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BACKGROUND Hypoglycemia is a common complication following total gastrectomy, primarily caused by dumping syndrome and severe malnutrition, with late dumping syndrome being particularly significant. However, for recurrent fasting hypoglycemia, the possibility of insulinoma should be considered. Hypoglycemia caused by insulinoma can lead to severe consequences, including seizures and even death. Thus, it is crucial to differentially diagnose hypoglycemia occurring after total gastrectomy. CASE REPORT In this report, we present the case of a 36-year-old Chinese woman who underwent total gastrectomy for gastric cancer and subsequently received chemotherapy. Four months after surgery, she began experiencing recurrent seizures, and multiple tests confirmed hypoglycemia. A series of laboratory and imaging examinations ultimately led to a diagnosis of insulinoma. After surgical resection of the tumor, the patient's hypoglycemic symptoms resolved, and pathology results confirmed an insulinoma. CONCLUSIONS This case report highlights the rapid weight loss and severe hypoglycemia observed in a patient only 4 months after total gastrectomy for gastric cancer. Although dumping syndrome was initially suspected based on the clinical course, the final diagnosis turned out to be insulinoma. The case underscores the importance of comprehensive evaluation and appropriate diagnostic investigations for patients experiencing hypoglycemia after total gastrectomy. Furthermore, the case suggests that the increased levels of enteroglucagon following changes in the gastrointestinal tract resulting from total gastrectomy may promote the development of insulinomas. This case report also contributes to the existing literature regarding atypical presentations of insulinomas and their association with gastric resection.

Hypoglycemia in the pediatric population tends to present in the newborn period or during metabolic crisis triggered by prolonged fasting and intercurrent illness. Current recommendations to investigate all children presenting with hypoglycemia for the first time are cumbersome and costly but necessary to identify those with serious conditions who predispose to hypoglycemia. We describe a practical and cost-effective method of evaluating children who present to the emergency department with previously undiagnosed hypoglycemia. Glucose and point-of-care (POC) beta-hydroxybutyrate levels should be measured on all children with a low screening POC glucose level, and a full history and physical examination will identify those requiring further investigation. This approach is suggested to identify patients with serious and life-threatening disease with the same fidelity as the currently recommended approach of performing a critical sample on all children with hypoglycemia. Our streamlined approach will reduce the cost to approximately 10% of the current approach per patient diagnosed with a serious underlying disease. Further, children without underlying hypoglycemia-predisposing disorders will be identified and discharged without unnecessary intervention., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To improve the clinical utility of the Maintain High Blood Glucose subscale of the Hypoglycemia Fear Surveys (HFS) by identifying clinically meaningful cut points associated with glycemic outcomes., Methods: Youth (N = 994; 13.96 ± 2.3 years) with type 1 diabetes and their caregivers (N = 1,111; 72% female) completed the Child or Parent version of the HFS. Modal Score Distribution, Standard Deviation Criterion, and Elevated Item Criterion approaches were used to identify proposed preliminary cut points for the Maintain High Blood Glucose subscale. The association between proposed preliminary cut points was examined with youth glycemic outcomes., Results: A cut point of ≥7 for the Maintain High Blood Glucose subscale on the Child HFS was associated with a greater percentage of blood glucose readings >180 mg/dl (p < .01), higher mean blood glucose (p < .001), and a higher hemoglobin A1c (p < .05). In subsequent multiple regression analyses, controlling for other factors associated with glycemia, the significant association between scores above ≥7 and higher mean blood glucose and higher hemoglobin A1c remained. A clinically useful cut point was not identified for caregivers. However, elevated youth scores on the Maintain High Blood Glucose subscale were positively associated with elevated caregiver scores (phi = .171, p < .001)., Conclusions: The proposed preliminary cut point for the Maintain High Blood Glucose subscale will aid the type 1 diabetes care team in identifying youth whose behaviors may be contributing to their suboptimal glycemia., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Perinatal stress and fetal growth restriction increase the risk of neonatal hypoglycemia. The underlying pathomechanism is poorly understood. In a sheep model, elevated catecholamine concentrations were found to suppress intrauterine insulin secretion, followed by hyperresponsive insulin secretion once the adrenergic stimulus subsided., Objective: To determine whether neonates with risk factors for hypoglycemia have higher catecholamine concentrations in umbilical cord blood (UCB) and/or amniotic fluid (AF) and whether catecholamines are correlated with postnatal glycemia., Design, Setting, and Participants: In a prospective cohort study of 328 neonates at a tertiary perinatal center from September 2020 through May 2022 in which AF and UCB were collected immediately during and after delivery, catecholamines and metanephrines were analyzed using liquid chromatography with tandem mass spectrometry. Participants received postnatal blood glucose (BG) screenings., Exposure: Risk factor for neonatal hypoglycemia., Main Outcomes and Measures: Comparison of catecholamine and metanephrine concentrations between at-risk neonates and control participants, and correlation of concentrations of catecholamines and metanephrines with the number and severity of postnatal hypoglycemic episodes., Results: In this study of 328 neonates (234 in the risk group: median [IQR] gestational age, 270 [261-277] days; and 94 in the control group: median [IQR] gestational age, 273 [270-278] days), growth-restricted neonates showed increased UCB median (IQR) concentrations of norepinephrine (21.10 [9.15-42.33] vs 10.88 [5.78-18.03] nmol/L; P < .001), metanephrine (0.37 [0.13-1.36] vs 0.12 [0.08-0.28] nmol/L; P < .001), and 3-methoxytyramine (0.149 [0.098-0.208] vs 0.091 [0.063-0.149] nmol/L; P = .001). Neonates with perinatal stress had increased UCB median (IQR) concentrations of norepinephrine (22.55 [8.99-131.66] vs 10.88 [5.78-18.03] nmol/L; P = .001), normetanephrine (1.75 [1.16-4.93] vs 1.25 [0.86-2.56] nmol/L; P = .004), and 3-methoxytyramine (0.120 [0.085-0.228] vs 0.091 [0.063-0.149] nmol/L; P = .008) (P < .0083 was considered statistically significant). Concentrations of UCB norepinephrine, metanephrine, and 3-methoxytyramine were negatively correlated with AF C-peptide concentration (rs = -0.212, P = .005; rs = -0.182, P = .016; and rs = -0.183, P = .016, respectively [P < .017 was considered statistically significant]). Concentrations of UCB norepinephrine, metanephrine, and 3-methoxytyramine were positively correlated with the number of hypoglycemic episodes (BG concentration of 30-45 mg/dL) (rs = 0.146, P = .01; rs = 0.151, P = .009; and rs = 0.180, P = .002, respectively). Concentrations of UCB metanephrine and 3-methoxytyramine were negatively correlated with the lowest measured BG concentration (rs = -0.149, P = .01; and rs = -0.153, P = .008, respectively)., Conclusions and Relevance: Neonates at risk for hypoglycemia displayed increased catecholamine and metanephrine concentrations that were correlated with postnatal hypoglycemic episodes and lower BG levels; these results are consistent with findings in a sheep model that fetal catecholamines are associated with neonatal β-cell physiology and that perinatal stress or growth restriction is associated with subsequent neonatal hyperinsulinemic hypoglycemia. Improving the pathomechanistic understanding of neonatal hypoglycemia may help to guide management of newborns at risk for hypoglycemia.

We aimed to evaluate the utility of the FreeStyle Libre 2 device for reducing time below range level 1 and level 2 compared with the Freestyle Libre device (without alarms) in people with type 1 diabetes mellitus. We conducted longitudinal observational follow-up study of a cohort of 100 people with type 1 diabetes mellitus who had switched from FreeStyle Libre to FreeStyle Libre 2 as part of routine clinical practice. Three months after switching to FreeStyle Libre 2, compared with results with FreeStyle Libre, there were a significant improvements in time below range level 1 (p = 0.02) and level 2 (p <0.001), time in range (p <0.001), time above range level 1 (p = 0.002), glucose management indicator (p= 0.04) and mean glucose (p= 0.04) during follow-up. Furthermore there was a significant direct association between age and change in TIR with a coefficient of 0.23, and a significant inverse association between age and change in TAR-1 with a coefficient of 0.11. Switching to a flash glucose monitoring system with alarms improves time below range, time in range and coefficient of variation in people with type 1 diabetes mellitus., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Carratala Munuera, C reports financial support was provided by Spain Ministry of Science and Innovation. Quesada, JA reports financial support was provided by Spain Ministry of Science and Innovation., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To explore the optimal blood glucose-lowering strategies for patients with diabetic ketoacidosis (DKA) to enhance personalized treatment effects using machine learning techniques based on the United States Critical Care Medical Information Mart for Intensive Care- IV (MIMIC- IV)., Methods: Utilizing the MIMIC- IV database, the case data of 2 096 patients with DKA admitted to the intensive care unit (ICU) at Beth Israel Deaconess Medical Center from 2008 to 2019 were analyzed. Machine learning models were developed, and receiver operator characteristic curve (ROC curve) and precision-recall curve (PR curve) were plotted to evaluate the model's effectiveness in predicting four common adverse outcomes: hypoglycemia, hypokalemia, reductions in Glasgow coma scale (GCS), and extended hospital stays. The risk of adverse outcomes was analyzed in relation to the rate of blood glucose decrease. Univariate and multivariate Logistic regression analyses were conducted to examine the relationship between relevant factors and the risk of hypokalemia. Personalized risk interpretation methods and predictive technologies were applied to individualize the analysis of optimal glucose control ranges for patients., Results: The machine learning models demonstrated excellent performance in predicting adverse outcomes in patients with DKA, with areas under the ROC curve (AUROC) and 95% confidence interval (95%CI) for predicting hypoglycemia, hypokalemia, GCS score reduction, and extended hospital stays being 0.826 (0.803-0.849), 0.850 (0.828-0.870), 0.925 (0.903-0.946), and 0.901 (0.883-0.920), respectively. Analysis of the relationship between the rate of blood glucose reduction and the risk of four adverse outcomes showed that a maximum glucose reduction rate > 6.26 mmol×L -1 ×h -1 significantly increased the risk of hypoglycemia (P < 0.001); a rate > 2.72 mmol×L -1 ×h -1 significantly elevated the risk of hypokalemia (P < 0.001); a rate > 5.53 mmol×L -1 ×h -1 significantly reduced the risk of GCS score reduction (P < 0.001); and a rate > 8.03 mmol×L -1 ×h -1 significantly shortened the length of hospital stay (P < 0.001). Multivariate Logistic regression analysis indicated significant correlations between maximum bicarbonate levels, blood urea nitrogen levels, and total insulin doses with the risk of hypokalemia (all P < 0.01). In terms of establishing personalized optimal treatment thresholds, assuming optimal glucose reduction thresholds for hypoglycemia, hypokalemia, GCS score reduction, and extended hospital stay were x 1 , x 2 , x 3 , x 4 , respectively, the recommended glucose reduction rates to minimize the risks of hypokalemia and hypoglycemia should be ≤min{x 1 , x 2 }, while those to reduce GCS score decline and extended hospital stay should be ≥ max{x 3 , x 4 }. When these ranges overlap, i.e., max{x 3 , x 4 } ≤ min{x 1 , x 2 }, this interval was the recommended optimal glucose reduction range. If there was no overlap between these ranges, i.e., max{x 3 , x 4 } > min{x 1 , x 2 }, the treatment strategy should be dynamically adjusted considering individual differences in the risk of various adverse outcomes., Conclusions: The machine learning models shows good performance in predicting adverse outcomes in patients with DKA, assisting in personalized blood glucose management and holding important clinical application prospects.

Context: Insulinoma is a neuroendocrine tumor derived from pancreatic β -cells whose clinical manifestation is recurrent hypoglycemia. Insulinoma in a patient with preexisting diabetes is extraordinarily rare, and the unmasking of type 2 diabetes (T 2 DM) after insulinoma surgery is even rarer., Case Report: This article reports a 49-year-old male patient with insulinoma that masked the diagnosis of T 2 DM. The patient was admitted to the hospital with symptoms of hypoglycemia, such as repeated sweating, palpitations, and asthenia for over 4 years. The patient was diagnosed with insulinoma after completing relevant examinations. The emergence of hyperglycemia after the removal of insulinoma is attributable to the coexistence of T 2 DM. Surprisingly, a reversible decrease in cortisol levels was observed during the diagnostic process. We searched the previously published reports of this type of case from PubMed to determine why type 2 diabetes was covered by insulinoma and why glucocorticoids decreased., Conclusions: The diagnosis of T 2 DM in the patient after surgery may be related to increased food intake and insulin resistance induced by hyperinsulinemia caused by long-term hypoglycemia. The reversible decrease in cortisol levels, not adrenocortical insufficiency during the diagnostic process, may be caused by a transient abnormality in glucose counterregulation., (© 2024. The Author(s).)

Aims: Recent clinical trials and real-world studies highlighted those variations in ECG waveforms and HRV recurrently occurred during hypoglycemic and hyperglycemic events in patients with diabetes. However, while several studies have been carried out for adult age, there is lack of evidence for paediatric patients. The main aim of the study is to identify the correlations of variations in ECG Morphology waveforms with blood glucose levels in a paediatric population., Methods: T1D paediatric patients who use CGM were enrolled. They wear an additional non-invasive wearable device for recording physiological data and respiratory rate. Glucose metrics, ECG parameters and HRV features were collected, and Wilcoxon rank-sum test and Spearman's correlation analysis were used to explore if different levels of blood glucose were associated to ECG morphological changes., Results: Results showed that hypoglycaemic events in paediatric patients with T1D are strongly associated with variations in ECG morphology and HRV., Conclusions: Results showed the opportunity of using the ECG as a non-invasive adding instrument to monitor the hypoglycaemic events through the integration of the ECG continuous information with CGM data. This innovative approach represents a promising step forward in diabetes management, offering a more comprehensive and effective means of detecting and responding to critical changes in glucose levels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Fulminant type 1 diabetes (FT1D) is a unique subtype of type 1 diabetes, characterized by acute absolute insulin deficiency, severe ketosis, and increased risk of hypoglycemia, glycemic variability and microvascular complications. Seven people with FT1D were identified from two tertiary centers in Singapore. Six were Chinese, the mean age was 35 years and all were lean (mean body mass index 20.3 kg/m 2 ). All presented with diabetes ketosis or ketoacidosis and low C-peptide. All but one had low glutamic acid decarboxylase antibodies. Nearly half had a missed/delayed diagnosis of FT1D. Three had frequent hypoglycemia, which improved after transition to continuous subcutaneous insulin infusion therapy. Individuals with FT1D experience unique diagnostic and management challenges associated with rapid absolute insulin deficiency. Greater awareness about this clinical entity is required., (© 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Point-of-care (POC) glucometry is commonly used in horses; however, measurement error with this method when analysing hypoglycaemic samples (<4 mmol/L) is unknown. The objective of this study was to determine the precision and accuracy of glucometry in hypoglycaemic horses in comparison to a laboratory method of glucose measurement (LAB). Repeatability coefficients were 0.47 mmol/L for POC and 0.09 mmol/L for LAB, and coefficients of variation were 10 % and 2.11 %, for the POC and LAB methods, respectively. Systemic bias with the POC method was present, with a mean bias of -0.26 mmol/L (95 % limits of agreement: -0.88 - 0.37) in comparison to LAB, and <70% of measurements were within 20 % of paired LAB results. Prior to use of glucometers, assessment of the diagnostic performance of the equipment is necessary, including determination of acceptable criteria and reference ranges for hypoglycaemic samples., Competing Interests: Declaration of Competing Interest None of the authors have financial or personal relationships that could inappropriately influence or bias the content of this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The diagnosis of insulinoma can be challenging, requiring documentation of hypoglycaemia associated with non-suppressed insulin and C-peptide, often achieved during a prolonged 72 h fast performed in inpatient setting. Our goal is to predict weather a shorter outpatient fasting test initiated overnight and prolonged up until 24 h could be a sensitive method for diagnosing insulinoma., Methods: We conducted a retrospective monocentric study on subjects admitted to our Unit of Endocrinology from 2019 to 2022 for clinical suspicion of insulinoma and underwent the short fasting test. A comparison between the short test group and the group of subjects who underwent the standard prolonged fasting test (from 2003 to 2018) has also been performed. The short fasting test was initiated by the patient overnight at home and proceeded the following day in outpatient setting (Day Hospital). As in the standard protocol, symptoms and capillary blood glucose (CBG) were strictly monitored. Venous blood was drawn for glycaemia, insulin and C-peptide at admission and at established intervals, in case of symptoms of hypoglycaemia or if CBG ≤ 45 mg/dl, when the fast would be suspended., Results: The final sample consisted of 37 patients, with mean age of 44.5 ± 12.6 years (17-74). Short and standard tests were performed in 15 and 22 subjects, respectively. Diagnostic values for insulinoma were observed in 12 patients: in 5/15 who underwent the short fasting test, in 6/22 who underwent the prolonged test and in 1 patient who was initially negative on the short test and subsequently showed diagnostic values during the prolonged test. The diagnosis of insulinoma was achieved in 11/12 cases within 24 h of the beginning of the fast (91.7%)., Conclusions: A short fasting test could be a valid, sensitive and reliable first-line workup in diagnosing insulinoma., (© 2024. The Author(s).)

We herein report a case in which diazoxide was effective in treating reactive hypoglycemia caused by late dumping syndrome in a patient with end-stage renal disease (ESRD). A 50-year-old man with ESRD and a history of gastrectomy underwent hemodialysis. Although he was administered voglibose to treat recurrent reactive hypoglycemia caused by late dumping syndrome, he had difficulty continuing treatment because of gastrointestinal side effects. When he began diazoxide treatment, the reactive hypoglycemia improved. The dose was gradually increased with no apparent side effects, and the hypoglycemic attacks disappeared one year after the start of treatment.

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

Neonatal hypoglycemia (NH) is broadly defined as a low plasma glucose concentration that elicits hypoglycemia-induced impaired brain function. To date, no universally accepted threshold (reference range) for plasma glucose levels in newborns has been published, as data consistently indicate that neurologic responses to hypoglycemia differ at various plasma glucose concentrations. Infants at risk for NH include infants of diabetic mothers, small or large for gestational age, and premature infants. Common manifestations include jitteriness, poor feeding, irritability, and encephalopathy. Neurodevelopmental morbidities associated with NH include cognitive and motor delays, cerebral palsy, vision and hearing impairment, and poor school performance. This article offers a timely discussion of the state of the science of NH and recommendations for neonatal providers focused on early identification and disease prevention., (© Copyright 2024 Springer Publishing Company, LLC.)

Rationale: Non-islet cell tumor hypoglycemia (NICTH) is a paraneoplastic syndrome caused by tumors other than insulinoma that is primarily due to excessive production of insulin-like growth factor-II (IGF-II). The prevalence of NICTH is likely underestimated because of a lack of clinical recognition., Patient Concerns: A 41-year-old male with massive malignant liver tumors presented with recurrent severe hypoglycemia, weight loss, and liver cirrhosis., Diagnosis: NICTH related to IGF-II produced by hepatocellular carcinoma was diagnosed based on clinical symptoms, biochemical tests, and elevated IGF-II/IGF-I ratio., Intervention: Initial treatment with intravenous glucose and parenteral nutrition showed limited efficacy. Glucocorticoids and recombinant human growth hormone led to progressive improvement in blood glucose levels., Outcome: Due to extensive tumor burden and liver failure, surgical resection was not feasible, and the patient ultimately succumbed to refractory hypoglycemia and passed away in two weeks., Lessons: Early recognition and diagnosis of NICTH are crucial in patients with recurrent hypoglycemia and large tumors. Surgical resection is the preferred treatment option, but supportive care and pharmacological interventions, such as glucocorticoids and growth hormone, can help manage refractory hypoglycemia. Further research is needed to explore novel treatment options, including anti-IGF-I and -IGF-II neutralizing antibodies., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Pyruvate dehydrogenase complex (PDHC) deficiency is a common genetic disorder leading to lactic acidosis, which can also result from several nongenetic conditions, such as septic shock. The present study reports a case of PDHC deficiency masked by septic shock-induced lactic acidosis. This case involved a 16-year-old adolescent with poor exercise tolerance compared with his peers, and no underlying diseases. The disease onset was characterized by cough, fever, and dyspnea, with hypotension and elevated lactate levels, which indicated septic shock. However, severe hypoglycemia and lactic acidosis persisted despite resolution of a pulmonary infection and correction of septic shock, requiring continuous intravenous infusion of 50% glucose. Although the patient did not experience acute kidney injury and had normal urine output, continuous renal replacement therapy was used to regulate the internal environment owing to the severity of the acidosis. The diagnosis of PDHC deficiency was considered on the basis of the persistent hypoglycemia and hyperlactatemia, before genetic mutation testing was completed. The clinical thinking process required a rich accumulation of pathophysiological knowledge. This article reports a case of PDHC deficiency masked by septic shock-induced lactic acidosis to raise awareness of the disease and avoid misdiagnosis and missed diagnosis., Competing Interests: Declaration of conflicting interestThe authors declare that there are no conflicts of interest.

Background and Aims: Hypoglycemia may lead to anxiety, poor adherence, and hypoglycemia unawareness and is especially a threat during the night in patients with insulin-treated type 2 diabetes (T2D). It would therefore be beneficial to warn patients at risk of hypoglycemia at bedtime so they can react accordingly and avoid the episode. Hence, the aim of the present study was to develop a model for predicting nocturnal hypoglycemia., Methods: Continuous glucose monitoring (CGM), mealtime, and insulin data were collected from 67 insulin-treated patients with T2D (NCT01819129). Data were structured into 24-hour periods and labeled as nocturnal hypoglycemia or not depending on whether 15 consecutive minutes were spent below 3.0 mmol/L (54 mg/dL) during the following night. Each period was divided into "last night," "morning," "day," and "evening" for feature extraction purposes, and 72 potential features were extracted for every period. A five-fold cross-validation was used to select features by forward selection and for training and validating a model based on logistic regression., Results: The prediction model was based on 30 patients with 60/496 periods resulting in nocturnal hypoglycemia. Forward selection revealed that the best features were based on CGM and involved the last value and mean value during the evening, as well as the relative difference in maximum value during the day between the present period and previous periods. The model obtained a mean area under the receiver operating characteristics curve (AUC) of 0.82 with an accuracy of 0.79., Conclusions: The model was able to predict nocturnal hypoglycemia with an acceptable accuracy and could therefore prevent such cases., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Glycogen storage disease type 1 is a congenital abnormality of metabolism caused by the deficiency of the glucose-6-phosphatase enzyme, essential in glucose homeostasis. Patients with this disease are at high risk of developing hypoglycemia, hyperlipidemia, lactic acidemia, growth retardation, neutropenia, inflammatory bowel disease, and many other severe complications, such as hepatic adenomas converting into hepatocellular carcinomas. To prevent these complications, a liver transplant is the ultimate method of treatment. We present the successful anesthesia management for a 21-year-old man who had gross hepatomegaly, severe hypoglycemia, and hyperlactatemia and who received a liver transplant from his mother, which is a substantial challenge for anesthesiologists. Anesthesiologists should know the underlying pathophysiological condition and perform a comprehensive preoperative evaluation to determine the correct anesthesia plan in patients with glycogen storage disease type 1 who will undergo an orthotopic liver transplant due to multiple system disorders. Successful perioperative management of patients with glycogen storage disease type 1 relies on effective communication and collaboration between specialists through a multidisciplinary team approach.

Background: ALERTT1 showed that switching from intermittently scanned continuous glucose monitoring (isCGM) without alerts to real-time CGM (rtCGM) with alert functionality improved time in range (TIR; 70-180 mg/dL), glycated hemoglobin (HbA1c), time <54 mg/dL, and Hypoglycemia Fear Survey version II worry subscale (HFS-worry) score after six months in adults with type 1 diabetes (T1D). Moderator analyses aimed to identify certain subgroups that would benefit more from switching to rtCGM than others., Methods: Post hoc analyses of ALERTT1 evaluated the impact of 14 baseline characteristics on the difference (delta) in mean TIR, HbA1c, time <54 mg/dL, and HFS-worry score at six months between rtCGM and isCGM. Therefore, the delta was allowed to depend on each of these variables by including interactions in the moderator analysis model. Analyses were performed separately for each variable; variables with P < .10 in the univariable analysis were combined into a single model., Results: Univariable analyses showed no dependency of delta TIR, HbA1c, or time <54 mg/dL on variables other than CGM type. Only delta HFS-worry score depended on baseline HbA1c ( P = .0059), indicating less worries with rtCGM in people with baseline HbA1c <6.5% or ≥8%. Given P < .10 for dependency of delta TIR on insulin therapy type (favoring multiple daily injections), baseline HbA1c, and baseline TIR, these variables were combined into a multivariable analysis; interactions were not statistically significant., Conclusions: Except for HFS-worry score, no interactions between 14 baseline characteristics and the six-month intervention effect of rtCGM on TIR, HbA1c, or time <54 mg/dL were observed, supporting the conclusion of ALERTT1 that switching from isCGM without alerts to rtCGM with alert functionality is beneficial for a wide range of people with T1D., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: UZ Leuven received nonfinancial support for travel from Novo Nordisk, and Boehringer-Ingelheim for M.M.V. M.M.V. serves or has served on the speakers bureau for Dexcom—financial compensation for these activities has been received by KU Leuven. KU Leuven received nonfinancial support for travel from Medtronic, and financial support for travel from Roche for S.C. C.D.B. reports consulting fees and honoraria for speaking for Abbott, AstraZeneca, Boehringer-Ingelheim, A. Menarini Diagnostics, Eli Lilly, Medtronic, Novo Nordisk, and Roche. R.H. serves or has served on the advisory panel for Merck Sharp and Dohme, Boehringer-Ingelheim, and Eli Lilly. L.V.H. reports consulting fees and honoraria for speaking for Abbott, AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Medtronic, Merck Sharp and Dohme, Novo Nordisk, and Sanofi-Aventis. G.V. serves or has served on the advisory panel for Merck Sharp and Dohme, Boehringer-Ingelheim, and Eli Lilly. G.V. reports consulting fees and honoraria for speaking from Merck Sharp and Dohme, Boehringer-Ingelheim, AstraZeneca, Sanofi-Aventis, Novo Nordisk, and Eli Lilly. E.D. has served on the advisory panel for Novo Nordisk. E.D. reports speaking fees from Novo Nordisk, Boehringer-Ingelheim, Eli Lilly, and AstraZeneca. N.M. serves or has served on the advisory panel for Boehringer-Ingelheim. N.M. reports speaking fees from Merck Sharp and Dohme, Boehringer-Ingelheim, AstraZeneca, Sanofi-Aventis, Novo Nordisk, and Eli Lilly. C.V. reports consulting and speaking fees from Medtronic, Boehringer-Ingelheim, AstraZeneca, and Sanofi-Aventis. F.N. reports consulting fees and honoraria for speaking from Abbott, AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Johnson and Johnson, Medtronic, Merck Sharp and Dohme, Novo Nordisk, Roche, and Sanofi-Aventis. C.M. serves or has served on the advisory panel for Novo Nordisk, Sanofi-Aventis, Merck Sharp and Dohme, Eli Lilly, Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, Medtronic, ActoBio Therapeutics, Pfizer, and Zealand Pharma. Financial compensation for these activities has been received by KU Leuven; KU Leuven has received research support for C.M. from Medtronic, Novo Nordisk, Sanofi-Aventis, Merck Sharp and Dohme, Eli Lilly, Roche, Abbott, ActoBio Therapeutics, and Novartis; C.M. serves or has served on the speakers bureau for Novo Nordisk, Sanofi-Aventis, Merck Sharp and Dohme, Eli Lilly, Boehringer-Ingelheim, AstraZeneca, and Novartis. Financial compensation for these activities has been received by KU Leuven. P.G. serves or has served on the advisory panel for Novo Nordisk, Sanofi-Aventis, Boehringer-Ingelheim, Janssen Pharmaceuticals, Roche, Medtronic, and Bayer. Financial compensation for these activities has been received by KU Leuven. P.G. serves or has served on the speakers bureau for Merck Sharp and Dohme, Boehringer-Ingelheim, Bayer, Medtronic, Insulet, Novo Nordisk, Abbott, Roche, and Dexcom. Financial compensation for these activities has been received by KU Leuven. KU Leuven received nonfinancial support for travel from Sanofi-Aventis, A. Menarini Diagnostics, Medtronic, and Roche for P.G. All disclosures were unrelated to the present work. S.F., T.M., and B.K. have nothing to disclose.

Background: Sepsis is a life-threatening condition for which critically important antimicrobials are often indicated. The value of blood culture for sepsis is indisputable, but appropriate guidelines on sampling and interpretation are currently lacking in cattle., Objective: Compare the diagnostic accuracy of 2 blood culture media (pediatric plus [PP] and plus aerobic [PA]) and hypoglycemia for bacteremia detection. Estimate the contamination risk of blood cultures in critically ill calves., Animals: One hundred twenty-six critically ill calves, 0 to 114 days., Methods: Retrospective cross-sectional study in which the performance of PP, PA and hypoglycemia to diagnose sepsis was assessed using a Bayesian latent class model. A Cox proportional hazards model was used to compare time to positivity (TTP). Potential contamination was descriptively analyzed. Isolates were considered relevant when they were; member of the Enterobacterales, isolated from both blood cultures vials, or well-known, significant bovine pathogens., Results: The sensitivities for PP, PA, and hypoglycemia were higher when excluding assumed contaminants; 68.7% (95% credibility interval = 30.5%-93.7%), 87.5% (47.0%-99.5%), and 61.3% (49.7%-72.4%), respectively. Specificity was estimated at 95.1% (82.2%-99.7%), 94.2% (80.7%-99.7%), and 72.4% (64.6%-79.6%), respectively. Out of 121 interpretable samples, 14.9% grew a presumed contaminant in PA, PP, or both. There was no significant difference in the TTP between PA and PP., Conclusions and Clinical Importance: PA and PP appear to outperform hypoglycemia as diagnostic tests for sepsis. PA seems most sensitive, but a larger sample size is required to verify this. Accuracy increased greatly after excluding assumed contaminants. The type of culture did not influence TTP or the contamination rate., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

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

Hypoglycaemic syndromes are rare in apparently healthy individuals and their diagnosis can be a difficult challenge for clinicians as there are no shared guidelines that suggest how to approach patients with a suspect hypoglycaemic disorder. Since hypoglycaemia symptoms are common and nonspecific, it's necessary to document the Whipple Triad (signs and/or symptoms compatible with hypoglycaemia; relief of symptoms following glucose administration; low plasma glucose levels) before starting any procedure. Once the triad is documented, a meticulous anamnesis and laboratory tests (blood glucose, insulin, proinsulin, C-peptide, β-hydroxybutyrate and anti-insulin antibodies) should be performed. Results can guide the physician towards further specific tests, concerning the suspected disease. In this review, we consider all current causes of hypoglycaemia, including rare diseases such as nesidioblastosis and Hirata's syndrome, describe appropriate tests for diagnosis and suggest strategies to differentiate hypoglycaemia aetiology., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Hypoglycemia is common in individuals with type 1 diabetes, especially during exercise. We investigated the accuracy of two different continuous glucose monitoring systems during exercise-related hypoglycemia in an experimental setting., Materials and Methods: Fifteen individuals with type 1 diabetes participated in two separate euglycemic-hypoglycemic clamp days (Clamp-exercise and Clamp-rest) including five phases: 1) baseline euglycemia, 2) plasma glucose (PG) decline ± exercise, 3) 15-minute hypoglycemia ± exercise, 4) 45-minute hypoglycemia, and 5) recovery euglycemia. Interstitial PG levels were measured every five minutes, using Dexcom G6 (DG6) and FreeStyle Libre 1 (FSL1). Yellow Springs Instruments 2900 was used as PG reference method, enabling mean absolute relative difference (MARD) assessment for each phase and Clarke error grid analysis for each day., Results: Exercise had a negative effect on FSL1 accuracy in phase 2 and 3 compared to rest (ΔMARD = +5.3 percentage points [(95% CI): 1.6, 9.1] and +13.5 percentage points [6.4, 20.5], respectively). In contrast, exercise had a positive effect on DG6 accuracy during phase 2 and 4 compared to rest (ΔMARD = -6.2 percentage points [-11.2, -1.2] and -8.4 percentage points [-12.4, -4.3], respectively). Clarke error grid analysis showed a decrease in clinically acceptable treatment decisions during Clamp-exercise for FSL1 while a contrary increase was observed for DG6., Conclusion: Physical exercise had clinically relevant impact on the accuracy of the investigated continuous glucose monitoring systems and their ability to accurately detect hypoglycemia., Competing Interests: SE is currently employed by Novo Nordisk and holds stock in Novo Nordisk. UP-b has served on advisory boards for and/or received lecture fees from Novo Nordisk and Sanofi. FK has served on advisory panels at, been part of speaker’s bureaus for, served as a consultant to, and/or received research support from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gubra, MSD/Merck, Novo Nordisk, Sanofi, ShouTi, Zealand Pharma and Zucara. TV has served on scientific advisory panels at, been part of speaker’s bureaus for, served as a consultant to, and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gilead, GSK, Mundipharma, MSD/Merck, Novo Nordisk, Sanofi, and Sun Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Maytham, Hagelqvist, Engberg, Forman, Pedersen-Bjergaard, Knop, Vilsbøll and Andersen.)

Objective: To determine the diagnostic yield of the critical sample and fast-tests as dynamic function tests for the work-up of hypoglycemia in children., Methods: A retrospective record review of children (0-18 years) with a diagnosis of hypoglycemia (glucose ≤ 50 mg/dL) was performed. A comparison of results of critical sample (obtained during an episode of hypoglycemia) and fast-test (performed to induce hypoglycemia in fasting state) was done., Results: In 317 patients with hypoglycemia, data of 89 critical samples and 52 fast-tests were taken. Only 7 (7.8%) patients who underwent critical sample testing received an endocrine or metabolic diagnosis. No confirmatory diagnoses were made using the fast-tests. Idiopathic ketotic hypoglycemia was detected in 33/89 (37.1%) of critical samples and 21/52 (40.4%) of fast-tests. The completeness of workup including the hormonal and metabolic profile was <80% in both tests., Conclusion: The confirmatory yield of critical sample was better than fast-test. The processing of metabolic analytes was incomplete in a few, suggesting the need to rationalize the dynamic function testing.

Introduction: Recent publications relate the presence of hypoglycemia in venlafaxine (VLX) poisoning depending on the dose. Our aim was to analyze the clinical characteristics of patients who presented hypoglycemia induced by VLF overdose., Patients and Methods: Retrospective study carried out in the Balearic Islands (2020-2023)., Inclusion Criteria: serum concentrations of VLX + O-desmethyl-venlafaxine (O-VLX)>800 ng/mL. The characteristics of patients with and without hypoglycemia were compared., Results: Twenty-one patients were included, 8 (38.1%) with hypoglycemia. No differences were found in the doses referred to in both groups. Peak concentrations of VLX + O-VLX (ng/mL) were 9,783 [4,459-17,976] in patients with hypoglycemia and 1,413 [930-1,719] in patients without hypoglycemia (p<0.0001). The presence of hypoglycemia was associated with: lower age and level of consciousness; and higher frequency of suicide attempts, seizures, mydriasis, tachycardia and serotonin syndrome, invasive respiratory support, fluid therapy and ICU admission (p<0.05)., Conclusions: The detection of hypoglycemia in a VLX overdose case is a readily available marker to suspect the severity of the patient. In any case, serum concentrations when available allow us to confirm intoxication., (Copyright © 2023. Published by Elsevier España, S.L.U.)

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

Patients 80 years or older with HbA1c <7.0% (53 mmol/mol) treated with multiple daily insulin injections had low rates of rapid-acting insulin deprescription and initiation of diabetes medications with lower risk of hypoglycemia. Further investigation is needed to elucidate factors contributing to potentially inappropriately aggressive treatment of these patients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Aim: To evaluate the efficacy of the application of intraoperative segmental pancreatic occlusion and insulin assay in surgical procedures for pancreatic hypoglycemia., Methods: We retrospectively analyzed the clinical data of 11 pancreatic hypoglycemia cases treated in the China-Japan Friendship Hospital between September 2015 and August 2021. Intraoperative segmental pancreatic occlusion and insulin assay were used to enhance hypersecretory pancreatic tissues' localization and to achieve a complete resection. Intraoperative testing of insulin levels (peripheral venous blood) was carried out at several time points starting from before the resection of hypersecretory tissues (base value) and at 1 minute, 5 minutes, 15 minutes, 30 minutes, and 60 minutes after resection. Additional testing every 30 minutes until the end of the operation was carried out when necessary., Results: A total of 11 pancreatic hypoglycemia cases were included; 9 cases were insulinomas (all with single pancreatic lesions, with 4 located in the head, 1 in the body, and 4 in the tail), 1 MEN-1, and 1 nesidioblastosis. The insulin assay (30 minutes after the resection of hypersecretory tissues) enhanced the ability to locate target tissues and the accuracy of complete resection to 100%. As for intraoperative blood glucose monitoring, the accuracy 30 minutes after resection was as low as 36.6%. Postoperative levels of insulin and glucose were normal in all patients, with no recurrence of hypoglycemic symptoms during postoperative follow-up visits (9 to 72 months)., Conclusion: Intraoperative segmental pancreatic occlusion and insulin assay in pancreatic hypoglycemia is a simple, accurate, and fast approach that enhances the localization and complete resection of hypersecretory tissues. Such a combination is highly significant in challenging cases of hypoglycemia., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim: The transition to the ICD-10-CM coding system has reduced the utility of hypoglycaemia algorithms based on ICD-9-CM diagnosis codes in real-world studies of antidiabetic drugs. We mapped a validated ICD-9-CM hypoglycaemia algorithm to ICD-10-CM codes to create an ICD-10-CM hypoglycaemia algorithm and assessed its performance in identifying severe hypoglycaemia., Materials and Methods: We assembled a cohort of Medicare patients with DM and linked electronic health record (EHR) data to the University of North Carolina Health System and identified candidate severe hypoglycaemia events from their Medicare claims using the ICD-10-CM hypoglycaemia algorithm. We confirmed severe hypoglycaemia by EHR review and computed a positive predictive value (PPV) of the algorithm to assess its performance. We refined the algorithm by removing poor performing codes (PPV ≤0.5) and computed a Cohen's κ statistic to evaluate the agreement of the EHR reviews., Results: The algorithm identified 642 candidate severe hypoglycaemia events, and we confirmed 455 as true severe hypoglycaemia events, PPV of 0.709 (95% confidence interval: 0.672, 0.744). When we refined the algorithm, the PPV increased to 0.893 (0.862, 0.918) and missed <2.42% (<11) true severe hypoglycaemia events. Agreement between reviewers was high, κ  = 0.93 (0.89, 0.97)., Conclusions: We translated an ICD-9-CM hypoglycaemia algorithm to an ICD-10-CM version and found its performance was modest. The performance of the algorithm improved by removing poor performing codes at the trade-off of missing very few severe hypoglycaemia events. The algorithm has the potential to be used to identify severe hypoglycaemia in real-world studies of antidiabetic drugs., (© 2024 John Wiley & Sons Ltd.)

Introduction: Introduction and objective: neonatal hypoglycemia persistently offers multiple diagnostic controversies. This study aims to present the current situation regarding neonatal hypoglycaemia detection, and to gain insiht into the most widely used portable glucometers in neonatal units today. Methods: an online questionnaire was prepared and sent to the members of the Spanish Society of Neonatology; a total of 75 hospitals participated. Results: portable glucometers continue to be widely used in the neonatal population. More than 75 % of units perform neonatal hypoglycemia screening in specific clinical circumstances, and 13 % of units continue to perform protocolized screening on all newborns at neonatal units. The higher the level of care, the higher the percentage of hypoglycaemia detection by other tests (such as blood gas analysis): chi2, p = 0.019. Multiple models of portable glucometers are currently used, with differences according to level of care (chi2, p = 0.01). Nova Biomedical, Abbott, and Roche Diagnostics models are most commonly used. Conclusions: differences in the performance of neonatal hypoglycaemia screening are observed, so standardised procedures and limiting the neonatal population at risk are important to reduce variability in clinical practice, and to improve the quality of neonatal care. [ABSTRACT FROM AUTHOR]

Hypoglycaemia in term infants is very common. Deciding on appropriate investigations and management is often challenging. The aims of this article are to help with understanding when, how and why to investigate symptoms of hypoglycaemia in full-term infants (born ≥37 weeks' gestational age)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Insulinomas are hormone-producing pancreatic neuroendocrine neoplasms with an estimated incidence of 1 to 4 cases per million per year. Extrapancreatic insulinomas are extremely rare. Most insulinomas present with the Whipple triad: (1) symptoms, signs, or both consistent with hypoglycemia; (2) a low plasma glucose measured at the time of the symptoms and signs; and (3) relief of symptoms and signs when the glucose is raised to normal. Nonmetastatic insulinomas are nowadays referred to as "indolent" and metastatic insulinomas as "aggressive." The 5-year survival of patients with an indolent insulinoma has been reported to be 94% to 100%; for patients with an aggressive insulinoma, this amounts to 24% to 67%. Five percent to 10% of insulinomas are associated with the multiple endocrine neoplasia type 1 syndrome. Localization of the insulinoma and exclusion or confirmation of metastatic disease by computed tomography is followed by endoscopic ultrasound or magnetic resonance imaging for indolent, localized insulinomas. Glucagon-like peptide 1 receptor positron emission tomography/computed tomography or positron emission tomography/magnetic resonance imaging is a highly sensitive localization technique for seemingly occult, indolent, localized insulinomas. Supportive measures and somatostatin receptor ligands can be used for to control hypoglycemia. For single solitary insulinomas, curative surgical excision remains the treatment of choice. In aggressive malignant cases, debulking procedures, somatostatin receptor ligands, peptide receptor radionuclide therapy, everolimus, sunitinib, and cytotoxic chemotherapy can be valuable options., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

A patient without a diagnosis of diabetes mellitus presented to the hospital due to a fall and hypoglycaemia on admission. The patient was found to have recurrent nocturnal fasting hypoglycaemia. CT revealed a large lung mass consistent with a solitary pleural fibroma, a rare tumour associated with insulin-like growth factor 2 (IGF-2) production. This case is an important reminder that potential causes of hypoglycaemia should be considered in non-diabetic patients., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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

Continuous Glucose Monitoring Data: HOW CAN THEY BE COLLECTED AND USED IN PRACTICE? Continuous glucose monitoring (CGM) is becoming an essential part of diabetes management. The AGP report is obtained over a 14-day period, with at least 70% of captured data. The time spent in the 70-180 mg/dl targel range, withe a target of over 70% or 50% in frail patients, is a new parameter that is essential for assessing glycemic control via CGM. Complemented by estimated HBA1c, now called GMI (Glucose Management Indicator), the time spent in hypoglycemia (target inférieur 5% or even inférieur 1% for frail patients) and the coefficient of variation (target inférieur 36%), the CGM offers a very comprehensive analysis of blood glucose levels, with individualized treatment adjustments based on ambulatory blood glucose profiles., Competing Interests: L'auteur déclare avoir reçu des honoraires pour des interventions ponctuelles (essais cliniques, travaux scientifiques, activité de conseil, conférence ou colloque) de la part des entreprises Abbott, Amgen, AstraZeneca, Beohringer Ingelheim, Dexcom, Isis, Medtronic, Novo Nordisk, Sanofi, Eli Lilly.

Neonatal hypoglycemia is a major source of concern for pediatricians since it has commonly been related to poor neurodevelopmental outcomes. Diagnosis is challenging, considering the different operational thresholds provided by each guideline. Screening of infants at risk plays a crucial role, considering that most hypoglycemic infants show no clinical signs. New opportunities for prevention and treatment are provided by the use of oral dextrose gel. Continuous glucose monitoring systems could be a feasible tool in the next future. Furthermore, there is still limited evidence to underpin the current clinical practice of administering, in case of hypoglycemia, an intravenous "mini-bolus" of 10% dextrose before starting a continuous dextrose infusion. This brief review provides an overview of the latest advances in this field and neurodevelopmental outcomes according to different approaches.   Conclusion: To adequately define if a more permissive approach is risk-free for neurodevelopmental outcomes, more research on continuous glucose monitoring and long-term follow-up is still needed. What is Known: • Neonatal hypoglycemia (NH) is a well-known cause of brain injury that could be prevented to avoid neurodevelopmental impairment. • Diagnosis is challenging, considering the different suggested operational thresholds for NH (<36, <40, <45, <47 or <50 mg/dl). What is New: • A 36 mg/dl threshold seems to be not associated with a worse psychomotor development at 18 months of life when compared to the "traditional" threshold (47 mg/dl). • Further studies on long-term neurodevelopmental outcomes are required before suggesting a more permissive management of NH., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: To investigate differences in maternal and foetal outcomes in pregnancy, where patients developed hypoglycaemia following the 2-hour 75g oral glucose tolerance test (OGTT)., Method: A retrospective cohort study of 200 pregnancies attending the Antenatal Clinic at Tameside General Hospital between 2018 and 2022. Outcomes were compared between 4 groups: normal OGTT [G1; (n = 39, 20%), diagnosis of gestational diabetes mellitus (GDM) based on OGTT [G2; BG ≥ 5.6 mmol/L or 2-h OGTT ≥7.8 (n = 41, 21%)], hypoglycaemia [G3; 2 h OGTT 3.0-3.9 mmol/L (n = 93, 47%)], or clinically significant hypoglycaemia [G4; 2 h OGTT <3.0 mmol/L (n = 27, 14%)]. Maternal BMI, foetal birth weight (FBW), neonatal complications, neo-natal intensive care unit (NICU) stay and conversion to GDM were assessed., Results: Maternal BMI was lower in G3 and G4 (27.3 kg/m 2 and 28.1 kg/m 2 respectively) compared to G1 (30.4 kg/m 2 ) (p = 0.02). NICU stay was more frequent in G3 (12%, n = 11) and G4 (8%, n = 2) compared to G1 (5%, n = 2). Foetal complications occurred in 27% of G3 (n = 25) and 33% of G4 (n = 9) compared to 23% in G1 (n = 9) and 17% in G2 (n = 7). FBW was similar in G1 when compared to G3 and G4 (p = 0.34). Of the 120 patients in G3 and G4, 25 patients self-monitored blood glucose for two weeks; 28% (n = 7) subsequently developed GDM., Conclusion: Higher rates of NICU stay and foetal complications were seen in both hypoglycaemic groups. In patients with hypoglycaemia following OGTT there is evidence to support self-monitoring blood glucose as 28% were later diagnosed with GDM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Background: The insulin ordering process is an opportunity to provide clinicians with hypoglycemia risk predictions, but few hypoglycemia models centered around the insulin ordering process exist., Methods: We used data on adult patients, admitted in 2019 to non-ICU floors of a large teaching hospital, who had orders for subcutaneous insulin. Our outcome was hypoglycemia, defined as a blood glucose (BG) <70 mg/dL within 24 hours after ordering insulin. We trained and evaluated models to predict hypoglycemia at the time of placing an insulin order, using logistic regression, random forest, and extreme gradient boosting (XGBoost). We compared performance using area under the receiver operating characteristic curve (AUCs) and precision-recall curves. We determined recall at our goal precision of 0.30., Results: Of 21 052 included insulin orders, 1839 (9%) were followed by a hypoglycemic event within 24 hours. Logistic regression, random forest, and XGBoost models had AUCs of 0.81, 0.80, and 0.79, and recall of 0.44, 0.49, and 0.32, respectively. The most significant predictor was the lowest BG value in the 24 hours preceding the order. Predictors related to the insulin order being placed at the time of the prediction were useful to the model but less important than the patient's history of BG values over time., Conclusions: Hypoglycemia within the next 24 hours can be predicted at the time an insulin order is placed, providing an opportunity to integrate decision support into the medication ordering process to make insulin therapy safer., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Diabetic nephropathy is currently the leading cause of end-stage kidney disease. The present methods of assessing diabetes control, such as glycated hemoglobin or self-monitoring of blood glucose, have limitations. Over the past decade, the field of continuous glucose monitoring has been greatly improved and expanded. This review examines the use of continuous glucose monitoring in people with end-stage kidney disease treated with hemodialysis (HD), peritoneal dialysis (PD), or kidney transplantation. We assessed the use of both real-time continuous glucose monitoring and flash glucose monitoring technology in terms of hypoglycemia detection, glycemic variability, and efficacy, defined as an improvement in clinical outcomes and diabetes control. Overall, the use of continuous glucose monitoring in individuals with end-stage kidney disease may improve glycemic control and detection of hypoglycemia. However, most of the published studies were observational with no control group. Moreover, not all studies used the same assessment parameters. There are very few studies involving subjects on peritoneal dialysis. The small number of studies with limited numbers of participants, short follow-up period, and small number of manufacturers of continuous glucose monitoring systems are limitations of the review. More studies need to be performed to obtain more reliable results., (© 2023. The Author(s).)

Background: Monitoring glucose excursions is important in diabetes management. This can be achieved using continuous glucose monitors (CGMs). However, CGMs are expensive and invasive. Thus, alternative low-cost noninvasive wearable sensors capable of predicting glycemic excursions could be a game changer to manage diabetes., Methods: In this article, we explore two noninvasive sensor modalities, electrocardiograms (ECGs) and accelerometers, collected on five healthy participants over two weeks, to predict both hypoglycemic and hyperglycemic excursions. We extract 29 features encompassing heart rate variability features from the ECG, and time- and frequency-domain features from the accelerometer. We evaluated two machine learning approaches to predict glycemic excursions: a classification model and a regression model., Results: The best model for both hypoglycemia and hyperglycemia detection was the regression model based on ECG and accelerometer data, yielding 76% sensitivity and specificity for hypoglycemia and 79% sensitivity and specificity for hyperglycemia. This had an improvement of 5% in sensitivity and specificity for both hypoglycemia and hyperglycemia when compared with using ECG data alone., Conclusions: Electrocardiogram is a promising alternative not only to detect hypoglycemia but also to predict hyperglycemia. Supplementing ECG data with contextual information from accelerometer data can improve glucose prediction., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: D.J.D. serves as an independent consultant for Dexcom separate from the present work. The remaining authors have no potential conflict of interests relevant to this article.

Introduction: Severe hypoglycemia (SH) in older adults (OAs) with type 1 diabetes is associated with profound morbidity and mortality, yet its etiology can be complex and multifactorial. Enhanced tools to identify OAs who are at high risk for SH are needed. This study used machine learning to identify characteristics that distinguish those with and without recent SH, selecting from a range of demographic and clinical, behavioral and lifestyle, and neurocognitive characteristics, along with continuous glucose monitoring (CGM) measures., Research Design and Methods: Data from a case-control study involving OAs recruited from the T1D Exchange Clinical Network were analyzed. The random forest machine learning algorithm was used to elucidate the characteristics associated with case versus control status and their relative importance. Models with successively rich characteristic sets were examined to systematically incorporate each domain of possible risk characteristics., Results: Data from 191 OAs with type 1 diabetes (47.1% female, 92.1% non-Hispanic white) were analyzed. Across models, hypoglycemia unawareness was the top characteristic associated with SH history. For the model with the richest input data, the most important characteristics, in descending order, were hypoglycemia unawareness, hypoglycemia fear, coefficient of variation from CGM, % time blood glucose below 70 mg/dL, and trail making test B score., Conclusions: Machine learning may augment risk stratification for OAs by identifying key characteristics associated with SH. Prospective studies are needed to identify the predictive performance of these risk characteristics., Competing Interests: Competing interests: RW participated in multicenter clinical trials through her institution, sponsored by Insulet, Medtronic, Eli Lilly, Novo Nordisk, and Boehringer Ingelheim, and has used donated DexCom CGMs and Tandem insulin pumps in projects sponsored by the NIH and the Leona M and Harry B Helmsley Charitable Trust., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hypoglycaemia has been shown to induce a systemic pro-inflammatory response, which may be driven, in part, by the adrenaline response. Prior exposure to hypoglycaemia attenuates counterregulatory hormone responses to subsequent hypoglycaemia, but whether this effect can be extrapolated to the pro-inflammatory response is unclear. Therefore, we investigated the effect of antecedent hypoglycaemia on inflammatory responses to subsequent hypoglycaemia in humans., Methods: Healthy participants (n = 32) were recruited and randomised to two 2-h episodes of either hypoglycaemia or normoglycaemia on day 1, followed by a hyperinsulinaemic hypoglycaemic (2.8 ± 0.1 mmol/L) glucose clamp on day 2. During normoglycaemia and hypoglycaemia, and after 24 h, 72 h and 1 week, blood was drawn to determine circulating immune cell composition, phenotype and function, and 93 circulating inflammatory proteins including hs-CRP., Results: In the group undergoing antecedent hypoglycaemia, the adrenaline response to next-day hypoglycaemia was lower compared to the control group (1.45 ± 1.24 vs 2.68 ± 1.41 nmol/l). In both groups, day 2 hypoglycaemia increased absolute numbers of circulating immune cells, of which lymphocytes and monocytes remained elevated for the whole week. Also, the proportion of pro-inflammatory CD16 + -monocytes increased during hypoglycaemia. After ex vivo stimulation, monocytes released more TNF-α and IL-1β, and less IL-10 in response to hypoglycaemia, whereas levels of 19 circulating inflammatory proteins, including hs-CRP, increased for up to 1 week after the hypoglycaemic event. Most of the inflammatory responses were similar in the two groups, except the persistent pro-inflammatory protein changes were partly blunted in the group exposed to antecedent hypoglycaemia. We did not find a correlation between the adrenaline response and the inflammatory responses during hypoglycaemia., Conclusion: Hypoglycaemia induces an acute and persistent pro-inflammatory response at multiple levels that occurs largely, but not completely, independent of prior exposure to hypoglycaemia. Clinical Trial information Clinicaltrials.gov no. NCT03976271 (registered 5 June 2019)., (© 2024. The Author(s).)

Hypoglycemia is a common clinical finding, especially in the inpatient setting. However, laboratory testing may show falsely low blood glucose levels. It is crucial for clinicians to recognize the existence of pseudohypo- glycemia and know when and how to test for it.