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Background: Older adults with diabetes mellitus require drug treatment considering their frailty, cognitive function, and hypoglycemia. Objective: We investigated the association between diabetic pharmacologic therapy and both diabetic complications and frailty across eight diabetes-specific outpatient clinics nationwide. Methods: Participants (aged 60–80 years) who had type 2 diabetes and did not require nursing care were included in the study. Basic attributes, patient background, complications, hypoglycemic status, body weight, body composition, blood tests, grip strength, and Kihon Checklist (a frailty index) and self-care scores were obtained. Descriptive statistics, t-test, chi-square test, and regression analyses were employed for evaluation. Results: Overall, 417 participants were included (224 men, 193 women, mean age 70.1 ± 5.4 years, diabetes duration 14.9 ± 10.9 years, body mass index 24.5 ± 3.8, glycated hemoglobin 7.22 ± 0.98%, proportion of individuals with frailty and prefrailty, 19.9% and 41.0%, respectively). All drugs were used more frequently in prefrailty conditions. Each diabetes medication was related to complications, body composition, and frailty, as follows: sulfonylurea (lower hypoglycemia); glinide (severe hypoglycemia, retinopathy, weaker grip strength, high Kihon Checklist score, decreased physical activities); alpha-glucosidase inhibitors (no association); biguanide (high body mass index, high body fat, stronger grip strength); thiazolidinedione (decreased instrumental activities of daily living); dipeptidyl‐peptidase‐4 inhibitors (no association); sodium-glucose cotransporter 2 inhibitors; retinopathy, high body mass index and Kihon Checklist score, and depressive mood); glucagon-like peptide-1 receptor agonists (high body mass index and body fat and poor nutritional status); and insulin preparations (hypoglycemia, retinopathy, neuropathy, nephropathy, cardiovascular diseases, weaker grip strength, and high Kihon Checklist score and physical inactivity). Conclusions: Some formulations, such as glinide, sodium-glucose cotransporter 2 inhibitors, and insulin, are associated with an increased frequency of frailty, warranting careful and individualized diabetes treatment. [ABSTRACT FROM AUTHOR]

Key Clinical Message: An 86‐year‐old geriatric patient with sepsis presented cibenzoline‐induced hypoglycaemia, although within the boundary range of cibenzoline blood concentration. An 86‐year‐old geriatric patient taking cibenzoline for ametropic hypertrophic cardiac tendinopathy was admitted to our hospital for the treatment of sepsis. Upon admission, blood cibenzoline levels of 400.1 ng/mL were observed. Antibiotic therapy was initiated and cibenzoline was discontinued. On Day 16, cibenzoline was administered orally at a reduced dose of 50 mg/day. Several days after restarting cibenzoline, the patient developed hypoglycaemia (64 mg/dL), prompting the administration of 20% glucose. The present case demonstrates a rational timeline for cibenzoline administration, considering the patient's renal dysfunction and sepsis. Clinicians should exercise caution when managing older patients with severe infections who are receiving cibenzoline, and should consider the possibility of blood glucose fluctuations regardless of cibenzoline blood levels. Further research is warranted to better understand and address the potential side effects of cibenzoline administration in geriatric populations. [ABSTRACT FROM AUTHOR]

Neonatal hypoglycemia is a common disease in newborns, which can precipitate energy shortage and follow by irreversible brain and neurological injury. Herein, we present a novel approach for treating neonatal hypoglycemia involving an adhesive polyvinylpyrrolidone/gallic acid (PVP/GA) film loading glucose. The PVP/GA film with loose cross-linking can be obtained by mixing their ethanol solution and drying complex. When depositing this soft film onto wet tissue, it can absorb interfacial water to form a hydrogel with a rough surface, which facilitates tight contact between the hydrogel and tissue. Meanwhile, the functional groups in the hydrogels and tissues establish both covalent and non-covalent bonds, leading to robust bioadhesion. Moreover, the adhered PVP/GA hydrogel can be detached without damaging tissue as needed. Furthermore, the PVP/GA films exhibit excellent antibacterial properties and biocompatibility. Notably, these films effectively load glucose and deliver it to the sublingual tissue of newborn rabbits, showcasing a compelling therapeutic effect against neonatal hypoglycemia. The strengths of the PVP/GA film encompass excellent wet adhesion in the wet and highly dynamic environment of the oral cavity, on-demand detachment, antibacterial efficacy, biocompatibility, and straightforward preparation. Consequently, this innovative film holds promise for diverse biomedical applications, including but not limited to wearable devices, sealants, and drug delivery systems. [Display omitted] [ABSTRACT FROM AUTHOR]

Older people with type 1 diabetes represent a heterogeneous group, with varying ability to self-manage their condition. A multidisciplinary approach to management, tailored to the individual, and co-ordinated by the GP is recommended for older people with type 1 diabetes, with hypoglycaemia avoidance a priority. Regular review is essential as their health circumstances may change with time, requiring altered management, including simplified insulin regimens and de-escalating therapies. [ABSTRACT FROM AUTHOR]

Introduction: Post‐bariatric hypoglycaemia (PBH) is a rare yet disabling clinical condition, mostly reported after Roux‐en‐Y gastric bypass (RYGB) surgery. RYGB is one of the most widely used and effective bariatric procedures. The pathophysiology of PBH remains unclear, and treatment options are limited in effectiveness and/or carry significant side effects. Acarbose slows carbohydrates digestion and absorption and is generally considered first‐line pharmacological treatment for PBH but its gastrointestinal side effects limit patient compliance. Canagliflozin inhibits intestinal and renal sodium‐dependent glucose absorption and reduces postprandial excursions of glucose, insulin and incretins after RYGB – effects that could be beneficial in ameliorating PBH. Aims: The trial aims to investigate how blood glucose levels are affected during daily living in subjects with PBH during treatment with canagliflozin or acarbose compared with placebo, and to study the meal‐induced entero‐endocrine mechanisms implied in the treatment responses. Methods: In a double‐blinded, randomized, crossover clinical trial, HypoBar I will investigate the effectiveness in reducing the risk of PBH, safety, ambulatory glucose profile and entero‐endocrine responses when PBH is treated with canagliflozin 300 mg twice daily during a 4‐week intervention period, compared with acarbose 50 mg thrice daily or placebo. Ethics and Dissemination: HypoBar I is approved by the Local regulatory entities. Results will be published in peer‐reviewed journals. Conclusion: If effective, well‐tolerated and safe, canagliflozin could be a novel treatment for people with PBH. HypoBar I might also unravel new mechanisms underlying PBH, potentially identifying new treatment targets. Trial Registration: EudraCT number 2022–000157‐87. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Efficacy and safety of the fixed ratio combination of insulin degludec and liraglutide (IDegLira) has been largely documented. However, long-term data are limited. This study aimed at describing persistence in therapy and the effectiveness at 48 months of IDegLira. Methods: We conducted an observational study based on retrospective chart review. All patients treated with IDegLira during 2018–2022 were included. Data on treatment approaches and clinical outcomes were collected at the first prescription of IDegLira (T0) and after 6, 12, 24, 36, and 48 months. Results: Overall, 156 patients (mean age 68 years, 64.1% men) started IDegLira, of whom 88 (56.4%) were previously treated with basal-oral therapy (BOT) and 68 (43.6%) with basal-bolus schemes (BB). Before starting IDegLira, 23.8% were treated with ≥ 2 oral antihyperglycemic agents in association with insulin; at T0, the proportion decreased to 3.2%. Short-acting insulin was discontinued after the first week. After 48 months, levels of HbA1c were significantly reduced by 1.34% in the BOT group and 1.07% in the BB group (p < 0.0001 in both groups). In the BOT group, FBG levels decreased by about 50 mg/dl and body weight was unchanged. In the BB group, FBG levels decreased by about 40 mg/dl and body weight was significantly reduced by an average of 7.7 kg. Five patients (3.2%) interrupted therapy with IDegLira during 48 months, and no severe hypoglycemia occurred. Conclusions: Our study emphasizes the important role of IDegLira in maintaining a good metabolic control while minimizing the risk of major hypoglycemia and weight gain in the long term. The substantial simplification of treatment schemes can increase adherence. [ABSTRACT FROM AUTHOR]

Introduction: Health2Sync (H2S) is a digital health technology platform that provides coaching and titration support to patients with diabetes. The Mallya cap converts a conventional insulin pen into a smart connected device that can automatically synchronize dose values and associated timestamps (upon injection) to the H2S platform. This single-arm real-world study evaluated the effectiveness of insulin glargine 300 U/mL (Gla-300) combined with H2S and Mallya cap (Gla-300 + Cap + App program) on clinical outcomes among users with type 2 diabetes (T2D) in Taiwan. Methods: Adults (aged ≥ 20 years) with T2D who were registered H2S users and initiated Mallya cap for a new/existing Gla-300 regimen (identification period May 1, 2021–May 31, 2022) were included in this retrospective cohort study. Follow-up data from H2S were collected for 90 days. Glycated hemoglobin (HbA1c) change (baseline to follow-up) and HbA1c goal attainment were primary outcomes. Hypoglycemia incidence and usage metrics of Mallya cap were secondary outcomes. Results: Of 83 participants, 38.6% were new Gla-300 users. HbA1c was reduced in both new (− 2.4 [2.7] %, − 26.2 [29.5] mmol/mol) and previous Gla-300 users (− 0.5 [1.6] %, − 5.5 [17.5] mmol/mol). Reduction in HbA1c was significant (p < 0.05) in both groups. At follow-up, 43.4% of users had a reduction of > 0.5%. Mean HbA1c reductions increased numerically with higher baseline HbA1c and with longer duration of Mallya cap usage. Conclusions: Use of digital technology within a connected ecosystem such as Gla-300 + Cap + App program could help people with type 2 diabetes to improve their glycemic condition. [ABSTRACT FROM AUTHOR]

Although the discovery of insulin 100 years ago revolutionized the treatment of diabetes, its therapeutic potential is compromised by its short half-life and narrow therapeutic index. Current long-acting insulin analogs, such as insulin-polymer conjugates, are mainly used to improve pharmacokinetics by reducing renal clearance. However, these conjugates are synthesized without sacrificing the bioactivity of insulin, thus retaining the narrow therapeutic index of native insulin, and exceeding the efficacious dose still leads to hypoglycemia. Here, we report a kind of di-PEGylated insulin that can simultaneously reduce renal clearance and receptor-mediated clearance. By impairing the binding affinity to the receptor and the activation of the receptor, di-PEGylated insulin not only further prolongs the half-life of insulin compared to classical mono-PEGylated insulin but most importantly, increases its maximum tolerated dose 10-fold. The target of long-term glycemic management in vivo has been achieved through improved pharmacokinetics and a high dose. This work represents an essential step towards long-acting insulin medication with superior safety in reducing hypoglycemic events. Distinct from conventional mono-PEGylated insulin, this work developed a kind of di-PEGylated insulin that could simultaneously reduce renal clearance and receptor-mediated clearance. [Display omitted] [ABSTRACT FROM AUTHOR]

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

Congenital hyperinsulinism (CHI) is a rare condition but is a common cause of severe and persistent hypoglycemia in early life. Prompt recognition of CHI is critical to prevent the impact of neuroglycopenia and consequent lifelong neurodisability. It is important to be alert to the possibility of CHI in newborn babies with recurrent hypoglycemia associated with high glucose requirements. Pediatricians are advised to mitigate the risk of hypoglycemia by early treatment with high concentration dextrose and intravenous glucagon infusions. Specific medical therapies with diazoxide and/or somatostatin receptor analogues may be commenced after the finding of detectable insulin at hypoglycemia, a biochemical characteristic of CHI. Early exploration of genetic etiology is recommended, chiefly in the search for a focal form, amenable to limited pancreatic surgery. Genetic ascertainment is also useful to understand the basis of disease, variable responses to medical therapies and escalation of conservative treatment to subtotal pancreatectomy. CHI is a heterogeneous disorder with varying natural history. Many newborns and infants with CHI have severe and complex illness features; their long-term care is best achieved through review at specialist centers. [ABSTRACT FROM AUTHOR]

Growth hormone (GH) is secreted by somatotropic cells of the anterior pituitary gland. The classical effects of GH comprise the stimulation of cell proliferation, tissue and body growth, lipolysis, and insulin resistance. The GH receptor (GHR) is expressed in numerous brain regions. Notably, a growing body of evidence indicates that GH-induced GHR signaling in specific neuronal populations regulates multiple physiological functions, including energy balance, glucose homeostasis, stress response, behavior, and several neurological/cognitive aspects. The importance of central GHR signaling is particularly evident when the organism is under metabolic stress, such as pregnancy, chronic food deprivation, hypoglycemia, and prolonged exercise. These particular situations are associated with elevated GH secretion. Thus, central GH action represents an internal signal that coordinates metabolic, neurological, neuroendocrine, and behavioral adaptations that are evolutionarily advantageous to increase the chances of survival. This review summarizes and discusses recent findings indicating that the brain is an important target of GH, and GHR signaling in different neuronal populations regulates essential physiological functions. [ABSTRACT FROM AUTHOR]

Hypoglycemia is an uncommon clinical problem among non-diabetic patients. It requires systematic evaluation to determine the etiology. It may be related to critical illness, hepatic insufficiency, renal insufficiency, cardiac insufficiency, drugs, alcohol, cortisol insufficiency, growth hormone insufficiency, insulinoma, gastric bypass surgery, and paraneoplastic (insulin-like growth factor-2–related) immune-mediated or inherited metabolic disorders. We aimed to summarize the literature and present a case who suffered from hypoglycemia throughout his life and was diagnosed with fructose-1, 6 bisphosphatase deficiency in adulthood to attract attention to the rare causes of hypoglycemia in adulthood. [ABSTRACT FROM AUTHOR]

The given text is a collection of information about various aspects of Mabel Tolkien's life and death, as well as the challenges faced by her family. It discusses topics such as Mabel's illness, her will, her sons' education, and the potential impact of her illness on her behavior. The text also explores the cultural and historical context of the time period, including the challenges faced by Catholics in England and the Victorian era's approach to terminal diagnoses. However, the text lacks a clear focus or narrative structure. [Extracted from the article]

Introduction: Hypoglycemia has been associated with cardiovascular events, and glucose variability has been suggested to be associated with increased cardiovascular risk. Therefore, in this study, we examined the effect on proteomic cardiovascular risk protein markers of (i) mild iatrogenic hypoglycemia and (ii) severe iatrogenic hypoglycemia followed by rebound hyperglycemia. Methods: Two iatrogenic hypoglycemia studies were compared; firstly, mild hypoglycemia in 18 subjects (10 type 2 diabetes (T2D), 8 controls; blood glucose to 2.8 mmoL/L (50 mg/dL) for 1 h), and secondly, severe hypoglycemia in 46 subjects (23 T2D, 23 controls; blood glucose to <2.2 mmoL/L (<40 mg/dL) transiently followed by intravenous glucose reversal giving rebound hyperglycemia). A SOMAscan assay was used to measure 54 of the 92 cardiovascular protein biomarkers that reflect biomarkers involved in inflammation, cellular metabolic processes, cell adhesion, and immune response and complement activation. Results: Baseline to euglycemia showed no change in any of the proteins measured in the T2D cohort. With severe hypoglycemia, the study controls showed an increase in Angiopoietin 1 (ANGPT1) (p < 0.01) and Dickkopf-1 (DKK1) (p < 0.01), but no changes were seen with mild hypoglycemia. In both the mild and severe hypoglycemia studies, at the point of hypoglycemia, T2D subjects showed suppression of Brother of CDO (BOC) (p < 0.01). At 1 h post-hypoglycemia, the changes in ANGPT1, DKK1, and BOC had resolved, with no additional protein biomarker changes despite rebound hyperglycemia from 1.8 ± 0.1 to 12.2 ± 2.0 mmol/L. Conclusions: Proteomic biomarkers of cardiovascular disease showed changes at hypoglycemia that resolved within 1 h following the hypoglycemic event and with no changes following hyperglycemia rebound, suggesting that any cardiovascular risk increase is due to the hypoglycemia and not due to glucose fluctuation per se. [ABSTRACT FROM AUTHOR]

A microfluidic sweat monitoring patch that collects human sweat for a long time is designed to achieve the effect of detecting the rise and fall of human sweat glucose over a long period of time by increasing the use time of a single patch. Five collection pools, four serpentine channels, and two different valves are provided. Among them, the three-dimensional valve has a large burst pressure as a balance between the internal and external air pressures of the patch. The bursting pressure of the two-dimensional diverter valve is smaller than that of the three-dimensional gas valve, and its role is to control the flow direction of the liquid. Through plasma hydrophilic treatment of different durations, the optimal hydrophilic duration is obtained. The embedded chromogenic disc detects the sweat glucose value at two adjacent time intervals and compares the information of the human body to increase or reduce glucose. The patch has good flexibility and can fit well with human skin, and because polydimethylsiloxane (PDMS) has good light transmission, it reduces the measurement error caused by the color-taking process and makes the detection results more accurate. [ABSTRACT FROM AUTHOR]

Plasmodium parasite causes malaria and affects the biochemical, physiological, and histoarchitecture of the hepatocytes and blood. The resultant effect leads to alterations in the metabolic activities of the liver, erythrocytes, as well as the buffer system. Therefore, we investigated the antiplasmodial activity, histomorphological studies of the hepatocytes and alterations in biochemical parameters in Plasmodium berghei-infected mice administered with the herbal formulation of aqueous extracts of Mangifera indica stem bark and leaves. The plant coarse leaves (250.71 g) and stem bark (509.34 g) were weighed to obtain their ratios, macerated in boiled distilled water (5 L) for 72 h, filtered, and concentrated to obtain the various extracts whereas LD50 calculation gave 5500.19 mg/kg. The extracts were administered to eleven groups of mice at a dosage of 300 mg/kg whereas artesunate and ACT served as the positive control drugs; the antiplasmodial profiling, biochemical, and histological evaluations followed standard protocols. The schizonticidal activity of the extracts were remarkable; moreover, the histological section of the liver (negative control) had increased deposition of hemozoin, sinusoidal congestions, activation of kupffer cells, and portal tract inflammations; however, the other treatment groups in the study drastically reduced inflammation. The biochemical parameters' results revealed metabolic acidosis mitigation; hypocholesterolemia induction; enhanced hyperproteinemia, as well as hypoglycemia mitigation. The antiplasmodial therapeutic response, and biochemical derangements reversal corroborated with improved hepatocytes histoarchitecture of mice highlights the plant's pharmacological efficacy. (Word counts: 227). [ABSTRACT FROM AUTHOR]

Basal insulin continues to be a vital part of therapy for many people with diabetes. First attempts to prolong the duration of insulin formulations were through the development of suspensions that required homogenization prior to injection. These insulins, which required once- or twice-daily injections, introduced wide variations in insulin exposure contributing to unpredictable effects on glycemia. Advances over the last 2 decades have resulted in long-acting, soluble basal insulin analogues with prolonged and less variable pharmacokinetic exposure, improving their efficacy and safety, notably by reducing nocturnal hypoglycemia. However, adherence and persistence with once-daily basal insulin treatment remains low for many reasons including hypoglycemia concerns and treatment burden. A soluble basal insulin with a longer and flatter exposure profile could reduce pharmacodynamic variability, potentially reducing hypoglycemia, have similar efficacy to once-daily basal insulins, simplify dosing regimens, and improve treatment adherence. Insulin icodec (Novo Nordisk) and insulin efsitora alfa (basal insulin Fc [BIF], Eli Lilly and Company) are 2 such insulins designed for once-weekly administration, which have the potential to provide a further advance in basal insulin replacement. Icodec and efsitora phase 2 clinical trials, as well as data from the phase 3 icodec program indicate that once-weekly insulins provide comparable glycemic control to once-daily analogues, with a similar risk of hypoglycemia. This manuscript details the technology used in the development of once-weekly basal insulins. It highlights the clinical rationale and potential benefits of these weekly insulins while also discussing the limitations and challenges these molecules could pose in clinical practice. [ABSTRACT FROM AUTHOR]

Background: There is limited evidence evaluating the impact of insulin treatment strategies on glucose variability in critically ill patients without preexisting diabetes. Objective: Compare basal plus insulin (BPI) and sliding scale insulin (SSI) impact on glycemic control outcomes in critically ill patients without preexisting diabetes experiencing hyperglycemia. Methods: This multicenter, retrospective review analyzed critically ill patients with hyperglycemia who received either BPI or SSI. Patients with a hemoglobin A1C >6.5% during the admission of interest or in the previous 3 months, or a diagnosis of diabetes at the time of discharge were excluded. The primary outcome was glucose variability during the intensive care unit (ICU) admission. Secondary outcomes included hypoglycemia frequency, frequency of goal glucose levels, mortality, and length of stay. Results: The analysis included 228 patients (39 in BPI, 189 in SSI). Average glucose variability was higher in the BPI group compared with the SSI group (85.8 mg/dL ± 33.1 vs 70.2 mg/dL ± 30.7; P = 0.009), which remained when controlling for baseline confounding (−12.1 [5.6], 95% CI −23.2 to −0.99; P = 0.033). Hypoglycemia incidence was similar between groups. BPI patients had a lower incidence of glucose values within goal range than SSI patients (P = 0.046). There was no difference in length of stay or hospital mortality. Conclusions and Relevance: The use of SSI compared with a BPI regimen may result in reduced glycemic variability in critically ill patients without preexisting diabetes. Future prospective studies, with a larger sample size, are warranted to confirm our exploratory findings and characterize clinically significant benefits. [ABSTRACT FROM AUTHOR]

\nIntroduction: To evaluate and describe the diagnostic process, medical, nutritional, and surgical approach, and neurological outcome, we report data from a large Italian cohort of patients with congenital hyperinsulinism (CHI). Methods: We retrospectively analyzed 154 CHI patients admitted to Ospedale Pediatrico Bambino Gesù from 1985 to 2022. Results: Hypoglycemia occurred within the first year of life in 85.5% of patients, median time to diagnosis was 1 day (IQR 14 days). Ninety-two percent of patients were treated with diazoxide: 66.9% were responsive. Octreotide was administered to 28.6% of patients: 61.4% were responsive. Forty percent of patients were off-therapy, mostly from diazoxide. Thirty-four percent of patients carried mutations in ABCC8, 12.6% were syndromic, and 9.2% were transient CHI. Surgery was performed in 23/47 diazoxide-unresponsive and 2/95 diazoxide-responsive patients: 64.0% were focal at histology. Combining data from genetics, pancreatic venous sampling, 18F-DOPA PET/CT, and histology, 80.6% resulted diffuse, 16.7% focal, and 2.8% atypical CHI. Post-surgical diabetes developed in 6 patients. Neurocognitive evaluation revealed developmental delay or intellectual disability in 15.7% of 70 patients, mostly of a mild degree. Epilepsy was documented in 13.7% of 139 patients. Conclusion: Our diagnostic and therapeutic results are mainly consistent with the international indications and the CHI Global Registry data, with relatively low rates of neurological outcomes. Good outcomes were likely associated with early diagnosis and prompt management of patients because the majority of patients were diagnosed within 2 weeks. Remarkably, it is of utmost importance to spread the knowledge and refer CHI patients to multidisciplinary expert centers. We present retrospective data from the largest Italian cohort of patients with congenital hyperinsulinism, in order to evaluate our diagnostic and therapeutic process and the neurological outcome. We focused the discussion on some differences from the literature regarding the timing of molecular analysis performed by the use of virtual panels from clinical exome, regardless of diazoxide responsiveness. We also reported a different approach with the surgical intervention, recording a lower rate of subtotal pancreatectomy in case of diffuse forms unresponsive to medical therapy. Furthermore, we have a different strategy of drug discontinuation to test the remission of disease, without the need of the fasting tolerance test. Despite the mentioned deviations from the recent guidelines, the neurological outcome in our cohort is superimposable and lower than other cohorts. [ABSTRACT FROM AUTHOR]

Background. Children and adolescents with type 1 diabetes mellitus (T1DM) are frequently hospitalised for severe hypoglycaemia, hyperglycaemia, and diabetic ketoacidosis (DKA). While several risk factors have been recognised, clinically identifying these children at high risk of acute decompensation remains challenging. Objective. To develop a risk prediction model to accurately estimate the risk of acute healthcare utilisation due to severe hypoglycaemia, hyperglycaemia, and DKA in children and adolescents with T1DM. Materials and Methods. Using a retrospective dataset, baseline demographic and clinical data were collected from patients (<18 years) seen at a regional paediatric diabetes clinic from 1 January 2018 to 1 January 2020. The outcome was the number of emergency department presentations or hospital admissions for severe hypoglycaemia, hyperglycaemia, and DKA across the study period. Variables that were significant in univariate analysis were entered into a multivariable model. Receiver operator characteristic (ROC) curves assessed the model's discrimination and generated cut-offs for risk group stratification (low, medium, and high). Kaplan–Meier survival analysis measured time to acute healthcare utilisation across the risk groups. Results. Our multivariable risk prediction model consisted of five predictors (continuous glucose monitoring device, previous acute healthcare utilisation, missed appointments, and child welfare services involvement and socioeconomic status). The model exhibited good discrimination (area under the ROC = 0.81), accurately stratified children into low-, medium-, and high-risk groups, and demonstrated significant differences between median time to healthcare utilisation. Conclusion. Our model identified patients at an increased risk of acute healthcare utilisation due to severe hypoglycaemia, hyperglycaemia, and DKA. [ABSTRACT FROM AUTHOR]

This perspective work by academic neonatal providers is written specifically for the audience of newborn care providers and neonatologists involved in neonatal hypoglycemia screening. Herein, we propose adding a screen for congenital hyperinsulinism (CHI) by measuring glucose and ketone (i.e., β-hydroxybutyrate (BOHB)) concentrations just prior to newborn hospital discharge and as close to 48 h after birth as possible, at the same time that the mandated state Newborn Dried Blood Spot Screen is obtained. In the proposed protocol, we do not recommend specific metabolite cutoffs, as our primary objective is to simply highlight the concept of screening for CHI in newborns to newborn caregivers. The premise for our proposed screen is based on the known effect of hyperinsulinism in suppressing ketogenesis, thereby limiting ketone production. We will briefly discuss genetic CHI, other forms of neonatal hypoglycemia, and their shared mechanisms; the mechanism of insulin regulation by functional pancreatic islet cell membrane KATP channels; adverse neurodevelopmental sequelae and brain injury due to missing or delaying the CHI diagnosis; the principles of a good screening test; how current neonatal hypoglycemia screening programs do not fulfill the criteria for being effective screening tests; and our proposed algorithm for screening for CHI in newborns. [ABSTRACT FROM AUTHOR]

This study investigates how missing data samples in continuous blood glucose data affect the prediction of postprandial hypoglycemia, which is crucial for diabetes management. We analyzed the impact of missing samples at different times before meals using two datasets: virtual patient data and real patient data. The study uses six commonly used machine learning models under varying conditions of missing samples, including custom and random patterns reflective of device failures and arbitrary data loss, with different levels of data removal before mealtimes. Additionally, the study explored different interpolation techniques to counter the effects of missing data samples. The research shows that missing samples generally reduce the model performance, but random forest is more robust to missing samples. The study concludes that the adverse effects of missing samples can be mitigated by leveraging complementary and informative non-point features. Consequently, our research highlights the importance of strategically handling missing data, selecting appropriate machine learning models, and considering feature types to enhance the performance of postprandial hypoglycemia predictions, thereby improving diabetes management. [ABSTRACT FROM AUTHOR]

Type 1 diabetes mellitus (T1DM) refers to a metabolic condition where a lack of insulin impairs the usual homeostatic mechanisms to control blood glucose levels. Historically, participation in competitive sport has posed a challenge for those with T1DM, where the dynamic changes in blood glucose during exercise can result in dangerously high (hyperglycaemia) or low blood glucoses (hypoglycaemia) levels. Over the last decade, research and technological development has enhanced the methods of monitoring and managing blood glucose levels, thus reducing the chances of experiencing hyper‐ or hypoglycaemia during exercise. The introduction of continuous glucose monitoring (CGM) systems means that glucose can be monitored conveniently, without the need for frequent fingerpick glucose checks. CGM devices include a fine sensor inserted under the skin, measuring levels of glucose in the interstitial fluid. Readings can be synchronized to a reader or mobile phone app as often as every 1–5 min. Use of CGM devices is associated with lower HbA1c and a reduction in hypoglycaemic events, promoting overall health and athletic performance. However, there are limitations to CGM, which must be considered when being used by an athlete with T1DM. These limitations can be addressed by individualized education plans, using protective equipment to prevent sensor dislodgement, as well as further research aiming to: (i) account for disparities between CGM and true blood glucose levels during vigorous exercise; (ii) investigate the effects of temperature and altitude on CGM accuracy, and (iii) explore of the sociological impact of CGM use amongst sportspeople without diabetes on those with T1DM. [ABSTRACT FROM AUTHOR]

Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset HH caused by ABCC8 gene mutations. In the first patient, who presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330-1)del] that correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C>T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of the focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) positron emission tomography/computed tomography (PET/CT) was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH. [ABSTRACT FROM AUTHOR]

Background: Tight diabetes control is often applied in older persons with neurocognitive disorder resulting in increased hypoglycemic episodes but little is known about the pattern of brain injury in these overtreated patients. This study aims to: (a) quantify the prevalence of diabetes overtreatment in cognitively impaired older adults in a clinical population followed in an academic memory clinic (b) identify risk factors contributing to overtreatment; and (c) explore the association between diabetes overtreatment and specific brain region volume changes. Methods: Retrospective study of older patients with type 2 diabetes and cognitive impairment who were diagnosed in a memory clinic from 2013 to 2020. Patients were classified into vulnerable and dependent according to their health profile. Overtreatment was defined when glycated hemoglobin was under 7% for vulnerable and 7.6% for dependent patients. Characteristics associated to overtreatment were examined in multivariable analysis. Grey matter volume in defined brain regions was measured from MRI using voxel-based morphometry and compared in patients over- vs. adequately treated. Results: Among 161 patients included (median age 76.8 years, range 60.8–93.3 years, 32.9% women), 29.8% were considered as adequately treated, 54.0% as overtreated, and 16.2% as undertreated. In multivariable analyses, no association was observed between diabetes overtreatment and age or the severity of cognitive impairment. Among patients with neuroimaging data (N = 71), associations between overtreatment and grey matter loss were observed in several brain regions. Specifically, significant reductions in grey matter were found in the caudate (adj β coeff: -0.217, 95%CI: [-0.416 to -0.018], p =.033), the precentral gyri (adj βcoeff:-0.277, 95%CI: [-0.482 to -0.073], p =.009), the superior frontal gyri (adj βcoeff: -0.244, 95%CI: [-0.458 to -0.030], p =.026), the calcarine cortex (adj βcoeff:-0.193, 95%CI: [-0.386 to -0.001], p =.049), the superior occipital gyri (adj βcoeff: -0.291, 95%CI: [-0.521 to -0.061], p =.014) and the inferior occipital gyri (adj βcoeff: -0.236, 95%CI: [-0.456 to – 0.015], p =.036). Conclusion: A significant proportion of older patients with diabetes and neurocognitive disorder were subjected to excessively intensive treatment. The association identified with volume loss in several specific brain regions highlights the need to further investigate the potential cerebral damages associated with overtreatment and related hypoglycemia in larger sample. [ABSTRACT FROM AUTHOR]

Hypoglycemia is the most common metabolic alteration in the clinical routine of newborn dogs, acting as a predictor of mortality in these patients. The neonatal dog shows hepatic insufficiency and homeostatic mechanisms not yet fully developed, with limited glycogen reserves and limited capacity to perform glycogenolysis and gluconeogenesis. These physiological particularities make newborn dogs particularly susceptible to hypoglycemia when of fasting, even for short periods. Several maternal and neonatal factors may be related to a higher risk of developing hypoglycemia in neonates. This paper reviews glycemic homeostasis, the pathophysiology of neonatal hypoglycemia, the main causes involved and the diagnostic and therapeutic approaches to this condition. [ABSTRACT FROM AUTHOR]

Introduction: In 2022, updated guidance from NICE expanded the options for self-monitoring of blood glucose for patients with type 2 diabetes (T2DM), to include continuous glucose monitoring (CGM). In this budget impact analysis, the cost impact of CGM was compared with traditional self-monitoring of blood glucose (SMBG) in adults with T2DM over 1 year from the commissioner perspective in England. Research Design and methods: The NICE-eligible T2DM cohort was split into 4 subgroups to enable nuanced costing by insulin administration frequency: basal human insulin, premixed insulin, basal-bolus insulin and bolus insulin. The model's cost components comprised mild and severe hypoglycaemia (SH), diabetic ketoacidosis (DKA), consumables and healthcare resource utilisation in primary and secondary care. Results: The introduction of CGM is estimated to be cost additive by approximately £4.6 million in the basecase, driven by increased spending on the CGM device. Overall, healthcare activity was reduced by approximately 20,000 attendances, due to fewer SH and DKA episodes in the CGM arm. General Practitioner (GP) practice-based activity is expected to drop after the first year as patients requiring CGM training is reduced. The budget impact could be neutralised if the CGM sensor was discounted by 13.2% (£29.76 to £25.83). Conclusions: CGM may result in increased spending in the NICE-eligible T2DM cohort but is expected to reduce demand on secondary care services and GP time. These findings may be of interest to local decision-makers who wish to resolve the COVID-19 backlog with transformational investment in primary care to reduce secondary care activity. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate comorbidities, clinical features, laboratory values, and diagnoses in non-diabetic patients experiencing hypoglycemic episodes. Methods: A retrospective observational study was conducted at Shariati Hospital in Iran from 2016 to 2023. Seventy-four non-diabetic patients admitted with a diagnosis of hypoglycemia were included, while patients with diabetes were excluded. Demographic data, symptoms, and biochemical assessments were obtained from the hospital information system. Hypoglycemic episodes were identified based on low measured blood glucose, recorded medications for hypoglycemia treatment, or recorded codes indicating hypoglycemia. Hypoglycemia was defined as blood glucose below 70 mg/dL (3.9 mmol/L) along with two other criteria of the Whipple triad. Statistical analysis was performed using SPSS software (version 26). Results: Among the enrolled patients, 63.5% were female, and 13.5% were elderly (≥ 65 years). The most common comorbidities observed were cardiovascular disease (20.3%), psychological disorders (20.3%), hypothyroidism (14.9%), and hypertension (8.1%). The prevalent symptoms included weakness, loss of consciousness, sweating, palpitations, dizziness, and tremors. Non-diabetic hypoglycemia was caused by factitious disorders, insulinoma, organ failure, and infection, respectively. Conclusion: Due to the diverse range of clinical symptoms, hypoglycemia in non-diabetic patients may be diagnosed late, leading to misdiagnoses such as psychological disorders or seizures. It is crucial to consider the possibility of hypoglycemia in non-diabetic patients and determine its underlying cause. Given the poor prognosis associated with hypoglycemia, timely interventions are essential. [ABSTRACT FROM AUTHOR]

Objectives: Several studies have compared the basal-bolus (BB) and premixed (PM) insulin regimens with varying results. This study aimed to evaluate the glycemic control and occurrence of hypoglycemia with these regimens in insulin-naïve patients with type 2 diabetes mellitus (T2D) in the Indian subpopulation. Materials and Methods: This was a 12-week (wk) prospective, observational study in 60 adult patients (distributed 1:1) with >7 years of T2D and uncontrolled with three oral drugs. Changes in glycemic parameters at wk4 and wk12 were assessed, and hypoglycemia events were also recorded. Results: The PM insulin showed a significant decrease in fasting plasma glucose (FPG) at wk4 from baseline (P = 0.02) and at wk12 (P < 0.001), while in the BB insulin group, the change was significant only at wk12 (P < 0.0001). There were greater reductions in the PM group in FPG at wk4 (PM vs. BB: P = 0.04) and wk12 (P = 0.03) compared to the BB group. The post-prandial plasma glucose in both groups significantly reduced from baseline at wk4 (PM group P = 0.034; BB group; P = 0.034) and wk12 (PM group P < 0.0001 and BB group: P < 0.0001). However, there were no between-group differences at wk4 (P = 0.12) but only at wk12 (P = 0.009) with greater reductions in the PM group. The PM group showed a slightly greater reduction in glycated hemoglobin versus the BB group (9.18% vs. 7.08%; P = 0.39). There was no significant difference (P = 0.49) in the incidence of hypoglycemia. Conclusion: Both treatments significantly improved glycemic control and were not associated with any severe episodes of hypoglycemia. Therefore, the choice should instead be guided by the insulin-related (posology, complexity) and patient-related (dietary habits, adherence levels) factors. [ABSTRACT FROM AUTHOR]

This case report delineates the clinical presentation of a 77-year-old male who experienced falls and sustained a humerus fracture attributed to hypoglycemia. Despite the absence of insulin use and normal laboratory results for cortisol, TSH, blood count, and liver and kidney function, a fasting test revealed diminished C-peptide and insulin levels, ruling out insulinoma, exogenous insulin use, or β-cell hyperplasia. Subsequent laboratory investigations demonstrated lowered IGF-1 and elevated IGF-2 levels, indicative of an IGF-2-producing tumor as the etiology of the hypoglycemia. A positron emission tomography computed tomography scan identified a right-sided thoracic cavity tumor, prompting an open resection. Postoperatively, hypoglycemic episodes abated within 2 days, and pathology confirmed a 14.9-cm solitary fibrous tumor. Nonislet cell tumor hypoglycemia (NICTH), also known as Doege Potter syndrome, arises from aberrant production of IGF-2 or its precursors. Elevated IGF-2 levels induce hypoglycemia through heightened glucose uptake on binding to insulin receptors. The literature supports the efficacy of both surgical intervention and corticosteroids in managing NICTH. This case underscores the importance of considering NICTH as a rare etiology in unexplained hypoglycemia cases, advocating for the utility of fasting tests in diagnosis, and suggesting surgical resection as a viable treatment option when radical excision is feasible. [ABSTRACT FROM AUTHOR]

Background: Guidelines recommend deintensifying hypoglycemia-causing medications for older adults with diabetes whose hemoglobin A1c is below their individualized target, but this rarely occurs in practice. Objective: To understand physicians' decision-making around deintensifying diabetes treatment. Design: National physician survey. Participants: US physicians in general medicine, geriatrics, or endocrinology providing outpatient diabetes care. Main Measures: Physicians rated the importance of deintensifying diabetes medications for older adults with type 2 diabetes, and of switching medication classes, on 5-point Likert scales. They reported the frequency of these actions for their patients, and listed important barriers and facilitators. We evaluated the independent association between physicians' professional and practice characteristics and the importance of deintensifying and switching diabetes medications using multivariable ordered logistic regression models. Key Results: There were 445 eligible respondents (response rate 37.5%). The majority of physicians viewed deintensifying (80%) and switching (92%) diabetes medications as important or very important to the care of older adults. Despite this, one-third of physicians reported deintensifying diabetes medications rarely or never. While most physicians recognized multiple reasons to deintensify, two-thirds of physicians reported barriers of short-term hyperglycemia and patient reluctance to change medications or allow higher glucose levels. In multivariable models, geriatricians rated deintensification as more important compared to other specialties (p=0.027), and endocrinologists rated switching as more important compared to other specialties (p<0.006). Physicians with fewer years in practice rated higher importance of deintensification (p<0.001) and switching (p=0.003). Conclusions: While most US physicians viewed deintensifying and switching diabetes medications as important for the care of older adults, they deintensified infrequently. Physicians had ambivalence about the relative benefits and harms of deintensification and viewed it as a potential source of conflict with their patients. These factors likely contribute to clinical inertia, and studies focused on improving shared decision-making around deintensifying diabetes medications are needed. [ABSTRACT FROM AUTHOR]

Aim: The sympathetic nervous and hormonal counterregulatory responses to hypoglycaemia differ between people with type 1 and type 2 diabetes and may change along the course of diabetes, but have not been directly compared. We aimed to compare counterregulatory hormone and symptom responses to hypoglycaemia between people with type 1 diabetes, insulin-treated type 2 diabetes and controls without diabetes, using a standardised hyperinsulinaemic-hypoglycaemic clamp. Materials: We included 47 people with type 1 diabetes, 15 with insulin-treated type 2 diabetes, and 32 controls without diabetes. Controls were matched according to age and sex to the people with type 1 diabetes or with type 2 diabetes. All participants underwent a hyperinsulinaemic–euglycaemic-(5.2 ± 0.4 mmol/L)-hypoglycaemic-(2.8 ± 0.13 mmol/L)-clamp. Results: The glucagon response was lower in people with type 1 diabetes (9.4 ± 0.8 pmol/L, 8.0 [7.0–10.0]) compared to type 2 diabetes (23.7 ± 3.7 pmol/L, 18.0 [12.0–28.0], p < 0.001) and controls (30.6 ± 4.7, 25.5 [17.8–35.8] pmol/L, p < 0.001). The adrenaline response was lower in type 1 diabetes (1.7 ± 0.2, 1.6 [1.3–5.2] nmol/L) compared to type 2 diabetes (3.4 ± 0.7, 2.6 [1.3–5.2] nmol/L, p = 0.001) and controls (2.7 ± 0.4, 2.8 [1.4–3.9] nmol/L, p = 0.012). Growth hormone was lower in people with type 2 diabetes than in type 1 diabetes, at baseline (3.4 ± 1.6 vs 7.7 ± 1.3 mU/L, p = 0.042) and during hypoglycaemia (24.7 ± 7.1 vs 62.4 ± 5.8 mU/L, p = 0.001). People with 1 diabetes had lower overall symptom responses than people with type 2 diabetes (45.3 ± 2.7 vs 58.7 ± 6.4, p = 0.018), driven by a lower neuroglycopenic score (27.4 ± 1.8 vs 36.7 ± 4.2, p = 0.012). Conclusion: Acute counterregulatory hormone and symptom responses to experimental hypoglycaemia are lower in people with type 1 diabetes than in those with long-standing insulin-treated type 2 diabetes and controls. [ABSTRACT FROM AUTHOR]

Objective: Determine whether continuous glucose monitor (CGM) metrics can provide actionable advance warning of an emergency department (ED) visit or hospitalization for hypoglycemic or hyperglycemic (dysglycemic) events. Research Design and Methods: Two nested case–control studies were conducted among insulin-treated diabetes patients at Kaiser Permanente, who shared their CGM data with their providers. Cases included dysglycemic events identified from ED and hospital records (2016–2021). Controls were selected using incidence density sampling. Multiple CGM metrics were calculated among patients using CGM >70% of the time, using CGM data from two lookback periods (0–7 and 8–14 days) before each event. Generalized estimating equations were specified to estimate odds ratios and C-statistics. Results: Among 3626 CGM users, 108 patients had 154 hypoglycemic events and 165 patients had 335 hyperglycemic events. Approximately 25% of patients had no CGM data during either lookback; these patients had >2 × the odds of a hypoglycemic event and 3–4 × the odds of a hyperglycemic event. While several metrics were strongly associated with a dysglycemic event, none had good discrimination. Conclusion: Several CGM metrics were strongly associated with risk of dysglycemic events, and these can be used to identify higher risk patients. Also, patients who are not using their CGM device may be at elevated risk of adverse outcomes. However, no CGM metric or absence of CGM data had adequate discrimination to reliably provide actionable advance warning of an event and thus justify a rapid intervention. [ABSTRACT FROM AUTHOR]

Older adults with type 1 diabetes may face challenges driving safely. Glucose "above-5-to-drive" is often recommended for insulin-treated diabetes to minimize hypoglycemia while driving. However, the effectiveness of this recommendation among older adults has not been evaluated. Older drivers with type 1 diabetes were assessed while using sensor-augmented insulin pumps during a 2-week clinical trial run-in. Twenty-three drivers (median age 69 years [interquartile range; IQR 65–72]; diabetes duration 37 years [20–45]) undertook 618 trips (duration 10 min [5–21]). Most trips (n = 535; 87%) were <30 min duration; 9 trips (1.5%) exceeded 90 min and 3 trips (0.5%) exceeded 120 min. Pre-trip continuous glucose monitoring (CGM) was >5.0 mmol/L for 577 trips (93%) and none of these had CGM <3.9 mmol/L during driving (including 8 trips >90 min and 3 trips >120 min). During 41 trips with pre-trip CGM ≤5.0 mmol/L, 11 trips had CGM <3.9 mmol/L. Seventy-one CGM alerts occurred during 60 trips (10%), of which 54 of 71 alerts (76%) were unrelated to hypoglycemia. Our findings support a glucose "above-5-to-drive" recommendation to avoid CGM-detected hypoglycemia among older drivers, including for prolonged drives, and highlight the importance of active CGM low-glucose alerts to prevent hypoglycemia during driving. Driving-related CGM usability and alert functionality warrant investigation. Clinical trial ACTRN1261900515190 [ABSTRACT FROM AUTHOR]

Background: Few studies have evaluated the implications of the alarm thresholds of continuous glucose monitoring (CGM) systems for individuals with diabetes. The present study aimed to investigate the influence of hypoglycemia and hyperglycemia alarm thresholds on glycemic control in adults with type 1 diabetes (T1DM) and the characteristics of patients who use these alarms more frequently. Methods: This observational cross-sectional study included 873 users of the FreeStyle Libre 2 system (501 men, median age 48 years, range 18–90 years) with T1DM from a single center. We investigated the role of demographic and metabolic factors on the use of alarms and the impact of hypoglycemia and hyperglycemia alarms and their thresholds on glycemic control. Results: Alarm users were older than nonusers (median age 49 vs. 43 years, respectively; P < 0.001). The hypoglycemia alarms were set by 76.1% of women and by 69.1% of men (P = 0.022). The hypoglycemia alarms reduced hypoglycemia features and glucose variability, although at the expense of shorter time in range. The higher the hypoglycemia alarm threshold, the greater these effects. The hyperglycemia alarms were effective in reducing hyperglycemia and lowering the glucose management indicator, although at the expense of a greater tendency to hypoglycemia. The lower the hyperglycemia alarm threshold, the greater these effects. Conclusions: CGM alarms contribute to better glycemic control. However, hypoglycemia and hyperglycemia alarms have advantages and disadvantages. Adults with T1DM should explore, under medical supervision, which alarm thresholds will best help them achieve their individual glycemic goals. [ABSTRACT FROM AUTHOR]

Background: Altered prandial glycemic response after Roux‐en‐Y gastric bypass (RYGB) is exaggerated in patients with post‐RYGB hypoglycemia. Increased contribution of glucagon‐like peptide 1 (GLP‐1) to prandial insulin secretion plays a key role in developing hypoglycemia after RYGB, but the role of nonhormonal gut factors remains unknown. Here, the effect of vagal activation on prandial bile acid (BA) composition in relation to glucose, insulin and gut hormone responses was examined in a small size group of nondiabetic subjects after RYGB with intact gallbladder compared to nonoperated controls. Methods: Concentrations of blood glucose, hormones, and BAs were measured in two RYGB subjects with documented hypoglycemia (HGB), three asymptomatic RYGB‐treated subjects (AGB), and four nonoperated controls with intact gallbladders during a meal‐tolerance test with (MTT‐Sham) and without (MTT) preceding modified sham feeding (chew and spit). Key Results: Meal ingestion raised serum total BAs in RYGB‐treated subjects without any effect in nonoperated controls. Modified sham feeding similarly increased meal‐induced responses of conjugated BAs (CBAs) in all subjects (p < 0.05 compared to MTT alone), whereas unconjugated BAs (UBAs), mainly deoxycholic and chenodeoxycholic acid, were raised only in the HGB group (p < 0.001 for interaction). Prandial UBAs had an inverse correlation with glucose nadir (r = −0.75, p < 0.05) and were directly associated with ISR and GLP‐1 during MTT‐Sham. Conclusions & Inferences: In this small cohort, vagal activation by modified sham feeding increases prandial CBAs in both operated and nonoperated subjects but enhances UBAs only in patients with documented post‐RYGB hypoglycemia. Our findings highlight a potential role for nonhormonal gut factors, such as BA and gut microbiome, in glucose abnormalities after RYGB. [ABSTRACT FROM AUTHOR]

Background: The utility of sodium‐glucose cotransporter 2 inhibitors (SGLT2i) has not been reported in insulin‐treated diabetic dogs. Hypothesis: Canagliflozin, a PO‐administered SGLT2i, decreases interstitial glucose concentration (IG) in insulin‐treated diabetic dogs. Animals: Five insulin‐treated diabetic dogs. Methods: Uncontrolled open label longitudinal study. Canagliflozin (2‐4 mg/kg/day PO) was added to an unchanged insulin dose for 7 days. Fractional excretion of glucose was calculated by dividing the product of urine glucose and serum creatinine concentrations by the product of serum glucose and urine creatinine concentrations. Hypoglycemia was defined as IG <60 mg/dL. Results: Median IG in 2869 measurements obtained while dogs were treated with insulin and canagliflozin was 87 mg/dL (range, 40‐500 mg/dL) and was significantly lower than median IG in 1426 measurements obtained while dogs were treated with insulin alone (212 mg/dL; range, 41‐500 mg/dL; P <.001). Median fractional excretion of glucose when dogs were treated with insulin and canagliflozin was 1.1% (range, 0.9%‐2.0%), significantly higher than when dogs were treated with insulin alone (0.3%; range, 0.01%‐1.0%; P =.04). The frequency of hypoglycemia was higher in dogs treated with insulin and canagliflozin (544 of 2869 IG measurements, 19%) compared with the frequency of hypoglycemia in dogs treated with insulin alone (52 of 1426 IG measurements, 4%; P <.001). Conclusions and Clinical Importance: Canagliflozin may have a role in improving glycemic control in insulin‐treated diabetic dogs, but the dose of insulin should be decreased when adding canagliflozin to insulin treatment. [ABSTRACT FROM AUTHOR]

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

Objective: Diabetes is a chronic disease that causes the development of microalbuminuria. CoQlO deficiency is common in people with type 2 diabetes. This study aims to evaluate whether coenzyme Q10 (CoQlO) levels are a risk factor for diabetes and microalbuminuria in newly diagnosed diabetes and advanced microalbuminuria. Material and Method: The study was conducted with patients who came to the internal medicine outpatient clinic. Plasma CoQlO and malondialdehyde (MDA) values of 90 people in total, including 30 people in each group, newly diagnosed Type 2 diabetes (Group D), diabetes mellitus with microalbuminuria (Group M), and the control group (Group C) were examined. Results: There was no difference between plasma CoQlO and MDA levels of newly diagnosed type 2 diabetes patients and those with microalbuminuria (p>0.05). There was a negative correlation between CoQlO and fasting glucose and HbAlc in all groups (p<0.05). A positive correlation was observed between CoQlO and MDA (p<0.05). CoQlO level of the control group was found to be higher than Group D and M (p<0.05); the difference between Group M and Group D was not significant (p>0.05). As a result of regression analysis, increasing the CoQlO value was found to have a protective effect on the risk of diabetes (95 %CI: p=0.005). Conclusion: This study showed that individuals with low blood sugar and HbAlc had high CoQlO levels. We think that CoQlO can be considered a risk factor for diabetes, and further studies examining total CoQlO and ubiquinol/ubiquinone ratio would be beneficial. [ABSTRACT FROM AUTHOR]

Background: Hypophosphatemia due to excessive carbohydrate administration is considered the primary pathogenesis of refeeding syndrome. However, its association with liver injury and hypoglycemia, often seen in severe malnutrition before re-nutrition, remains unclear. Autophagy reportedly occurs in the liver of patients with severe malnutrition. This study aimed to clarify the pathophysiology of liver injury and hypoglycemia by focusing on liver volume. Methods: Forty-eight patients with anorexia nervosa with a body mass index (BMI) of < 13 kg/m2 were included (median BMI: 10.51 kg/m2 on admission). Liver volume was measured in 36 patients who underwent abdominal computed tomography (CT), and the "estimated liver weight/ideal body weight" was used as the liver volume index. Seventeen blood test items were analyzed during the first 60 days. Results: Liver volume significantly decreased when abdominal CTs were conducted shortly before or after hypoglycemia compared to when the scans were performed during periods without hypoglycemia. Five patients with severe hypoglycemia on days 13–18 after admission had a very low nutritional intake; of them, four showed a marked decrease in liver volume. Severe hypoglycemia was accompanied by low serum triglycerides and liver dysfunction. Patients experiencing hypoglycemia of blood glucose levels < 55 mg/dL (< 3.05 mmol/L) (32 patients; median lowest BMI: 9.45 kg/m2) exhibited significantly poorer blood findings for most of the 17 items, except serum phosphorus and potassium, than did those not experiencing hypoglycemia (16 patients; median lowest BMI: 11.2 kg/m2). All patients with a poor prognosis belonged to the hypoglycemia group. Empirically, initiating re-nutrition at 500 kcal/day (20–25 kcal/kg/day), increasing to 700–800 kcal/day after a week, and then gradually escalating can reduce serious complications following severe hypoglycemia. Conclusions: Liver volume reduction accompanied by hypoglycemia, low serum triglyceride levels, and liver dysfunction occurs when the body's stored energy sources are depleted and external nutritional intake is inadequate, suggesting that the liver was consumed as a last resort to obtain energy essential for daily survival. This pathophysiology, distinct from refeeding syndrome, indicates the terminal stage of malnutrition and is a risk factor for complications and poor prognosis. In treatment, extremely low nutrient levels should be avoided. Plain English summary: This study aimed to clarify the pathophysiology of severe malnutrition in patients with anorexia nervosa by focusing on liver volume. The small size of the liver was almost always accompanied by hypoglycemia within a week. In several cases, extremely low nutritional intake, continued for approximately 2 weeks after admission, resulted in severe hypoglycemia and a marked decrease in liver volume. The 32 patients with hypoglycemia presented worse blood test items related to liver function, nutrition, and blood cell count compared to the 16 patients without such a condition. All cases with poor prognosis were in the hypoglycemia group. These findings suggest that severe hypoglycemia with decreased liver volume indicates the end stage of malnutrition. Liver volume reduction is considered a reflection of the liver's consumption of itself as a last resort for energy procurement for daily survival when the body's stored energy sources are depleted, and external nutritional intake is insufficient. When managing such patients, extremely low nutritional administration should be avoided. [ABSTRACT FROM AUTHOR]

Introduction: Neonatal hypoglycemia is a common complication associated with gestational diabetes and therefore relevant to consider in evaluations of maternal treatment. We aimed to investigate the risk of neonatal hypoglycemia in offspring exposed to metformin treatment alone (MT) or combined with insulin (MIT) in comparison with nutrition therapy alone (NT), and insulin treatment alone (IT). In addition, we investigated MT in comparison with MIT. Secondary outcomes included neonatal anthropometrics, respiratory morbidity, hyperbilirubinemia, 5‐min Apgar score, and preterm birth. Material and methods: This Swedish population‐based cohort included 16 181 women diagnosed with gestational diabetes, and their singleton offspring born in 2019–2021. We estimated risk as adjusted odds ratio (aOR) with 95% confidence interval (CI), using individual‐level, linkage register‐data in multivariable logistic regression models. Results: In the main analysis, MT was associated with a lower risk of neonatal hypoglycemia vs NT (aOR 0.85, 95% CI: 0.74–0.96), vs MIT (0.74 [0.64–0.87]), and vs IT (0.47 [0.40–0.55]), whereas MIT was associated with a similar risk of neonatal hypoglycemia vs NT (1.14 [0.99–1.30]) and with lower risk vs IT (0.63 [0.53–0.75]). However, supplemental feeding rates were lower for NT vs pharmacological treatments (p < 0.001). In post hoc subgroup analyses including only exclusively breastfed offspring, the risk of neonatal hypoglycemia was modified and similar among MT and NT, and higher in MIT vs NT. Insulin exposure, alone or combined with metformin, was associated with increased risk of being large for gestational age. Compared with NT, exposure to any pharmacological treatment was associated with significantly lower risk of 5‐min Apgar score < 4. All other secondary outcomes were comparable among the treatment categories. Conclusions: The risk of neonatal hypoglycemia appears to be comparable among offspring exposed to single metformin treatment and nutrition therapy alone, and the lower risk that we observed in favor of metformin is probably explained by a difference in supplemental feeding practices rather than metformin per se. By contrast, the lower risk favoring metformin exposure over insulin exposure was not explained by supplemental feeding. However, further investigations are required to determine whether the difference is an effect of metformin per se or mediated by other external factors. [ABSTRACT FROM AUTHOR]

One of the most important bulbs crops farmed in India is garlic (Allium sativum L.). It is a rich source of bioactive substances that satisfy a person’s daily nutritional demands for well-being. Allicin is the most prominent bioactive compound in garlic that exhibits various pharmacological properties including highly antioxidant, anticancer, anti-inflammatory, cardioprotective, neuroprotective, anti-diabetic, antimicrobial, anti-aging, and anti-hyperlipidemic effects. It offers defense against a variety of malignancies such as asthma, bronchitis, hemorrhoids, fever, cough, headache, stomach discomfort, low and high blood sugar, and snakebites can all be treated with garlic. Raw garlic has been proven the ‘Panacea’ for cardiovascular and heart-related diseases since earlier ago. This review emphasizes the biological role of this wonderful medicinal plant in the treatment of various ailments. The medicinal effects of different constituents of this plant have been also addressed. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore 24-h postexercise glycemia and hypoglycemia risk, data from the Type 1 Diabetes Exercise Initiative Pediatric (T1DEXIP) study were analyzed to examine factors that may influence glycemia. RESEARCH DESIGN AND METHODS: This was a real-world observational study with participant self-reported physical activity, food intake, and insulin dosing (multiple daily injection users). Heart rate, continuous glucose data, and available pump data were collected. RESULTS: A total of 251 adolescents (42% females), with a mean ± SD age of 14 ± 2 years, and hemoglobin A1c (HbA1c) of 7.1 ± 1.3% (54 ± 14.2 mmol/mol), recorded 3,319 activities over ∼10 days. Trends for lower mean glucose after exercise were observed in those with shorter disease duration and lower HbA1c; no difference by insulin delivery modality was identified. Larger glucose drops during exercise were associated with lower postexercise mean glucose levels, immediately after activity (P < 0.001) and 12 to <16 h later (P = 0.02). Hypoglycemia occurred on 14% of nights following exercise versus 12% after sedentary days. On nights following exercise, more hypoglycemia occurred when average total activity was ≥60 min/day (17% vs. 8% of nights, P = 0.01) and on days with longer individual exercise sessions. Higher nocturnal hypoglycemia rates were also observed in those with longer disease duration, lower HbA1c, conventional pump use, and if time below range was ≥4% in the previous 24 h. CONCLUSIONS: In this large real-world pediatric exercise study, nocturnal hypoglycemia was higher on nights when average activity duration was higher. Characterizing both participant- and event-level factors that impact glucose in the postexercise recovery period may support development of new guidelines, decision support tools, and refine insulin delivery algorithms to better support exercise in youth with diabetes. [ABSTRACT FROM AUTHOR]

Glucose, the primary energy substrate for fetal oxidative processes and growth, is transferred from maternal to fetal circulation down a concentration gradient by placental facilitative glucose transporters. In sheep, SLC2A1 and SLC2A3 are the primary transporters available in the placental epithelium, with SLC2A3 located on the maternal-facing apical trophoblast membrane and SLC2A1 located on the fetal-facing basolateral trophoblast membrane. We have previously reported that impaired placental SLC2A3 glucose transport resulted in smaller, hypoglycemic fetuses with reduced umbilical artery insulin and glucagon concentrations, in addition to diminished pancreas weights. These findings led us to subject RNA derived from SLC2A3-RNAi (RNA interference) and NTS-RNAi (non-targeting sequence) fetal pancreases to qPCR followed by transcriptomic analysis. We identified a total of 771 differentially expressed genes (DEGs). Upregulated pathways were associated with fat digestion and absorption, particularly fatty acid transport, lipid metabolism, and cholesterol biosynthesis, suggesting a potential switch in energetic substrates due to hypoglycemia. Pathways related to molecular transport and cell signaling in addition to pathways influencing growth and metabolism of the developing pancreas were also impacted. A few genes directly related to gluconeogenesis were also differentially expressed. Our results suggest that fetal hypoglycemia during the first half of gestation impacts fetal pancreas development and function that is not limited to β cell activity. [ABSTRACT FROM AUTHOR]

Background: Hyperinsulinism (HI) due to dysregulation of pancreatic beta-cell insulin secretion is the most common and most severe cause of persistent hypoglycemia in infants and children. In the 65 years since HI in children was first described, there has been a dramatic advancement in the diagnostic tools available, including new genetic techniques and novel radiologic imaging for focal HI; however, there have been almost no new therapeutic modalities since the development of diazoxide. Summary: Recent advances in neonatal research and genetics have improved our understanding of the pathophysiology of both transient and persistent forms of neonatal hyperinsulinism. Rapid turnaround of genetic test results combined with advanced radiologic imaging can permit identification and localization of surgically-curable focal lesions in a large proportion of children with congenital forms of HI, but are only available in certain centers in "developed" countries. Diazoxide, the only drug currently approved for treating HI, was recently designated as an "essential medicine" by the World Health Organization but has been approved in only 16% of Latin American countries and remains unavailable in many under-developed areas of the world. Novel treatments for HI are emerging, but they await completion of safety and efficacy trials before being considered for clinical use. Key Messages: This international consensus statement on diagnosis and management of HI was developed in order to assist specialists, general pediatricians, and neonatologists in early recognition and treatment of HI with the ultimate aim of reducing the prevalence of brain injury caused by hypoglycemia. A previous statement on diagnosis and management of HI in Japan was published in 2017. The current document provides an updated guideline for management of infants and children with HI and includes potential accommodations for less-developed regions of the world where resources may be limited. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Transport of neonates from peripheral health centres to advanced neonatal intensive care units which are concentrated in urban areas is a necessity in India. The transport of newborn baby by a skilled and organised team reduces neonatal mortality and morbidity. Among the various pretransport and posttransport neonatal assessment scores, TOPS score, a bedside score to assess acute physiological parameters was chosen for the study. AIMS: To study the correlation of TOPS Score with survival rate among referred neonates. MATERIALS AND METHODS: TOPS score was assessed for 101 outborn neonates referred to tertiary teaching hospital during the study period. RESULTS: Among the study population, 67% were male, 57% were term, 60% had normal birth weight. At time of admission, 38% neonates had hypoxia, 12% had hypoperfusion, 10% had hypothermia, 2% had hypoglycaemia. TOPS score <2 was associated with survival and >2 was associated with significant mortality. CONCLUSION: TOPS score is a simple, bedside test to determine prognosis of referred neonates. It also helps to monitor care received by the neonates during transport. Appropriate care during transport is essential to decrease neonatal mortality. [ABSTRACT FROM AUTHOR]

Aims: Combining insulin with a glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) to treat type 2 diabetes (T2D) is common. While many studies have investigated concomitant therapy with basal insulin+GLP‐1RA, few have reported on premixed insulin+GLP‐1RA. We aimed to address this gap using data from the Clinical Practice Research Datalink Aurum database in England. Methods: This retrospective cohort study with propensity score matching assessed glycaemic levels and other clinical outcomes in people with T2D, comparing biphasic insulin aspart 30/70 (BIAsp 30) + GLP‐1RA with basal insulin (insulin detemir/glargine U100) + GLP‐1RA (from 2006 to 2021). Results: In total, 4770 eligible people were identified; 1511 had a BIAsp 30 + GLP‐1RA regimen and were propensity score‐matched to an equal number receiving basal+GLP‐1RA. There was no significant difference in glycated haemoglobin (HbA1c) reduction between cohorts at 6 months (p = 0.15), with a decrease of −1.07 (95% CI: −1.16; −0.98) %‐points (−11.7 mmol/mol [95% CI: −12.7; –10.7]) in the BIAsp 30 + GLP‐1RA cohort, versus −0.97 (95% CI: −1.07; −0.88) %‐points (−10.6 mmol/mol [95% CI: −11.7; –9.6]) in the basal+GLP‐1RA cohort. Body mass index (BMI) decreased by −0.35 kg/m2 (95% CI: −0.52;−0.18) at 6 months with BIAsp 30 + GLP‐1RA, versus −0.72 kg/m2 (95% CI: −0.90;−0.54) with basal+GLP‐1RA (p = 0.003). BMI was influenced by the initiation sequence of GLP‐1RA in relation to insulin (p < 0.0001). Hypoglycaemia rates were low and not significantly different between cohorts. Conclusions: Combining BIAsp 30 + GLP‐1RA provides glycaemic control with no significant difference to that of propensity score‐matched people receiving basal insulin+GLP‐1RA, with no increase in hypoglycaemia risk or weight gain. [ABSTRACT FROM AUTHOR]