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Aims: To capture the types and content of healthcare encounters following severe hypoglycemia requiring emergency medical services (EMS) and to correlate their features with subsequent risk of severe hypoglycemia., Methods: A retrospective cohort was obtained by linking data from a multi-state health system and an advanced life support ambulance service. This identified 1977 EMS calls by 1028 adults with diabetes experiencing hypoglycemia between 1/1/2013-12/31/2019. We evaluated the healthcare engagement over the following 7 days to identify rates of discussion of hypoglycemia, change of diabetes medications, glucagon prescribing, and referral for diabetes., Results: Rates of hypoglycemia discussion increased with escalating levels of care, from 11.5 % after EMS calls without emergency department (ED) transport or outpatient clinical encounters to 98 % among hospitalized patients with outpatient follow-up. EMS transport and outpatient follow-up were associated with significantly higher odds of discussion of hypoglycemia (OR 60 and OR 22.1, respectively). Interventions were not impacted by previous severe hypoglycemia within 30 days. Prescription of glucagon was rare among all patients., Conclusions: Interventions to prevent recurrent hypoglycemia increase with escalating levels of care but remain inadequate and inconsistent with clinical guidelines. Greater attention is needed to ensure timely diabetes-related follow-up and treatment modification for patients experiencing severe hypoglycemia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hypoglycemia in critical care is a well-documented phenomenon, linking both physiological and clinical evidence to harmful outcomes and an increased risk of mortality. Its implications span medical and non-medical consequences, such as cardiovascular and cerebrovascular complications, and escalated health care expenses and hospitalization duration. Mitigation measures for modifiable risk factors and education for both patients and health care providers on hypoglycemia can effectively prevent the onset of inpatient hypoglycemia. This concise clinical review offers a brief overview of hypoglycemia in critically ill patients, encompassing its pathophysiology, etiology, diagnosis, management, and prevention., Competing Interests: The authors have no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: To assess the cost-effectiveness of HARPdoc (Hypoglycaemia Awareness Restoration Programme for adults with type 1 diabetes and problematic hypoglycaemia despite optimised care), focussed upon cognitions and motivation, versus BGAT (Blood Glucose Awareness Training), focussed on behaviours and education, as adjunctive treatments for treatment-resistant problematic hypoglycaemia in type 1 diabetes, in a randomised controlled trial., Methods: Eligible adults were randomised to either intervention. Quality of life (QoL, measured using EQ-5D-5L); cost of utilisation of health services (using the adult services utilization schedule, AD-SUS) and of programme implementation and curriculum delivery were measured. A cost-utility analysis was undertaken using quality-adjusted life years (QALYs) as a measure of trial participant outcome and cost-effectiveness was evaluated with reference to the incremental net benefit (INB) of HARPdoc compared to BGAT., Results: Over 24 months mean total cost per participant was £194 lower for HARPdoc compared to BGAT (95% CI: -£2498 to £1942). HARPdoc was associated with a mean incremental gain of 0.067 QALYs/participant over 24 months post-randomisation: an equivalent gain of 24 days in full health. The mean INB of HARPdoc compared to BGAT over 24 months was positive: £1521/participant, indicating comparative cost-effectiveness, with an 85% probability of correctly inferring an INB > 0., Conclusions: Addressing health cognitions in people with treatment-resistant hypoglycaemia achieved cost-effectiveness compared to an alternative approach through improved QoL and reduced need for medical services, including hospital admissions. Compared to BGAT, HARPdoc offers a cost-effective adjunct to educational and technological solutions for problematic hypoglycaemia., (© 2024 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

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.)

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.)

Background and Objective: Severe hypoglycaemia (SH) imposes a significant burden for people with diabetes (PwD), their caregivers (CGs), and the healthcare system. The study aimed to identify barriers and solutions in the management of SH in PwD in Spain, gathering consensus from physicians and nurses., Material and Methods: Expert opinion from physicians and nurses who manage PwD was collected via a 2-round online Delphi method. Consensus was predefined as ≥ 70% of the panellists agreeing or disagreeing with the statement., Results: Physicians (n = 25) and nurses (n = 17) reached ≥ 90% consensus on the following barriers for the management of SH: absence of symptoms, cost to the health system, lack of implementation of glucose monitoring devices, lack of patient training to identify and manage SH, and the fear of SH in children and CGs. Main solutions, identified with ≥ 70% consensus, included training, education, and psychological support using diabetes nurse educators and the use of new glucose monitoring technologies and applications., Conclusions: This study provides valuable insights on the barriers and solutions in the management of SH in Spain. Structured self-management training, the support of diabetes educators, and the use of insulin delivery devices and glucose monitoring technologies is required for the management of SH., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Post-bariatric hypoglycaemia (PBH) is a metabolic complication of bariatric surgery (BS), consisting of low post-prandial glucose levels in patients having undergone bariatric procedures. While BS is currently the most effective and relatively safe treatment for obesity and its complications, the development of PBH can significantly impact patients' quality of life and mental health. The diagnosis of PBH is still challenging, considering the lack of definitive and reliable diagnostic tools, and the fact that this condition is frequently asymptomatic. However, PBH's prevalence is alarming, involving up to 88% of the post-bariatric population, depending on the diagnostic tool, and this may be underestimated. Given the prevalence of obesity soaring, and an increasing number of bariatric procedures being performed, it is crucial that physicians are skilled to diagnose PBH and promptly treat patients suffering from it. While the milestone of managing this condition is nutritional therapy, growing evidence suggests that old and new pharmacological approaches may be adopted as adjunct therapies for managing this complex condition., (© 2023 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Objective: Patients with severe hypoglycemia (SH) or diabetic ketoacidosis (DKA) experience high hospital readmission after being discharged. Cognitive impairment (CI) may further increase the risk, especially in those experiencing an interruption of medical care after discharge. This study examined the effect modification role of postdischarge care (PDC) on CI-associated readmission risk among U.S. adults with diabetes initially admitted for DKA or SH., Research Design and Methods: We used the Nationwide Readmissions Database (NRD) (2016-2018) to identify individuals hospitalized with a diagnosis of DKA or SH. Multivariate Cox regression was used to compare the all-cause readmission risk at 30 days between those with and without CI identified during the initial hospitalization. We assessed the CI-associated readmission risk in the patients with and without PDC, an effect modifier with the CI status., Results: We identified 23,775 SH patients (53.3% women, mean age 65.9 ± 15.3 years) and 140,490 DKA patients (45.8% women, mean age 40.3 ± 15.4 years), and 2,675 (11.2%) and 1,261 (0.9%), respectively, had a CI diagnosis during their index hospitalization. For SH and DKA patients discharged without PDC, CI was associated with a higher readmission risk of 23% (adjusted hazard ratio [aHR] 1.23, 95% confidence interval 1.08-1.40) and 35% (aHR 1.35, 95% confidence interval 1.08-1.70), respectively. However, when patients were discharged with PDC, we found PDC was an effect modifier to mitigate CI-associated readmission risk for both SH and DKA patients (P < 0.05 for all)., Conclusions: Our results suggest that PDC can potentially mitigate the excessive readmission risk associated with CI, emphasizing the importance of postdischarge continuity of care for medically complex patients with comorbid diabetes and CI., (© 2024 by the American Diabetes Association.)

We developed a machine learning (ML) model for the detection of patients with high risk of hypoglycaemic events during their hospital stay to improve the detection and management of hypoglycaemia. Our model was trained on data from a regional local health care district in Australia. The model was found to have good predictive performance in the general case (AUC 0.837). We conducted subgroup analysis to ensure that the model performed in a way that did not disadvantage population subgroups, in this case based on gender or indigenous status. We found that our specific problem domain assisted us in reducing unwanted bias within the model, because it did not rely on practice patterns or subjective judgements for the outcome measure. With careful analysis for equity there is great potential for ML models to automate the detection of high-risk cohorts and automate mitigation strategies to reduce preventable errors.

Aims: Among adults with insulin- and/or secretagogue-treated diabetes in the United States, very little is known about the real-world descriptive epidemiology of iatrogenic severe (level 3) hypoglycaemia. Addressing this gap, we collected primary, longitudinal data to quantify the absolute frequency of events as well as incidence rates and proportions., Materials and Methods: iNPHORM is a US-wide, 12-month ambidirectional panel survey (2020-2021). Adults with type 1 diabetes mellitus (T1DM) or insulin- and/or secretagogue-treated type 2 diabetes mellitus (T2DM) were recruited from a probability-based internet panel. Participants completing ≥1 follow-up questionnaire(s) were analysed., Results: Among 978 respondents [T1DM 17%; mean age 51 (SD 14.3) years; male: 49.6%], 63% of level 3 events were treated outside the health care system (e.g. by family/friend/colleague), and <5% required hospitalization. Following the 12-month prospective period, one-third of individuals reported ≥1 event(s) [T1DM 44.2% (95% CI 36.8%-51.8%); T2DM 30.8% (95% CI 28.7%-35.1%), p = .0404, α = 0.0007]; and the incidence rate was 5.01 (95% CI 4.15-6.05) events per person-year (EPPY) [T1DM 3.57 (95% CI 2.49-5.11) EPPY; T2DM 5.29 (95% CI 4.26-6.57) EPPY, p = .1352, α = 0.0007]. Level 3 hypoglycaemia requiring non-transport emergency medical services was more common in T2DM than T1DM (p < .0001, α = 0.0016). In total, >90% of events were experienced by <15% of participants., Conclusions: iNPHORM is one of the first long-term, prospective US-based investigations on level 3 hypoglycaemia epidemiology. Our results underscore the importance of participant-reported data to ascertain its burden. Events were alarmingly frequent, irrespective of diabetes type, and concentrated in a small subsample., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Hypoglycemia is commonly encountered in the emergency department. Patients can present with a myriad of symptoms and its presentation can mimic other more serious diagnoses. Despite the relative ease of its management, clinicians often miss the diagnosis or mismanage it even when discovered. Glucose is an important energy source for the brain and failing to recognize hypoglycemia or mismanaging it can lead to permanent neurologic disability or death. Although it is important to replenish glucose in a rapid fashion, it is equally important to discover and manage the underlying etiology to prevent further episodes of hypoglycemia., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Objective: Late preterm (LPT) and low birth weight (LBW) infants are populations at increased risk for NICU admission, partly due to feeding-related conditions. This study was aimed to increase the percentage of LPT and LBW infants receiving exclusive nursery care using quality improvement methodologies., Methods: A multidisciplinary team implemented interventions at a single academic center. Included infants were 35 to 36 weeks gestational age and term infants with birth weights <2500 g admitted from the delivery room to the nursery. Drivers of change included feeding protocol, knowledge, and care standardization. We used statistical process control charts to track data over time. The primary outcome was the percentage of infants receiving exclusive nursery care. Secondary outcomes included rates of hypoglycemia, phototherapy, and average weight loss. Balancing measures were exclusive breast milk feeding rates and length of stay., Results: Included infants totaled 1336. The percentage of LPT and LBW infants receiving exclusive nursery care increased from 83.9% to 88.8% with special cause variation starting 1 month into the postintervention period. Reduction in neonatal hypoglycemia, 51.7% to 45.1%, coincided. Among infants receiving exclusive nursery care, phototherapy, weight loss, exclusive breast milk feeding, and length of stay had no special cause variation., Conclusions: Interventions involving a nursery feeding protocol, knowledge, and standardization of care for LPT and LBW infants were associated with increased exclusive nursery care (4.9%) and reduced rates of neonatal hypoglycemia (6.6%) without adverse effects. This quality initiative allowed for the preservation of the mother-infant dyad using high-value care., (Copyright © 2023 by the American Academy of Pediatrics.)

Objectives: In infants with hypoxic-ischemic encephalopathy (HIE), conflicting information on the association between early glucose homeostasis and outcome exists. We characterized glycemic profiles in the first 12 hours after birth and their association with death and neurodevelopmental impairment (NDI) in neonates with moderate or severe HIE undergoing therapeutic hypothermia., Methods: This post hoc analysis of the High-dose Erythropoietin for Asphyxia and Encephalopathy trial included n = 491 neonates who had blood glucose (BG) values recorded within 12 hours of birth. Newborns were categorized based on their most extreme BG value. BG >200 mg/dL was defined as hyperglycemia, BG <50 mg/dL as hypoglycemia, and 50 to 200 mg/dL as euglycemia. Primary outcome was defined as death or any NDI at 22 to 36 months. We calculated odds ratios for death or NDI adjusted for factors influencing glycemic state (aOR)., Results: Euglycemia was more common in neonates with moderate compared with severe HIE (63.6% vs 36.6%; P < .001). Although hypoglycemia occurred at similar rates in severe and moderate HIE (21.4% vs 19.5%; P = .67), hyperglycemia was more common in severe HIE (42.3% vs 16.9%; P < .001). Compared with euglycemic neonates, both, hypo- and hyperglycemic neonates had an increased aOR (95% confidence interval) for death or NDI (2.62; 1.47-4.67 and 1.77; 1.03-3.03) compared to those with euglycemia. Hypoglycemic neonates had an increased aOR for both death (2.85; 1.09-7.43) and NDI (2.50; 1.09-7.43), whereas hyperglycemic neonates had increased aOR of 2.52 (1.10-5.77) for death, but not NDI., Conclusions: Glycemic profile differs between neonates with moderate and severe HIE, and initial glycemic state is associated death or NDI at 22 to 36 months., (Copyright © 2023 by the American Academy of Pediatrics.)

Introduction: While bariatric surgery remains the most effective treatment for obesity that allows substantial weight loss with improvement and possibly remission of obesity-associated comorbidities, some postoperative complications may occur. Managing physicians need to be familiar with the common problems to ensure timely and effective management. Of these complications, postoperative hypoglycemia is an increasingly recognized complication of bariatric surgery that remains underreported and underdiagnosed., Area Covered: This article highlights the importance of identifying hypoglycemia in patients with a history of bariatric surgery, reviews pathophysiology and addresses available nutritional, pharmacological and surgical management options. Systemic evaluation including careful history taking, confirmation of hypoglycemia and biochemical assessment is essential to establish accurate diagnosis. Understanding the weight-dependent and weight-independent mechanisms of improved postoperative glycemic control can provide better insight into the causes of the exaggerated responses that lead to postoperative hypoglycemia., Expert Opinion: Management of post-operative hypoglycemia can be challenging and requires a multidisciplinary approach. While dietary modification is the mainstay of treatment for most patients, some patients may benefit from pharmacotherapy (e.g. GLP-1 receptor antagonist); Surgery (e.g. reversal of gastric bypass) is reserved for unresponsive severe cases. Additional research is needed to understand the underlying pathophysiology with a primary aim in optimizing diagnostics and treatment options.

Hypoglycemia is due to defects in the metabolic systems involved in the transition from the fed to the fasting state or in the hormone control of these systems. In children, hypoglycemia is considered a metabolic-endocrine emergency, because it may lead to brain injury, permanent neurological sequelae and, in rare cases, death. Symptoms are nonspecific, particularly in infants and young children. Diagnosis is based on laboratory investigations during a hypoglycemic event, but it may also require biochemical tests between episodes, dynamic endocrine tests and molecular genetics. This narrative review presents the age-related definitions of hypoglycemia, its pathophysiology and main causes, and discusses the current diagnostic and modern therapeutic approaches.

Objectives: To assess in newborns with neonatal encephalopathy (NE), presumptively related to a peripartum hypoxic-ischemic event, the frequency of dysglycemia and its association with neonatal adverse outcomes., Study Design: We conducted a secondary analysis of LyTONEPAL (Long-Term Outcome of Neonatal hypoxic EncePhALopathy in the era of neuroprotective treatment with hypothermia), a population-based cohort study including 545 patients with moderate-to-severe NE. Newborns were categorized by the glycemia values assessed by routine clinical care during the first 3 days of life: normoglycemic (all glycemia measurements ranged from 2.2 to 8.3 mmol/L), hyperglycemic (at least 1 measurement >8.3 mmol/L), hypoglycemic (at least 1 measurement <2.2 mmol/L), or with glycemic lability (measurements included at least 1 episode of hypoglycemia and 1 episode of hyperglycemia). The primary adverse outcome was a composite outcome defined by death and/or brain lesions on magnetic resonance imaging, regardless of severity or location., Results: In total, 199 newborns were categorized as normoglycemic (36.5%), 74 hypoglycemic (13.6%), 213 hyperglycemic (39.1%), and 59 (10.8%) with glycemic lability, based on the 2593 glycemia measurements collected. The primary adverse outcome was observed in 77 (45.8%) normoglycemic newborns, 37 (59.7%) with hypoglycemia, 137 (67.5%) with hyperglycemia, and 40 (70.2%) with glycemic lability (P < .01). With the normoglycemic group as the reference, the aORs and 95% 95% CIs for the adverse outcome were significantly greater for the group with hyperglycemia (aOR 1.81; 95% CI 1.06-3.11)., Conclusions: Dysglycemia affects nearly two-thirds of newborns with NE and is independently associated with a greater risk of mortality and/or brain lesions on magnetic resonance imaging., Trial Registration: NCT02676063., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim: It is aimed to evaluate the knowledge of Pre-Hospital Emergency Health Services (PHEMS) staff about the treat and release criteria in hypoglycemia cases and their attitudes in the decision-making processes related to hospitalization., Materials and Methods: The sample of this descriptive cross-sectional study consisted of 714 paramedics working in PHEMS in Turkey. A survey developed in Microsoft Forms, which includes various features such as age, gender, years of professional experience, developed in line with the literature, and questions covering treat and release in hypoglycemia cases and absolute hospital transport criteria, was used in the collection of data. Participants who agreed to participate in the study answered the online survey., Findings: Of the 714 participants, 402 (56.30%) were female and 312 (43.70%) were male. 598 (83.75%) of the participants, who had a dilemma regarding the transfer of hypoglycemia cases that became stable after treatment to the hospital, decide to transfer the patient to the emergency room. 706 (98.88%) reported that the presence of another emergency that needs intervention in addition to hypoglycemia was decisive in the decision to transfer to the absolute hospital, and 586 (82.07%) reported that the patient's who did not return to his normal mental state after emergency medical intervention was decisive in the treatment and release decision., Conclusion: PHEMS employees have high knowledge and awareness related to treat and release criteria in hypoglycemia cases with which they have high experience. PHEMS employee, who has a dilemma related to making a treat and release decision, decides to transfer to the hospital with a high rate. PHEMS systems should define the treat and release protocols for hypoglycemia cases more clearly in order to use emergency services and health resources effectively., 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 Ltd. All rights reserved.)

Malaises are often attributed to hypoglycaemia in nondiabetic people who don't have any other serious medical problem. Reactive hypoglycaemia, the most frequent one, may be considered as a functional disorder. However, its diagnosis is often overused, because not really demonstrated in most instances. The diagnosis of hypoglycaemia should be structured, based upon the Whipple triad. First, the medical interrogatory must search for adrenergic and neuroglucopenic symptoms that suggest hypoglycaemia. Second, if the malaise is due to a hypoglycaemia, it should resume rapidly after the administration of sugar. Third, hypoglycaemia must be confirmed by a measurement of a low glucose level at the time of a malaise. The latter approach is facilitated by the use of home blood monitoring, a strategy that is now preferred to the use of an oral glucose tolerance test, a non-physiological test far from real-life conditions. When the diagnosis is made based upon this triad, the medical interview should precise the severity of the symptoms and focus on the chronology of the malaises, typically 2-3 hours after a sugar-enriched meal in case of a reactive hypoglycaemia. Therapeutic approach of this functional disorder mostly relies on dietary advices.

Type 1 glycogen storage disease (GSDI) is a rare autosomal recessive disorder caused by glucose-6-phosphatase (G6Pase) deficiency. We discuss a case of a 29-year-old gentleman who had GSDI with metabolic complications of hypoglycemia, hypertriglyceridemia, hyperuricemia, and short stature. He also suffered from advanced chronic kidney disease, nephrotic range proteinuria, and hepatic adenomas. He presented with acute pneumonia and refractory metabolic acidosis despite treatment with isotonic bicarbonate infusion, reversal of hypoglycemia, and lactic acidosis. He eventually required kidney replacement therapy. The case report highlights the multiple contributing mechanisms and challenges to managing refractory metabolic acidosis in a patient with GSDI. Important considerations for dialysis initiation, decision for long-term dialysis modality and kidney transplantation for patients with GSDI are also discussed in this case report.

Background: The fear of hypoglycemia in type 2 diabetes mellitus (T2DM) patients with hypoglycemia has seriously affected their quality of life. They are always afraid of hypoglycemia and often take excessive action to avoid it. Yet, researchers have investigated the relationship between hypoglycemia worries and excessive avoiding hypoglycemia behavior using total scores on self-report measures. However, network analysis studies of hypoglycemia worries and excessive avoiding hypoglycemia behavior in T2DM patients with hypoglycemia are lacking., Purpose: The present study investigated the network structure of hypoglycemia worries and avoiding hypoglycemia behavior in T2DM patients with hypoglycemia and aimed to identify bridge items to help them correctly treat hypoglycemia and properly deal with hypoglycemia fear., Methods: A total of 283 T2DM patients with hypoglycemia were enrolled in our study. Hypoglycemia worries and avoiding hypoglycemia behavior were evaluated with the Hypoglycemia Fear Scale. Network analyses were used for the statistical analysis., Results: B9 "Had to stay at home for fear of hypoglycemia" and W12 "I am worried that hypoglycemia will affect my judgment" have the highest expected influences in the present network. In the community of hypoglycemia worries, W17 "I worry about hypoglycemia during sleep" has the highest bridge expected influence. And in the community of avoiding hypoglycemia behavior, B9 "Had to stay at home for fear of hypoglycemia" has the highest bridge expected influence., Conclusion: Complex patterns of associations existed in the relationship between hypoglycemia worries and avoiding hypoglycemia behavior in T2DM patients with hypoglycemia. From the perspective of network analysis, B9 "Had to stay at home for fear of hypoglycemia" and W12 "I am worried that hypoglycemia will affect my judgment" have the highest expected influence, indicating their highest importance in the network. W17 "I worry about hypoglycemia during sleep" aspect of hypoglycemia worries and B9 "Had to stay at home for fear of hypoglycemia" aspect of avoiding hypoglycemia behavior have the highest bridge expected influence, indicating they have the strongest connections with each community. These results have important implications for clinical practice, which provided potential targets for interventions to reduce hypoglycemia fear and improve the quality of life in T2DM patients with hypoglycemia., (© 2023. The Author(s).)

Aim: To evaluate medical and surgical treatment of postbariatric hypoglycaemia (PBH) in daily practice., Materials and Methods: Retrospective data were extracted from medical records from four hospitals. PBH was defined by neuroglycopenic symptoms together with a documented glucose <3.0 mmol/L in the postprandial setting after previous bariatric surgery. Data were scored semiquantitatively on efficacy and side effects by two reviewers independently. Duration of efficacy and of use were calculated., Results: In total, 120 patients were included with a median follow-up of 27 months with a mean baseline age of 41 years, total weight loss of 33% and glucose nadir 2.3 mmol/L. Pharmacotherapy consisted of acarbose, diazoxide, short- and long-acting octreotide and glucagon-like peptide-1 receptor agonist analogues (liraglutide and semaglutide) with an overall efficacy in 45%-75% of patients. Combination therapy with two drugs was used by 30 (25%) patients. The addition of a second drug was successful in over half of the patients. Long-acting octreotide and the glucagon-like peptide-1 receptor agonist analogues scored best in terms of efficacy and side effects with a median duration of use of 35 months for octreotide. Finally, 23 (19%) patients were referred for surgical intervention. Efficacy of the surgical procedures, pouch banding, G-tube placement in remnant stomach and Roux-en-Y gastric bypass reversal, pooled together, was 79% with a median duration of initial effect of 13 months., Conclusions: In daily practice, pharmacotherapy for PBH was successful in half to three quarters of patients. Combination therapy was often of value. One in five patients finally needed a surgical procedure, with overall good results., (© 2022 John Wiley & Sons Ltd.)

Objectives: The objectives of this study were to describe the characteristics, management, and outcomes of patients treated by paramedics for hypoglycemia, and to determine the predictors of hospital admission for these patients within 72 hours of the initial hypoglycemia event., Methods: We performed a health record review of paramedic call reports and emergency department records over a 12-month period. We queried prehospital databases to identify cases, which included all patients ⩾18 years with prehospital glucose readings of <72 mg/dl (<4.0 mmol/L) and excluded terminally ill and cardiac arrest patients. We developed and piloted a standardized data collection tool and obtained consensus on all data definitions before initiation of data extraction by trained investigators. Data analyses included descriptive statistics univariate and logistic regression presented as adjusted odds ratios (aOR) with 95% confidence intervals (95%CI)., Results: There were 791 patients with the following characteristics: mean age 56.2, male 52.3%, type 1 diabetes 11.6%, on insulin 43.3%, median initial glucose 54.0 mg/dl (3.0 mmol/L), from home 56.4%. They were treated by advanced care paramedics 80.1%, received intravenous D50 37.8%, intramuscular glucagon 17.8%, oral complex carbs/protein 25.7%, and accepted transport to hospital 70.2%. Among those transported, 134 (24.3%) were initially admitted and four more were admitted within 72 hours. One patient was admitted, discharged, and admitted again within 72 hours. Patients without documented histories of diabetes (aOR 2.35, CI 1.13-4.86), with cardiovascular disease (aOR 1.81, CI 1.10-3.00), on corticosteroids (aOR 4.63, CI 2.15-9.96), on oral hypoglycemic agent(s) (aOR 1.92, CI 1.02-3.62), or those given glucagon (aOR 1.77, CI 1.07-2.93) on scene were more likely to be admitted to hospital, whereas patients on insulin (aOR 0.49, CI 0.27-0.91), able to tolerate complex oral carbs/protein (aOR 0.22, CI 0.10-0.48), with final GCS scores of 15 (aOR 0.53, CI 0.34-0.83), or from public locations (aOR 0.40, CI 0.21-0.75) were less likely to be admitted., Conclusions: There are several patient and prehospital management characteristics which, in combination, could be incorporated into a safe clinical decision tool for patients who present with hypoglycemia.

Transplants comprised of encapsulated islets have shown promise in treating insulin-dependent diabetes. A question raised in the scientific and clinical communities is whether the insulin released from an implanted encapsulation device damaged in an accident could cause a serious hypoglycemic event. In this commentary, we consider the different types of damage that a device can sustain, including the encapsulation membrane and the islets within, and the amount of insulin released in each case. We conclude that the probability that device damage would cause an adverse hypoglycemic event is indeed very low.

Introduction: Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) is the most common inherited metabolic disorder of β-oxidation. Patients with MCADD present with hypoketotic hypoglycemia, which may quickly progress to lethargy, coma, and death. Prognosis for MCADD patients is highly promising once a diagnosis has been established, though management strategies may vary depending on the severity of illness and the presence of comorbidities., Methods and Results: Given the rapid developments in the world of gene therapy and implementation of newborn screening for inherited metabolic disorders, the provision of concise and contemporary knowledge of MCADD is essential for clinicians to effectively manage patients. Thus, this review aims to consolidate current information for physicians on the pathogenesis, diagnostic tools, and treatment options for MCADD patients., Conclusion: MCADD is a commonly inherited metabolic disease with serious implications for health outcomes, particularly in children, that may be successfully managed with proper intervention., (© 2022 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Objectives: Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes. Our objective was to determine if children with severe DKA without alteration in mental status can be managed safely on a general children's medical unit., Methods: Single center retrospective study of 191 patient encounters among 168 children admitted to the children's medical unit (CMU) at Primary Children's Hospital between 2007 and 2017 with severe DKA (pH <7.1 and/or bicarbonate <5 mmol/L). Chart review identified complications including death, transfer to the intensive care unit (ICU), incidence of cerebral edema, and hypoglycemia. We compared patients requiring ICU transfer with those who did not with respect to demographics, laboratory findings at presentation, therapeutic interventions, length of stay, and cost., Results: Of 191 patient encounters, there were 0 deaths (0%, 95% CI 0-2.4%), 22 episodes of alteration of mental status concerning for developing cerebral edema (11.5%, 95% CI 7.7-16.9%), 19 ICU transfers (10%, 95% CI 6.4-15.1%), and 7 episodes of hypoglycemia (3.7%, 95% CI 1.6-7.5%). ICU transfer was associated lower initial pH (7.03 ± 0.06 vs. 7.07 ± 0.07, p<0.05), increased length of stay (3.0 ± 0.8 vs. 2.2 ± 0.9 days, p<0.05), and increased cost of hospitalization (mean ± SD $8,073 ± 2,042 vs. $5,217 ± 1,697, p<0.05)., Conclusions: The majority of children with severe DKA without alteration in mental status can be managed safely on a medical unit. Implementing a pH cutoff may identify high-risk patients that require ICU level of care., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

In the century since the discovery of insulin, diabetes has changed from an early death sentence to a manageable chronic disease. This change in longevity and duration of diabetes coupled with significant advances in therapeutic options for patients has fundamentally changed the landscape of diabetes management, particularly in patients with type 1 diabetes mellitus. However, hypoglycemia remains a major barrier to achieving optimal glycemic control. Current understanding of the mechanisms of hypoglycemia has expanded to include not only counter-regulatory hormonal responses but also direct changes in brain glucose, fuel sensing, and utilization, as well as changes in neural networks that modulate behavior, mood, and cognition. Different strategies to prevent and treat hypoglycemia have been developed, including educational strategies, new insulin formulations, delivery devices, novel technologies, and pharmacologic targets. This review article will discuss current literature contributing to our understanding of the myriad of factors that lead to the development of clinically meaningful hypoglycemia and review established and novel therapies for the prevention and treatment of hypoglycemia., (© 2022 New York Academy of Sciences.)

Postprandial hyperinsulinaemic hypoglycaemia is a common complication of bariatric surgery. Although in general its evolution is mild and self-limited, it can lead to neuroglycopaenia and compromise the patient's safety and quality of life. The aim of this document is to offer some recommendations to facilitate the clinical care of these complex patients, reviewing the aetiopathogenesis, its diagnosis and treatment that, sequentially, will include dietary and pharmacological measures and surgery in refractory cases. In the absence of high-quality studies, the diagnostic and therapeutic approach proposed is based on the consensus of experts of the Grupo de Obesidad de la Sociedad Española de Endocrinología y Nutrición [Obesity Group of the Spanish Society of Endocrinology and Nutrition], GOSEEN. Those undergoing bariatric surgery should be informed of the possibility of developing this complication., (Copyright © 2021 SEEN and SED. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Few studies have examined the association between hypoglycemic episodes among people with type 2 diabetes (T2DM) at the time of hospitalization for heart failure (HF) and cardiovascular outcomes., Methods: From March 2016 to June 2018, we conducted a retrospective cohort study to investigate hypoglycemia during HF hospitalization in the emergency department, three-point major adverse cardiovascular events (3P-MACE), and all-cause mortality; these were followed up through June 2021. HF hospitalization was defined according to American Heart Association criteria. Hypoglycemia was defined as a glucose level < 3.9 mmol/L at the time of HF hospitalization. We classified the enrolled patients into three groups (reference group, those without T2DM or hypoglycemia; those diagnosed with T2DM without hypoglycemia; and those with hypoglycemia and T2DM). We used Cox proportional hazard regression analysis to investigate the association between the three groups and the development of the first occurrence of 3P-MACE and all-cause mortality., Results: During a median of 25 months of follow-up, a total of 783 patients admitted due to HF were analyzed. In total, 159 (20.3%) cases of 3P-MACE were identified, and the mortality rate was 20.2% (n = 158). The median age of patients was 76.0 (65.0-82.0) years, and 49.0% were men. Patients with 3P-MACE had a lower body mass index (22.6 [20.4-25.1] vs. 23.8 [21.3-26.7]), higher frequency of previous history of HF (24.5% vs. 15.7%), T2DM (64.2% vs. 47.3%), higher rates of hypoglycemia at the time of HF hospitalization (19.5% vs. 7.7%), and lower eGFR levels (61.1 [36.0-80.7] mL/min/1.73 m 2 vs. 69.2 [45.8-89.5] mL/min/1.73 m 2 ) than those without 3P-MACE. The multivariable adjusted HR of 3P-MACE was as follows: group with hypoglycemia and T2DM: HR, 2.29; 95% CI: 1.04-5.06; group with T2DM without hypoglycemia: HR: 1.42; 95% CI: 0.86-2.33; and all-cause mortality group with hypoglycemia and T2DM: HR: 2.58; 95% CI: 1.26-5.31, group with T2DM without hypoglycemia: HR: 1.32; 95% CI: 0.81-2.16; compared to the reference group (group without T2DM or hypoglycemia)., Conclusions: T2DM and hypoglycemia are independent risk factors for 3P-MACE and all-cause mortality compared to those without hypoglycemia during HF hospitalization., (© 2022. The Author(s).)

Purpose of Review: Glycogen storage disease is a group of disorders primarily characterized by hepatomegaly and fasting hypoglycemia. This group of disorders may also affect the muscle, kidneys, and neurodevelopment. With an overall prevalence of 1 : 20 000, GSDs are disorders that clinicians should diagnose in a timely manner because adequate management can prevent complications, such as neurodevelopmental delay and liver disease [1] . As there are numerous types of GSDs, being able to distinguish one type from another can be overwhelming. In this review, we focus on hepatic GSDs to provide a concise review of clinical presentation, diagnosis, and current management., Recent Findings: GSDs are considered rare disorders, and one of the main challenges is the delay in diagnosis, misdiagnosis, or under diagnosis. However, with molecular genetic testing now readily available, confirming the diagnosis is no longer as difficult or invasive as it was in the past., Summary: Current therapy for this group of disorders requires maintaining stable glucose levels. Avoiding hypoglycemia, as well as hyperglycemia, is critical in managing these patients. Being able to distinguish the types of GSDs and understanding the specific treatments for each enzymatic defect will optimize patient care., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To examine factors associated with emergency department (ED) transport after hypoglycemia treated by emergency medical services (EMS) and assess the impact of ED transport on severe hypoglycemia recurrence., Research Design and Methods: We retrospectively analyzed electronic health records of a multistate advanced life support EMS provider and an integrated healthcare delivery system serving an overlapping geographic area in the upper Midwest. For adults with diabetes treated by EMS for hypoglycemia between 2013 and 2019, we examined rates of ED transport, factors associated with it, and its impact on rates of recurrent hypoglycemia requiring EMS, ED, or hospital care within 3, 7, and 30 days., Results: We identified 1,977 hypoglycemia-related EMS encounters among 1,028 adults with diabetes (mean age 63.5 years [SD 17.7], 55.2% male, 87.4% non-Hispanic White, 42.4% rural residents, and 25.6% with type 1 diabetes), of which 46.4% resulted in ED transport (31.1% of calls by patients with type 1 diabetes and 58.0% of calls by patients with type 2 diabetes). Odds of ED transport were lower in patients with type 1 diabetes (odds ratio [OR] 0.44 [95% CI 0.31-0.62] vs. type 2 diabetes) and higher in patients with prior ED visits (OR 1.38 [95% CI 1.03-1.85]). Within 3, 7, and 30 days, transported patients experienced recurrent severe hypoglycemia 2.8, 5.2, and 10.6% of the time, respectively, compared with 7.4, 11.2, and 22.8% of the time among nontransported patients (all P < 0.001). This corresponds to OR 0.58 (95% CI 0.42-0.80) for recurrent severe hypoglycemia within 30 days for transported versus nontransported patients. When subset by diabetes type, odds of recurrent severe hypoglycemia among transported patients were 0.64 (95% CI 0.43-0.96) and 0.42 (95% CI 0.24-0.75) in type 1 and type 2 diabetes, respectively., Conclusions: Transported patients experienced recurrent hypoglycemia requiring medical attention approximately half as often as nontransported patients, reinforcing the importance of engaging patients in follow-up to prevent recurrent events., (© 2022 by the American Diabetes Association.)

Aims: To collect and analyse representative data of structural and process quality in the management of diabetic emergencies in Germany in 2020., Methods: A standardised questionnaire comprising detailed items concerning clinically relevant parameters on the structural and process quality of out-of-hospital management of diabetic emergencies was sent nationwide to medical directors of emergency medical service districts (EMSDs). Results were compared with those from a similar study conducted in 2001., Results: The return rate of the questionnaires represented 126 EMSDs, serving a total population of > 40.1 million. Only 4% of ambulances carried glucagon (6% in 2001). In 2020, blood glucose determination increased significantly to 71% of all emergency interventions and to 29% of suspected cardiac emergencies (24% and 15%, respectively, in 2001). In 100% of EMSDs severe hypoglycaemia (SH) was treated by paramedics by administering intravenous dextrose before the arrival of a doctor compared to 63% in 2001. The potential value of nasal glucagon was acknowledged by 43% of responders. In selected patients, treatment of SH was conducted without hospital admission in 78% of EMDs (60% in 2001). Fifty-three percent of medical directors acknowledged the need for further training in diabetic emergencies (47% in 2001). Cooperation for medical education between emergency teams and a diabetes centre was reported by 14% (41% in 2001)., Conclusion: Structural and process quality of the management of diabetic emergencies in Germany has improved considerably since 2001. Persisting deficiencies could be improved by providing better medical equipment in ambulances and ongoing education to the entire emergency teams., Competing Interests: A. Holstein has received personal fees from Eli Lilly and Company and Novo Nordisk. B.M. Frier has received honoraria for lectures from Novo Nordisk, Eli Lilly, Sanofi, Roche, MSD, and Abbott, and for advisory board membership for Zucara Pharmaceuticals. The remaining authors have no competing interests to declare., (Thieme. All rights reserved.)

Electronic Health Records offer an opportunity to improve patient care (in terms of quality and/or safety) by making available patient health information stored in a single Clinical Data Repository. We aimed to estimate the frequency of hypoglycemic recurrences in hospitalized adult patients in non-critical areas. We designed a cross sectional study with hospitalizations between 2017 and 2018, which included patients with at least one hypoglycemia health record (defined as a value <70 mg/dL, either by capillary glycemic monitoring or serum measurement). Recurrence was defined as those who presented a second event, with at least 2 hours of difference. We included 1884 patients, and 573 presented recurrences, yielding a global prevalence of 30.41% (95%CI 28.34-32.54). Due to the high frequency, it is important to identify vulnerable populations, to implement preventive measures to assist clinicians for decision-making tasks, as a clinical decision support system.

Aims: Clinical inertia behaviour affects family physicians managing chronic disease such as diabetes. Literature addressing clinical inertia in the management of hypoglycemia is scarce. The objectives of this study were to create a measurement for physician clinical inertia in managing hypoglycemia (ClinInert&#95;InHypoDM), and to determine physicians' characteristics associated with clinical inertia., Methods: The study was a secondary analysis of data provided by family physicians from the InHypo-DM Study, applying exploratory factor analysis. Principal axis factoring with an Oblimin rotation was employed to detect underlying factors associated with physician behaviors. Multiple linear regression was used to determine association between the ClinInert&#95;InHypoDM scores and physician characteristics., Results: Factor analysis identified a statistically sound 12-item one-factor scale for clinical inertia behavior. No statistically significant differences in clinical inertia score for the studied independent variables were found., Conclusions: This study provides a scale for assessing clinical inertia in the management of hypoglycemia. Further testing this scale in other family physician populations will provide deeper understanding about the characteristics and factors that influence clinical inertia. The knowledge derived from better understanding clinical inertia in primary care has potential to improve outcomes for patients with diabetes., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Neonatal hypoglycemia is a common diagnosis for which management strategies vary. Our goal was to implement hypoglycemia algorithms (HGA) to streamline management of neonatal hypoglycemia within our hospital system and improve outcomes related to promoting the mother-infant dyad and decreasing hospital costs., Patients and Methods: A retrospective cohort study analyzed data on 4,666 asymptomatic infants at risk for hypoglycemia and born at two, large, community hospitals between 2010 and 2016. The first algorithm (HGA1) was created in 2012 and subsequently updated (HGA2) in 2014 to include the use of dextrose gel. Infants were separated into three groups by epoch: pre-HGA (2010-2011), HGA1 (2012-2013), and HGA2 (2014-2016). Outcomes between groups were then analyzed. Cost savings were calculated using linear regression., Results: Compared with the pre-HGA group, the HGA1 group had decreased intravenous dextrose use (3.9 vs. 2.5%, p  < .001). Compared with the HGA1 group, the HGA2 group had decreased intravenous dextrose use (2.5 vs. 1.0%, p  < .001) and increased breastfeeding rates (88.4% vs. 86.7%, p  = .003). Neonatal intensive care unit admission rates decreased when comparing the pre-HGA group with the HGA2 group (10.6% vs 9.4%, p  = .03). Length of stay was overall unchanged. Total cost savings were approximately $222 per case., Conclusions: By implementing HGA1 and providing resources to unify care for asymptomatic infants at risk for hypoglycemia, short-term outcomes in our hospital system improved. By updating HGA2 to include the use of dextrose gel, the advantages gained by HGA1 were maintained and further enhanced. Overall cost of care was reduced.

Introduction: With the increasing performance of bariatric surgery, rare complications are becoming prevalent. We review the diagnosis and treatment of dysautonomia after bariatric surgery and the limited treatment options available. We summarize the suggested mechanisms and explain why a complete understanding of the etiology has yet to be determined., Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was performed., Results: Of 448 studies identified in the literature search, 4 studies were reviewed, describing 87 patients diagnosed with dysautonomia. We present a patient who developed severe dysautonomia following conversion of sleeve gastrectomy to gastric bypass., Conclusion: Treatment needs to focus on optimizing nutrition, avoiding hypoglycemia, and optimizing volume status., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: An increasing number of pediatric patients with inherited metabolic disorders are reaching adulthood. In addition, many patients are diagnosed for the first time in adult life due to improved awareness of these disorders and the availability of advanced diagnostic technology. Knowledge of these inherited metabolic disorders in adults is crucial for the emergency physician to promptly recognize their acute illness and appropriately manage them in the emergency department., Objective: This review provides an overview of various inherited metabolic disorders which present to the emergency department with acute metabolic decompensation., Evaluation and Management: Acute illness in these patients is often triggered by a catabolic event such as intercurrent illness, fasting, postpartum, or use of certain medication. It may present in a variety of ways related to severe hyperammonemia, metabolic acidosis, leucine encephalopathy or hypoglycemia. In this review, we describe the clinical presentation, evaluation and immediate management of their critical illness in the emergency department., Conclusion: Acute metabolic decompensation is a life-threatening condition. The emergency physician is usually the first provider to evaluate these patients when they present to the emergency department. Early recognition of their illness and prompt management of these cases improve patient outcomes., Competing Interests: Declaration of Competing Interest All authors declare no competing interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Following bariatric surgery, patients can develop non-specific symptoms self-described as hypoglycemia. However, confirming hypoglycemia can be technically challenging, and therefore, these individuals are frequently treated empirically. This study aimed to describe what diagnostic evaluation and therapeutic interventions patients referred for post-bariatric surgery hypoglycemia undergo., Methods: Retrospective observational cohort study of patients with a history of bariatric surgery was evaluated for post-bariatric surgery hypoglycemia in a tertiary referral center from 2008 to 2017. We collected demographic and bariatric surgery information, clinical presentation of symptoms referred to as hypoglycemia, laboratory and imaging studies performed to evaluate these symptoms, and symptom management and outcomes., Results: A total of 60/2450 (2.4%) patients who underwent bariatric surgery were evaluated in the Department of Endocrinology for hypoglycemia-related symptoms. The majority were middle-aged women without type 2 diabetes who had undergone Roux-en-Y gastric bypass. Thirty-nine patients (65%) completed a biochemical assessment for hypoglycemia episodes. Six (10%) had confirmed hypoglycemia by Whipple's triad, and four (6.7%) met the criteria for post-bariatric surgery hypoglycemia based on clinical and biochemical criteria. All patients were recommended dietary modification as the initial line of treatment, and this intervention resulted in most patients reporting at least some improvement in their symptoms. Eight patients (13%) were prescribed pharmacotherapy, and two patients required additional interventions for symptom control., Conclusions: In our experience, evaluation for hypoglycemia-related symptoms after bariatric surgery was rare. Hypoglycemia was confirmed in the minority of patients. Even without establishing a diagnosis of hypoglycemia, dietary changes were a helpful strategy for symptom management for most patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: An increasing number of patients in hospital have diabetes, with most of them cared for by non-specialist staff. The effect of diabetes education for staff on patient outcomes, as well as the most effective method of staff education is unclear. Therefore, the aim of this study was to compare diabetes outcomes in medical wards where nursing staff were offered one face-to-face (F2F) session followed by access to online education (online), F2F education only, or standard care (control)., Methods: We conducted a pilot cluster randomised controlled trial involving 16-weeks baseline/rollout followed by a 28-week post-intervention period across three medical wards (clusters) in a Sydney Teaching Hospital. The online ward provided an online competency-based diabetes education program and 1-h F2F teaching from a diabetes nurse educator (DNE), the F2F ward provided four separate 1-h teaching sessions by a DNE, with no additional sessions in the control ward. The primary outcome was length of stay (LOS); secondary outcomes included good diabetes days (GDD), hypoglycaemia and medication errors. Poisson and binary logistic regression were used to compare clusters., Results: Staff attendance/completion of ≥ 2 topics was greater with online than F2F education [39/48 (81%) vs 10/33 (30%); p < 0.001]. Among the 827/881 patients, there was no difference in LOS change between online [Median(IQR) 5(2-8) to 4(2-7) days], F2F [7(4-14) to 5(3-13) days] or control wards [5(3-9) to 5(3-7) days]. GDD improved only in the online ward 4.7(2.7-7.0) to 6.0(2.3-7.0) days; p = 0.038. Total patients with hypoglycaemia and appropriately treated hypoglycaemia increased in the online ward., Conclusions: The inclusion of online education increased diabetes training uptake among nursing staff. GDD and appropriate hypoglycaemia management increased in the online education wards., Trial Registration: Prospectively registered on the Australia New Zealand Clinical Trials Registry (ANZCTR) on 24/05/2017: ACTRN12617000762358 ., (© 2022. The Author(s).)

Objective: Many emergency medical services (EMS) protocols for out-of-hospital cardiac arrests (OHCA) include point-of-care (POC) glucose measurement and administration of dextrose, despite limited knowledge of benefit. The objective of this study was to describe the incidence of hypoglycemia and dextrose administration by EMS in OHCA and subsequent patient outcomes. Methods: This was a retrospective analysis of OHCA in a large, regional EMS system from 2011 to 2017. Patients ≥18 years old with non-traumatic OHCA and attempted field resuscitation by paramedics were included. The primary outcomes were frequency of POC glucose measurement, hypoglycemia (glucose <60 mg/dl), and dextrose/glucagon administration (treatment group). The secondary outcomes included field return of spontaneous circulation (ROSC), survival to hospital discharge (SHD), and survival with good neurologic outcome. Results: There were 46,211 OHCAs during the study period of which 33,851 (73%) had a POC glucose test performed. Glucose levels were documented in 32,780 (97%), of whom 2,335 (7%) were hypoglycemic. Among hypoglycemic patients, 41% (959) received dextrose and/or glucagon. Field ROSC was achieved in 30% (286) of hypoglycemic patients who received treatment. Final outcome was determined for 1,714 (73%) of the hypoglycemic cases, of whom 120 (7%) had SHD and 66 (55%) had a good neurologic outcome. Of the 32,780 patients with a documented POC glucose result who were identified as hypoglycemic, only 27 (0.08%) received field treatment, and survived to discharge with good neurologic outcome. 48 (6%) of patients in the treatment group had SHD vs. 72 (8%) without treatment, risk difference -2.0% (95%CI -4.4%, 0.4%), p  = 0.1. Conclusion: In this EMS system, POC glucose testing was common in adult OHCA, yet survival to hospital discharge with good neurologic outcome did not differ between patients treated and untreated for hypoglycemia. These results question the common practice of measuring and treating hypoglycemia in OHCA patients.

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.)

Objectives: To identify what is known empirically about the screening, treatment and harm of exposure to neonatal hypoglycaemia., Design: Scoping review that applied a preregistered protocol based on established frameworks., Data Sources: Medline and Embase, up to 12 May 2020., Study Selection: Comparative and case-series studies, as well as guidelines, published in English or French, on the topic of immediate inpatient postnatal glucose screening in newborns., Data Gathering: Article selection and characterisation were performed in duplicate using predefined data extraction forms specific to primary studies and guidelines., Results: 12 guidelines and 74 primary studies were included. A neurodevelopmental outcome was primary in 32 studies: 30 observational studies followed up posthypoglycaemic, and the 2 intervention studies included 1 randomised controlled trial (RCT) about treatment thresholds. Three other RCTs assessed dextrose gel (two) and oral sucrose (one). 12 of 30 studies that evaluated non-neurodevelopmental primary outcomes were intervention studies. Only one cohort study compared outcomes in screened vs unscreened newborns. The guidelines did not arrive at a consensus definition of postnatal hypoglycaemic, and addressed potential harms of screening more often than primary studies., Conclusions: The primary literature that informs hypoglycaemia screening is a series of studies that relate neurodevelopmental outcomes to postnatal hypoglycaemia. Further research is needed to better define an optimal threshold for hypoglycaemia that warrants intervention, based on long-term neurodevelopmental outcomes and a better delineation of potential screening harms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Islet transplantation is a treatment for selected adults with type 1 diabetes and severe hypoglycemia. Islets from two or more donor pancreases, a scarce resource, are usually required to impact glycemic control, but the treatment falls short of a cure. Islets are avascular when transplanted into the hypoxic liver environment and subjected to inflammatory insults, immune attack, and toxicity from systemic immunosuppression. The Collaborative Islet Transplant Registry, with outcome data on over 1,000 islet transplant recipients, has demonstrated that larger islet numbers transplanted and older age of recipients are associated with better outcomes. Induction with T-cell depleting agents and the TNF-α inhibitor etanercept and maintenance systemic immunosuppression with mTOR inhibitors in combination with calcineurin inhibitors also appear advantageous, but concerns remain over immunosuppressive toxicity. We discuss strategies and therapeutics that address specific challenges of islet transplantation, many of which are at the preclinical stage of development. On the horizon are adjuvant cell therapies with mesenchymal stromal cells and regulatory T cells that have been used in preclinical models and in humans in other contexts; such a strategy may enable reductions in immunosuppression in the early peri-transplant period when the islets are vulnerable to apoptosis. Human embryonic stem cell-derived islets are in early-phase clinical trials and hold the promise of an inexhaustible supply of insulin-producing cells; effective encapsulation of such cells or, silencing of the human leukocyte antigen (HLA) complex would eliminate the need for immunosuppression, enabling this therapy to be used in all those with type 1 diabetes.

Purpose: Real-time continuous glucose monitoring (RT-CGM) provides information on glycemic variability (GV), time in range (TIR), and guidance to avoid hypoglycemia, thereby complimenting HbA1c for diabetes management. We investigated whether GV and TIR were independently associated with chronic and acute diabetes complications., Methods: Between September 2014 and January 2017, 515 subjects with type 1 diabetes using sensor-augmented pump therapy were followed for 24 months. The link between baseline HbA1c and CGM-derived glucometrics (TIR [70-180 mg/dL], coefficient of variation [CV], and SD) obtained from the first 2 weeks of RT-CGM use and the presence of complications was investigated. Complications were defined as: composite microvascular complications (presence of neuropathy, retinopathy, or nephropathy), macrovascular complications, and hospitalization for hypoglycemia and/or ketoacidosis., Results: Individuals with microvascular complications were older (P < 0.001), had a longer diabetes duration (P < 0.001), a higher HbA1c (7.8 ± 0.9 vs 7.5 ± 0.9%, P < 0.001), and spent less time in range (60.4 ± 12.2 vs 63.9 ± 13.8%, P = 0.022) compared with those without microvascular complication. Diabetes duration (odds ratio [OR] = 1.12 [1.09-1.15], P < 0.001) and TIR (OR = 0.97 [0.95-0.99], P = 0.005) were independent risk factors for composite microvascular complications, whereas SD and CV were not. Age (OR = 1.08 [1.03-1.14], P = 0.003) and HbA1c (OR = 1.80 [1.02-3.14], P = 0.044) were risk factors for macrovascular complications. TIR (OR = 0.97 [0.95-0.99], P = 0.021) was the only independent risk factor for hospitalizations for hypoglycemia or ketoacidosis., Conclusions: Lower TIR was associated with the presence of composite microvascular complications and with hospitalization for hypoglycemia or ketoacidosis. TIR, SD, and CV were not associated with macrovascular complications., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Competing interests: The BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none. Further details of The BMJ policy on financial interests are here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests.