Mild Hypoglycemia Research Articles

Metabolically-Driven Active Targeting of Magnetic Nanoparticles Functionalized with Glucuronic Acid to Glioblastoma: Application to MRI-Tracked Magnetic Hyperthermia Therapy.

Glioblastoma continues to pose a major global health challenge due to its incurable nature. The need for new strategies to combat this devastating tumor is therefore paramount. Nanotechnology offers unique opportunities to develop innovative and more effective therapeutic approaches. However, most nanosystems developed to treat glioblastomas, especially those based on metallic nanoparticles (NPs), have proven unsuccessful due to their inability to efficiently target these tumors, which are particularly inaccessible due to the restrictions imposed by the blood-brain tumor barrier (BBTB). Here, an innovative strategy is presented to efficiently target metallic NPs to glioblastomas through glucose transporters (GLUT) overexpressed on the endothelial cells of glioblastoma microvasculature, particularly GLUT1. Specifically, Iron Oxide Nanoparticles (IONPs) are functionalized with glucuronic acid to promote GLUT-mediated transcytosis which is drastically boosted by inducing mild hypoglycemia. This metabolically-driven active targeting strategy has yielded unprecedented efficacy in targeting metallic NPs to glioblastomas. Moreover, these IONPs, designed to act as magnetic hyperthermia (MH) mediators, are used to conduct a proof-of-concept preclinical study on MRI-tracked MH therapy following intravenous administration, resulting in significant tumor growth delay. These findings demonstrate unparalleled efficiency in glioblastoma targeting and lay the ground for developing alternative therapeutic strategies to combat glioblastoma.

High-dose intranasal insulin in an adaptive dose-escalation study in healthy human participants.

Intranasal insulin is a putative neuroprotective therapy after cardiac arrest, but safety in humans at doses extrapolated from animal models is unknown. This phase I, open-label adaptive dose-escalation study explores the maximum tolerated dose of intranasal insulin in healthy human participants. Placebo or insulin at doses from 0 to 1000 units was given to healthy participants intranasally on repeated weekly visits. Serum glucose, insulin, and C-peptide levels were measured serially at 0, 15, 30, 60, 120, 180, and 240 min after administration. Twenty-four participants (12 female, median age 53, IQR 35-61) were enrolled. There was minimal change in average serum glucose after administration of intranasal insulin. Average serum insulin increased slightly in a dose-dependent manner, reaching maximum concentrations at 15 min. C-peptide decreased over time from administration in all groups. One participant had severe hypoglycemia (24 mg/dL at 45 min) and a different participant had mild hypoglycemia (51 mg/dL at 30 min), both after receiving 600 U intranasal insulin. Hypoglycemic episodes were associated with increases in serum insulin. Both participants continued in the study without hypoglycemia after additional doses. High-dose intranasal insulin up to 1000 U was generally well tolerated, with minimal measurable systemic absorption and without significant aggregate changes in mean glucose. Idiosyncratic episodic systemic absorption and hypoglycemia require further study and additional caution in potential clinical application. Further study of its target engagement and efficacy as a neuroprotective therapy after cardiac arrest at these doses is warranted.

Efficacy of propranolol and pingyangmycin combination therapy in infantile hemangiomas: Correlation with VEGF Levels

BackgroundInfantile hemangiomas (IH) represent the most prevalent vascular tumors in infants, often necessitating prompt medical intervention due to their potential for rapid growth and complications. This retrospective study aims to evaluate the efficacy of propranolol combined with Pingyangmycin in the treatment of IH and to investigate its correlation with vascular endothelial growth factor (VEGF) levels. MethodsA prospective, observational study was conducted over 12 months, enrolling 120 IH patients. Patients received a combination therapy of propranolol and pingyangmycin for 3 to 6 months. Hemangioma Activity Score (HAS) and serum VEGF levels were assessed at baseline, 30th day, and 90th day post-treatment. ResultsA total of 120 patients diagnosed with IH, including 68 males and 52 females with a mean age of 1.2 years, were enrolled in this study. The HAS at baseline was 8.5 ± 1.7, which significantly decreased to 4.2 ± 1.0 by Day 30 and further reduced to 2.1 ± 0.8 by Day 90 (P < 0.001 for both comparisons). Serum VEGF levels also showed a significant reduction from a baseline of 235.6 ± 42.1 pg/mL to 180.3 ± 34.7 pg/mL at Day 30 and to 122.8 ± 28.9 pg/mL at Day 90 (P = 0.02 and P = 0.01, respectively). The correlation analysis revealed a positive correlation between VEGF levels and HAS scores at all time points, with Pearson correlation coefficients ranging from -0.82 to -0.89 (P < 0.001). Adverse events were mild and transient, occurring in 15% of patients, with the most common being mild hypoglycemia (8%), transient bronchospasm (5%), and gastrointestinal discomfort (2%). All adverse events resolved with symptomatic treatment, and no patient discontinued therapy due to adverse reactions. ConclusionPropranolol treatment for infants with proliferative hemangiomas is significantly effective with minor adverse effects. The mechanism of action may be associated with the downregulation of serum VEGF levels.

9376 Successful Implementation Of Continuous Glucose Monitoring In An Internal Medicine Residency Clinic

Abstract Disclosure: A.E. Manov: None. A. Donepudi: None. A.S. Dhaliwal: None. J. Tam: None. Y. Badi: None. M. Sharaf: None. R. Haddadin: None. A. Wang: None. K. Mefferd: None. Abstract In this 3-year retrospective observational cohort study, data from fifty-one patients with type 1 or type 2 Diabetes Mellitus (DM), receiving a minimum of 3-to 4 insulin injections per day, and self-monitoring their blood glucose (SMBG) 4-times a day, were derived from our internal medicine residency primary care clinic. The patients were equipped with a Continuous Glucose Monitoring (CGM) device that shared 24-hour glucose data with the clinic. They were assigned to members of our CGM team which included internal medicine or transitional year medical residents who functioned under the supervision of a board-certified endocrinologist. In consultation with our endocrinologist, the resident assessed the patients' glucose management data and adjusted their treatment regimens bi-weekly by calling the patients, and monthly by seeing them in the clinic. The rationale of the study which was confirmatory was to show that in the Internal Medicine Residency clinic in a project governed by the medicine residents, the CGM will lead to improvement in diabetes mellitus control compared to SMBG and this can be done not only in specialized endocrine clinics. The inclusion criteria for selecting the patients were as follows: Age-18-90, diagnosis of Type 1 or type 2 Diabetes Mellitus using 3-4 Injections of Insulin per day +/- other per oral antidiabetic medications and SMBG 4 times a day, HbA1c above 7% while using SMBG, patients who can use the CGM device and receive their primary medical care in our Internal medicine Residency clinic.To assess for differences in A1C, TIR, average blood glucose, percent of time spent in mild hypoglycemia, and percent of time spent in pronounced hypoglycemia, five paired t-tests were conducted. A Bonferroni correction set the new accepted alpha level at 0.01. Significant results from the study include a reduction of HbA1c from 9.9% to 7.6%, average blood glucose decrement from 242 mg/dL to 169 mg/dl, reduction of the incidence of mild hypoglycemia below 70 mg/dl to 54 mg/dl from 4.68% to 0.76% per day, and more pronounced hypoglycemia with glucose less than 54 mg/dl from 3.1% per day to 0.2% per day. We observed a significant increase in the time in the range of blood glucose from 33% to 67% per day. Furthermore, 9.5% of the patients in this study eventually discontinued daily insulin injections and continued treatment with oral diabetic medications with or without the use of injectable GLP-1 receptors once a week.This study affirms that CGM devices significantly improved glycemic control compared to SMBG, supporting its efficacy in optimizing glycemic control in real-world clinical practice. The results imply this can be accomplished in internal medicine residency clinics and not exclusively in specialized endocrine clinics. As far as we know, this is the first study of this kind in a residency clinic in the USA. Presentation: 6/1/2024

8132 Prolonged Refractory Hypoglycemia For Seven Days After Discontinuation Of Neutral Protamine Hagedorn (NPH) Insulin And Injectable Semaglutide

Abstract Disclosure: A. Musleh: None. M.T. Rauf: None. E. Afroze: None. S. Al-Bacha: None. A 75-year-old male with Type 2 Diabetes was brought to the emergency department (ED) by emergency medical services (EMS) due to altered mentation. The patient’s wife found him unresponsive with seizure-like activity. EMS was called to the scene and obtained a capillary blood glucose reading of 31 mg/dL. Despite initial treatment with 50% dextrose the patient’s capillary blood glucose came down to 21 mg/dL in the ED and was confirmed by venous glucose. Workup including Computed Tomography (CT) imaging was inconsistent with a cerebrovascular accident. Given refractory hypoglycemia and delirium, the patient was started on a dextrose 10% infusion at 150 milliliters per hour. He was admitted to the intensive care unit for closer monitoring. His wife states that the patient had a few episodes of mild hypoglycemia overnight for the past several weeks, which improved after eating. His home medications included NPH insulin 46 units twice daily, empagliflozin 25 mg once daily, and injectable semaglutide 2 mg once weekly. The last dose of NPH insulin was the night before the presentation and the last dose of semaglutide was 5 days prior to admission. Serum creatinine levels were stable at 1.3-1.5 mg/dL throughout the hospitalization, which was below his baseline creatinine of 1.7 mg/dL. Laboratory results were as follows: hemoglobin A1c 5.9%, c-peptide level was 0.3 ng/mL (normal range 0.8-3.9 ng/mL) with a glucose of 68 mg/dL (normal range 70-100 mg/dL), insulin 203.8 mcIU/mL (normal range less than 24 mcIU/mL), proinsulin 3.2 pmol/L (normal range less than or equal to 8 pmol/L), beta-hydroxybutyrate 0.06 mmol/L (normal range 0.02-0.27), cortisol 66.6 mcg/dL (normal range 6.7-22.6 mcg/dL), insulin-like growth factor 1 123 ng/mL (normal range 53-222), and hypoglycemic agent panel was negative. On ICU Day 2, his mentation improved, he was allowed to eat but continued to require dextrose infusion to prevent hypoglycemia. Repeat fasting insulin levels even four days from prior showed an incremental decrease to 59.4 mcIU/mL with a glucose of 77 mg/dL. It took 7 days before the patient was able to maintain glucose above 70 mg/dL off of dextrose infusion. After which he had hyperglycemia requiring gradual reintroduction of his diabetes medicines other than insulin. It is rare to see such prolonged refractory hypoglycemia from an exogenous source of insulin as exhibited in this case. Notably, the patient was on semaglutide and had stable chronic kidney disease without acute kidney injury. Although multiple mechanisms explain the prolonged insulin duration of action in kidney disease, the effects of semaglutide on insulin action are unknown. Presentation: 6/3/2024

Assessment of neonatal glycaemic status and comorbidities in infants of diabetic mothers admitted to the neonatal care unit of Al-Ramadi Teaching Hospital for maternity and childhood, Iraq.

To assess neonatal and maternal characteristics, glycaemic status and comorbidities in the neonates of diabetic mothers. The cross-sectional study was conducted from October 2021 to May 2022 at the Department of Physiology, College of Medicine, University of Mustansiriyah, Baghdad, Iraq, and comprised healthy women. Samples were raised by simple random technique. Digital pulse waves were captured using a fingertip pulse wave transducer. Lab Chart Pro version 7.2 was used to automatically detect and quantify the amplitude of A, B, C, D and E waves expressed by the second derivative. QT interval of each beat was recorded by electrocardiogram, and was calculated automatically via Lab chart Pro version 7.2 without averaging. Data was spread out on Microsoft Office Excel 2013 and analysed using SPSS version 26. Among the 70 mothers, aged between 18 to 44 years, gestational diabetes was the commonest type 52(74.3%), and, among the 70 neonates, 52(74.3%) developed mild hypoglycaemia, 12(17.1%) hypocalcaemia, 26(37.1%) congenital heart disease, 50(71.4%) respiratory distress syndrome, 24(34.3%) hyperbilirubinaemia, 2(2.9%) congenital anomalies, 6(8.6%) prematurity, and 4(5.7%) developed birth asphyxia. Prematurity, female gender and low birthweight were significantly associated with hypoglycaemia (p<0.05). No significant differences were detected in terms of neonatal complications between pregestational and gestational diabetic mothers (p>0.05). Diabetic pregnancies were linked to a higher risk of neonatal complications.

Postoperative Hydration in Children Using Intermittent Boluses of Balanced Salt Solution: Results of a Randomized Control Trial

BackgroundPostoperative maintenance fluids are traditionally provided via hypotonic dextrose containing fluids administered intravenously by continuous infusion. We hypothesized that scheduled weight-based boluses of balanced salt solution would be more physiologic, reduce fluid volumes, and improve patient comfort. MethodsAs part of an IRB-approved randomized controlled trial (Boluses of Ringer's in Surgical Kids, BRiSK), we randomized patients aged 1–21 years undergoing elective abdominal or thoracic surgery to post-operatively receive weight-based D50.45NS+20mEq/L KCl at a continuous rate or intermittent boluses of Lactated Ringer's solution until oral liquid toleration. Patients with nephropathy, diabetes, or receiving parenteral nutrition were excluded. We analyzed electrolytes, urine output, fluid volume, and adverse events. ResultsWe enrolled and randomized 60 patients: 29 to continuous fluids and 31 to bolus fluids. One patient from the bolus group dropped out. No patients crossed over due to difficulties with application of the bolus protocol. There were no baseline differences between groups with a mean age of 12.6 ± 1.4yr and weight of 50.9 ± 7.2 kg. There were no serious adverse events or electrolyte disturbances in either group. Patients in the bolus group received significantly less total fluid than those in the continuous group (0.43 mL/kg/h vs 1.1 mL/kg/h, p < 0.001) with no difference in urine output [1.4 ± 0.2 mL/kg/h vs 1.6 ± 0.3 mL/kg/h, p = 0.211]. There were two episodes of mild hypoglycemia in the bolus group compared to seven episodes of mild hyperglycemia in the continuous group. ConclusionsAdministration of post-operative intravenous fluids as boluses of balanced salt solution is feasible, safe, and results in significantly less fluid administered compared to a traditional continuous protocol. Level of EvidenceII.

Retrospective, Longitudinal, One-Group Study on the Implementation of Continuous Glucose Monitoring To Improve Quality of Care for Patients With Type I or II Diabetes Mellitus in an Internal Medicine Residency Continuity Community Clinic.

In this three-year retrospective study, data from 51 patients with type 1 or type 2 diabetes mellitus (DM), receiving a minimum of 3-4 insulin injections per day and self-monitoring their blood glucose (SMBG) four times a day, were derived from our internal medicine residency primary care clinic. The patients were equipped with a continuous glucose monitoring (CGM) device that shared 24-hour glucose data with the clinic. They were assigned to members of our CGM team, which included internal medicine or transitional year medical residents who functioned under the supervision of a board-certified endocrinologist. The residents, in consultation with our endocrinologist, assessed the patients' glucose management data and adjusted their treatment regimens biweekly by calling the patients, and monthly by seeing the patients in the clinic. Significant results from the study include a reduction in HbA1c from 9.9% to 7.6%, an average blood glucose decrement from 242 mg/dL to 169 mg/dL, a reduction in the incidence of mild hypoglycemia from below 70 mg/dL to 54 mg/dL, from 4.68% to 0.76% per day, and a more pronounced hypoglycemia with glucose less than 54 mg/dL from 3.1% per day to 0.2% per day. We observed a significant increase in the time in the range of the blood glucose from 33% to 67% per day. Furthermore, 9.5% of the patients in this study eventually discontinued their daily insulin injections and continued treatment with oral diabetic medications with or without the use of injectable GLP-1 receptors once a week. Our study affirms that CGM devices significantly improve glycemic control compared to SMBG, supporting its efficacy in optimizing glycemic control in real-world clinical practice. The results imply that this can be accomplished in internal medicine residency clinics and not exclusively in specialized endocrine clinics. As far as we know, this is the first study of its kind in a residency clinic in the USA. This study confirms the benefits of widening the application of CGM in DM, along with the challenges that must be overcome to realize the evidence-based benefits of this technology. CGM needs to become a part of routine monitoring for type 1 and type 2 DM.

Evaluating the effectiveness and safety of empagliflozin versus liraglutide in managing diabetic dyslipidemia: An observational study

Background: Diabetic dyslipidemia poses a significant risk factor for cardiovascular complications in patients with diabetes mellitus. Empagliflozin and liraglutide are two commonly used medications in diabetes management, yet their comparative efficacy and safety in treating diabetic dyslipidemia remain under-explored. Aims and Objectives: This study aimed to assess the effectiveness and safety of Empagliflozin versus liraglutide in managing diabetic dyslipidemia. Materials and Methods: The study enrolled 100 participants with diabetes and dyslipidemia, divided equally into empagliflozin and liraglutide treatment groups. Baseline characteristics, including age, gender distribution, ethnicity, and duration of diabetes, were assessed and compared between the groups. Lipid profiles, encompassing total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides, were evaluated at baseline and after 6 months of treatment. Safety outcomes, such as the occurrence of mild gastrointestinal symptoms, hypoglycemia, and serious adverse events, were also monitored. Results: Both treatment groups exhibited comparable baseline characteristics. Following 6 months of treatment, both empagliflozin and liraglutide demonstrated significant improvements in lipid profiles. Reductions in total cholesterol, LDL cholesterol, and triglycerides, along with increases in HDL cholesterol, were observed in both groups. Moreover, there were no significant differences in the occurrence of adverse events between the two treatment groups, indicating similar safety profiles. Conclusion: This study provides evidence supporting the effectiveness and safety of empagliflozin and liraglutide in managing diabetic dyslipidemia. These findings highlight the potential of both medications as viable therapeutic options for patients with diabetes and dyslipidemia.

Continuous Insulin Therapy to Prevent Post-Transplant Diabetes Mellitus: A Randomized Controlled Trial

Rationale & ObjectivesHyperglycemia is frequently observed early after transplantation and associated with development of post-transplant diabetes mellitus (PTDM). Here, we assessed continuous subcutaneous insulin infusion (CSII) targeting afternoon hyperglycemia. Study DesignOpen label randomized parallel three-arm design. Settings & ParticipantsN=85 kidney transplant recipients (KTRs) without previous diabetes diagnosis were randomized to postoperative CSII therapy, basal insulin or control. InterventionsInsulin was to be initiated at afternoon capillary blood glucose ≥140 mg/dL (7.8 mmol/L; CSII and basal insulin) or fasting plasma glucose ≥200 mg/dL (11.1 mmol/L; control). OutcomesHbA1c at 3 months post transplant (primary endpoint). PTDM assessed by OGTT at 12 and 24 months. ResultsCSII therapy lasted until median day 18 and maximum day 88. Median HbA1c at month 3 was 5.6% (38 mmol/mol) in the CSII group versus 5.7% (39 mmol/mol) in the control group (p=0.70) and 5.4% (36 mmol/mol) in the basal insulin group (p=0.02). At months 12 and 24, the odds for PTDM were similar compared to the control group (odds ratios [95% confidence intervals], 0.80 [0.18-3.49] and 0.71 [0.15-3.16], respectively) and the basal insulin group 0.96 [0.18-5.68] and 1.51 [0.24-12.84], respectively). Mild hypoglycemia events occurred in the CSII and the basal insulin groups. LimitationsThis study is limited by outdated insulin pump technology, frequent discontinuations of CSII, a complex protocol and concerns regarding reliability of HbA1c measurements. ConclusionsCSII therapy was not superior at reducing HbA1c at month 3 or PTDM prevalence at months 12 and 24 compared to the control or basal insulin group.

Wearable monitoring device based on an internet management platform improves metabolic parameters in type 2 diabetes patients: a prospective pilot study

ABSTRACT Objectives This pilot study aimed to prospectively investigate the effects of a wearable monitoring device, based on an Internet management platform, on the comprehensive management of type 2 diabetes mellitus (T2DM) patients. Methods A total of 120 hospitalized patients with T2DM were enrolled and randomly divided into the control group and the intervention group. Patients in the control group only received conventional diabetes treatments, while patients in the intervention group were provided with a wearable monitoring device in addition to conventional diabetes treatments. Moreover, the wearable device could connect to an Internet platform for diabetes management and upload self-monitoring data. All patients were followed for 3 months. The changes in parameters representing glucose metabolism, blood lipids, renal function, and patient satisfaction were compared between the two groups. All results were analyzed on an intention-to-treat basis. Results One hundred twenty subjects met all criteria and agreed to participate in this study. During the follow-up period, 5 and 4 subjects were lost to follow-up in the intervention and control groups, respectively. Compared with the control group, the blood glucose of the intervention group decreased significantly after 3 months (p < 0.05). Subgroup analysis found that females, those younger than 60 years, with baseline glycated hemoglobin A1c (HbA1c) levels of 8% or greater, and patients with good adherence showed significant improvements in HbA1c (p < 0.05). However, there was no significant difference in blood lipid and renal function. The intervention group showed a better adherence rate to blood glucose, comprehensive adherence rate, and diabetes treatment satisfaction (p < 0.05). One subject in the intervention group and two subjects in the control group reported mild hypoglycemia. No other adverse events such as infections and skin allergies occurred in the two groups. Conclusion The intervention of a wearable monitoring device based on an Internet management platform significantly improved blood glucose control in T2DM patients, as well as the overall adherence rate and patient satisfaction with treatment. Clinical Trial Registration NCT04973644.

Generalization of a Deep Learning Model for Continuous Glucose Monitoring-Based Hypoglycemia Prediction: Algorithm Development and Validation Study.

Predicting hypoglycemia while maintaining a low false alarm rate is a challenge for the wide adoption of continuous glucose monitoring (CGM) devices in diabetes management. One small study suggested that a deep learning model based on the long short-term memory (LSTM) network had better performance in hypoglycemia prediction than traditional machine learning algorithms in European patients with type 1 diabetes. However, given that many well-recognized deep learning models perform poorly outside the training setting, it remains unclear whether the LSTM model could be generalized to different populations or patients with other diabetes subtypes. The aim of this study was to validate LSTM hypoglycemia prediction models in more diverse populations and across a wide spectrum of patients with different subtypes of diabetes. We assembled two large data sets of patients with type 1 and type 2 diabetes. The primary data set including CGM data from 192 Chinese patients with diabetes was used to develop the LSTM, support vector machine (SVM), and random forest (RF) models for hypoglycemia prediction with a prediction horizon of 30 minutes. Hypoglycemia was categorized into mild (glucose=54-70 mg/dL) and severe (glucose<54 mg/dL) levels. The validation data set of 427 patients of European-American ancestry in the United States was used to validate the models and examine their generalizations. The predictive performance of the models was evaluated according to the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). For the difficult-to-predict mild hypoglycemia events, the LSTM model consistently achieved AUC values greater than 97% in the primary data set, with a less than 3% AUC reduction in the validation data set, indicating that the model was robust and generalizable across populations. AUC values above 93% were also achieved when the LSTM model was applied to both type 1 and type 2 diabetes in the validation data set, further strengthening the generalizability of the model. Under different satisfactory levels of sensitivity for mild and severe hypoglycemia prediction, the LSTM model achieved higher specificity than the SVM and RF models, thereby reducing false alarms. Our results demonstrate that the LSTM model is robust for hypoglycemia prediction and is generalizable across populations or diabetes subtypes. Given its additional advantage of false-alarm reduction, the LSTM model is a strong candidate to be widely implemented in future CGM devices for hypoglycemia prediction.

Effect of Hypoglycemia and Rebound Hyperglycemia on Proteomic Cardiovascular Risk Biomarkers.

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.

Budget impact analysis of continuous glucose monitoring in individuals with type 2 diabetes on insulin treatment in England

IntroductionIn 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 methodsThe 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.ResultsThe 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).ConclusionsCGM 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.

Impact of macronutrients intake on glycemic homeostasis of preterm infants: evidence from continuous glucose monitoring

Nutritional intake could influence the blood glucose profile during early life of preterm infants. We investigated the impact of macronutrient intake on glycemic homeostasis using continuous glucose monitoring (CGM). We analyzed macronutrient intake in infants born ≤ 32 weeks gestational age (GA) and/or with birth weight ≤ 1500 g. CGM was started within 48 h of birth and maintained for 5 days. Mild and severe hypoglycemia were defined as sensor glucose (SG) < 72 mg/dL and <47 mg/dL, respectively, while mild and severe hyperglycemia were SG > 144 mg/dL and >180 mg/dL. Data from 30 participants were included (age 29.9 weeks (29.1; 31.2), birthweight 1230.5 g (1040.0; 1458.6)). A reduced time in mild hypoglycemia was associated to higher amino acids intake (p = 0.011) while increased exposure to hyperglycemia was observed in the presence of higher lipids intake (p = 0.031). The birthweight was the strongest predictor of neonatal glucose profile with an inverse relationship between the time spent in hyperglycemia and birthweight (p = 0.007). Conclusions: Macronutrient intakes influence neonatal glucose profile as described by continuous glucose monitoring. CGM might contribute to adjust nutritional intakes in preterm infants.What is Known:• Parenteral nutrition may affect glucose profile during the first days of life of preterm infants.What is New:• Continuous glucose monitoring describes the relationship between daily parenteral nutrient intakes and time spent in hypo and hyperglycemic ranges.

Risk factors for neonatal cholestasis in small gestational age infants: case report and literature review

Cholestatic jaundice, defined as conjugated bilirubin levels higher than 1 mg/dl, is a bile formation and excretion disturbance. Its incidence is estimated at 1 case in 2500 live births, being 100-200 times higher in preterm infants less than 28 weeks gestational age. It occurs in biliary atresia, infectious diseases, endocrine and inherited metabolic diseases, Alagille Syndrome, preterm and intrauterine growth-restricted newborns, lack of enteral feeding, and is more frequent in male gender. It is a frequent complication of parenteral nutrition. In preterm and small for gestational age (SGA) infants, the etiology of cholestasis is multifactorial. Early diagnosis enables early therapeutic intervention. We report the case of an SGA male preterm infant. He was born by C-section for fetal distress at 30 weeks gestational age with an 800 g birth weight. He developed mild respiratory distress, hypoglycemia, meconium ileus, and early cholestasis. Complex hematological, serological, and immunological tests were carried out; ultrasound evaluations were performed. The final diagnosis was cholestasis of multifactorial etiology in a preterm infant with severe intrauterine growth restriction (IUGR). Treatment with ursodeoxycholic acid was started. Three months later, the transaminases, bilirubin, gammaglutamyl transferase (GGT), and alkaline phosphatase (ALP) triglycerides returned to normal. Conclusion. Cholestasis in SGA infants is a severe condition potentially associated with life-threatening complications, requiring complex diagnostic evaluation.

Obesity and hypoglycaemia in type 2 diabetes mellitus outpatients on insulin therapy in Nigeria–data from the multicentre evaluation of type 2 diabetes mellitus outpatients patients on insulin therapy (METOIN) study

Background and Objective: Despite the obvious benefits of early insulin use in achieving good glycaemic control, insulin linked overweight/obesity and hypoglycaemia are sources of concern and worry. Burden of these side effects among type 2 diabetes mellitus (T2DM) outpatients on insulin therapy in Nigeria is unknown.&#x0D; Subjects and Methods: This was a prospective, cross sectional and observational study in which consenting T2DM outpatients that meet the inclusion criteria for the study in five tertiary health facilities were simultaneously recruited and relevant data obtained via investigator-administered questionnaire. Data obtained which included gender, arthropometric measures, hypoglycaemia and where it was treated were analyzed using Statistical Package for Social Sciences (SPSS) version 23.0 software.&#x0D; Results: A total of 245 T2DM outpatients were recruited into the study, made up of 107 (43.7%) male and 138 (56.3%) female. Of this, 121 (49.8%) patients were overweight while 70 (28.7%) were obese. Among the patients, 104 (42.4%) T2DM outpatients on insulin therapy reported hypoglycaemia which was mild in 83 (79.8%) of the patients&#x0D; Conclusion: A significant number of the type 2 DM outpatients on insulin therapy were overweight/obese with mild hypoglycaemia in a majority of them.

Hypoglycemia in hospitalized patients: A sleeping monster

ABSTRACT Objective: This study describes the incidence and clinical profile of hypoglycemia (including mild, moderate, severe, and recurrent) and its correlation with the time of the day, duration of diabetes mellitus (DM), administration of insulin/oral hypoglycemic agents (OHAs) and diagnosis at admission in hospitalized adult patients. Materials and Methods: This retrospective, observational study analyzed the data of hospitalized patients with episode(s) of hypoglycemia. For each patient, clinical profiles such as age, gender, antidiabetic therapy, timing of hypoglycemic event, duration of diabetes, working diagnosis, place of hypoglycemia, dietary changes, and mode of corrective action were studied. Results: Of 100 patients with a mean ± standard deviation age of 62.72 ± 3.54 years, hypoglycemia was the most common among those aged 61–90 years. There were 134 hypoglycemic events and mild hypoglycemia was the most common (72.39% vs. moderate 21.64% and severe 5.97%). There were 59 (44%) events of recurrent hypoglycemia. Hypoglycemic events were maximum during 4:00 am–7:59 am (34%). Longer duration of DM (&gt;15 years, 42%) and insulin therapy were the high-risk factors. There was a statistically significant association between hypoglycemia and duration of diabetes (P &lt; 0.0133), insulin therapy (P &lt; 0.0001), OHA (P &lt; 0.0192), and a combination of insulin and OHA (P &lt; 0.0059) within 24 h before the event but not with the incidence and dietary changes. Conclusion: Patients above 60 years were the most vulnerable population for hypoglycemia, especially during the early hours of the day. Patients who had diabetes for &gt;15 years, on insulin therapy, and those with pulmonary and renal diseases were the most vulnerable to overall and recurrent hypoglycemic events, respectively.

Association Between Fear of Hypoglycemia and Treatment Satisfaction Among Patients With Diabetes Mellitus

Background: Treatment satisfaction is one of the main factors of assessing care quality in patients with chronic diseases. Some factors may influence treatment satisfaction and improve or impair clinical outcomes. This study aimed to determine the relationship between fear of hypoglycemia and satisfaction with treatment in patients with type 2 diabetes treated with oral antidiabetic drugs. Methods: This cross-sectional study was carried out in one of the hospitals of Qazvin Province, Iran, in 2021. The research sample was 390 patients with type 2 diabetes who used oral antidiabetic drugs, selected through convenience sampling. The data were collected using the hypoglycemic fear survey (HFS) and the diabetes medication satisfaction (DiabMedSat) questionnaire. Then, the obtained data were analyzed using the independent t-test, one-way analysis of variance, and multiple linear regression in SPSS software, version 26. Statistical significance was set at P&lt;0.05. Results: Patients’ Mean±SD age was 53.4±11.49 years, and most (57.4%) were female. Treatment satisfaction score was lower in females (β=-0.12, P&lt;0.007) and patients with diabetes complications (β=-0.138, P&lt;0.005). Patients with college education had higher treatment satisfaction (β=0.173, P&lt;0.001). Patients with very severe (β=-0.29, P&lt;0.001) or severe hypoglycemia (β=-0.157, P&lt;0.034) experienced lower treatment satisfaction than those with mild hypoglycemia. Low treatment satisfaction scores were associated with fear of hypoglycemia (β=-0.39, P&lt;0.001). Conclusion: In this study, fear of hypoglycemia was associated with a decreased level of satisfaction with treatment. As a consequence, patients with type 2 diabetes must be assessed for hypoglycemia fears and their adverse effects. Also, to prevent complications caused by not taking antihyperglycemic drugs, nursing managers and clinical nurses are recommended to prepare appropriate programs to implement psychological interventions to reduce the fear of hypoglycemia.

Screening of Individuals with Type 2 Diabetes on Anti-Diabetic Agents for Probable Hypoglycaemia Using the Stanford Hypoglycemia Questionnaire (SHQ) in Outpatient Settings: A Cross-Sectional Study from Outpatient Diabetes Care Centres in North India.

The study was aimed at identifying the incidence of unreported probable hypoglycaemia in individuals with type 2 diabetes (T2DM) on anti-diabetic medications, using the screening Stanford Hypoglycemia Questionnaire (SHQ) in real-world situations. It was a multicentre cross-sectional study on consecutive individuals attending 10 diabetes care centres in Lucknow, Uttar Pradesh, India. The inclusion criteria were as follows: known individuals with T2DM, literate, age greater than or equal to 18 years, on at least one anti-diabetic agent for more than a month and not engaged in regular self-monitoring of blood glucose (SMBG). This study was conducted from August 2017 to April 2018, involving 1198 participants. The mean age of the individuals enrolled was 53.45 years (±10.83), with males comprising 55.3% of the population. It was found that 63.6% of patients were on sulphonylurea (SU), 14.5% were on pioglitazone, 92.2% on metformin, 62.3% on Dipeptidyl peptidase (DPP4i) and 12.8% on Sodium-glucose cotransporter (SGLT2i). The mean SHQ score was 1.81 (±1.59). Probable hypoglycaemia was mild in 57.59%, moderate in 14.69% and severe in 1.41%. Those with diabetic neuropathy (P = <0.001), retinopathy (P = <0.001) and nephropathy (P = <0.001) had significantly higher SHQ scores. Insulin or SU use was associated with a significantly higher SHQ score. Concomitant statin use was associated with a lower incidence of mild, moderate and severe hypoglycaemia (P = 0.01). On multivariate analysis, we found that age, sex, systolic blood pressure (SBP), insulin use and fasting blood sugar were the most important factors associated with an increased risk of hypoglycaemia with an R2 cut-off of 0.7. SHQ was discovered to be a simple and cost-effective screening tool for outpatient detection of hypoglycaemia in an Indian setting, and it can add value to management.