Impact on diabetes control and patient-reported outcomes of a newer implantable continuous glucose monitoring system (Eversense® CGM System): a single-centre retro- and prospective observational study.

AIMS OF THE STUDY: The Eversense® CGM System is the first and only continuous glucose monitoring system (CGMS) that uses a fully subcutaneous implanted sensor. This study aimed to evaluate effectiveness, safety and patient-reported outcomes in patients using the Eversense® CGM System in a realistic clinical setting, assessed at a single Swiss diabetes centre (Luzerner Kantonsspital) with prolonged follow-up. METHODS: This was a prospective and retrospective observational study that included patients with type 1 diabetes mellitus in whom at least one Eversense® glucose sensor was implanted between 2017 and 2022. The primary endpoint was the change in HbA1c levels from the baseline (before implantation of the sensor) to 6 ± 2 and 12 ± 2 months and the last follow-up (newest available value) after implantation. The secondary outcome measures were the number of premature sensor breakdowns, adverse events related to the implantation procedure (infection, bleeding, difficulties with implantation or explantation) and patient-related outcomes (assessed with a questionnaire). RESULTS: A total of 33 patients participated in this study. The median follow-up time was 50 (IQR 22.3-58.5) months. In total, 178 sensor implantations were performed. Valid HbA1c results were available for 26 participants. Compared to the baseline values, HbA1c levels at 6 and 12 months and the last follow-up changed by -0.25%, -0.45 and -0.2 (p = 0.278, 0.308 and 0.296, respectively). We recorded 16 (9%) premature sensor breakdowns, all occurring between 2019 and 2020. Apart from one late-onset infection and four complicated sensor removals, no major complications were assessed. The results of the questionnaire showed a subjective improvement in hypoglycaemia rates, a better perception of hypoglycaemia and the impression of better diabetes management. Common issues with the device reported by the patients were technical errors (connection problems) and problems with the removal procedure. CONCLUSIONS: The use of the Eversense® CGM System resulted in changes in HbA1c of between -0.2% and -0.45%. The rate of premature sensor breakdown was low. Major complications following sensor implantation or removal were absent, apart from one case of infection and four cases of complicated removal. Patient-reported outcomes with the Eversense® CGM System showed a subjective positive impact on hypoglycaemia rates, greater confidence in managing hypoglycaemia and diabetes in general, and easy handling of the transmitter and mobile app. Technical issues must be considered but are nowadays, with the use of the newest sensor generation, very rare.

Long-term assessment of the NHS hybrid closed-loop real-world study on glycaemic outcomes, time-in-range, and quality of life in children and young people with type 1 diabetes.

Hybrid closed-loop (HCL) systems seamlessly interface continuous glucose monitoring (CGM) with insulin pumps, employing specialised algorithms and user-initiated automated insulin delivery. This study aimed to assess the efficacy of HCLs at 12 months post-initiation on glycated haemoglobin (HbA1c), time-in-range (TIR), hypoglycaemia frequency, and quality of life measures among children and young people (CYP) with type 1 diabetes mellitus (T1DM) and their caregivers in a real-world setting. Conducted between August 1, 2021, and December 10, 2022, the prospective recruitment took place in eight paediatric diabetes centres across England under the National Health Service England's (NHSE) HCL pilot real-world study. A cohort of 251 CYP (58% males, mean age 12.3 years) with T1DM participated (89% white, 3% Asian, 4% black, 3% mixed ethnicity, and 1% other). The study utilised three HCL systems: (1) Tandem Control-IQ AP system, which uses the Tandem t:slim X2 insulin pump (Tandem Diabetes Care, San Diego, CA, USA) with the Dexcom G6® CGM (Dexcom, San Diego, CA, USA) sensor; (2) Medtronic MiniMed™ 780G with the Guardian 4 sensor (Medtronic, Northridge, CA, USA); and (3) the CamAPS FX (CamDiab, Cambridge, UK) with the Ypsomed insulin pump (Ypsomed Ltd, Escrick, UK) and Dexcom G6® CGM.All systems were fully funded by the NHS. Results demonstrated significant improvements in HbA1c (average reduction at 12 months 7 mmol/mol; P < 0.001), time-in-range (TIR) (average increase 13.4%; P < 0.001), hypoglycaemia frequency (50% reduction), hypoglycaemia fear, and quality of sleep (P < 0.001) among CYP over a 12-month period of HCL usage. Additionally, parents and carers experienced improvements in hypoglycaemia fear and quality of sleep after 6 and 12 months of use. In addition to the improvements in glycaemic management, these findings underscore the positive impact of HCL systems on both the well-being of CYP with T1DM and the individuals caring for them.

Multimodal In-Vehicle Hypoglycemia Warning for Drivers With Type 1 Diabetes: Design and Evaluation in Simulated and Real-World Driving.

BACKGROUND: Hypoglycemia threatens cognitive function and driving safety. Previous research investigated in-vehicle voice assistants as hypoglycemia warnings. However, they could startle drivers. To address this, we combine voice warnings with ambient LEDs. OBJECTIVE: The study assesses the effect of in-vehicle multimodal warning on emotional reaction and technology acceptance among drivers with type 1 diabetes. METHODS: Two studies were conducted, one in simulated driving and the other in real-world driving. A quasi-experimental design included 2 independent variables (blood glucose phase and warning modality) and 1 main dependent variable (emotional reaction). Blood glucose was manipulated via intravenous catheters, and warning modality was manipulated by combining a tablet voice warning app and LEDs. Emotional reaction was measured physiologically via skin conductance response and subjectively with the Affective Slider and tested with a mixed-effect linear model. Secondary outcomes included self-reported technology acceptance. Participants were recruited from Bern University Hospital, Switzerland. RESULTS: The simulated and real-world driving studies involved 9 and 10 participants with type 1 diabetes, respectively. Both studies showed significant results in self-reported emotional reactions (P<.001). In simulated driving, neither warning modality nor blood glucose phase significantly affected self-reported arousal, but in real-world driving, both did (F2,68=4.3; P<.05 and F2,76=4.1; P=.03). Warning modality affected self-reported valence in simulated driving (F2,68=3.9; P<.05), while blood glucose phase affected it in real-world driving (F2,76=9.3; P<.001). Skin conductance response did not yield significant results neither in the simulated driving study (modality: F2,68=2.46; P=.09, blood glucose phase: F2,68=0.3; P=.74), nor in the real-world driving study (modality: F2,76=0.8; P=.47, blood glucose phase: F2,76=0.7; P=.5). In both simulated and real-world driving studies, the voice+LED warning modality was the most effective (simulated: mean 3.38, SD 1.06 and real-world: mean 3.5, SD 0.71) and urgent (simulated: mean 3.12, SD 0.64 and real-world: mean 3.6, SD 0.52). Annoyance varied across settings. The standard warning modality was the least effective (simulated: mean 2.25, SD 1.16 and real-world: mean 3.3, SD 1.06) and urgent (simulated: mean 1.88, SD 1.55 and real-world: mean 2.6, SD 1.26) and the most annoying (simulated: mean 2.25, SD 1.16 and real-world: mean 1.7, SD 0.95). In terms of preference, the voice warning modality outperformed the standard warning modality. In simulated driving, the voice+LED warning modality (mean rank 1.5, SD rank 0.82) was preferred over the voice (mean rank 2.2, SD rank 0.6) and standard (mean rank 2.4, SD rank 0.81) warning modalities, while in real-world driving, the voice+LED and voice warning modalities were equally preferred (mean rank 1.8, SD rank 0.79) to the standard warning modality (mean rank 2.4, SD rank 0.84). CONCLUSIONS: Despite the mixed results, this paper highlights the potential of implementing voice assistant-based health warnings in cars and advocates for multimodal alerts to enhance hypoglycemia management while driving. TRIAL REGISTRATION: ClinicalTrials.gov NCT05183191; https://classic.clinicaltrials.gov/ct2/show/NCT05183191, ClinicalTrials.gov NCT05308095; https://classic.clinicaltrials.gov/ct2/show/NCT05308095.

Current barriers to initiating insulin therapy in individuals with type 2 diabetes.

Insulin is an essential drug in the treatment of diabetes, often necessary for managing hyperglycemia in type 2 diabetes mellitus (T2DM). It should be considered in cases of severe hyperglycemia requiring hospitalization, after the failure of other treatments, in advanced chronic kidney disease, liver cirrhosis, post-transplant diabetes, or during pregnancy. Moreover, in specific patient subgroups, early initiation of insulin is crucial for hyperglycemia control and prevention of chronic complications. Clinical guidelines recommend initiating insulin when other treatments fail, although there are barriers that may delay its initiation. The timing of initiation depends on individual patient characteristics. Typically, insulinization starts by adding basal insulin to the patient's existing treatment and, if necessary, progresses by gradually introducing prandial insulin. Several barriers have been identified that hinder the initiation of insulin, including fear of hypoglycemia, lack of adherence, the need for glucose monitoring, the injection method of insulin administration, social rejection associated with the stigma of injections, weight gain, a sense of therapeutic failure at initiation, lack of experience among some healthcare professionals, and the delayed and reactive positioning of insulin in recent clinical guidelines. These barriers contribute, among other factors, to therapeutic inertia in initiating and intensifying insulin treatment and to patients' non-adherence. In this context, the development of once-weekly insulin formulations could improve initial acceptance, adherence, treatment satisfaction, and consequently, the quality of life for patients. Currently, two once-weekly basal insulins, insulin icodec and basal insulin BIF, which are in different stages of clinical development, may help. Their longer half-life translates to lower variability and reduced risk of hypoglycemia. This review addresses the need for insulin in T2DM, its positioning in clinical guidelines under specific circumstances, the current barriers to initiating and intensifying insulin treatment, and the potential role of once-weekly insulin formulations as a potential solution to facilitate timely initiation of insulinization, which would reduce therapeutic inertia and achieve better early control in people with T2DM.

Secondary Polycythemia and Non-Islet Cell Tumor-induced Hypoglycemia in Advanced Hepatocellular Carcinoma: A Case Report.

Continuously holding its position as the sixth most common cause of cancer and the third leading cause of cancer death, globally, Hepatocellular Carcinoma (HCC) remains as a healthcare priority. Production of various substances may result into systemic or metabolic complications, often known as paraneoplastic phenomena of HCC. A 56-year-old male with history of untreated chronic hepatitis B arrived with generalized weakness and intermittent headache in the last two days prior to admission. Laboratory findings demonstrated elevated hemoglobin (20.5 g/dl), alpha-fetoprotein (29,845 ng/dl), and d-Dimer (2,120 ng/ml) levels. Hypoglycemia (44 mg/dl) was documented with normal basal insulin level, confirming non-islet cell tumor hypoglycemia. Abdominal multiphasic CT-scan demonstrated a large solid lesion involving the whole right liver lobe, hyper-enhanced at arterial phase and wash-out pattern at venous and delayed phases, with portal vein thrombosis; thus, confirming HCC BCLC C. Further examinations revealed hypercellularity from bone marrow biopsy with the absence of JAK2 mutation. He underwent serial phlebotomy and received 80 mg acetylsalicylic acid orally, as well as cytoreductive agent to reduce the risk of thrombosis. Despite applications of different interventions, control of hypoglycemia could not be achieved without parenteral administration of high dextrose load. He was planned to receive oral multikinase inhibitor, however, he passed away due to severe hospital-acquired pneumonia. Paraneoplastic phenomena are common in HCC. Increased risk of blood hyper-viscosity and thrombosis attributed to polycythemia, as well as medical emergency resulting from hypoglycemia showed that both conditions should not be overlooked since they may worsen the patient's prognosis.

[Acute heart failure in a neonate]. / æ–°ç”Ÿå„¿æ€¥æ€§å¿ƒåŠŸèƒ½ä¸å ¨1例.

The male patient, one day old, was admitted to the hospital due to hypoglycemia accompanied by apnea appearing six hours after birth. The patient had transient hypoglycemia early after birth, and acute heart failure suddenly occurred on the eighth day after birth. Laboratory tests showed significantly reduced levels of adrenocorticotropic hormone and cortisol, and pituitary magnetic resonance imaging was normal. Genetic testing results showed that the patient had probably pathogenic compound heterozygous mutations of the TBX19 gene (c.917-2A>G+c.608C>T), inherited respectively from the parents. The patient was conclusively diagnosed with congenital isolated adrenocorticotropic hormone deficiency caused by mutation of the TBX19 gene. Upon initiating hydrocortisone replacement therapy, cardiac function rapidly returned to normal. After being discharged, the patient continued with the hydrocortisone replacement therapy. By the 18-month follow-up, the patient was growing and developing well. In neonates, unexplained acute heart failure requires caution for possible endocrine hereditary metabolic diseases, and timely cortisol testing and genetic testing should be conducted.

Is polyethylene glycol loxenatide 100 µg the preferred glucagon-like peptide-1 receptor agonist for type 2 diabetes mellitus? A meta-analysis and trial sequential analysis.

OBJECTIVE: This study aimed to systematically evaluate the efficacy, safety and optimal dose of polyethylene glycol loxenatide (PEX168) for treating type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Clinical trials of PEX168 for T2DM were identified in 8 databases, with a build time limit of January 2023. Included studies were subjected to meta-analysis and trial sequential analysis (TSA). RESULTS: On the efficacy endpoint, the meta-analysis showed that PEX168 100 µg significantly reduced 0.86% glycated hemoglobin type A1c (HbA1c) (MD -0.86, 95% CI -1.02 - -0.70,  p<0.00001), 1.11 mmol/L fasting plasma glucose (FPG) (MD -1.11, 95% CI -1.49 - -0.74, p<0.00001) and 1.91 mmol/L 2h postprandial glucose (PPG) (MD -1.91, 95% CI -3.35 - -0.46, p=0.01) compared with placebo. The TSA showed that all these benefits were conclusive. On safety endpoints, total adverse events (AEs), gastrointestinal (GI) AEs, serious AEs, and hypoglycemia were comparable to placebo for PEX168 100 µg (p>0.05). In the dose comparison, the HbA1c, FPG, and 2h PPG of PEX168 200 µg were comparable to 100 µg (p>0.05), while GI AEs were significantly higher than 100 µg (RR=2.84, 95% CI 1.64-4.93,  p=0.0002). CONCLUSIONS: PEX168 100 µg can significantly lower blood glucose and does not increase the risk of total AEs, GI AEs, and hypoglycemia, which may be a preferred glucagon-like peptide-1 receptor agonist for type 2 diabetes mellitus.

Pathogenic Potential of a PCK1 Gene Variant in Cytosolic PEPCK Deficiency: A Compelling Case Study.

BACKGROUND Cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) deficiency is an extremely rare autosomal recessive inherited error of metabolism in which gluconeogenesis is impaired, resulting in life-threatening episodes of hypoglycemia and metabolic acidosis. The diagnosis of gluconeogenesis disorders is challenging. In the diagnostic pathway, the molecular test plays a paramount role. CASE REPORT The aim of the paper is to present the case report of a girl with recurrent episodes of severe hypoglycemia, in whom molecular diagnosis enabled the confirmation of PEPCK - C deficiency. The patient experienced 4 episodes of severe hypoglycemia. Most of them were accompanied by hyperlacticaemia, metabolic acidosis, and elevated liver enzymes. All of the metabolic decompensations were triggered by infectious agents. The episodes resolved after continuous infusion of high-dose glucose. Due to the recurrent character of the disease, a genetic condition was suspected. The differential diagnosis included metabolic and endocrinological causes of hypoglycemia. Two variants in the PCK1 gene were detected: c.265G>A p.(Glu89Lys) in exon 3 and c.925G>A p.(Gly309Arg) in exon 6. As c.925G>A p.(Gly309Arg) is a known pathogenic variant, the second variant was first described in June 2023 in the ClinVar database and described as "with unknown clinical significance". CONCLUSIONS According to the clinical symptoms observed in the presented case, the variant c.265G>A p.(Glu89Lys) in PCK1 gene should be considered likely pathogenic. We suggest considering molecular diagnostics in every patient presented with recurrent, severe hypoglycemia with accompanying liver damage as most accurate, feasible, and reliable method.

Brain magnetic resonance imaging review suggests unrecognised hypoglycaemia in childhood.

Introduction: Neonatal and early-life hypoglycaemia, is a frequent finding but is often non-specific and asymptomatic, making detection and diagnosis challenging. Hypoglycaemia-induced cerebral injury can be identified by magnetic resonance imaging (MRI) changes in cerebral white matter, occipital lobes, and posterior parietotemporal regions. It is unknown if children may have hypoglycaemic brain injury secondary to unrecognised hypoglycaemia in early life. We have examined retrospective radiological findings of likely brain injury by neuroimaging to investigate the existence of previous missed hypoglycaemic events. Methods: Retrospective MRI data in children in a single tertiary centre, over a ten-year period was reviewed to identify potential cases of unrecognised early-life hypoglycaemia. A detailed search from an electronic radiology repository involved the term "hypoglycaemia'' from text-based reports. The initial report was used for those who required serial scanning. Images specific to relevant reports were further reviewed by a designated paediatric neuroradiologist to confirm likely hypoglycaemia induced brain injury. Medical records of those children were subsequently reviewed to assess if the hypoglycaemia had been diagnosed prior to imaging. Results: A total of 107 MR imaging reports were identified for review, and 52 (48.5%) showed typical features strongly suggestive of hypoglycaemic brain injury. Medical note review confirmed no documented clinical information of hypoglycaemia prior to imaging in 22 (42%) patients, raising the likelihood of missed hypoglycaemic events resulting in brain injury. Conclusions: We have identified the existence of unrecognised childhood hypoglycaemia through neuroimaging review. This study highlights the need for heightened awareness of early life hypoglycaemia to prevent adverse neurological outcomes later in childhood.

Clinical spectrum, over 12-year follow-up and experience of SGLT2 inhibitors treatment on patients with glycogen storage disease type Ib: a single-center retrospective study.

BACKGROUND: Glycogen storage disease type Ib (GSD Ib) is a rare disorder characterized by impaired glucose homeostasis caused by mutations in the SLC37A4 gene. It is a severe inherited metabolic disease associated with hypoglycemia, hyperlipidemia, lactic acidosis, hepatomegaly, and neutropenia. Traditional treatment consists of feeding raw cornstarch which can help to adjust energy metabolism but has no positive effect on neutropenia, which is fatal for these patients. Recently, the pathophysiologic mechanism of the neutrophil dysfunction and neutropenia in GSD Ib has been found, and the treatment with the SGLT2 inhibitor empaglifozin is now well established. In 2020, SGLT2 inhibitor empagliflozin started to be used as a promising efficient remover of 1,5AG6P in neutrophil of GSD Ib patients worldwide. However, it is necessary to consider long-term utility and safety of a novel treatment. RESULTS: In this study, we retrospectively examined the clinical manifestations, biochemical examination results, genotypes, long-term outcomes and follow-up of thirty-five GSD Ib children who visited our department since 2009. Fourteen patients among them underwent empagliflozin treatment since 2020. This study is the largest cohort of pediatric GSD Ib patients in China as well as the largest cohort of pediatric GSD Ib patients treated with empagliflozin in a single center to date. The study also discussed the experience of long-term management on pediatric GSD Ib patients. CONCLUSION: Empagliflozin treatment for pediatric GSD Ib patients is efficient and safe. Increase of urine glucose is a signal for pharmaceutical effect, however attention to urinary infection and hypoglycemia is suggested.

Comparing Equil patch versus traditional catheter insulin pump in type 2 diabetes using continuous glucose monitoring metrics and profiles.

AIMS: It is not clear whether there are differences in glycemic control between the Equil patch and the MMT-712 insulin pump. Our objective was to compare two types of insulin pumps in the treatment of type 2 diabetes mellitus (T2DM), using continuous glucose monitoring (CGM) metrics and profiles. METHODS: This was a randomized case-crossover clinical trial. Participants were hospitalized and randomly allocated to two groups and underwent two types of insulin pump treatments (group A: Equil patch-Medtronic MMT-712 insulin pump; group B: Medtronic MMT-712-Equil patch insulin pump) separated by a 1-day washout period. Glycemic control was achieved after 7-8 days of insulin pump therapy. Each patient received CGM for 5 consecutive days (from day 1 to day 5). On day 3 of CGM performance, the Equil patch insulin pump treatment was switched to Medtronic MMT-712 insulin pump treatment at the same basal and bolus insulin doses or vice versa. CGM metrics and profiles including glycemic variability (GV), time in range (TIR, 3.9-10.0 mmol/L), time below range (TBR, <3.9 mmol/L), time above range (TAR, >10.0 mmol/L), and postprandial glucose excursions, as well as incidence of hypoglycemia. RESULTS: Forty-six T2DM patients completed the study. There was no significant difference in parameters of daily GV and postprandial glucose excursions between the Equil patch insulin pump treatment and the Medtronic insulin pump treatment. Similarly, there was no between-treatment difference in TIR, TBR, and TAR, as well as the incidence of hypoglycemia. CONCLUSION: The Equil patch insulin pump was similar to the traditional MMT-712 insulin pump in terms of glycemic control. Equil patch insulin pump is a reliable tool for glycemic management of diabetes mellitus.

Efficacy and safety of basal insulins in people with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized clinical trials.

Aim: The comparative effectiveness of basal insulins has been examined in several studies. However, current treatment algorithms provide a list of options with no clear differentiation between different basal insulins as the optimal choice for initiation. Methods: A comprehensive search of MEDLINE, Embase, Cochrane Library, ISI, and Scopus, and a reference list of retrieved studies and reviews were performed up to November 2023. We identified phase III randomized controlled trials (RCTs) comparing the efficacy and safety of basal insulin regimens. The primary outcomes evaluated were HbA1c reduction, weight change, and hypoglycemic events. The revised Cochrane ROB-2 tool was used to assess the methodological quality of the included studies. A random-effects frequentist network meta-analysis was used to estimate the pooled weighted mean difference (WMD) and odds ratio (OR) with 95% confidence intervals considering the critical assumptions in the networks. The certainty of the evidence and confidence in the rankings was assessed using the GRADE minimally contextualized approach. Results: Of 20,817 retrieved studies, 44 RCTs (23,699 participants) were eligible for inclusion in our network meta-analysis. We found no significant difference among various basal insulins (including Neutral Protamine Hagedorn (NPH), ILPS, insulin glargine, detemir, and degludec) in reducing HbA1c. Insulin glargine, 300 U/mL (IGlar-300) was significantly associated with less weight gain (mean difference ranged from 2.9 kg to 4.1 kg) compared to other basal insulins, namely thrice-weekly insulin degludec (IDeg-3TW), insulin degludec, 100 U/mL (IDeg-100), insulin degludec, 200 U/mL (IDeg-200), NPH, and insulin detemir (IDet), but with low to very low certainty regarding most comparisons. IDeg-100, IDeg-200, IDet, and IGlar-300 were associated with significantly lower odds of overall, nocturnal, and severe hypoglycemic events than NPH and insulin lispro protamine (ILPS) (moderate to high certainty evidence). NPH was associated with the highest odds of overall and nocturnal hypoglycemia compared to others. Network meta-analysis models were robust, and findings were consistent in sensitivity analyses. Conclusion: The efficacy of various basal insulin regimens is comparable. However, they have different safety profiles. IGlar-300 may be the best choice when weight gain is a concern. In contrast, IDeg-100, IDeg-200, IDet, and IGlar-300 may be preferred when hypoglycemia is the primary concern.

Effectiveness of hospital-based oral dextrose gel in prevention and treatment of asymptomatic newborns at risk of hypoglycemia.

OBJECTIVE: To evaluate the effectiveness of using hospital-based 40% dextrose gel (DG) in preventing and treating asymptomatic hypoglycemia in infants of diabetic mothers (IDM), large for gestational age (LGA), and macrosomic neonates. METHODS: A medical chart review was conducted to compare data between before (April 2018 to March 2019, epoch 1) and after (September 2020 to November 2021, epoch 2) 40% DG implementation. DG, prepared by the hospital pharmaceutical unit, was applied within 30-45 min after birth, and three additional doses could be repeated during the first 6 h of life in combination with early feeding. The primary outcome was the rate of intravenous dextrose administration. Secondary outcomes were the incidence of hypoglycemia, first capillary blood glucose concentrations, and the length of hospital stay. RESULTS: Six hundred forty-three at-risk newborns were included (320 before and 323 after implementation of DG). Maternal and neonatal baseline characteristics were not different between the two epochs. The incidence of hypoglycemia was not different (17.8% in before versus 14.6% in after implementation, p = 0.26). The rate of intravenous dextrose administration after DG implementation was significantly lower than that before DG implementation (3.4% versus 10.3%, p < 0.001, risk reduction ratio = 0.33, 95% CI = 0.17-0.64). The length of hospital stay was not different between the two epochs. CONCLUSIONS: Implementing a protocol for administration of hospital-based 40% DG can reduce the need of intravenous dextrose administration among IDM, LGA and macrosomic neonates.

A novel electronic health record-based, machine-learning model to predict severe hypoglycemia leading to hospitalizations in older adults with diabetes: A territory-wide cohort and modeling study.

BACKGROUND: Older adults with diabetes are at high risk of severe hypoglycemia (SH). Many machine-learning (ML) models predict short-term hypoglycemia are not specific for older adults and show poor precision-recall. We aimed to develop a multidimensional, electronic health record (EHR)-based ML model to predict one-year risk of SH requiring hospitalization in older adults with diabetes. METHODS AND FINDINGS: We adopted a case-control design for a retrospective territory-wide cohort of 1,456,618 records from 364,863 unique older adults (age ≥65 years) with diabetes and at least 1 Hong Kong Hospital Authority attendance from 2013 to 2018. We used 258 predictors including demographics, admissions, diagnoses, medications, and routine laboratory tests in a one-year period to predict SH events requiring hospitalization in the following 12 months. The cohort was randomly split into training, testing, and internal validation sets in a 7:2:1 ratio. Six ML algorithms were evaluated including logistic-regression, random forest, gradient boost machine, deep neural network (DNN), XGBoost, and Rulefit. We tested our model in a temporal validation cohort in the Hong Kong Diabetes Register with predictors defined in 2018 and outcome events defined in 2019. Predictive performance was assessed using area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC) statistics, and positive predictive value (PPV). We identified 11,128 SH events requiring hospitalization during the observation periods. The XGBoost model yielded the best performance (AUROC = 0.978 [95% CI 0.972 to 0.984]; AUPRC = 0.670 [95% CI 0.652 to 0.688]; PPV = 0.721 [95% CI 0.703 to 0.739]). This was superior to an 11-variable conventional logistic-regression model comprised of age, sex, history of SH, hypertension, blood glucose, kidney function measurements, and use of oral glucose-lowering drugs (GLDs) (AUROC = 0.906; AUPRC = 0.085; PPV = 0.468). Top impactful predictors included non-use of lipid-regulating drugs, in-patient admission, urgent emergency triage, insulin use, and history of SH. External validation in the HKDR cohort yielded AUROC of 0.856 [95% CI 0.838 to 0.873]. Main limitations of this study included limited transportability of the model and lack of geographically independent validation. CONCLUSIONS: Our novel-ML model demonstrated good discrimination and high precision in predicting one-year risk of SH requiring hospitalization. This may be integrated into EHR decision support systems for preemptive intervention in older adults at highest risk.

Umbilical cord milking and delayed cord clamping for the prevention of neonatal hypoglycaemia: a systematic review and meta-analysis.

BACKGROUND: Placental management strategies such as umbilical cord milking and delayed cord clamping may provide a range of benefits for the newborn. The aim of this review was to assess the effectiveness of umbilical cord milking and delayed cord clamping for the prevention of neonatal hypoglycaemia. METHODS: Three databases and five clinical trial registries were systematically reviewed to identify randomised controlled trials comparing umbilical cord milking or delayed cord clamping with control in term and preterm infants. The primary outcome was neonatal hypoglycaemia (study defined). Two independent reviewers conducted screening, data extraction and quality assessment. Quality of the included studies was assessed using the Cochrane Risk of Bias tool (RoB-2). Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Meta-analysis using a random effect model was done using Review Manager 5.4. The review was registered prospectively on PROSPERO (CRD42022356553). RESULTS: Data from 71 studies and 14 268 infants were included in this review; 22 (2 537 infants) compared umbilical cord milking with control, and 50 studies (11 731 infants) compared delayed with early cord clamping. For umbilical cord milking there were no data on neonatal hypoglycaemia, and no differences between groups for any of the secondary outcomes. We found no evidence that delayed cord clamping reduced the incidence of hypoglycaemia (6 studies, 444 infants, RR = 0.87, CI: 0.58 to 1.30, p = 0.49, I2 = 0%). Delayed cord clamping was associated with a 27% reduction in neonatal mortality (15 studies, 3 041 infants, RR = 0.73, CI: 0.55 to 0.98, p = 0.03, I2 = 0%). We found no evidence for the effect of delayed cord clamping for any of the other outcomes. The certainty of evidence was low for all outcomes. CONCLUSION: We found no data for the effectiveness of umbilical cord milking on neonatal hypoglycaemia, and no evidence that delayed cord clamping reduced the incidence of hypoglycaemia, but the certainty of the evidence was low.

Análisis retrospectivo de las hipoglucemias inducidas por venlafaxina en pacientes con sobredosis / Retrospective analysis of venlafaxine-induced hypoglycemia in patients with overdose

Introducción: Estudios recientes en intoxicaciones por venlafaxina (VLF) relacionan la presencia de hipoglucemia con la dosis. Nuestro objetivo fue analizar las características clínicas de los pacientes que presentaron hipoglucemia inducida por sobredosis de VLF.Pacientes y métodosEstudio retrospectivo realizado en las Islas Baleares (2020-2023). Como criterios de inclusión se tomaron en cuenta las concentraciones séricas de VLF + ortodesmetilvenlafaxina (O-VLF) > 800 ng/mL. Se compararon las características de los pacientes con y sin hipoglucemia.ResultadosSe incluyeron 21 pacientes, ocho (38,1%) con hipoglucemia. No se hallaron diferencias en las dosis referidas en ambos grupos. Las concentraciones máximas de VLF + O-VLF (ng/mL) fueron 9.783 (4.459-17.976) en sujetos con hipoglucemia y 1.413 (930-1.769) en aquellos sin esta enfermedad (p<0,0001). La presencia de hipoglucemia se asoció con: menor edad y nivel de conciencia; y mayor frecuencia de tentativas suicidas, convulsiones, midriasis, taquicardia y síndrome serotoninérgico, soporte respiratorio invasivo, sueroterapia e ingreso en la Unidad de Cuidados Intensivos (UCI) (p < 0,05).ConclusionesLa detección de hipoglucemia en individuos intoxicados por VLF es un marcador fácilmente disponible para sospechar la gravedad del paciente. En cualquier caso, las concentraciones séricas, cuando se disponen, permiten confirmar la intoxicación. (AU)

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

From liver to hormones: The endocrine consequences of cirrhosis.

Hepatocrinology explores the intricate relationship between liver function and the endocrine system. Chronic liver diseases such as liver cirrhosis can cause endocrine disorders due to toxin accumulation and protein synthesis disruption. Despite its importance, assessing endocrine issues in cirrhotic patients is frequently neglected. This article provides a comprehensive review of the epidemiology, pathophysiology, diagnosis, and treatment of endocrine disturbances in liver cirrhosis. The review was conducted using the PubMed/Medline, EMBASE, and Scielo databases, encompassing 172 articles. Liver cirrhosis is associated with endocrine disturbances, including diabetes, hypoglycemia, sarcopenia, thyroid dysfunction, hypogonadotropic hypogonadism, bone disease, adrenal insufficiency, growth hormone dysfunction, and secondary hyperaldosteronism. The optimal tools for diagnosing diabetes and detecting hypoglycemia are the oral glucose tolerance test and continuous glucose monitoring system, respectively. Sarcopenia can be assessed through imaging and functional tests, while other endocrine disorders are evaluated using hormonal assays and imaging studies. Treatment options include metformin, glucagon-like peptide-1 analogs, sodium-glucose co-transporter-2 inhibitors, and insulin, which are effective and safe for diabetes control. Established standards are followed for managing hypoglycemia, and hormone replacement therapy is often necessary for other endocrine dysfunctions. Liver transplantation can address some of these problems.

Self-care activities in pediatric patients with type 1 diabetes mellitus.

INTRODUCTION: Effective diabetes self-management and collaborative responsibility sharing with parents are imperative for pediatric patients with type 1 diabetes mellitus, particularly as they gradually assume more self-care responsibilities. The primary goal of this study was to assess differences in adherence to self-care activities regarding sociodemographics and clinical characteristics in pediatric patients with type 1 diabetes. The secondary goal of this study was to understand the level of parental involvement in diabetes management and to assess the pediatric patients' behaviors (independent or dependent on disease self-management) that relate to sociodemographic and clinical characteristics. METHODS: This was a comparative cross-sectional and correlational study. The study sample included 182 children and adolescents who had been diagnosed with type 1 diabetes at least 3 months prior. Data collection instruments included a sociodemographic and questionnaire about Adherence to self-care activities and parental involvement in diabetes self-management, as well as a documentation sheet for recording clinical data. RESULTS: A majority of participants (71%) exhibited non-adherence to self-care tasks, despite 78.0% asserting their independence in diabetes self-management. Notably, insufficient parental involvement in administering insulin therapy significantly predicted severe hypoglycemic episodes. CONCLUSIONS: Pediatric patients dealing with type 1 diabetes demonstrate a substantial degree of autonomy in managing their condition, paradoxically coupled with self-reported non-adherence to critical self-care responsibilities. Notably, children (aged 8-12) rely more heavily on parental support, especially concerning insulin therapy administration. The study underscores the crucial role of parental engagement in insulin therapy, as its deficiency significantly predicts the likelihood of severe hypoglycemic episodes.

Severe hypoglycemia and hypoglycemia awareness are associated with preclinical atherosclerosis in patients with type 1 diabetes without an estimated high cardiovascular risk.

AIMS: To explore the relationship between severe hypoglycemia (SH) and hypoglycemia awareness with preclinical atherosclerosis in type 1 diabetes (T1D). MATERIALS AND METHODS: Cross-sectional study in patients with T1D without cardiovascular disease (CVD), and with ≥1 of the following: ≥40 years, diabetic kidney disease, or ≥10 years of T1D duration with another risk factor. CVD risk was estimated with the Steno T1 Risk Engine (Steno-Risk). Carotid plaque was evaluated using standardised ultrasonography protocol. Logistic regression models adjusted for CVD risk factors were constructed to test the independent associations with SH or hypoglycemia awareness assessed by the Clarke questionnaire (Clarke). The inclusion of SH and Clarke in Steno-Risk was further evaluated. RESULTS: We included 634 patients (52.4% men, age 48.3 ± 10.8 years, T1D duration 27.4 ± 11.1 years, 39.9% harbouring plaque). A stepped increase in the presence of plaque according to Steno-Risk was observed (13.5%, 37.7%, and 68.7%, for low, moderate, and high risk, respectively; p < 0.001). SH history (OR 4.4 [1.3-14.6]) and Clarke score (OR 1.7 [1.2-2.2]) were associated with plaque in low-risk patients (n = 192). Clarke score was also associated with plaque burden in low-moderate-risk participants (n = 436; ≥2 plaques: OR 1.2 [1.0-1.5], p = 0.031; ≥3 plaques: OR 1.4 [1.1-2.0], p = 0.025). The inclusion of SH and Clarke scores in Steno-Risk significantly improved the identification of low-risk individuals with atherosclerosis (area under the curve: 0.658 vs. 0.576; p = 0.036). CONCLUSIONS: In patients with T1D without an estimated high CVD risk, SH and hypoglycemia awareness assessment score were independently associated with preclinical atherosclerosis and improved identification of patients who would benefit from an intensive approach.