Hypoglycemic State Research Articles

Advances in Label-Free Glucose Detection Using Self-Assembled Nanoparticles and Surface-Enhanced Raman Spectroscopy.

In the landscape of biomolecular detection, surface-enhanced Raman spectroscopy (SERS) confronts notable obstacles, particularly in the label-free detection of biomolecules, with glucose and other sugars presenting a quintessential challenge. This study heralds the development of a pioneering SERS substrate, ingeniously engineered through the self-assembly of nanoparticles of diverse sizes (Ag1@Ag2NPs). This configuration strategically induces 'hot spots' within the interstices of nanoparticles, markedly amplifying the detection signal. Rigorous experimental investigations affirm the platform's rapidity, precision, and reproducibility, and the detection limit of this detection method is calculated to be 6.62 pM. Crucially, this methodology facilitates nondestructive glucose detection in simulated samples, including phosphate-buffered saline and urine. Integrating machine learning algorithms with simulated serum samples, the approach adeptly discriminates between hypoglycemic, normoglycemic, and hyperglycemic states. Moreover, the platform's versatility extends to the detection and differentiation of monosaccharides, disaccharides, and methylated glycosides, underscoring its universality and specificity. Comparative Raman spectroscopic analysis of various carbohydrate structures elucidates the unique SERS characteristics pertinent to these molecules. This research signifies a major advance in nonchemical, label-free glucose determination with enhanced sensitivity via SERS, laying a new foundation for its application in precision medicine and advancing structural analysis in the sugar domain.

Long-diagnosed primary adrenal insufficiency in the setting of Werlhof’s disease. A clinical case report

Chronic adrenal insufficiency is an endocrine disease caused by insufficient secretion of adrenal hormones due to dysfunction of one or more links of the hypothalamic-pituitary-adrenal axis. The highest prevalence has been documented in Scandinavian countries: 15–22 people per 100,000 population, while other European countries report 10 cases per 100,000 population. Autoimmune adrenalitis is the most common cause of primary adrenal insufficiency in adults, and it can be either alone (40 %) or a component of autoimmune polyglandular syndromes (60 %). The etiologic factors of primary adrenal insufficiency include tuberculosis or AIDS. These causes of adrenal cortical insufficiency are particularly relevant in Ukraine. The article describes a clinical case of a patient with both primary adrenal insufficiency and Werlhof’s disease. The prevalence of adrenal insufficiency and etiologic factors of primary adrenal insufficiency are highlighted. A detailed differential diagnosis of primary adrenal insufficiency with other diseases that could cause clinical symptoms such as hypoglycemic states, severe weight loss, hypotension, severe muscle weakness, hyponatremia, hyperkalemia is performed. The basic principles of diagnosis, treatment, and prognosis in primary adrenal insufficiency are discussed. Despite typical, specific manifestations of adrenal insufficiency, diagnosis in real clinical practice is difficult. Awareness and vigilance of doctors regarding the symptoms of adrenal insufficiency is necessary. Late detection of chronic adrenal insufficiency can lead to complications. Timely diagnosis and treatment of chronic adrenal insufficiency improves disease prognosis and quality of life.

Bilateral Abducens Nerve Palsy and Nystagmus Resolved Upon Intravenous Dextrose Administration in Hypoglycemic Young Female: A Case Report and Review of the Literature

Hypoglycemia can cause a variety of neurological symptoms ranging from mild confusion to seizures and coma. The brain depends heavily on glucose as its main energetic resource, and a decrease in glucose levels can lead to impaired cerebral function. A 38-year-old female presented to the Emergency department with a history of headache, dizziness and asymmetric reactive pupils in addition to bilateral medial strabismus, nystagmus and photophobia. A non-contrast brain Computed Tomography scan was performed showed no significant radiological findings. Laboratory tests were within normal ranges except for a clinically significant hypoglycemia (level II). Intravenous dextrose was administered and strabismus gradually resolved, and headache subsided gradually within an hour. Hypoglycemic state should be investigated first in any patient with sudden neurological deficit.

Automated Insulin Delivery in Women with Pregnancy Complicated by Type 1 Diabetes

BackgroundHybrid closed-loop insulin therapy has shown promise for management of type 1 diabetes during pregnancy; however, its efficacy is unclear.MethodsIn this multicenter, controlled trial, we randomly assigned pregnant women with type 1 diabetes and a glycated hemoglobin level of at least 6.5% at nine sites in the United Kingdom to receive standard insulin therapy or hybrid closed-loop therapy, with both groups using continuous glucose monitoring. The primary outcome was the percentage of time in the pregnancy-specific target glucose range (63 to 140 mg per deciliter [3.5 to 7.8 mmol per liter]) as measured by continuous glucose monitoring from 16 weeks’ gestation until delivery. Analyses were performed according to the intention-to-treat principle. Key secondary outcomes were the percentage of time spent in a hyperglycemic state (glucose level >140 mg per deciliter), overnight time in the target range, the glycated hemoglobin level, and safety events.ResultsA total of 124 participants with a mean (±SD) age of 31.1±5.3 years and a mean baseline glycated hemoglobin level of 7.7±1.2% underwent randomization. The mean percentage of time that the maternal glucose level was in the target range was 68.2±10.5% in the closed-loop group and 55.6±12.5% in the standard-care group (mean adjusted difference, 10.5 percentage points; 95% confidence interval [CI], 7.0 to 14.0; P<0.001). Results for the secondary outcomes were consistent with those of the primary outcome; participants in the closed-loop group spent less time in a hyperglycemic state than those in the standard-care group (difference, −10.2 percentage points; 95% CI, −13.8 to −6.6); had more overnight time in the target range (difference, 12.3 percentage points; 95% CI, 8.3 to 16.2), and had lower glycated hemoglobin levels (difference, −0.31 percentage points; 95% CI, −0.50 to −0.12). Little time was spent in a hypoglycemic state. No unanticipated safety problems associated with the use of closed-loop therapy during pregnancy occurred (6 instances of severe hypoglycemia, vs. 5 in the standard-care group; 1 instance of diabetic ketoacidosis in each group; and 12 device-related adverse events in the closed-loop group, 7 related to closed-loop therapy).ConclusionsHybrid closed-loop therapy significantly improved maternal glycemic control during pregnancy complicated by type 1 diabetes. (Funded by the Efficacy and Mechanism Evaluation Program; AiDAPT ISRCTN Registry number, ISRCTN56898625.)

THU267 A Novel In Vitro Assay Correlates Insulin Receptor Autoantibodies To Fasting Insulin In Type B Insulin Resistance

Abstract Disclosure: B. Abel: None. W. Minich: Stock Owner; Self; ImmunometriX GmbH. C. Schwiebert: Employee; Self; Bruker Corporation. T. Welsink: Employee; Self; Bruker Corporation. P. Seemann: Stock Owner; Self; ImmunometriX GmbH, selenOmed GmbH. L. Schomburg: Stock Owner; Self; selenOmed GmbH. R.J. Brown: None. Severe insulin resistance (IR) in the presence of insulin receptor autoantibodies (InsR-aAb) is known as type B IR (TBIR). TBIR has a spectrum of phenotypes, including severe IR with uncontrolled diabetes (DM), milder IR without uncontrolled DM, hypoglycemia, and remission states. Considerable progress in therapy has been achieved, but diagnosis and monitoring of InsR-aAb remains a challenge. We aimed to develop a robust in vitro method for InsR-Ab quantification and correlate it with clinical outcomes. 28 longitudinal serum samples from 9 patients with TBIR were collected before, during, and after immunosuppression. Samples included 11 in states of remission, 4 in hypoglycemia, 6 in mild IR, and 7 in severe IR. Samples from 8 patients with IR not due to TBIR (type 1 DM, N=1; type 2 DM, N=4; lipodystrophy, N=2; and INSR mutation, N=1) were used as controls. A bridge-assay for InsR-aAb detection was established using recombinant human insulin receptor as bait and detector and validated using monoclonal antibodies as positive controls. The assay consists of an immobilized recombinant InsR at a plastic surface and an InsR-Luc fusion protein for detection of InsR-aAb. There was dose-dependent increase in intensity over &amp;gt;2 orders of magnitude with InsR-specific commercial mAb, but not with control mAb. In the presence of insulin, strong InsR phosphorylation was observed in cells incubated with Ig from control sera, but not those incubated with Ig from TBIR patient sera. Fasting insulin was highest in severe TBIR (median 1000 [IQR 273-1000] mcU/mL), followed by mild (71[32-230]), and lower in hypoglycemia (6 [3,103]) and remission (14[6,35]), P=0.0014, and was moderately elevated in insulin resistant controls (55[11,120]). A1c was elevated in severe TBIR &amp; controls (9.9±3.0 &amp; 9.1±3.8%) and near-normal in mild, hypoglycemic, and remission states of TBIR (5.7±1.3, 6.0±0.7, 5.7±1.1). InsR-aAb titers changed in parallel to changes in TBIR state and severity: highest in severe TBIR (median 700 [IQR 365-977]), followed by mild (176[98-254]), and lower in hypoglycemia (14[1.3-189]) and remission (17[3-28]). All TBIR samples showed clearly elevated signal intensities versus controls (0.9[0.7-1.1], Bonferroni corrected P&amp;lt;0.05 for all TBIR states vs controls). During treatment, InsR-aAb for each subject declined with amelioration of disease symptoms. Fasting insulin strongly correlated with InsR-aAb titers (r=0.825, p&amp;lt;0.001). The assay correctly identified all samples from patients with TBIR vs controls with non-autoimmune IR, and thus is an easy to interpret diagnostic tool. InsR-aAb titers correlated with fasting insulin, supporting direct relevance of InsR-aAb as causal for disease severity and as therapeutic targets for Ab depletion. By easing diagnosis and monitoring of TBIR, the new assay for InsR-aAb quantification should enhance access to timely and effective treatment for TBIR. Presentation: Thursday, June 15, 2023

Whole-Exome sequencing identifies GYS2 biallelic variants in individuals with suspected epilepsy

BackgroundAdequate glucose supply is essential for brain function, therefore hypoglycemic states may lead to seizures. Since blood glucose supply for brain is buffered by liver glycogen, an impairment of liver glycogen synthesis by mutations in the liver glycogen synthase gene (GYS2) might result in a substantial neurological involvement. Here, we describe the phenotypes of affected siblings of two families harboring biallelic mutations in GYS2. MethodsTwo suspected families - a multiplex Pakistani family (family A) with three affected siblings and a family of Moroccan origin (family B) with a single affected child who presented with seizures and reduced fasting blood glucose levels were genetically characterized. Whole exome sequencing (WES) was performed on the index patients, followed by Sanger sequencing-based segregation analyses on all available members of both families. ResultsThe variant prioritization of WES and later Sanger sequencing confirmed three mutations in the GYS2 gene (12p12.1) consistent with an autosomal recessive pattern of inheritance. A homozygous splice acceptor site variant (NM_021957.3, c. 1646 -2A>G) segregated in family A. Two novel compound heterozygous variants (NM_021957.3: c.343G>A; p.Val115Met and NM_021957.3: c.875A>T; p.Glu292Val) were detected in family B, suggesting glycogen storage disorder. A special diet designed to avoid hypoglycemia, in addition to change of the anti-seizure medication led to reduction in seizure frequency. ConclusionsThis study suggests that the seizures in patients initially diagnosed with epilepsy might be directly caused, or influenced by hypoglycemia due to pathogenic variants in the GYS2 gene.

Hypoglycemia Detection Using Hand Tremors: Home Study of Patients With Type 1 Diabetes

Diabetes affects millions of people worldwide and is steadily increasing. A serious condition associated with diabetes is low glucose levels (hypoglycemia). Monitoring blood glucose is usually performed by invasive methods or intrusive devices, and these devices are currently not available to all patients with diabetes. Hand tremor is a significant symptom of hypoglycemia, as nerves and muscles are powered by blood sugar. However, to our knowledge, no validated tools or algorithms exist to monitor and detect hypoglycemic events via hand tremors. In this paper, we propose a noninvasive method to detect hypoglycemic events based on hand tremors using accelerometer data. We analyzed triaxial accelerometer data from a smart watch recorded from 33 patients with type 1 diabetes for 1 month. Time and frequency domain features were extracted from acceleration signals to explore different machine learning models to classify and differentiate between hypoglycemic and nonhypoglycemic states. The mean duration of the hypoglycemic state was 27.31 (SD 5.15) minutes per day for each patient. On average, patients had 1.06 (SD 0.77) hypoglycemic events per day. The ensemble learning model based on random forest, support vector machines, and k-nearest neighbors had the best performance, with a precision of 81.5% and a recall of 78.6%. The results were validated using continuous glucose monitor readings as ground truth. Our results indicate that the proposed approach can be a potential tool to detect hypoglycemia and can serve as a proactive, nonintrusive alert mechanism for hypoglycemic events.

Hypoglycemia in patients with COVID-19: risk factors and prevention of complications

The aim of the work is to analyze the available scientific information and generalize the main results of modern research on the causes and risk factors of hypoglycemia in patients with COVID-19. Materials and methods. A search and analysis of full-text articles was carried out in the PubMed, Web of Science, Google Scholar, and Scopus databases. The search was conducted using the key terms: COVID-19 and hypoglycemia, hypoglycemia in COVID-19 patients and treatment of COVID-19 and hypoglycemia from the beginning of the pandemic in December 2019 to July 1, 2022. Results. The analysis of literary sources made it possible to identify three groups of factors that lead to the occurrence of hypoglycemia in patients with COVID-19: peculiarities of the diabetes course in patients with COVID-19 and the influence of concomitant diseases, side effects of certain groups of drugs and methods of therapy and prevention; shortcomings in the organization of treatment and patient care. Hypoglycemia has been shown to be a risk factor for cardiovascular and total mortality in patients with diabetes, may trigger the development of a cytokine storm during COVID-19 disease, and negatively impact mortality and length of hospital stay in COVID-19. Conclusions. To prevent hypoglycemic states in patients, one should avoid sudden changes in the type and dose of hypoglycemic drugs, periodically monitor the HbA1c level, expand the reach of patients with virtual consultations and telemedicine programs. In the case of determining the program of treatment and vaccination against COVID-19 in patients with diabetes mellitus, the known and possible hypoglycemic effects of drugs and vaccines should be taken into account.

Oxidative stress: a common imbalance in diabetes and epilepsy.

The brain requires a large amount of energy. Its function can be altered when energy demand exceeds supply or during metabolic disturbances such as diabetes mellitus. Diabetes, a chronic disease with a high incidence worldwide, is characterized by high glucose levels (hyperglycemia); however, hypoglycemic states may also occur due to insulin treatment or poor control of the disease. These alterations in glucose levels affect the brain and could cause epileptic seizures and status epilepticus. In addition, it is known that oxidative stress states emerge as diabetes progresses, contributing to the development of diseases secondary to diabetes, including retinopathy, nephropathy, cardiovascular alterations, and alterations in the central nervous system, such as epileptic seizures. Seizures are a complex of transient signs and symptoms resulting from abnormal, simultaneous, and excessive activity of a population of neurons, and they can be both a cause and a consequence of oxidative stress. This review aims to outline studies linking diabetes mellitus and seizures to oxidative stress, a condition that may be relevant to the development of severe seizures in diabetes mellitus patients.

Clinical Practice Guidelines for Assessment and Management of Patients with Substance Intoxication Presenting to the Emergency Department.

Clinical Practice Guidelines for Assessment and Management of Patients with Substance Intoxication Presenting to the Emergency Department.

Hypoglycemia and cardiac arrhythmias in diabetes mellitus

The article provides an assessment of cardiovascular risks associated with episodes of hypoglycemia in patients with diabetes mellitus. The analysis has been performed for the experimental and clinical data on cardiac arrhythmias during induced hypoglycemia in animal models and in patients with diabetes. The pathogenetic mechanisms of the development of life‑threatening heart rhythm disorders during hypoglycemic states (in particular, changes in autonomic nervous system activation and in the serum level of potassium) have been considered. The nature of electrocardiographic changes preceding the development of arrhythmias during hypoglycemia is described and factors affecting QT interval duration during hypoglycemia are given. The authors highlight the results of clinical studies of spontaneous hypoglycemia in terms of the arrhythmias’ specific features in daytime and nocturnal hypoglycemia, and different mechanisms of the cardiac arrhythmias’ development at different periods of the day. Clinical data have been presented as regards the drug‑induced hypoglycemia during administration beta‑adrenergic receptor blockers, angiotensin‑converting enzyme inhibitors, fluoroquinolones, as well as mechanisms of dysglycemic effects of these drugs. It has been noted that β‑blockers can mask symptoms of catecholamine‑mediated hypoglycemia. It has been established that among hypoglycemic agents, insulin secretion stimulators (sulfonylureas, meglinides) and insulin have the highest risk of serious hypoglycemia. However, the use of basal and prandial insulin analogues was associated with a lower frequency of hypoglycemia compared to human insulin. It was emphasized that hypoglycemia should be avoided in clinical practice to improve prognosis and prevent arrhythmias. For this, it is necessary to individualize target glycemic values with their mitigation in high‑risk patients, to use the safest insulin and non‑insulin hypoglycemic agents, and to implement new technologies (pumps, continuous glucose monitoring) more widely. It is extremely important to take into account comorbidity and the effects on hypoglycemia risk of drugs used for the treatment of concomitant diseases.

224: ALTERNATIVE MANAGEMENT OF DIABETIC KETOACIDOSIS DUE TO REFRACTORY HYPOKALEMIA

Introduction: In a hypoglycemic state, potassium levels are falsely elevated due to potassium shifting extracellularly. Once insulin is initiated, potassium will reverse, returning intracellularly, and leading to a lower potassium level. It is this reason that the standard protocol of diabetic ketoacidosis (DKA) treatment is to not begin insulin until potassium is replenished above a designated level. Below we present a patient with DKA that required treatment outside of standard protocol due to refractory hypokalemia. Description: The patient is a 25-year-old male that presented to the emergency department (ED) with elevated glucose for the past few weeks. He is a type-2 diabetic, controlled with diet and exercise for the last year. Prior to which, he had been on insulin. The only exacerbating factor he can think of is receiving the J&J vaccine around the same time. Other associated symptoms are difficulty breathing, abdominal pain, mild nausea, but no vomiting. In the ED, he was found to be in DKA with labs significant for severe acidosis and critical hypokalemia of 1.6 mmol/L. A central line was placed and potassium repletion began prior to initiating insulin drip, with plan to start insulin once potassium corrected. Following aggressive potassium repletion with up to 40 mEq per hour, it persistently remained below 3 mmol/L. Thus, it was decided to start the patient on the lowest rate of the insulin drip at 0.02 units/kg/hr until his potassium rose above 3.3 mmol/L as per our protocol. While being on the insulin drip, he was also receiving 20 mEq potassium hourly via IV, 40 mEq orally every four hours, with frequent basic metabolic profiles every two hours. The patient remained on the insulin drip for three days until he was finally able to be transitioned to long-acting insulin, 73-hours after admission. Discussion: The treatment of refractory hypokalemia in the setting of DKA is intricate. Insulin, while imperative for the treatment of DKA, can worsen hypokalemia, therefore sequence of medication administration is important in treatment. It is important for providers to recognize and identify the side effects of these treatments. In this case, multidisciplinary rounds were crucial in both monitoring and replacing potassium while on an insulin drip.

Nesidioblastosis: an uncommon complication seen post Roux-en-Y gastric bypass.

Adult-onset nesidioblastosis is a rare complication of Roux-en-Y gastric bypass surgery and may occur months to years after the initial surgical procedure. It is manifested by a hyperinsulinemic, hypoglycemic state. The annual incidence of adult-onset hyperinsulinemic hypoglycemia is believed to be less than 0.1 in 1 000 000 with a mean age of onset of 47 years (1). Here, we describe a patient who presented with worsening hypoglycemic symptoms for 1 year prior to presentation that eventually progressed to hypoglycemic seizures. The onset of this hypoglycemia was 5 years after Roux-en-Y gastric bypass surgery. A full neurological evaluation, which included an EEG, head CT, and MRI, was performed to rule out epilepsy and other seizure-related disorders. After hypoglycemia was confirmed, extensive laboratory studies were obtained to elucidate the cause of the hypoglycemia and differentiate nesidioblastosis from insulinoma. Once the diagnosis of nesidioblastosis was established, a sub-total pancreatectomy was performed, and the patient was discharged and placed on acarbose, a competitive reversible inhibitor of pancreatic α-amylase and intestinal brush border α-glucosidases which slows carbohydrate absorption. The lack of information and understanding of nesidioblastosis due to its rarity makes any knowledge of this rare but important surgical complication essential. As incidence of obesity increases, the number of gastric bypasses being performed increases with it, and understanding this disease process will be essential for the primary care provider. This is the primary reason for the writing of this publication. Nesidioblastosis is a persistent hyperinsulinemic, hypoglycemic state, mostly seen after Roux-en-Y gastric bypass surgery, with symptoms occurring postprandially. The incidence is 0.1-0.3% of all post Roux-en-Y gastric bypass patients. The key diagnostic clue to identifying nesidioblastosis is a positive selective arterial calcium stimulation test, showing a diffuse pattern of increased basal hepatic venous insulin concentration, whereas insulinomas would show focal increases. Pathological specimen of pancreas will show diffuse hypertrophy of beta cells. Management includes acarbose and total or subtotal pancreatectomy, which can be curative. With the prevalence of obesity increasing and more patients turning to Roux-en-Y gastric bypass, more patients may be at risk of this potential surgical complication.

Distinct Metabolic States Are Observed in Hypoglycemia Induced in Mice by Ricin Toxin or by Fasting.

Hypoglycemia may be induced by a variety of physiologic and pathologic stimuli and can result in life-threatening consequences if untreated. However, hypoglycemia may also play a role in the purported health benefits of intermittent fasting and caloric restriction. Previously, we demonstrated that systemic administration of ricin toxin induced fatal hypoglycemia in mice. Here, we examine the metabolic landscape of the hypoglycemic state induced in the liver of mice by two different stimuli: systemic ricin administration and fasting. Each stimulus produced the same decrease in blood glucose and weight loss. The polar metabolome was studied using 1H NMR, quantifying 59 specific metabolites, and untargeted LC-MS on approximately 5000 features. Results were analyzed by multivariate analyses, using both principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), to identify global metabolic patterns, and by univariate analyses (ANOVA) to assess individual metabolites. The results demonstrated that while there were some similarities in the responses to the two stimuli including decreased glucose, ADP, and glutathione, they elicited distinct metabolic states. The metabolite showing the greatest difference was O-phosphocholine, elevated in ricin-treated animals and known to be affected by the pro-inflammatory cytokine TNF-α. Another difference was the alternative fuel source utilized, with fasting-induced hypoglycemia primarily ketotic, while the response to ricin-induced hypoglycemia involves protein and amino acid catabolism.

An Overlapping Presentation of Hypoglycemia and Catatonia—A Case Report and Literature Review

Catatonia is a clinical syndrome characterized by a distinct constellation of psychomotor disturbances. It is known as a clinical manifestation of many medical and psychiatric conditions. Neuroglycopenia is a term that refers to a shortage of glucose in the brain resulting in the alteration of neuronal function. Catatonia has been observed in hypoglycemic states. We present a single case report of a 36-year-old male, with no known medical or psychiatric history, presenting with catatonia and hypoglycemia due to malnutrition. Catatonia and hypoglycemia may present similarly, and can present a challenge in differentiating the underlying etiology. It is unclear whether the hypoglycemia-catatonia overlap phenomenon is rare or rather underdiagnosed.

ODP553 Hypoglycemia after sleeve gastrectomy: a rare case of an insulinoma

Abstract Background The obesity pandemic has become a great topic of interest due its implications for quality of life, comorbidities, increasing mortality and the economic impact on health services worldwide(1). Laparoscopic sleeve gastrectomy (LSG) has been proposed as an effective and durable treatment for severe obesity and glucose metabolism disorders, achieving weight loss due to its restrictive and humoral effects (2). Its prevalence has increased from 5 to 37% since 2008 (3). One common complication after bariatric surgery (BS) is the postprandial hyperinsulinemic hypoglycemic state (4). While rare, insulinomas can cause it, where symptoms are more common during the fasting state; thus, evaluation of insulin secretion is needed to exclude dumping syndrome or nesidioblastosis. Until now, this is the first report of insulinoma after LSG. Clinical Case We here present 43-year-old women who was referred to the Obesity Clinic two years after LSG was performed. She had symptoms of hypoglycemia predominantly in the fasting state with a documented glycemic level of less than 30 mg/dl, compatible with Whipple's Triad. Initially, we suspected dumping syndrome but after documentation of a second low fasting plasma glucose, we decided to perform a 72-hour fasting test, which tested positive. Computed tomography and endoscopic ultrasound were performed, identifying the presence of a homogeneous hypoechoic semioval tumoral lesion in the pancreas. The diagnosis was compatible with insulinoma. A laparoscopic enucleation of insulinoma was performed, and after that, the hypoglycemic symptoms and blood sugar levels improved, remaining asymptomatic until now. The histopathological report described a well-differentiated grade 2 neuroendocrine tumor with positive chromogranin and synaptophysin and Ki67 immunopositivity in 4% of the neoplastic cells. Conclusion This is the first case of insulinoma after sleeve gastrectomy, the suggested physiopathology is due to a combination of increased plasma concentrations of incretins, mainly glucagon-like peptide 1 (GLP-1), and an accelerated release of nutrients in the proximal duodenum (5). Although this is a very rare case condition, clinicians must be aware of it, especially if the patient has hypoglycemic symptoms during the fasting state.

Analysis of Blood Biochemistry and Pituitary-Gonadal Histology after Chronic Exposure to Bisphenol-A of Mice.

Bisphenol-A is an emerging pollutant that is widespread in the environment, and to which live beings are continuously and inadvertently exposed. It is a substance with an endocrine-disrupting capacity, causing alterations in the reproductive, immunological, and neurological systems, among others, as well as metabolic alterations. Our study aimed to assess its clinical signs, and effects on the most relevant blood biochemical parameters, and to evaluate pituitary and gonadal histology after a chronic exposure of adult mice to different BPA doses (0.5, 2, 4, 50 and 100 µg/kg BW/day) through their drinking water. The biochemical results showed that a marked significant reduction (p < 0.05) was produced in the levels of serum glucose, hypoproteinaemia and hypoalbuminemia in the groups exposed to the highest doses, whereas in the group exposed to 50 µg/kg BW/day the glucose and total protein levels dropped, and the animals exposed to 100 µg/kg BW/day experienced a diminution in albumin levels. In the case of the group exposed to 50 µg/kg BW/day, however, hypertriglyceridemia and hypercholesterolemia were determined, and the blood parameters indicating kidney alterations such as urea and creatinine experienced a significant increase (p < 0.05) with respect to the controls. Regarding the pituitary and gonads, none of the animals exposed presented histological alterations at the doses tested, giving similar images to those of the control group. These results suggest that continuous exposure to low BPA doses could trigger an inhibition of hepatic gluconeogenesis, which would result in a hypoglycaemic state, together with an induction of the enzymes responsible for lipidic synthesis, a mechanism by which the increase in the lipid and serum cholesterol levels could be explained. Likewise, the decline in the protein and albumin levels would be indicative of a possible hepatic alteration, and the increase in urea and creatinine would point to a possible renal perturbation, derived from continuous exposure to this xenobiotic. Based on our results, it could be said that chronic exposure to low BPA doses would not produce any clinical signs or histological pituitary-gonadal effects, but it could cause modifications in some blood biochemical parameters, that could initially indicate a possible hepatic and renal effect.

Intermittently Scanned Continuous Glucose Monitoring for Type 1 Diabetes

BackgroundIn persons with type 1 diabetes and high glycated hemoglobin levels, the benefits of intermittently scanned continuous glucose monitoring with optional alarms for high and low blood glucose levels are uncertain.MethodsIn a parallel-group, multicenter, randomized, controlled trial involving participants with type 1 diabetes and glycated hemoglobin levels between 7.5% and 11.0%, we investigated the efficacy of intermittently scanned continuous glucose monitoring as compared with participant monitoring of blood glucose levels with fingerstick testing. The primary outcome was the glycated hemoglobin level at 24 weeks, analyzed according to the intention-to-treat principle. Key secondary outcomes included sensor data, participant-reported outcome measures, and safety.ResultsA total of 156 participants were randomly assigned, in a 1:1 ratio, to undergo intermittently scanned continuous glucose monitoring (the intervention group, 78 participants) or to monitor their own blood glucose levels with fingerstick testing (the usual-care group, 78 participants). At baseline, the mean (±SD) age of the participants was 44±15 years, and the mean duration of diabetes was 21±13 years; 44% of the participants were women. The mean baseline glycated hemoglobin level was 8.7±0.9% in the intervention group and 8.5±0.8% in the usual-care group; these levels decreased to 7.9±0.8% and 8.3±0.9%, respectively, at 24 weeks (adjusted mean between-group difference, −0.5 percentage points; 95% confidence interval [CI], −0.7 to −0.3; P<0.001). The time per day that the glucose level was in the target range was 9.0 percentage points (95% CI, 4.7 to 13.3) higher or 130 minutes (95% CI, 68 to 192) longer in the intervention group than in the usual-care group, and the time spent in a hypoglycemic state (blood glucose level, <70 mg per deciliter [<3.9 mmol per liter]) was 3.0 percentage points (95% CI, 1.4 to 4.5) lower or 43 minutes (95% CI, 20 to 65) shorter in the intervention group. Two participants in the usual-care group had an episode of severe hypoglycemia, and 1 participant in the intervention group had a skin reaction to the sensor.ConclusionsAmong participants with type 1 diabetes and high glycated hemoglobin levels, the use of intermittently scanned continuous glucose monitoring with optional alarms for high and low blood glucose levels resulted in significantly lower glycated hemoglobin levels than levels monitored by fingerstick testing. (Funded by Diabetes UK and others; FLASH-UK ClinicalTrials.gov number, NCT03815006.)

Closed‐loop control of type 1 diabetes in young children

Journal of Paediatrics and Child HealthVolume 58, Issue 4 p. 734-734 Heads UpFree Access Closed-loop control of type 1 diabetes in young children First published: 26 February 2022 https://doi.org/10.1111/jpc.15929 edited by Craig Mellis (craig.mellis@sydney.edu.au) AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Management of type 1 diabetes in young children is difficult because of their unpredictable eating habits, variable insulin requirements and parents' fear of hypoglycaemia. Sensor-augmented pump therapy decreases hypoglycaemia and ketoacidosis in this age-group but has not been shown to improve glycaemic control. Hybrid closed-loop systems (i.e. artificial pancreas) in which an algorithm adjusts insulin delivery based on real-time sensor glucose levels have been used in adolescents. European researchers randomised 74 children aged 1–7 years, mean 5.6 (standard deviation = 1.6) years, to receive insulin via either a closed-loop system or sensor-augmented pump therapy (control) for 16 weeks; they then crossed over to the other treatment for 16 weeks in a multicentre, randomised, cross-over trial.1 The closed-loop period was significantly superior to standard pump therapy in terms of time with glucose levels in the target range (72 vs. 63%, P < 0.001, which equated to a clinically significant 125 min/day), time spent in a hyperglycaemic state, difference in glycated haemoglobin level and difference in mean sensor glucose level (Fig. 1). The time spent in a hypoglycaemic state was similar between treatments, but one child had a severe hypoglycaemic episode during the closed-loop period. A hybrid closed-loop system significantly improved glycaemic control in young children with type 1 diabetes. Fig. 1Open in figure viewerPowerPoint Sensor glucose levels. (), Closed-loop insulin delivery (), interquartile range (IQR)); (), sensor-augmented pump therapy (), IQR); (), target glucose range (N.B. 70 mg/dL = 3.9 mmol/L; 180 mg/dL = 10 mmol/L). Reference 1Ware J, Allen JM, Boughton CK et al. Randomized trial of closed-loop control in very young children with type 1 diabetes. N. Engl. J. Med. 2022; 386: 209– 19. CrossrefCASPubMedWeb of Science®Google Scholar Reviewers: David Isaacs, david.isaacs@health.nsw.gov.au, Children's Hospital at Westmead, Sydney; Lara Graves, lara.graves@health.nsw.gov.au, Children's Hospital at Westmead, Sydney Volume58, Issue4April 2022Pages 734-734 FiguresReferencesRelatedInformation

Administration of an Acidic Sphingomyelinase (ASMase) Inhibitor, Imipramine, Reduces Hypoglycemia-Induced Hippocampal Neuronal Death.

Severe hypoglycemia (below 35 mg/dL) appears most often in diabetes patients who continuously inject insulin. To rapidly cease the hypoglycemic state in this study, glucose reperfusion was conducted, which can induce a secondary neuronal death cascade following hypoglycemia. Acid sphingomyelinase (ASMase) hydrolyzes sphingomyelin into ceramide and phosphorylcholine. ASMase activity can be influenced by cations, pH, redox, lipids, and other proteins in the cells, and there are many changes in these factors in hypoglycemia. Thus, we expect that ASMase is activated excessively after hypoglycemia. Ceramide is known to cause free radical production, excessive inflammation, calcium dysregulation, and lysosomal injury, resulting in apoptosis and the necrosis of neurons. Imipramine is mainly used in the treatment of depression and certain anxiety disorders, and it is particularly known as an ASMase inhibitor. We hypothesized that imipramine could decrease hippocampal neuronal death by reducing ceramide via the inhibition of ASMase after hypoglycemia. In the present study, we confirmed that the administration of imipramine significantly reduced hypoglycemia-induced neuronal death and improved cognitive function. Therefore, we suggest that imipramine may be a promising therapeutic tool for preventing hypoglycemia-induced neuronal death.