Hypoglycemia in Critically Ill Patients: A Concise Clinical Review.

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.

Follow up care for adults with diabetes treated for severe hypoglycemia by emergency medical Services, 2013-2019.

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.

FREE: A randomized controlled feasibility trial of a cognitive behavioral therapy and technology-assisted intervention to reduce fear of hypoglycemia in young adults with type 1 diabetes.

OBJECTIVE: The purpose of this study was to test the preliminary effectiveness of a cognitive behavioral therapy intervention (Fear Reduction Efficacy Evaluation [FREE]) designed to reduce fear of hypoglycemia in young adults with type 1 diabetes. The primary outcome was fear of hypoglycemia, secondary outcomes were A1C, and glycemic variability. METHODS: A randomized clinical trial was used to test an 8-week intervention (FREE) compared to an attention control (diabetes education) in 50 young adults with type 1 diabetes who experienced fear of hypoglycemia at baseline. All participants wore a continuous glucose monitor for the 8-week study period. Self-reported fear of hypoglycemia point-of-care A1C testing, continuous glucose monitor-derived glucose variability were measured at baseline, Week 8, and Week 12 (post-program). RESULTS: Compared to controls, those participating in the FREE intervention experienced a reduction in fear of hypoglycemia (SMD B = -8.52, p = 0.021), change in A1C (SMD B = 0.04, p = 0.841) and glycemic variability (glucose standard deviation SMD B = -2.5, p = 0.545) by the end of the intervention. This represented an 8.52% greater reduction in fear of hypoglycemia. CONCLUSION: A cognitive behavioral therapy intervention (FREE) resulted in improvements in fear of hypoglycemia. CLINICALTRIALS: govNCT03549104.

Cost-effectiveness of a Novel Hypoglycaemia Programme: The 'HARPdoc vs BGAT' RCT.

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.

Equitable Machine Learning for Hypoglycaemia Risk Management.

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.

Associations Between Postdischarge Care and Cognitive Impairment-Related Hospital Readmissions for Ketoacidosis and Severe Hypoglycemia in Adults With Diabetes.

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.

Postbariatric surgery hypoglycemia: Nutritional, pharmacological and surgical perspectives.

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.

Barriers and solutions for the management of severe hypoglycaemia in people with diabetes in Spain: A Delphi survey.

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.

Approach to the Patient: Insulinoma.

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.

Increasing Exclusive Nursery Care of Late Preterm and Low Birth Weight Infants.

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.

Diagnosis and management of post-bariatric surgery hypoglycemia.

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.

Early Glycemic State and Outcomes of Neonates With Hypoxic-Ischemic Encephalopathy.

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.

Severe (level 3) hypoglycaemia occurrence in a real-world cohort of adults with type 1 or 2 diabetes mellitus (iNPHORM, United States).

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.

Approach to the Hypoglycemic Patient.

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.

Hypoglycemia in Children: Major Endocrine-Metabolic Causes and Novel Therapeutic Perspectives.

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.

[Reactive hypoglycaemia, a frequently mentioned functional disorder, yet overestimated in clinical practice]. / L'hypoglycémie réactionnelle : un trouble fonctionnel fréquemment évoqué, mais surestimé en pratique clinique.

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.

La survenue de malaises est souvent attribuée à une hypoglycémie chez des personnes non diabétiques et, a priori, sans autre problème de santé. L'hypoglycémie réactionnelle, la plus fréquente, peut être considérée comme un trouble fonctionnel. Son diagnostic est, cependant, souvent galvaudé, car l'hypoglycémie n'est habituellement pas authentifiée. Le diagnostic d'hypoglycémie doit se faire de façon structurée en se basant sur la «triade de Whipple¼. Tout d'abord, l'anamnèse doit rechercher les symptômes évocateurs d'hypoglycémie, adrénergiques et neuroglucopéniques. Ensuite, s'il s'agit bien d'une hypoglycémie, le malaise doit disparaître rapidement après resucrage. Enfin, l'hypoglycémie doit être authentifiée par une mesure d'une valeur basse au moment d'un malaise. Cette confirmation a été facilitée par l'utilisation des lecteurs de glycémie, une stratégie qui est dorénavant préférée à la réalisation d'une hyperglycémie provoquée par voie orale, test non physiologique fort éloigné des conditions de vraie vie. Une fois le diagnostic posé sur cette triade, l'anamnèse doit faire préciser, outre la sévérité des malaises, leur chronologie, typiquement 2-3 heures après un repas riche en glucides dans le cas d'une hypoglycémie réactive. Le traitement de ce trouble fonctionnel repose principalement sur des mesures diététiques.

Encapsulated Cells for the Treatment of Diabetes: Danger of Acute Hypoglycemia Following Injury?

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.