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Hypoglycemia is common in people with type 1 diabetes. Sometimes, severe hypoglycemia can be fatal. The underlying mechanisms by which severe hypoglycemia can lead to death are unclear. The sympathetic nervous system is thought to be proarrhythmic. We hypothesized that norepinephrine is the main mediator of severe hypoglycemia‐induced fatal cardiac arrhythmias. To test this hypothesis, adult, non‐diabetic Sprague–Dawley rats were subjected to hyperinsulinemic‐severe hypoglycemic clamps (3 h, 10–15 mg/dL) during two different experiments: (1) intracerebroventricular (ICV) norepinephrine (n = 26) or artificial cerebrospinal fluid (aCSF) (n = 20) infusion or (2) blockade of norepinephrine release by intraperitoneal reserpine (n = 20) or control (n = 29). In experiment 1, brain norepinephrine infusion during severe hypoglycemia led to a 2.5‐fold increase in third‐degree heart block and a 24% incidence of ST elevation compared to no ST elevation in aCSF controls. In experiment 2, reserpine successfully reduced plasma and cardiac norepinephrine levels. During severe hypoglycemia, reserpine completely prevented second and third‐degree heart block and T wave increases, a marker of myocardial infarction, compared to controls. In conclusion, norepinephrine increases while reserpine, used to reduce norepinephrine nerve terminal release, reduces heart block and markers of myocardial infarction during severe hypoglycemia. [ABSTRACT FROM AUTHOR]

Introduction: Tigecycline has a broad spectrum of activity, including activity against drug-resistant Gram-positive and -negative microorganisms. Its side effects are significant, but hypoglycemia is a rare finding during treatment. We aim to present an event of severe hypoglycemia in a patient with type 2 diabetes mellitus with replacement renal therapy, and hemodialysis after initiating tigecycline. Case presentation: A 54-year-old female diagnosed with type 2 diabetes mellitus was under treatment with basal-bolus insulin therapy and oral antihypertensive drugs. She started hemodialysis 24 months ago. She complained of recurrent fever for the last seven months and was treated with several antibiotics. In two separate blood cultures, she tested positive for methicillin-resistant Staphylococcus epidermidis (MRSE). Based on the antibiogram, we started treatment with tigecycline 100 mg/day. After 6-8 hours from the first dose, the patient is complicated with events of hypoglycemia and then continues with severe hypoglycemia (40-47 mg/dL). The patient continued to have hypoglycemia for about 16-18 hours after the last dose. We didn't find any reasons to explain the cause of episodes of hypoglycemia. She did not have high blood insulin levels (insulin 4.11 mIU/L [range 2.6-24.9]). We followed her for six months and the patient did not experience episodes of hypoglycemia. Conclusions: The association of severe hypoglycemia with tigecycline treatment is a very rare event and published papers on this topic are limited. Clinicians should be aware of this rare event when administering tigecycline and should routinely check blood glucose level during the treatment. [ABSTRACT FROM AUTHOR]

Abstract Hypoglycemia is common in people with type 1 diabetes. Sometimes, severe hypoglycemia can be fatal. The underlying mechanisms by which severe hypoglycemia can lead to death are unclear. The sympathetic nervous system is thought to be proarrhythmic. We hypothesized that norepinephrine is the main mediator of severe hypoglycemia‐induced fatal cardiac arrhythmias. To test this hypothesis, adult, non‐diabetic Sprague–Dawley rats were subjected to hyperinsulinemic‐severe hypoglycemic clamps (3 h, 10–15 mg/dL) during two different experiments: (1) intracerebroventricular (ICV) norepinephrine (n = 26) or artificial cerebrospinal fluid (aCSF) (n = 20) infusion or (2) blockade of norepinephrine release by intraperitoneal reserpine (n = 20) or control (n = 29). In experiment 1, brain norepinephrine infusion during severe hypoglycemia led to a 2.5‐fold increase in third‐degree heart block and a 24% incidence of ST elevation compared to no ST elevation in aCSF controls. In experiment 2, reserpine successfully reduced plasma and cardiac norepinephrine levels. During severe hypoglycemia, reserpine completely prevented second and third‐degree heart block and T wave increases, a marker of myocardial infarction, compared to controls. In conclusion, norepinephrine increases while reserpine, used to reduce norepinephrine nerve terminal release, reduces heart block and markers of myocardial infarction during severe hypoglycemia.

Introduction: Second-generation basal insulin analogues have been shown to reduce hypoglycemia in several trials and observational studies of select populations; however, it remains unclear whether these results persist in real-world settings. Using self-reported hypoglycemia events, we assessed whether second-generation basal insulin analogues reduce rates of hypoglycemia events (non-severe/severe; overall/daytime/nocturnal) compared to earlier intermediate/basal insulin analogues among people with insulin-treated type 1 or 2 diabetes. Methods: We used prospectively collected data from the Investigating Novel Predictions of Hypoglycemia Occurrence Using Real-World Models (iNPHORM) panel survey. This US-wide, 1-year internet-based survey assessed hypoglycemia experiences and related sociodemographic and clinical characteristics of people with diabetes (February 2020−March 2021). We estimated population-average rate ratios for hypoglycemia comparing second-generation to earlier intermediate/basal insulin analogues using negative binomial regression, adjusting for confounders. Within-person variability of repeated observations was addressed with generalized estimating equations. Results: Among iNPHORM participants with complete data, N = 413 used an intermediate/basal insulin analogue for ≥ 1 month during follow-up. After adjusting for baseline and time-updated confounders, average second-generation basal insulin analogue users experienced a 19% (95% CI 3–32%, p = 0.02) lower rate of overall non-severe hypoglycemia and 43% (95% CI 26–56%, p < 0.001) a lower rate of nocturnal non-severe hypoglycemia compared to earlier intermediate/basal insulin users. Overall severe hypoglycemia rates were similar among second-generation and earlier intermediate/basal insulin users (p = 0.35); however, the rate of severe nocturnal hypoglycemia was reduced by 44% (95% CI 10–65%, p = 0.02) among second-generation insulin users compared to earlier intermediate/basal insulin users. Conclusion: Our real-world results suggest second-generation basal insulin analogues reduce rates of hypoglycemia, especially nocturnal non-severe and severe events. Whenever possible and feasible, clinicians should prioritize prescribing these agents over first-generation basal or intermediate insulin in people with type 1 and 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Parents of pediatric patients with type I diabetes require competence in hypoglycemia management and skills in glucagon administration to deal with potentially life-threatening severe hypoglycemia. We aimed to compare parents' subjective self-ratings to an objective expert assessment of competences and skills in dealing with severe hypoglycemia. Methods: We interviewed 140 participants to assess their subjective self-ratings. The objective expert assessments used a standardized clinical case scenario of severe hypoglycemia and a practical demonstration of glucagon administration. Results: The participants self-rated their competence in hypoglycemia management as good (5) or very good (6), and their skills in administering glucagon as acceptable (3) [Scale: very poor (1) to very good (6)]. In the standardized clinical case scenario, 1.4% (2/140) of participants named all relevant steps of severe hypoglycemia management. In the practical demonstration of glucagon administration, 92.9% (130/140) of participants committed at least one drug handling error; 52.1% (73/140) committed at least one drug handling error rated with high clinical risk. Conclusions: We found discrepancies regarding participants' subjective self-ratings compared to their performance in the respective objective expert assessments. These discrepancies indicate a lack of error awareness and the need for intervention studies to improve competence in hypoglycemia management and glucagon administration. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to understand the actual status of multimorbidity and polypharmacy among patients with type 2 diabetes using glucose-lowering drugs, and to assess the effects of patient characteristics on severe hypoglycemia and glycemic control. Methods: We designed a retrospective cohort study using health insurance claims and medical checkup data in Japan from April 2016 to February 2021 and identified patients with type 2 diabetes who were prescribed glucose-lowering drugs. We analyzed data on patient characteristics, including multimorbidity and polypharmacy, calculated the incidence rate for severe hypoglycemic events, applied a negative binomial regression model to explore factors that affected severe hypoglycemia, and analyzed the status of glycemic control in the subcohort for which HbA1c data were available. Results: Within the analysis population (n = 93,801), multimorbidity was present in 85.5% and mean ± standard deviation for oral drug prescriptions was 5.6 ± 3.5 per patient, while for those aged 75 years or older these numbers increased to 96.3% and 7.1 ± 3.5, respectively. The crude incidence rate for severe hypoglycemia was 5.85 (95% confidence interval 5.37, 6.37) per 1000 person-years. Risk factors for severe hypoglycemia included younger and older age, prior severe hypoglycemia, use of insulin, sulfonylurea, two-drug therapy including sulfonylurea or glinides, three-or-more-drug therapy, excessive polypharmacy, and comorbidities including end-stage renal disease (ESRD) requiring dialysis. Subcohort analysis (n = 26,746) showed that glycemic control is not always maintained according to guidelines. Conclusion: Patients with type 2 diabetes, particularly older patients, experienced high multimorbidity and polypharmacy. Several risk factors for severe hypoglycemia were identified, most notably younger age, ESRD, history of severe hypoglycemia, and insulin therapy. Trial Registration: The University Hospital Medical Information Network Clinical Trials Registry (UMIN000046736). [ABSTRACT FROM AUTHOR]

This study aims to evaluate the determinants and clinical markers of patients at risk for severe hypoglycemia (SH) in children and adolescents with type 1 diabetes. In the EPI-GLUREDIA study, clinical parameters and continuous glucose monitoring metrics from children and adolescents with type 1 diabetes were retrospectively analyzed between July 2017 and June 2022. Their clinical parameters were collected during traditional and quarterly medical consultations according to whether they experienced severe hypoglycemia or not. Then, continuous glucose monitoring metrics were analyzed on days surrounding SH during specific periods. According to the glycemic parameters, glycemic hemoglobin and glycemic mean were significantly lower in the three months preceding a SH compared with during three normal months (p < 0.05). Moreover, the time spent in hypoglycemia(time below the range, TBR<3.3) and its strong correlation (R = 0.9, p < 0.001) with the frequency of SH represent a sensitive and specific clinical parameter to predict SH (cut-off: 9%, sensitivity: 71%, specificity: 63%). The second finding of the GLUREDIA study is that SH is not an isolated event in the glycemic follow-up of our T1DM patients. Indeed, most of the glycemic parameters (i.e., glycemic mean, glycemic variability, frequency of hypoglycemia, and glycemic targets) vary considerably in the month preceding an SH (all p < 0.05), whereas most of these studied glycemic parameters remain stable in the absence of a severe acute complication (all p > 0.05). Furthermore, the use of ROC curves allowed us to determine for each glycemic parameter a sensitive or specific threshold capable of more accurately predicting SH. For example, a 10% increase in the frequency of hypoglycemia predicts a risk of near SH with good combination of sensitivity and specificity (sensitivity: 80%, specificity: 60%). The GLUREDIA study aimed to target clinical and glycemic parameters to predict patients at risk for SH. First, we identified TBR<3.3 < 9% as a sensitive and specific tool to reduce the frequency of SH. In addition, SH was not an isolated event but rather it was accompanied by glycemic disturbances in the 30 days before SH. [ABSTRACT FROM AUTHOR]

Abstract Glucagon (traditional kits for intramuscular administration, Glucagon and Glucagen), although recommended as a remedy for severe hypoglycemia (SH), has been reported to be under-utilized, likely because of technical problems. The aims of this study were to evaluate the use of glucagon in persons with type 1 diabetes in several countries, and to investigate if the availability of new ready-to-use glucagons (Baqsimi, Gvoke, Zegalogue, years 2019 to 2021) has expanded the overall use of glucagon. The source of data was IQVIA-MIDAS (units of glucagon sold), while data on persons with type 1 diabetes in countries were derived from IDF Diabetes Atlas. The use of glucagon has been steady from 2014 to 2019, with a small but significant increase from 2019 to 2021, paradoxically only in countries where new ready-to-use glucagons were not available. The use of glucagon has always been ten fold greater in countries where new ready-to-use glucagons became available than in the other countries (population 108,000,000 vs 28,100,000, 480,291 vs 182,018 persons with type 1 diabetes). A significant correlation was observed in all years between units of glucagon and persons with type 1 diabetes. Availability of new ready-to-use glucagons was associated with a small increase of sales, due only to new ready-to-use glucagons themselves. The use of glucagon (any type) remains low, approximately 1/10 of persons with type 1 diabetes. We conclude that use of glucagon is scarce in most countries, and so far has not been expanded by new ready-to-use glucagons such as the ones considered in this study.

Abstract Aims/Introduction Several factors are associated with hypoglycemia unawareness and severe hypoglycemia, but few large studies have analyzed Japanese patients with type 1 diabetes. The aim of this study was to analyze the risk factors for hypoglycemia unawareness and severe hypoglycemia in Japanese type 1 diabetes patients. Materials and Methods A self‐administered questionnaire investigated events, complications and treatments associated with hypoglycemia in patients with type 1 diabetes. Multiple logistic regression analysis of factors associated with hypoglycemia unawareness and severe hypoglycemia requiring medical treatment was carried out. The coefficient of variation (CV) of blood glucose levels was determined using blood samples collected at six outpatient visits. Results Of the 1,619 participants, 44.2% and 10.4% experienced hypoglycemia unawareness and severe hypoglycemia, respectively. Mean HbA1c levels in patients with hypoglycemia unawareness were lower than those in patients without hypoglycemia unawareness. The type 1 diabetes subtype, glycated hemoglobin (HbA1c) level, CV of blood glucose levels and history of severe hypoglycemia requiring medical treatment were significant independent variables predicting the presence of hypoglycemia unawareness. The glucose CV and a history of hypoglycemia unawareness were significant independent variables predicting severe hypoglycemia requiring medical treatment. In stratified analyses of patients divided into four groups according to glucose CV and HbA1c levels, the high‐glucose‐CV/low‐HbA1c group had the highest odds ratios for hypoglycemia unawareness (2.60) and severe hypoglycemia requiring medical treatment (2.55). Conclusions The ambulant glucose CV correlated with both hypoglycemia unawareness and severe hypoglycemia. Patients with high glucose CV and low HbA1c are at high risk of such adverse events, and their treatment strategies should be reviewed.

Abstract Aims/Introduction We investigated the associations between a combination of lifestyle factors and changes to these factors and the subsequent risk of severe hypoglycemia (SH) in type 2 diabetes patients. Materials and Methods Individuals with adult type 2 diabetes who underwent consecutive 2‐year interval health screening programs from 2009 to 2012 from the Korean National Health Insurance Service database were included and followed up until 2018. Information on history of smoking status, alcohol consumption and physical activity, as well as changes to these factors, was obtained. The primary outcome was incident SH. Results Of the 1,490,233 type 2 diabetes patients, 30,539 (2.1%) patients developed SH. Current smokers and heavy drinkers had increased risk of SH, compared with non‐smokers and non‐drinkers, respectively (hazard ratio 1.28, 95% confidence interval 1.23–1.34; hazard ratio 1.22, 95% confidence interval 1.15–1.30). However, regular physical activity was associated with reduced SH risk (hazard ratio 0.79, 95% confidence interval 0.77–0.82). A combination of unhealthy lifestyle habits was associated with increased SH risk in a dose‐dependent fashion (P for trend

Background: We aimed to investigate associations between exposure to various trajectories of severe hypoglycemic events and risk of dementia in patients with type 2 diabetes. Methods: In 2002–2003, 677,618 patients in Taiwan were newly diagnosed as having type 2 diabetes. Among them, 35,720 (5.3%) experienced severe hypoglycemic events during the 3-year baseline period following diagnosis. All patients were followed from the first day after baseline period to the date of dementia diagnosis, death, or the end of 2011. A group-based trajectory model was used to classify individuals with severe hypoglycemic events during the baseline period. Cox proportional hazard models with the competing risk method were used to relate dementia risk to various severe hypoglycemia trajectories. Results: After a median follow-up 6.70 and 6.10 years for patients with and without severe hypoglycemia at baseline, respectively, 1,952 (5.5%) individuals with severe hypoglycemia and 23,492 (3.7%) without developed dementia during follow-up, for incidence rates of 109.80 and 61.88 per 10,000 person-years, respectively. Four groups of severe hypoglycemia trajectory were identified with a proportion of 18.06%, 33.19%, 43.25%, and 5.50%, respectively, for Groups 1 to 4. Groups 3 (early manifestation but with later decrease) and 4 (early and sustained manifestation) were associated with a significantly increased risk of dementia diagnosis, with a covariate-adjusted subdistribution hazard ratio of 1.22 (95% confidence interval, 1.14–1.31) and 1.25 (95% confidence interval, 1.02–1.54), respectively. Conclusion: Our analysis highlighted that early manifestation of severe hypoglycemic events may contribute more than does late manifestation to the risk of dementia among individuals newly diagnosed as having type 2 diabetes.

Abstract To estimate the trends in the prevalence of severe hypoglycemia (SH) in patients with type 2 diabetes in Korea, we investigated the total number of SH episodes among type 2 diabetes patients aged ≥30 years who visited the emergency department between 2002 and 2019, using the Korean National Health Insurance Service database. The prevalence of SH events increased from 2002 to 2012; however, it has decreased gradually since 2012. In 2019, the prevalence of SH was 0.6%, with an incidence rate of 4.43 per 1,000 person‐years. Approximately 23,000 SH events occur every year in Korea. Although the incidence is steadily decreasing, there are a considerable number of SH events in type 2 diabetes patients. The decline in the incidence of SH seems to most likely be due to the increased prescription rate of hypoglycemic agents without hypoglycemia risk, less‐strict treatment goals and the individualization of therapy.

Hypoglycemia is an often-observed acute complication in the management of children and adolescents with type 1 diabetes. It causes inappropriate glycemic outcomes and may impair the quality of life in the patients. Severe hypoglycemia with cognitive impairment, such as a convulsion and coma, is a lethal condition and is associated with later-onset cognitive impairment and brain-structural abnormalities, especially in young children. Therefore, reducing the frequency of hypoglycemia and minimizing the occurrence of severe hypoglycemia are critical issues in the management of children and adolescents with type 1 diabetes. Advanced diabetes technologies, including continuous glucose monitoring and sensor-augmented insulin pumps with low-glucose suspension systems, can reduce the frequency of hypoglycemia and the occurrence of severe hypoglycemia without aggravating glycemic control. The hybrid closed-loop system, an automated insulin delivery system, must be the most promising means to achieve appropriate glycemic control with preventing severe hypoglycemia. The use of these advanced diabetes technologies could improve glycemic outcomes and the quality of life in children and adolescents with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Glucagon (traditional kits for intramuscular administration, Glucagon and Glucagen), although recommended as a remedy for severe hypoglycemia (SH), has been reported to be under-utilized, likely because of technical problems. The aims of this study were to evaluate the use of glucagon in persons with type 1 diabetes in several countries, and to investigate if the availability of new ready-to-use glucagons (Baqsimi, Gvoke, Zegalogue, years 2019 to 2021) has expanded the overall use of glucagon. The source of data was IQVIA-MIDAS (units of glucagon sold), while data on persons with type 1 diabetes in countries were derived from IDF Diabetes Atlas. The use of glucagon has been steady from 2014 to 2019, with a small but significant increase from 2019 to 2021, paradoxically only in countries where new ready-to-use glucagons were not available. The use of glucagon has always been ten fold greater in countries where new ready-to-use glucagons became available than in the other countries (population 108,000,000 vs 28,100,000, 480,291 vs 182,018 persons with type 1 diabetes). A significant correlation was observed in all years between units of glucagon and persons with type 1 diabetes. Availability of new ready-to-use glucagons was associated with a small increase of sales, due only to new ready-to-use glucagons themselves. The use of glucagon (any type) remains low, approximately 1/10 of persons with type 1 diabetes. We conclude that use of glucagon is scarce in most countries, and so far has not been expanded by new ready-to-use glucagons such as the ones considered in this study. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Several factors are associated with hypoglycemia unawareness and severe hypoglycemia, but few large studies have analyzed Japanese patients with type 1 diabetes. The aim of this study was to analyze the risk factors for hypoglycemia unawareness and severe hypoglycemia in Japanese type 1 diabetes patients. Materials and Methods: A self‐administered questionnaire investigated events, complications and treatments associated with hypoglycemia in patients with type 1 diabetes. Multiple logistic regression analysis of factors associated with hypoglycemia unawareness and severe hypoglycemia requiring medical treatment was carried out. The coefficient of variation (CV) of blood glucose levels was determined using blood samples collected at six outpatient visits. Results: Of the 1,619 participants, 44.2% and 10.4% experienced hypoglycemia unawareness and severe hypoglycemia, respectively. Mean HbA1c levels in patients with hypoglycemia unawareness were lower than those in patients without hypoglycemia unawareness. The type 1 diabetes subtype, glycated hemoglobin (HbA1c) level, CV of blood glucose levels and history of severe hypoglycemia requiring medical treatment were significant independent variables predicting the presence of hypoglycemia unawareness. The glucose CV and a history of hypoglycemia unawareness were significant independent variables predicting severe hypoglycemia requiring medical treatment. In stratified analyses of patients divided into four groups according to glucose CV and HbA1c levels, the high‐glucose‐CV/low‐HbA1c group had the highest odds ratios for hypoglycemia unawareness (2.60) and severe hypoglycemia requiring medical treatment (2.55). Conclusions: The ambulant glucose CV correlated with both hypoglycemia unawareness and severe hypoglycemia. Patients with high glucose CV and low HbA1c are at high risk of such adverse events, and their treatment strategies should be reviewed. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) is increasingly being used to improve patient care and management. In this paper, we propose explainable AI (XAI) models for predicting severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) episodes in adults with type 1 diabetes (T1D) and relapses in adults with relapsing-remitting multiple sclerosis (RRMS). We follow a three-step process in this study: (1) develop baseline machine learning (ML) models, (2) improve the models using ReliefF feature selection technique, and develop sex-stratified models, (3) explain the models and their results using SHapley Additive exPlanations (SHAP). We built six ML models (XGBoost, LightGBM, CatBoost, AdaBoost, random forest, and linear regression) for all scenarios. Applying the ReliefF feature selection led to improved model performance in predicting all outcomes compared to the baseline models. Additionally, sex-stratified models further improved the prediction of SH episodes and relapses. The F1 scores for predicting SH episodes in male and female patients were 84.07% and 84.95%, respectively, and the DKA prediction model achieved an F1 score of 78.67%. The proposed relapse prediction models outperformed existing models with F1 scores of 84.55% (males) and 76.11% (females), and ROCs of 70.26% (males) and 69.05% (females). Our results highlight the importance of considering sex differences, socioeconomic factors, and physical and mental health in medical outcome prediction. Boosting ML algorithms were found to be effective in detecting SH and DKA in T1D patients and relapses in RRMS patients compared to conventional tree-based ML and statistical models.

Aims/Introduction: We investigated the associations between a combination of lifestyle factors and changes to these factors and the subsequent risk of severe hypoglycemia (SH) in type 2 diabetes patients. Materials and Methods: Individuals with adult type 2 diabetes who underwent consecutive 2‐year interval health screening programs from 2009 to 2012 from the Korean National Health Insurance Service database were included and followed up until 2018. Information on history of smoking status, alcohol consumption and physical activity, as well as changes to these factors, was obtained. The primary outcome was incident SH. Results: Of the 1,490,233 type 2 diabetes patients, 30,539 (2.1%) patients developed SH. Current smokers and heavy drinkers had increased risk of SH, compared with non‐smokers and non‐drinkers, respectively (hazard ratio 1.28, 95% confidence interval 1.23–1.34; hazard ratio 1.22, 95% confidence interval 1.15–1.30). However, regular physical activity was associated with reduced SH risk (hazard ratio 0.79, 95% confidence interval 0.77–0.82). A combination of unhealthy lifestyle habits was associated with increased SH risk in a dose‐dependent fashion (P for trend <0.001). Compared with participants without changes in their unhealthy lifestyles, participants who improved lifestyles had decreased risk of SH. Conclusions: Greater adherence to healthy lifestyle factors and any improvement in unhealthy lifestyle habits were associated with a substantially lower risk of SH in individuals with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Parents of pediatric patients with type I diabetes require competence in hypoglycemia management and skills in glucagon administration to deal with potentially life-threatening severe hypoglycemia. We aimed to compare parents’ subjective self-ratings to an objective expert assessment of competences and skills in dealing with severe hypoglycemia. Methods: We interviewed 140 participants to assess their subjective self-ratings. The objective expert assessments used a standardized clinical case scenario of severe hypoglycemia and a practical demonstration of glucagon administration. Results: The participants self-rated their competence in hypoglycemia management as good (5) or very good (6), and their skills in administering glucagon as acceptable (3) [Scale: very poor (1) to very good (6)]. In the standardized clinical case scenario, 1.4% (2/140) of participants named all relevant steps of severe hypoglycemia management. In the practical demonstration of glucagon administration, 92.9% (130/140) of participants committed at least one drug handling error; 52.1% (73/140) committed at least one drug handling error rated with high clinical risk. Conclusions: We found discrepancies regarding participants’ subjective self-ratings compared to their performance in the respective objective expert assessments. These discrepancies indicate a lack of error awareness and the need for intervention studies to improve competence in hypoglycemia management and glucagon administration.

Background: Self-management of blood glucose levels to avoid hypoglycemia is vital for patients with type 2 diabetes mellitus (T2DM). The association between specific metrics of glycemic variability (glycosylated hemoglobin A1c [HbA1c] and fasting plasma glucose [FPG]) and severe hypoglycemia has not been fully studied in patients with T2DM. Methods: In this post hoc analysis, patients with established T2DM with a high risk of cardiovascular disease were included in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. The Cox proportional hazards model was used to investigate the relationship between glycemic variability and hypoglycemia requiring medical assistance (HMA) and hypoglycemia requiring any third-party assistance (HAA). The prognostic value of HbA1c/FPG variability for our predefined outcomes was compared using Harrell's C method. Results: After adjusting for confounders, each increase in HbA1c variability of 1 standard deviation (SD) indicated a higher risk of HAA (hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.03-1.16; P < 0.01) and HMA events (HR: 1.11; 95% CI: 1.03-1.20; P < 0.01). Meanwhile, each increase in FPG variability of 1 SD increased the risk of HAA (HR: 1.40; 95% CI: 1.31-1.49; P < 0.01) and HMA events (HR: 1.46; 95% CI: 1.35-1.57; P < 0.01). Meanwhile, models, including FPG variability, had better prognostic value for our predefined outcomes than HbA1c variability (P < 0.01). Conclusions: Increased visit-to-visit variability in HbA1c and fasting glycemia is associated with a greater risk of severe hypoglycemic events in T2DM patients. FPG variability is a more sensitive indicator than HbA1c variability. [ABSTRACT FROM AUTHOR]

To estimate the trends in the prevalence of severe hypoglycemia (SH) in patients with type 2 diabetes in Korea, we investigated the total number of SH episodes among type 2 diabetes patients aged ≥30 years who visited the emergency department between 2002 and 2019, using the Korean National Health Insurance Service database. The prevalence of SH events increased from 2002 to 2012; however, it has decreased gradually since 2012. In 2019, the prevalence of SH was 0.6%, with an incidence rate of 4.43 per 1,000 person‐years. Approximately 23,000 SH events occur every year in Korea. Although the incidence is steadily decreasing, there are a considerable number of SH events in type 2 diabetes patients. The decline in the incidence of SH seems to most likely be due to the increased prescription rate of hypoglycemic agents without hypoglycemia risk, less‐strict treatment goals and the individualization of therapy. [ABSTRACT FROM AUTHOR]

Aims: To estimate the number of people with diabetes (PWD) requiring emergency services for severe hypoglycemia (SH) in France and the associated costs. Methods: PWD were identified using the National Health Insurance database (SNDS). Type of diabetes was determined by the medications used. Matching of the emergency department (ED) visits database (RPU) and the SNDS was used to identify ED visits for SH in 2016 and 2017. SH was identified in the RPU using specific ICD-10 codes. The main SH-related costs analyzed were costs of ED visits, hospitalization, and transport. Results: Of 3,236,600 PWD in 2017, 781,084 had at least one ED visit (11.5% type 1 diabetes [T1D]) and 9,160 patients had at least one ED visit for SH (40.2% T1D; 55.9% male; mean age 63.0 years; mean diabetes duration 17.2 years). Nearly 50% of ED visits for SH led to immediate hospitalization. The total cost of emergency services for SH was €12.39 million. The mean (SD) cost per patient was €1,352 (€2,540). Conclusions: SH accounts for nearly 1% of ED visits in PWD, and nearly half of these patients are hospitalized during the visit. Beyond the patient impact, SH is associated with a substantial economic burden.

Abstract Background The objective of this study was to describe the epidemiology of severe hypoglycaemia in Kuwait, aiming to provide a preliminary background to update the current guidelines and improve patient management. Method This was a prospective analysis of severe hypoglycaemia cases retrieved from emergency medical services (EMS) archived data between 1 January and 30 June 2020. The severe hypoglycaemia cases were then sub-grouped based on EMS personal initial management and compared in terms of scene time, transportation rate, complications and outcomes. The primary outcomes were GCS within 10–30 min and normal random blood glucose (RBS) within 10–30 min. Results A total of 167 cases met the inclusion criteria. The incidence of severe hypoglycaemia in the national EMS was 11 per 100,000. Intramuscular glucagon was used on scene in 89% of the hypoglycaemic events. Most of the severe hypoglycaemia patients regained normal GCS on scene (76.5%). When we compared the two scene management strategies for severe hypoglycaemia cases, parenteral glucose administration prolonged the on-scene time (P = .002) but was associated with more favourable scene outcomes than intramuscular glucagon, with normal GCS within 10–30 min (P = .05) and normal RBS within 10–30 min (P = .006). Conclusion: Severe hypoglycaemia is not uncommon during EMS calls. Appropriate management by EMS personals is fruitful, resulting in favourable scene outcomes and reducing the hospital transportation rate. More research should be invested in improving and structuring the prehospital management of severe hypoglycaemia. One goal is to clarify the superiority of parenteral glucose over intramuscular glucagon in the prehospital setting.

Glucose-lowering medication and lifestyle modification are essential for optimal glycemic control in patients with type 2 diabetes mellitus (T2DM). However, glucose-lowering agents, particularly insulin and insulin secretagogues, may cause hypoglycemia, which has multiple negative effects on the cardiovascular (CV) system and may cause death. Previous studies using institutional data from the Korean Nationwide Health Insurance database have consistently found a causal relationship between severe hypoglycemia and CV outcomes and mortality. Screening for high-risk patients, appropriate management, and intensive individualized education are the most effective measures and essential for the prevention of harmful hypoglycemic events. Based on identified risk factors that predict severe hypoglycemia, we developed an 1-year risk prediction model for severe hypoglycemia that can be used in clinical settings. In this review, we describe the current understanding of severe hypoglycemia and the clinical implications in patients with T2DM. Furthermore, we highlight the importance of intensive individualized education for high-risk patients and the risk prediction model to reduce severe hypoglycemia.

Introduction: Severe hypoglycemic events (SHE) represent a clinical and economic burden in patients with diabetes. Nasal glucagon (NG) is a novel treatment for SHEs with similar efficacy, but with a usability advantage over injectable glucagon (IG) that may translate to improved economic outcomes. The economic implications of this usability advantage on SHE-related spending in Spain were explored in this analysis. Methods: A cost-offset and budget impact analysis (BIA) was conducted using a decision tree model, adapted for the Spanish setting. The model calculated average costs per SHE over the SHE treatment pathway following a treatment attempt with IG or NG. Analyses were performed separately in three populations with insulin-treated diabetes: children and adolescents (4–17 years) with type 1 diabetes (T1D), adults with T1D and adults with type 2 diabetes (T2D), with respective population estimates applied in BIA. Treatment probabilities were assumed to be equal for IG and NG, except for treatment success following glucagon administration. Epidemiologic and cost data were obtained from Spanish-specific sources. BIA results were presented at a 3-year time horizon. Results: On a per SHE level, NG was associated with lower costs compared to IG (children and adolescents with T1D, EUR 820; adults with T1D, EUR 804; adults with T2D, EUR 725). Lower costs were attributed to reduced costs of professional medical assistance in patients treated with NG. After 3 years, BIA showed that relative to IG, the introduction of NG was projected to reduce SHE-related spending by EUR 1,158,969, EUR 142,162,371, and EUR 6,542,585 in children and adolescents with T1D, adults with T1D, and adults with insulin-treated T2D, respectively. Conclusions: In Spain, the usability advantage of NG over IG translates to potential cost savings per SHE in three populations with insulin-treated diabetes, and the introduction of NG was associated with a lower budget impact versus IG in each group. [ABSTRACT FROM AUTHOR]

Aims: The CRASH study examined severe hypoglycemia (SH) experiences among people with diabetes (PWD) and caregivers across eight countries. Here we report findings from the Japan cohort, with references to data from the United Kingdom (UK) cohort. Materials and Methods: Adults with type 1 (T1DM) or insulin-treated type 2 diabetes mellitus (T2DM) and caregivers (not necessarily related) were recruited from online patient panels. Participants who had experienced at least one SH event in the past 3 years were eligible for study inclusion. Participants completed an online survey regarding their experience with SH, its treatment, and actions during and after an event. Results: Of the 9367 PWD and caregivers from the online patient panels, 8475 participants were ineligible and a total of 53 Japanese participants (35 T1DM, 9 T2DM, 9 caregivers) completed the survey. Most SH incidents occurred at home and were unattended by a healthcare provider. For T1DM, 29% of Japan PWD and 13% of the UK PWD called an ambulance during an SH event; of these, 90% (Japan) and 50% (UK) were transported to hospital. Glucagon use was low (3% Japan and 10% UK for T1DM). Japanese respondents reported emotional impacts of SH, including feeling scared (86% T1DM, 56% T2DM), unprepared (63% T1DM, 78% T2DM), and helpless (60% T1DM, 33% T2DM). Despite the emotional burden, most PWD did not immediately discuss their SH event with a healthcare provider, with the majority (75% T1DM, 71% T2DM) waiting until their next doctor's appointment. Conclusion: Conversations around SH between healthcare providers and PWD appear to be insufficient in Japan. An emotional burden of SH was reported by PWD and caregivers. Education regarding the prevention of SH and available treatment options may reduce SH events and improve treatment preparation, while alleviating PWD concerns. [ABSTRACT FROM AUTHOR]

Type 1 diabetes is one of the most common chronic diseases in children and adolescents, with an increasing incidence globally. Major variations in serum glucose cause severe ketoacidosis and hypoglycemia, acute metabolic complications of the disease. We performed a retrospective study on a group of 119 children and adolescents with type 1 diabetes in whom only the cases with ketoacidosis and severe hypoglycemia that required emergency hospitalization were quantified. At the same time, we identified the causes and determinants of these acute complications. According to the case study, 28.6% of patients (34 cases) presented severe hypoglycemia, the most common causes of hypoglycemia being intense physical activity without additional carbohydrate intake, delayed carbohydrate intake, and excess insulin. 15.3% of patients (18 cases) had ketoacidosis, of which 55.55% were recurrent ketoacidosis. Ketoacidosis has been detected in patients with poor glycemic balance and poor treatment compliance by not following a diet and skipping insulin doses. Among the additional risk fac-tors, we identified age over 13 years and the age of diabetes greater than 5 years, for both acute complications.

The multinational CRASH study found that substantive recommendations from health care providers were predictive of actions taken by people with diabetes during and after a severe hypoglycemic event, which highlights the importance of equipping people with actionable strategies to prevent and treat severe hypoglycemia should a severe hypoglycemic event arise.

Purpose: Hospital pharmacists contribute to patient safety and quality initiatives by overseeing the prescribing of antidiabetic medications. A pharmacist-driven glycemic control protocol was developed to reduce the rate of severe hypoglycemia events (SHE) in high-risk hospitalized patients. Methods: We retrospectively analyzed the rates of SHE (defined as blood glucose ≤40 mg/dL), before and after instituting a pharmacist-driven glycemic control protocol over a 4-year period. A hospital glucose management team that included a lead Certified Diabetes Educator Pharmacist (CDEP), 5 pharmacists trained in diabetes, a lead hospitalist, critical care and hospital providers established a process to first identify patients at risk for severe hypoglycemia and then implement our protocol. Criteria from the American Diabetes Association and the American Association of Clinical Endocrinologists was utilized to identify and treat patients at risk for SHE. We analyzed and compared the rate of SHE and physician acceptance rates before and after protocol initiation. Results: From January 2015 to March 2019, 18 297 patients met criteria for this study; 139 patients experienced a SHE and approximately 80% were considered high risk diabetes patients. Physician acceptance rates for the new protocol ranged from 77% to 81% from the year of initiation (2016) through 2018. The absolute risk reduction of SHE was 9 events per 1000 hospitalized diabetic patients and the relative risk reduction was 74% SHE from the start to the end of the protocol implementation. Linear regression analysis demonstrated that SHE decreased by 1.5 events per 1000 hospitalized diabetic patients (95% confidence interval, −1.54 to −1.48, P <.001) during the 2 years following the introduction of the protocol. This represents a 15% relative reduction of SHE per year. Conclusion: The pharmacist-driven glycemic control protocol was well accepted by our hospitalists and led to a significant reduction in SHE in high-risk diabetes patient groups at our hospital. It was cost effective and strengthened our physician-pharmacist relationship while improving diabetes care. [ABSTRACT FROM AUTHOR]

Background: Hypoglycemia prognostic models contingent on prospective, self-reported survey data offer a powerful avenue for determining real-world event susceptibility and interventional targets. Objective: This protocol describes the design and implementation of the 1-year iNPHORM (Investigating Novel Predictions of Hypoglycemia Occurrence Using Real-world Models) study, which aims to measure real-world self-reported severe and nonsevere hypoglycemia incidence (daytime and nocturnal) in American adults with type 1 or 2 diabetes mellitus prescribed insulin and/or secretagogues, and develop and internally validate prognostic models for severe, nonsevere daytime, and nonsevere nocturnal hypoglycemia. As a secondary objective, iNPHORM aims to quantify the effects of different antihyperglycemics on hypoglycemia rates. Methods: iNPHORM is a prospective, 12-wave internet-based panel survey that was conducted across the United States. Americans (aged 18-90 years) with self-reported type 1 or 2 diabetes mellitus prescribed insulin and/or secretagogues were conveniently sampled via the web from a pre-existing, closed, probability-based internet panel (sample frame). A sample size of 521 baseline responders was calculated for this study. Prospective data on hypoglycemia and potential prognostic factors were self-assessed across 14 closed, fully automated questionnaires (screening, baseline, and 12 monthly follow-ups) that were piloted using semistructured interviews (n=3) before fielding; no face-to-face contact was required as part of the data collection. Participant responses will be analyzed using multivariable count regression and machine learning techniques to develop and internally validate prognostic models for 1-year severe and 30-day nonsevere daytime and nocturnal hypoglycemia. The causal effects of different antihyperglycemics on hypoglycemia rates will also be investigated. Results: Recruitment and data collection occurred between February 2020 and March 2021 (ethics approval was obtained on December 17, 2019). A total of 1694 participants completed the baseline questionnaire, of whom 1206 (71.19%) were followed up for 12 months. Most follow-up waves (10,470/14,472, 72.35%) were completed, translating to a participation rate of 179% relative to our target sample size. Over 70.98% (856/1206) completed wave 12. Analyses of sample characteristics, quality metrics, and hypoglycemia incidence and prognostication are currently underway with published results anticipated by fall 2022. Conclusions: iNPHORM is the first hypoglycemia prognostic study in the United States to leverage prospective, longitudinal self-reports. The results will contribute to improved real-world hypoglycemia risk estimation and potentially safer, more effective clinical diabetes management. [ABSTRACT FROM AUTHOR]

Background: Elderly adults with diabetes are at increased risk of severe hypoglycemia and hypoglycemic coma due to various conditions including decline in cognitive function, reduced activity of daily living (ADL) and reduced renal function; special cautions are, therefore, recommended to avoid these life-threatening events. Case presentation: A 92-year-old female was admitted to our institution because of severe coma. Upon arrival, her serum C-peptide was 1.64 ng/mL despite low plasma glucose (24 mg/dL) and serum glimepiride (40.85 ng/mL). She had past history of compression fracture of her lumbar spine, which substantially affected her ADL. Her score on the dementia assessment sheet for community-based integrated care system-8 items (DASC-8) was 26 points. She had been receiving 12 oral medications for diabetes, essential hypertension, chronic gastritis and constipation from her nearby clinic. Her physician-in-charge had found that she was not taking her medications properly and simplified her prescription regimen to 3 oral medications with vildagliptin 50 mg twice daily replaced by glimepiride 3 mg once daily and asked her son to assist in taking the drugs 6 days before her admission to our hospital. While her consciousness level was improved to some extent, she was transferred to a long-term care bed hospital because it had become too difficult to care for her at home. Conclusions: It is important to note that anti-diabetes drugs should be carefully selected based on each patient's cognitive function and ADL, and that the reasoning should be shared with the general practitioners involved to avoid severe hypoglycemic events. [ABSTRACT FROM AUTHOR]

Background: Severe hypoglycemia can cause cognitive impairment in diabetic patients, but the underlying molecular mechanism remains unclear. Objective: To assess the effect of severe hypoglycemia on cognitive function in diabetic mice to clarify the relationship between the mechanism and dysfunction of pericytes and the blood–brain barrier (BBB). Method: We established type 1 diabetes mellitus in 80 male C57BL/6J mice by intraperitoneal injection of streptozotocin (150 mg/kg). Further intraperitoneal injection of short-acting insulin induced severe hypoglycemia. The mice were divided into normal, diabetes, and diabetic + severe hypoglycemia groups, and their blood glucose and general weight index were examined. Pericyte and BBB morphology and function were detected by histological and western blot analyses, BBB permeability was detected by Evans blue staining, and cognitive function was detected with the Morris water maze. Results: Severe hypoglycemia aggravated the histological damage, BBB damage, brain edema, and pericyte loss in the diabetic mice. It also reduced the expression of the BBB tight junction proteins occludin and claudin-5, the expression of the pericyte-specific markers PDGFR-β (platelet-derived growth factor receptor-β) and α-SMA, and increased the expression of the inflammatory factor MMP9. At the same time, diabetic mice with severe hypoglycemia had significantly reduced cognitive function. Conclusion: Severe hypoglycemia leads to cognitive dysfunction in diabetic mice, and its possible mechanism is related to pericyte dysfunction and BBB destruction. [ABSTRACT FROM AUTHOR]

Background: Severe hypoglycemia can cause cognitive impairment in diabetic patients, but the underlying molecular mechanism remains unclear.Objective: To assess the effect of severe hypoglycemia on cognitive function in diabetic mice to clarify the relationship between the mechanism and dysfunction of pericytes and the blood–brain barrier (BBB).Method: We established type 1 diabetes mellitus in 80 male C57BL/6J mice by intraperitoneal injection of streptozotocin (150 mg/kg). Further intraperitoneal injection of short-acting insulin induced severe hypoglycemia. The mice were divided into normal, diabetes, and diabetic + severe hypoglycemia groups, and their blood glucose and general weight index were examined. Pericyte and BBB morphology and function were detected by histological and western blot analyses, BBB permeability was detected by Evans blue staining, and cognitive function was detected with the Morris water maze.Results: Severe hypoglycemia aggravated the histological damage, BBB damage, brain edema, and pericyte loss in the diabetic mice. It also reduced the expression of the BBB tight junction proteins occludin and claudin-5, the expression of the pericyte-specific markers PDGFR-β (platelet-derived growth factor receptor-β) and α-SMA, and increased the expression of the inflammatory factor MMP9. At the same time, diabetic mice with severe hypoglycemia had significantly reduced cognitive function.Conclusion: Severe hypoglycemia leads to cognitive dysfunction in diabetic mice, and its possible mechanism is related to pericyte dysfunction and BBB destruction.

ABSTRACT This is a retrospective report of the frequency of severe hypoglycemia and the association between common mental disorders and type 1 diabetes mellitus treated with insulin analogues. Patients with severe hypoglycemia compared with those without this complication had a higher prevalence of positive screening for common mental disorders (88% vs.77%, respectively, p = 0.03).

Abstract Background Heart failure (HF) is a common cardiovascular complication of type 2 diabetes (T2D). This secondary analysis investigated baseline factors and treatment differences associated with risk of hospitalization for HF (hHF), and the possible association between severe hypoglycemia and hHF. Methods DEVOTE was a treat-to-target, double-blind cardiovascular outcomes trial in patients (n = 7637) with T2D and high cardiovascular risk randomized to insulin degludec (degludec) or insulin glargine 100 units/mL (glargine U100). The main endpoint of this secondary analysis was time to first hHF (standardized MedDRA Query definition). Severe hypoglycemia was adjudicated (American Diabetes Association definition). The main endpoint and the temporal association between severe hypoglycemia and hHF were analyzed with a Cox proportional hazards regression model. Predictors of time to first hHF were identified using baseline variables. Results Overall, 372 (4.9%) patients experienced hHF (550 events). There was no significant difference in the risk of hHF between treatments (hazard ratio [HR] 0.88 [0.72;1.08]95% CI, p = 0.227). Prior HF (HR 4.89 [3.90;6.14]95% CI, p ≤ 0.0001) was the strongest predictor of future hHF events. The risk of hHF significantly increased after (HR 2.2), and within a week after (HR 11.1), experiencing a severe hypoglycemic episode compared with before an episode. Conclusions In patients with T2D and high cardiovascular risk there were no treatment differences in terms of hHF. Prior HF was the strongest predictor of future hHF events, and there was an association between severe hypoglycemia and subsequent hHF. Further research should evaluate whether the risk of hHF can be modified by treatments aimed at reducing hypoglycemia. Trial Registration NCT01959529

Abstract Background We investigated the association regarding severe hypoglycemia episodes with cardiovascular disease risk and all-cause mortality in patients with type 2 diabetes. Methods Baseline and follow-up data (n = 1,568,097) from patients with type 2 diabetes were retrieved from the National Health Insurance System database (covering the entire Korean population). Type 2 diabetes, severe hypoglycemia, and major comorbidities were identified using International Classification of Diseases 10 codes and medication information. Individuals who were classified as type 2 diabetes in the year of 2009 were screened, and we counted severe hypoglycemia episodes from 2007 to 2009. The primary outcome was newly developed myocardial infarction (MI), stroke, heart failure, or all-cause mortality. Participants were followed from the baseline index date to the date of death or until December 31, 2015. Results In total, 19,660 (1.2%) patients developed at least one severe hypoglycemia event during the period from 2007 to 2009. Mean follow-up was 5.7 years. After adjustment for confounding factors, the hazard ratio (HR) of MI significantly and sequentially increased: 0 vs. 1 episode, HR 1.56, 95% CI 1.46–1.64; 0 vs. 2 episodes, HR 1.86, 95% CI 1.61–2.15; 0 vs. 3 or more episodes, HR 1.86, 95% CI 1.48–2.35, P for trend

Abstract Aims/Introduction The present study aimed to describe hospital utilization and examine actual medical costs for severe hypoglycemic events in patients with type 2 diabetes mellitus in Japan. Materials and Methods Medical resource utilization associated with severe hypoglycemia was evaluated using a receipt database of acute‐care hospitals in Japan. Patients with type 2 diabetes treated with antihyperglycemic agents were included. Severe hypoglycemic events were identified and divided into two groups: with or without hospitalization. Total and attributable medical costs per event were calculated based on the actual medical treatment after severe hypoglycemic events. Attributable costs were estimated from the receipt codes directly associated with the treatment of severe hypoglycemia. Results In the hospitalized patients, the median length of hospital stay was 11 days, and the median total and attributable medical costs were ¥402,081 and ¥302,341, respectively. The majority of the hospitalized patients underwent a radiographic examination and general blood tests. Apart from the hospitalization costs, the costs associated with diagnosis accounted for 29.6% of the total medical costs. In the outpatients, 60.6% visited hospitals only once for the severe hypoglycemic event, whereas 11.4% visited hospitals daily for a week after the severe hypoglycemic event. The mean number of hospital visits of the outpatient after a severe hypoglycemic event was 2.7 ± 2.6 days. The median total and attributable medical costs were ¥265,432 and ¥4,628, respectively. Conclusions Significant medical resources are used for the treatment of severe hypoglycemic events of patients with type 2 diabetes in Japan.

Abstract Background Patients with type 1 diabetes mellitus (DM) have poor glycemic control owing to extreme impairments in glucose tolerance. There are few reports regarding dental implant surgery in patients with type 1 DM. We describe herein the perioperative glycemic management in an outpatient with type 1 DM who experienced a rare case of severe hypoglycemia during dental implant surgery. Only one such case has previously been reported. Case presentation A 60-year-old male patient diagnosed with type 1 DM was scheduled for dental implant primary surgery. Premedication with peroral antibiotics was carried out to prevent possible systemic infection as a complication of DM. The patient was treated to control intraoperative hypertension with diligent attention to cardiovascular conditions by using a bolus administration of nicardipine and diltiazem. During surgery, he abruptly complained of hypoglycemic symptoms and had a blood glucose level of 32 mg/dL. Following oral administration and electrolyte-combined infusion of glucose, he immediately recovered from the critical situation. The surgical procedure, involving a lower jaw implant fixture placement, was performed as planned and resulted in less invasion, limited to the area of implant fixture placement within the right mandibular region of the two molars, compared to implant surgery that spans the entire lower jaw. Conclusions The present case suggests that it is essential to promptly monitor possible signs of hypoglycemia-precipitated acute symptoms in patients with DM. In addition, it is also necessary to appropriately administer insulin with an electrolyte-combined infusion of glucose for deliberate glycemic control; this is particularly true in patients with type 1 DM undergoing relatively highly-invasive oral surgical manipulation such as commonly performed dental implant surgery spanning the entire jaw.

Background: Severe hypoglycemia occurs in 6% of type 2 DM patients with a 6 to 7% mortality rate. Amidst the COVID-19 pandemic, there has been a higher rate of fatality among diabetes patients, at least 22% of COVID-19 deaths in Wuhan, China. Furthermore, the condition impairs physiological defense against recurrent hypoglycemia in the future. Accordingly, the innovation in this study aims to prevent severe hypoglycemia among type 2 patients through early risk screening, the use of preventative protocols, and patient and family empowerment. This intervention bundle is called Hypoglycemia-Nursing Early Warning Score System (Hy-NEWSS). Design and Methods: The innovation was implemented in inpatient and outpatient settings, within two weeks with the following sequence: i) internal training, ii) Hy-NEWSS implementation, iii) outcomes evaluation. Results: Of the twenty-eight patients involved in the study, 3 patients (19%) had a high risk of hypoglycemia, while the remaining had a low risk for the condition. However, at the end of the study there was no event of severe hypoglycemia (0%), and only 1 event (6.33%) of mild hypoglycemia. The results also showed that the accuracy of nurses in implementing the protocols was 93% and that during the evaluation, 95.62% of the responses of the nurses from the inpatient and outpatient settings were positive. Finally, the scores of the sensitivity and specificity evaluation were 99% and 88%, respectively. Conclusion: It may be concluded from this initial study that Hy-NEWSS is effective in preventing severe hypoglycemia, accurate in identifying patient risk level for the condition, and has high applicability to be implemented in hospital settings.

Our endocrinology practice needed to protect its highest-risk patients with type 1 diabetes (T1D) during the COVID-19 pandemic. To do so, we needed to identify these patients and develop a protocol to keep them out of the hospital (to limit risk of infection and conserve medical resources), and do so without in-person visits. So we used our peer-reviewed software, Diabetes Reporting, to identify 87 patients whose glucose management indicator (GMI) scores were over 9%. The GMI is a method for estimating the laboratory A1C using the patient's actual blood glucose measurements over the past 90 days. A GMI (or A1C) over 9% indicates a heightened risk of diabetic ketoacidosis (DKA) and, possibly, a slightly higher risk of severe hypoglycemia (SH), the two most common acute complications leading patients with T1D to be hospitalized. We contacted these 87 at-risk patients and enrolled them in a quality improvement project. This project consisted of additional online meetings with their doctors as well as weekly reports generated by Diabetes Reporting for three months, between March 28, 2020 and June 28, 2020. We hypothesized that this heightened communication would reduce the incidence of DKA and SH among the participants by reducing their GMI. As a comparison group, we used data from the T1D Exchange, which showed that, among patients with an A1C over 9%, 6.7% were hospitalized for DKA and 7% experienced SH leading to loss of consciousness in a three-month period. This led us to predict 6 incidences of DKA and 6 incidences of SH among our 87 participants during the three-month period. Instead, we saw 2 incidences of DKA and 1 incidence of SH. Moreover, the mean GMI of our participants dropped from 9.91% to 9.25%, a clinically-significant 0.66% improvement, which supports the conclusion that our protocol helped avoid acute complications among a cohort of at-risk patients with T1D by improving glycemic control during a time when we were limited to largely online care. This telemedicine protocol merits further research for its potential to improve and lower costs of care for patients with T1D, particularly for those at higher risk for acute complications.

Background: The objective of this study was to describe the epidemiology of severe hypoglycaemia in Kuwait, aiming to provide a preliminary background to update the current guidelines and improve patient management.Method: This was a prospective analysis of severe hypoglycaemia cases retrieved from emergency medical services (EMS) archived data between 1 January and 30 June 2020. The severe hypoglycaemia cases were then sub-grouped based on EMS personal initial management and compared in terms of scene time, transportation rate, complications and outcomes. The primary outcomes were GCS within 10-30 min and normal random blood glucose (RBS) within 10-30 min.Results: A total of 167 cases met the inclusion criteria. The incidence of severe hypoglycaemia in the national EMS was 11 per 100,000. Intramuscular glucagon was used on scene in 89% of the hypoglycaemic events. Most of the severe hypoglycaemia patients regained normal GCS on scene (76.5%). When we compared the two scene management strategies for severe hypoglycaemia cases, parenteral glucose administration prolonged the on-scene time (P = .002) but was associated with more favourable scene outcomes than intramuscular glucagon, with normal GCS within 10-30 min (P = .05) and normal RBS within 10-30 min (P = .006).Conclusion: Severe hypoglycaemia is not uncommon during EMS calls. Appropriate management by EMS personals is fruitful, resulting in favourable scene outcomes and reducing the hospital transportation rate. More research should be invested in improving and structuring the prehospital management of severe hypoglycaemia. One goal is to clarify the superiority of parenteral glucose over intramuscular glucagon in the prehospital setting. [ABSTRACT FROM AUTHOR]

Background: Severe hypoglycemia occurs in 6% of type 2 DM patients with a 6 to 7% mortality rate. Amidst the COVID-19 pandemic, there has been a higher rate of fatality among diabetes patients, at least 22% of COVID-19 deaths in Wuhan, China. Furthermore, the condition impairs physiological defense against recurrent hypoglycemia in the future. Accordingly, the innovation in this study aims to prevent severe hypoglycemia among type 2 patients through early risk screening, the use of preventative protocols, and patient and family empowerment. This intervention bundle is called Hypoglycemia-Nursing Early Warning Score System (Hy-NEWSS). Design and Methods: The innovation was implemented in inpatient and outpatient settings, within two weeks with the following sequence: i) internal training, ii) Hy-NEWSS implementation, iii) outcomes evaluation. Results: Of the twenty-eight patients involved in the study, 3 patients (19%) had a high risk of hypoglycemia, while the remaining had a low risk for the condition. However, at the end of the study there was no event of severe hypoglycemia (0%), and only 1 event (6.33%) of mild hypoglycemia. The results also showed that the accuracy of nurses in implementing the protocols was 93% and that during the evaluation, 95.62% of the responses of the nurses from the inpatient and outpatient settings were positive. Finally, the scores of the sensitivity and specificity evaluation were 99% and 88%, respectively. Conclusion: It may be concluded from this initial study that Hy-NEWSS is effective in preventing severe hypoglycemia, accurate in identifying patient risk level for the condition, and has high applicability to be implemented in hospital settings. [ABSTRACT FROM AUTHOR]

Type B lactic acidosis secondary to the Warburg effect is a rare metabolic complication associated with hematological malignancies. Type B lactic acidosis occurs without tissue dysoxia due to increased aerobic glycolysis and excess lactic acid formation, commonly known as the Warburg effect. Here, we present a case of Burkitt lymphoma in a 69-year-old female with severe type B lactic acidosis and hypoglycemia that was effectively treated by the prompt initiation of chemotherapy. Type B lactic acidosis has been mostly described with hematological malignancies and rarely with solid malignancies. It is considered one of the oncological emergencies, and initiation of chemotherapy as soon as possible has been beneficial compared to alkali therapy. Lactic acidosis associated with malignancies carries a poor prognosis and high mortality., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Khanal et al.)

Severe hypoglycemia is defined as a condition with serious cognitive dysfunction, such as a convulsion and coma, requiring external help from other persons. This condition is still lethal and is reported to be the cause of death in 4–10% in children and adolescents with type 1 diabetes. The incidence of severe hypoglycemia in the pediatric population was previously reported as high as more than 50–100 patient-years; however, there was a decline in the frequency of severe hypoglycemia during the past decades, and relationship with glycemic control became weaker than previously reported. A lot of studies have shown the neurological sequelae with severe hypoglycemia as cognitive dysfunction and abnormalities in brain structure. This serious condition also provides negative psychosocial outcomes and undesirable compensatory behaviors. Various possible factors, such as younger age, recurrent hypoglycemia, nocturnal hypoglycemia, and impaired awareness of hypoglycemia, are possible risk factors for developing severe hypoglycemia. A low HbA1c level is not a predictable value for severe hypoglycemia. Prevention of severe hypoglycemia remains one of the most critical issues in the management of pediatric patients with type 1 diabetes. Advanced technologies, such as continuous glucose monitoring (CGM), intermittently scanned CGM, and sensor-augmented pump therapy with low-glucose suspend system, potentially minimize the occurrence of severe hypoglycemia without worsening overall glycemic control. Hybrid closed-loop system must be the most promising tool for achieving optimal glycemic control with preventing the occurrence of severe hypoglycemia in pediatric patients with type 1 diabetes.

Kyungdo Han,1,* Jae-Seung Yun,2,* Yong-Moon Park,3 Yu-Bae Ahn,2 Jae-Hyoung Cho,2 Seon-Ah Cha,2 Seung-Hyun Ko2 1Department of Biostatistics, The Catholic University of Korea, Seoul, Republic of Korea; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 3Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA *These authors contributed equally to this work Purpose: There is a scarcity of long-term prediction models for severe hypoglycemia (SH) in subjects with type 2 diabetes mellitus (T2DM). In this study, a model was developed and validated to predict the risk of SH in adult patients with T2DM. Patients and methods: Baseline and follow-up data from patients with T2DM who received health evaluations from January 1, 2009, to December 31, 2010 (n=1,676,885) were analyzed as development (n=1,173,820) and validation (n=503,065) cohorts using the National Health Insurance Database (DB) in Korea. New SH episodes were identified using ICD-10 codes. A Cox proportional hazards regression model and Cox model coefficients were used to derive a risk scoring system, and 14 predictive variables were selected. A risk score nomogram based on the risk prediction model was created to estimate the 1-year risk of SH. Results: In the development cohort, a total of 5,325 (0.45%) patients experienced SH episodes during the follow-up period. After multivariable adjustment, older age, female sex, current smoker, drinking, low body mass index, lack of exercise, previous SH events, insulin or multiple oral hypoglycemic agent use, presence of hypertension or chronic kidney disease, longer duration of diabetes, low or high glucose level, and high Charlson Comorbidity Index score were found to be significant risk factors for the development of SH and were incorporated into the risk model. The concordance indices were 0.871 (95% confidence interval, 0.863–0.881) in development cohort and 0.866 (95% CI, 0.856–0.879) in the validation cohort. The calibration plot showed a nearly 45° line, which indicates that this model predicts well an absolute SH event. Conclusion: This 14-variable prediction model for SH events may be a useful tool to identify high-risk patients and guide prevention of SH in adult patients with T2DM. Keywords: type 2 diabetes, severe hypoglycemia, risk model, risk prediction

Type 1 diabetes is one of the most common chronic diseases in children and adolescents, with an increasing incidence globally. Major variations in serum glucose cause severe ketoacidosis and hypoglycemia, acute metabolic complications of the disease. We performed a retrospective study on a group of 119 children and adolescents with type 1 diabetes in whom only the cases with ketoacidosis and severe hypoglycemia that required emergency hospitalization were quantified. At the same time, we identified the causes and determinants of these acute complications. According to the case study, 28.6% of patients (34 cases) presented severe hypoglycemia, the most common causes of hypoglycemia being intense physical activity without additional carbohydrate intake, delayed carbohydrate intake, and excess insulin. 15.3% of patients (18 cases) had ketoacidosis, of which 55.55% were recurrent ketoacidosis. Ketoacidosis has been detected in patients with poor glycemic balance and poor treatment compliance by not following a diet and skipping insulin doses. Among the additional risk factors, we identified age over 13 years and the age of diabetes greater than 5 years, for both acute complications. [ABSTRACT FROM AUTHOR]

Severe hypoglycemia is defined as a condition with serious cognitive dysfunction, such as a convulsion and coma, requiring external help from other persons. This condition is still lethal and is reported to be the cause of death in 4–10% in children and adolescents with type 1 diabetes. The incidence of severe hypoglycemia in the pediatric population was previously reported as high as more than 50–100 patient-years; however, there was a decline in the frequency of severe hypoglycemia during the past decades, and relationship with glycemic control became weaker than previously reported. A lot of studies have shown the neurological sequelae with severe hypoglycemia as cognitive dysfunction and abnormalities in brain structure. This serious condition also provides negative psychosocial outcomes and undesirable compensatory behaviors. Various possible factors, such as younger age, recurrent hypoglycemia, nocturnal hypoglycemia, and impaired awareness of hypoglycemia, are possible risk factors for developing severe hypoglycemia. A low HbA1c level is not a predictable value for severe hypoglycemia. Prevention of severe hypoglycemia remains one of the most critical issues in the management of pediatric patients with type 1 diabetes. Advanced technologies, such as continuous glucose monitoring (CGM), intermittently scanned CGM, and sensor-augmented pump therapy with low-glucose suspend system, potentially minimize the occurrence of severe hypoglycemia without worsening overall glycemic control. Hybrid closed-loop system must be the most promising tool for achieving optimal glycemic control with preventing the occurrence of severe hypoglycemia in pediatric patients with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Introduction: The associations of chronic kidney disease (CKD) severity, cardiovascular disease (CVD), and insulin with the risks of major adverse cardiovascular events (MACE), mortality, and severe hypoglycemia in patients with type 2 diabetes (T2D) at high cardiovascular (CV) risk are not known. This secondary, pooled analysis of data from the DEVOTE trial examined whether baseline glomerular filtration rate (GFR) categories were associated with a higher risk of these outcomes. Methods: DEVOTE was a treat-to-target, double-blind trial involving 7637 patients with T2D at high CV risk who were randomized to once-daily treatment with either insulin degludec (degludec) or insulin glargine 100 units/mL (glargine U100). Patients with estimated GFR data at baseline (n = 7522) were analyzed following stratification into four GFR categories. Results: The risks of MACE, CV death, and all-cause mortality increased with worsening baseline GFR category (P < 0.05), with a trend towards higher rates of severe hypoglycemia. Patients with prior CVD, CKD (estimated GFR < 60 mL/min/m2), or both were at higher risk of MACE, CV death, and all-cause mortality. Only CKD was associated with a higher rate of severe hypoglycemia, and the risk of MACE was higher in patients with CVD than in those with CKD (P = 0.0003). There were no significant interactions between randomized treatment and GFR category. Conclusion: The risks of MACE, CV death, and all-cause mortality were higher with lower baseline GFR and with prior CVD, CKD, or both. The relative effects of degludec versus glargine U100 on outcomes were consistent across baseline GFR categories, suggesting that the lower rate of severe hypoglycemia associated with degludec use versus glargine U100 use was independent of baseline GFR category. Funding: Novo Nordisk. [ABSTRACT FROM AUTHOR]