]; odds ratio, 0.506; 95% confidence interval, 0.283-0.903; P=.029) and cesarean deliveries (27.6% [metformin] vs 52.6% [insulin]; odds ratio, 0.345; 95% confidence interval, 0.187-0.625; P=.001) were significantly lower in the metformin-treated group. Mean birthweight, macrosomia, and large for gestational age and babies' complications were not different between treatment groups. The lower cesarean delivery rate for women treated with metformin was not associated with macrosomia, large or small for gestational age, or other complications of pregnancy., Conclusion: Metformin treatment was associated with a better postprandial glycemic control than insulin for some meals, a lower risk of hypoglycemic episodes, less maternal weight gain, and a low rate of failure as an isolated treatment. Most obstetrical and perinatal outcomes were similar between groups., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Postbariatric hypoglycemia (PBH) can be a devastating complication for which current therapies are often incompletely effective. More information is needed regarding frequency, incidence, and risk factors for PBH., Objectives: To examine hypoglycemia symptoms following Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) and baseline and in-study risk factors., Setting: Multicenter, at 10 US hospitals in 6 geographically diverse clinical centers., Methods: A prospective, longitudinal cohort study of adults undergoing RYGB or LAGB as part of clinical care between 2006 and 2009 were recruited and followed until January 31, 2015, with baseline and annual postoperative research assessments. We analyzed baseline prevalence and post-operative incidence and frequency of self-reported hypoglycemia symptoms as well as potential preoperative risk factors., Results: In all groups, postoperative prevalence of hypoglycemia symptoms was 38.5%. Symptom prevalence increased postoperatively from 2.8%-36.4% after RYGB in patients without preoperative diabetes (T2D), with similar patterns in prediabetes (4.9%-29.1%). Individuals with T2D had higher baseline hypoglycemia symptoms (28.9%), increasing after RYGB (57.9%). Hypoglycemia symptoms were lower after LAGB, with 39.1% reported hypoglycemia symptoms at only 1 postoperative visit with few (4.0%) having persistent symptoms at 6 or more annual visits. Timing of symptoms was not restricted to the postprandial state. Symptoms of severe hypoglycemia were reported in 2.6-3.6% after RYGB. The dominant risk factor for postoperative symptoms was preoperative symptoms; additionally, baseline selective serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitor use was also associated with increased risk in multivariable analysis. Weight loss and regain were not related to hypoglycemia symptom reporting., Conclusion: Hypoglycemia symptoms increase over time after RYGB, particularly in patients without diabetes. In a small percentage, symptoms can be persistent or severe and require hospitalization. Preoperative hypoglycemia symptoms and SSRI/SNRI use in RYGB patients without diabetes is associated with increased risk of symptoms., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: Hypoglycemia is a potentially life-threatening drug event under antidiabetic treatment. The aim of the study was to examine time trends in severe hypoglycemia in older adults with type 2 diabetes mellitus (T2DM) and antidiabetic treatment., Design: Multicenter prospective diabetes patient follow-up registry (DPV)., Setting and Participants: Patients aged ≥75 years with T2DM and documented treatment between 2005 and 2019., Methods: Outcomes of interest were rates of severe hypoglycemia, diabetes therapy, body mass index, HbA1c, and estimated glomerular filtration rate. Time trends of outcomes were analyzed in the whole cohort and compared between age groups (75-<80, 80-<85, ≥85 years)., Results: A total of 136,931 patients from 188 diabetes centers were included. The adjusted HbA1c decreased from 7.3% (95% confidence interval 7.3-7.4) in 2005 to 7.2% (7.2-7.2) in 2019 (P < .001), with no significant difference between age groups (P = .47). Rates of severe hypoglycemia decreased from 6.7 (6.0-7.4) to 4.1 of 100 person-years (3.7-4.5) (P < .001) in the entire population. Patients aged ≥85 years had constantly lower HbA1c levels compared with younger groups (P < .001). Although severe hypoglycemia decreased the most in the ≥85 age group (P < .001), severe hypoglycemia remained consistently higher in this group compared with the 75 to <80 years group (P < .001)., Conclusions and Implications: During the analyzed time, the risk for severe hypoglycemia decreased. Although drugs with intrinsic risk for hypoglycemia were used less frequently, antidiabetic treatment in older adults should be further improved to continue reducing severe hypoglycemia in this age group, potentially accepting less strict metabolic control and age-specific target ranges., (Copyright © 2021 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Insulin detemir, being used increasingly during pregnancy, may have pharmacologic benefits compared with neutral protamine Hagedorn., Objective: We evaluated the probability that compared with treatment with neutral protamine Hagedorn, treatment with insulin detemir reduces the risk for adverse neonatal outcome among individuals with type 2 or overt type 2 diabetes mellitus (gestational diabetes mellitus diagnosed at <20 weeks' gestation)., Study Design: We performed a multiclinic randomized controlled trial (September 2018 to January 2020), which included women with singleton gestation with type 2 or overt type 2 diabetes mellitus who sought obstetrical care at ≤21 weeks' gestation. Participants were randomized to receive either insulin detemir or neutral protamine Hagedorn by a clinic-stratified scheme. The primary outcome was a composite of adverse neonatal outcomes, including shoulder dystocia, large for gestational age, neonatal intensive care unit admission, respiratory distress (defined as the need of at least 4 hours of respiratory support with supplemental oxygen, continuous positive airway pressure or ventilation at the first 24 hours of life), or hypoglycemia. The secondary neonatal outcomes included gestational age at delivery, small for gestational age, 5-minute Apgar score of <7, lowest glucose level, need for intravenous glucose, respiratory distress syndrome, need for mechanical ventilation or continuous positive airway pressure, neonatal jaundice requiring therapy, brachial plexus injury, and hospital length of stay. The secondary maternal outcomes included hypoglycemic events, hospital admission for glucose control, hypertensive disorder of pregnancy, maternal weight gain, cesarean delivery, and postpartum complications. We used the Bayesian statistics to estimate a sample size of 108 to have >75% probability of any reduction in the primary outcome, assuming 80% power and a hypothesized effect of 33% reduction with insulin detemir. All analyses were intent to treat under a Bayesian framework with neutral priors (a priori assumed a 50:50 likelihood of either intervention being better; National Clinical Trial identifier 03620890)., Results: There were 108 women randomized in this trial (57 in insulin detemir and 51 in neutral protamine Hagedorn), and 103 women were available for analysis of the primary outcome (n=5 for pregnancy loss before 24 weeks' gestation). Bayesian analysis indicated an 87% posterior probability of reduced primary outcome with insulin detemir compared with neutral protamine Hagedorn (posterior adjusted relative risk, 0.88; 95% credible interval, 0.61-1.12). Bayesian analyses for secondary outcomes showed consistent findings of lower adverse maternal outcomes with the use of insulin detemir vs neutral protamine Hagedorn: for example, maternal hypoglycemic events (97% probability of benefit; posterior adjusted relative risk, 0.59; 95% credible interval, 0.29-1.08) and hypertensive disorders (88% probability of benefit; posterior adjusted relative risk, 0.81; 95% credible interval, 0.54-1.16)., Conclusion: In our comparative effectiveness trial involving individuals with type 2 or overt type 2 diabetes mellitus, use of insulin detemir resulted in lower rates of adverse neonatal and maternal outcomes compared with neutral protamine Hagedorn., (Published by Elsevier Inc.)

Objective: Intravenous glyburide has demonstrated safety when used for attenuation of cerebral edema, although safety data are lacking for enteral glyburide when used for this indication. We aimed to determine the prevalence of and risk factors for hypoglycemia in neurocritical care patients receiving enteral glyburide., Methods: We performed a retrospective case-control chart review (hypoglycemia vs. no hypoglycemia) of adult patients who received enteral glyburide for prevention or treatment of cerebral or spinal cord edema. Hypoglycemia was defined as a blood glucose <55.8 mg/dL. Descriptive statistics were used, with multivariate analysis to measure the association of risk factors and outcomes. Logistic regression was applied to outcomes with an exposure. Potential confounders were evaluated using the t-test or the Wilcoxon rank-sum test for continuous variables, and the χ 2 test or the Fisher exact test for categorical variables., Results: Seventy-one patients (60.6% men, median age 60 years) were included. The majority received 2.5 mg of enteral glyburide twice daily. Diagnoses included tumors (35.2%), intracerebral hemorrhage (28.2%), postspinal surgery (12.7%), and ischemic stroke (12.7%). Hypoglycemia occurred in 17 (23.9%) patients. Multivariate analysis identified admission serum creatinine (odds ratio, 27.2; [1.661, 445.3]; P < 0.05) as a risk factor for hypoglycemia, whereas body mass index >30 (odds ratio, 0.085; [0.008, 0.921]; P < 0.05) was protective., Conclusions: Hypoglycemic episodes are common following enteral glyburide in neurocritical care patients. Both patients with and without diabetes mellitus are at risk of hypoglycemia. Elevated admission serum creatinine may increase the risk of hypoglycemia when utilizing glyburide for prevention or treatment of cerebral or spinal cord edema., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim: To detail the extent and prevalence of post-exercise and nocturnal hypoglycemia following peri-exercise bolus insulin dose adjustments in individuals with type 1 diabetes (T1D) using multiple daily injections of insulins aspart (IAsp) and degludec (IDeg)., Methods and Results: Sixteen individuals with T1D, completed a single-centred, randomised, four-period crossover trial consisting of 23-h inpatient phases. Participants administered either a regular (100%) or reduced (50%) dose (100%; 5.1 ± 2.4, 50%; 2.6 ± 1.2 IU, p < 0.001) of individualised IAsp 1 h before and after 45-min of evening exercise at 60 ± 6% V̇O 2max . An unaltered dose of IDeg was administered in the morning. Metabolic, physiological and hormonal responses during exercise, recovery and nocturnal periods were characterised. The primary outcome was the number of trial day occurrences of hypoglycemia (venous blood glucose ≤ 3.9 mmol L - 1 ). Inclusion of a 50% IAsp dose reduction strategy prior to evening exercise reduced the occurrence of in-exercise hypoglycemia (p = 0.023). Mimicking this reductive strategy in the post-exercise period decreased risk of nocturnal hypoglycemia (p = 0.045). Combining this strategy to reflect reductions either side of exercise resulted in higher glucose concentrations in the acute post-exercise (p = 0.034), nocturnal (p = 0.001), and overall (p < 0.001) periods. Depth of hypoglycemia (p = 0.302), as well as ketonic and counter-regulatory hormonal profiles were similar., Conclusions: These findings demonstrate the glycemic safety of peri-exercise bolus dose reduction strategies in minimising the prevalence of acute and nocturnal hypoglycemia following evening exercise in people with T1D on MDI. Use of newer background insulins with current bolus insulins demonstrates efficacy and advances current recommendations for safe performance of exercise., Clinical Trials Register: DRKS00013509., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

As the prevalence of obesity has increased, bariatric surgery has become more common because of its proven efficacy at promoting weight loss and improving weight-related medical comorbidities. Although generally successful, bariatric surgery may also lead to complications and negatively affect health. This article highlights some common and rare complications of bariatric surgery. Specifically, it discusses the risk of nutrient deficiencies (which is influenced by surgery type) and their downstream effects, including ill-effects on bone health. Rarer complications, such as postbypass hypoglycemia and alcohol use disorder, are also discussed., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Hypoglycemia is defined by a low blood glucose level associated to clinical symptoms. Hypoglycemia may be related to treatment of diabetes, but also to drugs, alcohol, critical illness, cortisol insufficiency including hypopituitarism, insulinoma, bariatric or gastric surgery, pancreas transplantation or glucagon deficiency, or may be surreptitious. Some hypoglycemic episodes remain unexplained, and genetic, paraneoplastic and immune causes should be considered. Genetic causes may be related to endogenous hyperinsulinism and to inborn errors of metabolism (IEM). Endogenous hyperinsulinism is related to monogenic congenital hyperinsulinism, and especially to mutations of the glucokinase-activating gene or of insulin receptors, both characterised by postprandial hypoglycemia with major hyperinsulinism. In adulthood, IEM-related hypoglycemia can persist in a previously diagnosed childhood disease or may be a presenting sign. It is suggested by systemic involvement (rhabdomyolysis after fasting or exercising, heart disease, hepatomegaly), sometimes associated to a family history of hypoglycemia. The timing of hypoglycemic episodes with respect to the last meal also helps to orientate diagnosis. Fasting hypoglycemia may be related to type 0, I or III glycogen synthesis disorder, fatty acid oxidation or gluconeogenesis disorder. Postprandial hypoglycemia may be related to inherited fructose intolerance. Exercise-induced hyperinsulinism is mainly related to activating mutation of the SLC16A1 gene. Besides exceptional ectopic insulin secretion, paraneoplastic causes involve NICTH (Non-Islet-Cell Tumour Hypoglycemia), caused by Big-IGF2 secretion by a large tumour, with low blood levels of insulin, C-peptide and IGF1. Autoimmune causes involve antibodies against insulin (HIRATA syndrome), especially in case of Graves' disease, or against the insulin receptor. Medical history, timing, and insulin level orientate the diagnosis., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background: Hypoglycemia is a common acute complication in patients with diabetes and markedly impacts on medical resource use., Objectives: To make an initial assessment of the incidence of hypoglycemia and the associated utilization of medical resources and medical costs in insulin-treated patients with diabetes using medical records from 4 tertiary hospitals in China., Methods: A retrospective cohort study was conducted using electronic medical records from 4 tertiary hospitals in Beijing, Henan, and Guangzhou from 2012 to 2015. The targeted patients were those diagnosed with either type 1 or type 2 diabetes and treated with insulin. Diabetes was identified with International Classification of Diseases, Tenth Revision diagnosis codes. Hypoglycemia was identified based on glycemic value and the description of diagnosis. The incidence of hypoglycemia, medical resource utilization, and medical costs were analyzed. One-to-one propensity score matching was used to match age, sex, type of diabetes, and complications to patients with and without hypoglycemia and patients with severe and non-severe hypoglycemia, to compare their medical resource utilization and medical costs., Results: A total of 14 044 patients (95.3% had type 2 diabetes and 93.7% with complications) were treated with insulin. There were 1930 patients who had outpatient visits and 310 patients who had inpatient visits owing to hypoglycemia. Incidences of hypoglycemia were 111.3 events per 100 patient-years for outpatient visits and 5.9 events per 100 patient-years for inpatient visits. Patients with hypoglycemia had more outpatient visits (8.09 vs 6.22 times/year, P < .05) and higher annual medical costs ($2147.4 vs $1426.8/person, P < .05) compared with patients without hypoglycemia. Among patients with hypoglycemia, those with severe hypoglycemia had more inpatient visits (2.06 vs 1.13 times/year, P < .05) and higher annual inpatient medical costs ($6204.0 vs $2017.9/person, P < .05) compared with patients with non-severe hypoglycemia., Conclusion: The burden of hypoglycemia, especially severe hypoglycemia, is substantial and associated with increased use of medical resources and expenditures among the target population, which serves as a vital first glance at patients with insulin-treated diabetes in China overall., (Copyright © 2019 ISPOR--The professional society for health economics and outcomes research. Published by Elsevier Inc. All rights reserved.)

Background: A correlation between ACS and neonatal hypoglycemia has been recently demonstrated., Aims: The aim of the study was to evaluate the determinants of neonatal hypoglycemia in women exposed to ACS for respiratory distress syndrome prevention., Material and Methods: Retrospective, multicenter, cohort study conducted in two Tertiary University Units. All fetuses delivered from 2016 to 2017 after ACS (two doses i.m. of Betamethasone 12 mg 24 h apart) were considered eligible for the study purpose. The primary outcome was the incidence of hypoglycemia, defined as a glycemic value ≤45 mg/dl within the first 48 h of neonatal life. The effect on neonatal glycaemia due to timing (interval from exposure to delivery) and type (single completed, single partial or repeated course) of ACS administration was also assessed., Results: Overall, 99 neonates met the inclusion criteria. Hypoglycemia occurred in 38/99 (38.4%) of the included newborns. Compared to normoglycemic neonates, those with hypoglycemia had lower gestational age at delivery (33.06 ± 3.37 vs. 35.94 ± 3.17 g; p < 0.0001). Lower birthweight (1747.28 ± 815.29 vs. 2499.24 ± 780.51 g; p < 0.0001), a shorter interval time from administration to delivery (1.85 ± 2.59 vs. 3.34 ± 3.39 weeks; p = 0.02) and a higher incidence of single partial course (23.7 vs. 8.72%; p = 0.03). Multivariate logistic regression found that only birthweight was significantly associated with neonatal hypoglycemia (OR 0.4 95% CI -1.16/-0.04; p < 0.038)., Conclusion: Hypoglycemia occurs in a large proportion of fetuses exposed to ACS independently from the type of exposure (single partial/single completed) and from the time interval between ACS administration and delivery. Birthweight seems to be the strongest determinant for the occurrence neonatal hypoglycemia after antenatal administration of steroids for lung maturation., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Acute bacterial infectious diseases are major causes for outpatient visits for young children. Pivalate-conjugated antibiotics (PCAs) are frequently prescribed for these situations in Japan, while several literatures have shown a potential risk of hypoglycemia associated with PCAs. This study aimed to evaluate the incidence of PCA-induced hypoglycemia in children, compared with other oral beta-lactam antibiotics., Methods: This retrospective cohort study using a Japanese medical and pharmacy claims database was performed on children aged 1 month to 5 years old with at least once prescription of PCAs or other oral beta-lactam antibiotics from January 2011 to December 2013. Hypoglycemia was defined based on diagnostic codes or the prescription of 10% or 20% glucose injection. We examined the prevalence of hypoglycemic events and performed multivariate analysis to investigate the risk of hypoglycemia with PCAs compared with the control oral beta-lactam antibiotics., Results: We identified 179,594 eligible patients in this population. In the PCA and control groups, there were 454,153 and 417,287 prescriptions and 3356 (0.74%, 95% confidence intervals [CI] 0.71-0.76) and 2605 (0.62%, 95% CI 0.60-0.65) hypoglycemic events, respectively. Multivariate analysis revealed that PCAs were associated with hypoglycemia (adjusted odds ratios [OR] 1.18, 95% CI 1.12-1.24), and even a shorter duration of PCAs prescribing (≤7 days) was significantly associated with hypoglycemia (adjusted OR 1.17, 95% CI 1.11-1.24)., Conclusion: These results suggest that in young children PCA use, even for a short period, is a risk factor of hypoglycemia., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Hypoglycemia is a common and feared complication of insulin therapy. As in type 1 and type 2 diabetes, people with cystic fibrosis related diabetes are also at risk for hypoglycemia related to insulin therapy. Spontaneous hypoglycemia is also common in patients with CF without diabetes, who are not on glucose lowering medications. Spontaneous hypoglycemia in CF may also occur during or after an oral glucose tolerance test. In this review, we will discuss the definition, epidemiology, pathophysiology and impact of hypoglycemia, with a focus on people with cystic fibrosis. We will also review strategies to manage and prevent hypoglycemia., (Copyright © 2019 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Postprandial hypoglycemia and early dumping syndrome are common complications after bariatric surgery. Although sleeve gastrectomy (SG) has become a primary option for many bariatric surgeons, limited information was available for the prevalence and risk factors of the complications., Objective: To assess the prevalence and possible risk factors for postprandial hypoglycemia and early dumping syndrome based on self-reported symptoms of SG patients., Setting: The study was conducted at a bariatric surgery center in a university hospital., Methods: In this study, all patients who underwent an SG (n = 222) between December 2011 and May 2018 in our center were invited to participate in a questionnaire survey. The Edinburgh Hypoglycemia Scoring System and the Dumping Symptom Rating Scale were used to evaluate symptoms, and clinical data of the patients were collected. The median follow-up time was 1.1 years., Results: The questionnaire was completed and returned by 54.95% (122/222) of the patients and 62.30% (76/122) of the responders were women. The prevalence rates of mild and moderate symptoms suggestive of hypoglycemia were 65.57% (80/122) and .82%, respectively. An associated risk factor was younger age (adjusted for sex, body mass index, and waist circumference at baseline: odds ratio 3.69; 95% confidence interval [1.22-11.21]), but this association disappeared after further adjustment of low-density protein cholesterol (LDL-C) (odds ratio 6.42; 95% confidence interval [.38-108],;P > .05). The prevalence rate of mild symptoms suggestive of early dumping was 40.98% (50/122), associated risk factor was lower LDL-C., Conclusion: Mild-to-moderate symptoms suggestive of hypoglycemia and early dumping syndrome were common in patients after SG, with the prevalence rates of 66.39% (81/122) and 40.98% (50/122), respectively. Patients with both symptoms suggestive of early dumping syndrome and hypoglycemia accounted for 33.61% (41/122) of all patients. Younger age indicated higher risk of hypoglycemia after SG and lower LDL-C may play an important role in this relationship. Lower LDL-C was associated with higher risk of early dumping syndrome after SG., (Copyright © 2019 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Hypoglycemia represents a relevant burden in people with diabetes. Consequences of hypoglycemia/fear of hypoglycemia on quality of life (QoL) and behaviors of patients with T1DM and T2DM were assessed., Methods and Results: HYPOS-1 was an observational retrospective study. Fear of hypoglycemia (Fear of Hypoglycemia Questionnaire, FHQ), general health status (visual analog scale of EuroQol questionnaire, EQ5D-VAS) psychological well-being (WHO-5 well being index, WHO-5), diabetes related distress (Problem Areas in Diabetes 5, PAID-5), and corrective/preventive behaviors following hypoglycemia were compared between people with and without previous experience of severe and symptomatic hypoglycemia and by tertiles of FHQ scores. A multivariate analysis was performed to identify factors associated with the likelihood of being in the third tertile of FHQ score. Overall, 2229 patients were involved. Severe hypoglycemia had statistically significant and clinically relevant (measured as effect sizes) negative impact on EQ5D-VAS, WHO-5, PAID-5, and FHQ both in T1DM and T2DM. In T2DM, symptomatic episodes had similar impact of severe hypoglycemia. Moving from the first to the third FHQ tertile, lower scores of EQ-5D VAS and WHO-5, and higher levels of PAID-5 were found. Patients in the third tertile performed more frequently corrective/preventive actions that negatively impact on metabolic control. Previous hypoglycemia, insulin treatment, female gender, age, and school education were the independent factors associated with increased likelihood to be in the third tertile., Conclusion: Not only severe but also symptomatic hypoglycemia negatively affect patient QoL, especially in T2DM. Addressing fear of hypoglycemia should be a goal of diabetes education., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Although dietary treatment ameliorates symptoms in most patients with postbariatric hypoglycemia (PBH), there is a subgroup with severe symptoms that do not respond sufficiently to either diet or drugs. A clinical observation showed that those patients additionally experienced postprandial abdominal discomfort or pain., Objectives: This report describes patients with severe PBH following laparoscopic Roux-en Y gastric bypass undergoing corrective surgery to alleviate partial small bowel obstruction (kink, adhesions, dysfunctional anastomosis) and the subsequent outcome regarding symptoms of PBH., Setting: Sahlgrenska University Hospital, Sweden., Methods: Retrospective analysis regarding hypoglycemic symptoms from medical records and a complementary telephone interview., Results: Out of 80 patients treated for severe PBH at our tertiary academic surgical unit over the last 4 years, 38 underwent corrective surgery (adhesiolysis and/or a reconstructed jejuno-jejunostomy). Out of 21 patients using medications to control hypoglycemia before corrective surgery, 19 (90.5%) discontinued the medication, and 5 of 19 (26%) no longer needed to use a blood glucometer or a continuous glucose monitor. Although patients after surgical correction still could experience PBH, symptoms were less frequent and less severe. Postprandial abdominal symptoms decreased, and patients reported improved eating quality. Patient interviews revealed that 8% became entirely free of PBH symptoms after surgery and 71% experienced significant relief., Conclusions: We propose a possible association between severe hypoglycemic symptoms after laparoscopic Roux-en Y gastric bypass and partial small bowel obstruction. Patients with PBH not responding adequately to diet and drug treatment may benefit from assessment and intervention for partial small bowel obstruction., (Copyright © 2019 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Insulin therapy is most effective if dosage titrations are done regularly and frequently, which is seldom practical for most clinicians, resulting in an insulin titration gap. The d-Nav Insulin Guidance System (Hygieia, Livonia, MI, USA) is a handheld device that is used to measure glucose, determine glucose patterns, and automatically determine the appropriate next insulin dose. We aimed to determine whether the combination of the d-Nav device and health-care professional support is superior to health-care professional support alone., Methods: In this multicentre, randomised, controlled study, we recruited patients from three diabetes centres in the USA (in Detroit MI; Minneapolis, MN; and Des Moines IA). Patients were eligible if they were aged 21-70 years, diagnosed with type 2 diabetes with a glycated haemoglobin (HbA 1c ) concentration of 7·5% or higher (≥58 mmol/mol) and 11% or lower (≤97 mmol/mol), and had been using the same insulin regimen for the previous 3 months. Exclusion criteria included body-mass index of 45 kg/m 2 or higher; severe cardiac, hepatic, or renal impairment; and more than two severe hypoglycaemic events in the past year. Eligible participants were randomly assigned (1:1), with randomisation blocked within each site, to either d-Nav and health-care professional support (intervention group) or health-care professional support alone (control group). Both groups were contacted seven times (three face-to-face and four phone visits) during 6 months of follow-up. The primary objective was to compare average change in HbA 1c from baseline to 6 months. Safety was assessed by the frequency of hypoglycaemic events. The primary objective and safety were assessed in the intention-to-treat population. We used Student's t test to assess the primary outcome for statistical significance. This study was registered with ClinicalTrials.gov, number NCT02424500., Findings: Between Feb 2, 2015, and March 17, 2017, 236 patients were screened for eligibility, of whom 181 (77%) were enrolled and randomly assigned to the intervention (n=93) and control (n=88) groups. At baseline, mean HbA 1c was 8·7% (SD 0·8; 72 mmol/mol [SD 8·8]) in the intervention group and 8·5% (SD 0·8; 69 mmol/mol [SD 8·8]) in the control group. The mean decrease in HbA 1c from baseline to 6 months was 1·0% (SD 1·0; 11 mmol/mol [SD 11]) in the intervention group, and 0·3% (SD 0·9; 3·3 mmol/mol [9·9]) in the control group (p<0·0001). The frequency of hypoglycaemic events per month was similar between the groups (0·29 events per month [SD 0·48] in the intervention group vs 0·29 [SD 1·12] in the control group; p=0·96)., Interpretation: The combination of automated insulin titration guidance with support from health-care professionals offers superior glycaemic control compared with support from health-care professionals alone. Such a solution facilitated safe and effective insulin titration in a large group of patients with type 2 diabetes, and now needs to be evaluated across large health-care systems to confirm these findings and study cost-effectiveness., Funding: US National Institutes of Health, National Institute of Digestive and Kidney Diseases., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aims: This study aimed to characterize and estimate prevalence and frequency of mild to moderate hypoglycemia and potentially associated factors in a population of type 2 diabetes mellitus (T2DM) patients treated at ambulatory care level., Methods: HIPOS-PHARMA was a nationwide observational, cross-sectional, multicenter study conducted in community pharmacies, which surveyed T2DM patients treated for at least 3 months., Results: Overall, 233 pharmacies recruited 1890 patients (males: 50.6%) with mean 67.1 years. On average, participants reported having diabetes for 11.8 years. A total of 86.9% had at least one chronic illness or complication of diabetes, and 76.8% were usually followed in the primary care setting. Fifty eight percent were treated without a secretagogue or insulin. Overall prevalence of mild to moderate hypoglycemic episodes in the 3 months prior to recruitment was 17.8%. A 3.13% prevalence of severe hypoglycemia was observed in the last 12 months. Results suggested that men and patients on antihyperglycemic therapies excluding secretagogues or insulin were less likely to have mild to moderate hypoglycemic episodes., Conclusions: Mild to moderate hypoglycemic episodes were commonly reported, and factors like type of antihyperglycemic therapy, duration of disease and due complications may contribute. Almost half of episodes were not reported. Such factors should be considered in T2DM management., (Copyright © 2018 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Using mTOR inhibitors (mTORi) as anticancer drugs led to hyperglycemia (12-50%) and hyperlipidemia (7-73%) in phase-III trials. These high rates require adapted treatment in cancer patients. Before initiating mTORi treatment, lipid profile screening should be systematic, with fasting glucose assay in non-diabetic patients and HbA 1C in diabetic patients. After initiation, lipid profile monitoring should be systematic, with fasting glucose assay in non-diabetic patients, every 2 weeks for the first month and then monthly. The HbA 1C target is≤8%, before and after treatment initiation in known diabetic patients and in case of onset of diabetes under mTORi. LDL-cholesterol targets should be adapted to general health status and cardiovascular and oncologic prognosis. If treatment is indicated, pravastatin should be prescribed in first line; atorvastatin and simvastatin are contraindicated. Fenofibrate should be prescribed for hypertriglyceridemia>5g/l resisting dietary measures adapted to oncologic status. In non-controllable hypertriglyceridemia exceeding 10g/l, mTORi treatment should be interrupted and specialist opinion should be sought., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Tyrosine kinase inhibitors (TKI) interfere with glucose metabolism. Contrasting effects have been reported, even for a given molecule. Hyperglycemia rates range between 15 and 40%; nilotinib seems to be the molecule most liable to induce diabetes. Metabolic effects range from metabolic syndrome to onset of diabetes, requiring treatment based on insulin resistance, although pathophysiology is unclear. It is noteworthy that fulminant diabetes has never been reported under TKIs. TKIs may lead to hypoglycemia in type 1 or 2 diabetes. Several cases have been reported of improvement in glycemia and in HbA1c, with reduction or even termination of insulin therapy, mainly under imatinib and sunitinib. Fasting glucose levels should be checked before, during and after treatment, plus HbA1C in diabetic patients, with reinforced self-monitoring. These side-effects are transient and never contraindicate continuation of TKIs. Dyslipidemia under TKI has been reported, concerning both LDL-cholesterol and triglycerides. Although variations seem to be slight, lipid assessment is recommended before, during and after treatment., (Copyright © 2018. Published by Elsevier Masson SAS.)

Background: Literature directly looking at post-bariatric surgery hypoglycemia consists mostly of small case series. The rate, severity, and outcomes of treatment in a large bariatric population are less characterized., Objective: To determine the rate of post-bariatric surgery hypoglycemia, its clinical features and management outcomes over a 13-year period at our institution., Setting: An academic center in the United States., Methods: Patients who underwent bariatric surgery at a single academic center between 2002 and 2015 and had a postdischarge glucose level of ≤70 mg/dL were studied., Results: Of 6024 patients who underwent bariatric procedure, 118 patients (2.0%) had a postoperative glucose level ≤70 mg/dL. Eighty-three patients (1.4%) had symptomatic hypoglycemia. The known underlying causes of symptomatic hypoglycemia included postprandial hyperinsulinemic hypoglycemia (n = 32, 38%), infection (n = 8, 10%), diabetic medications (n = 8, 10%), and poor oral intake (n = 8, 10%). Overall, 9 patients required intervention for nutritional supplementation including enteral (n = 9) and intermittent parenteral (n = 2) nutrition. No patients required reversal of their bariatric surgeries or pancreatic resection for management of hypoglycemia. The majority of the symptomatic patients had resolution of their symptoms (n = 76, 92%). Thirty-two patients had postprandial hypoglycemia with a median onset of hypoglycemia after bariatric surgery of 790 days (interquartile range 388-1334). All 32 patients with postprandial hypoglycemia had dietary adjustment and 53% received pharmacotherapy, which resulted in complete resolution of hypoglycemia (n = 29, 91%) and resolution with minimal disability (n = 3, 9%)., Conclusion: The rate of symptomatic hypoglycemia and postprandial hypoglycemia after bariatric surgery were 1.4% and .5%. The majority of patients were successfully managed with dietary counseling, nutritional intervention, and occasionally pharmacotherapy. No surgical reversal or pancreatic procedures were performed., (Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)