Severe Hypoglycemic Episodes Research Articles

Cardiovascular, Metabolic, and Safety Outcomes with Semaglutide by Baseline Age: Post Hoc Analysis of SUSTAIN6 and PIONEER6.

The high risk of cardiovascular events in people with type2 diabetes increases with age. The cardiovascular effects of once-weekly subcutaneous and once-daily oral semaglutide versus placebo in people with type2 diabetes at high cardiovascular risk were investigated in the SUSTAIN6 and PIONEER6 cardiovascular outcomes trials, respectively. It is unknown whether the effects of semaglutide are age dependent. This post hoc analysis evaluated cardiovascular, metabolic, and safety outcomes with semaglutide versus placebo in age subgroups (≤ 60; > 60 to ≤ 65; > 65 to ≤ 70; and > 70years) pooled from SUSTAIN6 and PIONEER6. Major adverse cardiovascular events (composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke), changes from baseline in glycated hemoglobinA1c (HbA1c) and body weight, and adverse events were analyzed. Semaglutide reduced major adverse cardiovascular events and its components versus placebo across age subgroups (most hazard ratios < 1.0; pinteraction > 0.05). The treatment difference in HbA1c reduction was greater in those aged ≤ 60years than in older subgroups (pinteraction = 0.01). Reductions in body weight with semaglutide versus placebo were consistent across agesubgroups (pinteraction = 0.124). Serious adverse events or severe hypoglycemic episodes did not differ between semaglutide and placebo across age subgroups. Semaglutide consistently reduced major adverse cardiovascular events and body weight versus placebo across age subgroups; its safety profile did not differ with age. These results suggest that relaxing HbA1c targets based solely on age may not always be required for people with type2 diabetes. SUSTAIN6 (NCT01720446) and PIONEER6 (NCT02692716) are registered at ClinicalTrials.gov.

Characterising impaired awareness of hypoglycaemia and associated risks through HypoA-Q: findings from a T1D Exchange cohort.

We aimed to: (1) externally validate the five-item Hypoglycaemia Awareness Questionnaire (HypoA-Q) impaired awareness subscale (HypoA-Q IA); (2) examine how impaired awareness of hypoglycaemia (IAH) relates to the risk of severe hypoglycaemia and level 2 hypoglycaemia; and (3) identify factors associated with IAH. Nationwide survey of T1D Exchange registrants was conducted to collect data on demographics, 6 month severe-hypoglycaemia history, hypoglycaemia awareness status (via HypoA-Q IA, the Gold instrument and the Clarke instrument) and continuous glucose monitor (CGM) measures. The Clarke hypoglycaemia awareness factor (Clarke-HAF) was calculated to exclude severe-hypoglycaemia history items. Analyses included Cronbach's α, Spearman correlations and logistic regression. Valid survey responses were collected from N=1580 adults with type 1 diabetes (median age, 44 years; 52% female participants; median HbA1c, 48 mmol/mol [6.5%]). Of these, 94% of participants were using CGMs and 69% were using hybrid closed-loop (HCL) systems; 30% had at least one severe-hypoglycaemia episode in the past 6 months. The HypoA-Q IA had satisfactory internal reliability (α=0.79) and construct validity. Higher HypoA-Q IA scores were independently associated with greater risk of severe hypoglycaemia (p<0.001), performing comparably to the Gold instrument and the Clarke-HAF instrument. HypoA-Q IA-determined IAH was independently associated with 88% higher odds of developing severe hypoglycaemia (p<0.001) and twofold higher odds for spending ≥1% of time in level 2 hypoglycaemia (p=0.011). Higher age and longer diabetes duration were associated with higher IAH risk (p<0.001). CGM and HCL use was associated with lower IAH risk (p<0.001). The HypoA-Q IA is a brief, valid and reliable tool for assessing IAH in today's technology-oriented era. IAH was independently associated with severe hypoglycaemia and level 2 hypoglycaemia in a cohort with high prevalence of advanced diabetes technology use and HbA1c within the recommended range. CGM and HCL use was related to lower IAH risk.

Hypoglycaemia Prevention, Awareness of Symptoms, and Treatment (HypoPAST): protocol for a 24-week hybrid type 1 randomised controlled trial of a fully online psycho-educational programme for adults with type 1 diabetes

BackgroundManagement of type 1 diabetes (T1D) requires the use of insulin, which can cause hypoglycaemia (low blood glucose levels). While most hypoglycaemic episodes can be self-treated, all episodes can be sudden, inconvenient, challenging to prevent or manage, unpleasant and/or cause unwanted attention or embarrassment. Severe hypoglycaemic episodes, requiring assistance from others for recovery, are rare but potentially dangerous. Repeated exposure to hypoglycaemia can reduce classic warning symptoms (‘awareness’), thereby increasing risk of severe episodes. Thus, fear of hypoglycaemia is common among adults with T1D and can have a negative impact on how they manage their diabetes, as well as on daily functioning, well-being and quality of life. While advances in glycaemic technologies and group-based psycho-educational programmes can reduce fear, frequency and impact of hypoglycaemia, they are not universally or freely available, nor do they fully resolve problematic hypoglycaemia or associated worries. This study aims to determine the effectiveness of a fully online, self-directed, scalable, psycho-educational intervention for reducing fear of hypoglycaemia: the Hypoglycaemia Prevention, Awareness of Symptoms, and Treatment (HypoPAST) programme.MethodsA 24-week, two-arm, parallel-group, hybrid type 1 randomised controlled trial, conducted remotely (online and telephone). Australian adults (≥ 18 years) with self-reported T1D and fear of hypoglycaemia will be recruited, and allocated at random (1:1) to HypoPAST or control (usual care). The primary outcome is the between-group difference in fear of hypoglycaemia (assessed using HFS-II Worry score) at 24 weeks. A sample size of N = 196 is required to detect a 9-point difference, with 90% power and allowing for 30% attrition. Multiple secondary outcomes include self-reported psychological, behavioural, biomedical, health economic, and process evaluation data. Data will be collected at baseline, 12 and 24 weeks using online surveys, 2-week ecological momentary assessments, website analytics and semi-structured interviews.DiscussionThis study will provide evidence regarding the effectiveness, cost-effectiveness and acceptability of a novel, online psycho-educational programme: HypoPAST. Due to the fully online format, HypoPAST is expected to provide an inexpensive, convenient, accessible and scalable solution for reducing fear of hypoglycaemia among adults with T1D.Trial registrationAustralian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623000894695 (21 August 2023).

6567 Novel Indication of GLP-1 Receptor Agonists Beyond Weight Loss: Addressing Post-Gastric Bypass Late Dumping Syndrome

Abstract Disclosure: G. Arevalo: None. S. Gra Menendez: None. D. Soliman: None. R.J. Galindo: Consulting Fee; Self; Novo Nordisk, Eli Lilly &amp; Company, Sanofi, Bayer, Inc., Boehringer Ingelheim, Pfizer, Inc., Abbott Laboratories. Grant Recipient; Self; National Institute of Diabetes and Digestive and Kidney Diseases (2P30DK111024), National Institute of Diabetes and Digestive and Kidney Diseases (K23DK123384). Other; Self; Novo Nordisk, Eli Lilly &amp; Company, Dexcom. Background: Late dumping syndrome, characterized by postprandial hyperinsulinemic hypoglycemia (PHH), represents a complex clinical challenge in post-bariatric patients. GLP-1 receptor agonists are being explored as an effective therapeutic option. Clinical Case: A 47-year-old overweight (BMI of 29.86 kg/m²) woman, with a medical history of scleroderma and esophageal dysmotility, underwent a gastric sleeve gastrectomy later requiring conversion to Roux-en-Y gastric bypass to improve esophageal motility. Eleven months post-bypass, she began experiencing recurrent episodes of hypoglycemia (venous glucose 49-70 mg/dL, n &amp;gt;70 mg/dL) accompanied by sweating, palpitations, drowsiness, and weakness. Initial tests were consistent with postprandial hyperinsulinemic hypoglycemia: serum insulin (13.5 µIU/mL, n &amp;lt; 3 µIU/mL), and c-peptide (4.1 ng/mL, n &amp;lt; 0.6 ng/mL). The Sigstad score and the Arts dumping severity score were positive for late dumping syndrome with a score of 26 and 14, respectively. During glucagon administration, the patient's blood glucose level increased by up to 50 mg/dL within 10 minutes of administration. Both sulfonylurea screening and insulin antibody tests were negative. Real-time CGM measurements showed patterns of postprandial hyperglycemic peaks, up to 160-180 mg/dL (n &amp;lt;140 mg/dL), approximately 30 to 60 min after meals, followed by rapidly declining glucose (1-2 hours later), resulting in hypoglycemic events as low as 49 mg/dL. Initial management with dietary changes and pharmacological treatment was unsuccessful due to poor medication tolerability of acarbose and diazoxide, and low adherence to the prescribed diet due to her esophageal dysmotility. The CGM patterns and symptom presentation raised suspicion that late dumping syndrome was triggered by rapid hyperglycemic responses after oral ingestions of typical meals, resulting in the desynchronization of hormonal responses (insulin and GLP-1), and post-prandial hypoglycemia. Hence, the consideration for a GLP-1 receptor agonist emerged. A weekly subcutaneous injection of a long-acting GLP-1 receptor agonist, semaglutide 0.25 mg exhibited marked improvement in her glycemic profile: fewer episodes of postprandial hyperglycemia, and the subsequent descents in blood glucose were less pronounced. The patient demonstrated a favorable response with no severe hypoglycemic episodes reported during a follow-up period of three months. Conclusion: This is the first case to demonstrate semaglutide's efficacy as a standalone treatment for PHH in post-bariatric patients. In this case, semaglutide effectively controlled glycemia and improved the patient's quality of life, presenting a promising therapeutic option for such complex cases. Presentation: 6/1/2024

Lantidra: Cell Therapy for Treatment of Type 1 Diabetes Mellitus

The more recent cell treatment for type 1 Diabetes is called lantidra. Lantidra has recently received approval to treat type 1 Diabetes mellitus. The first allogeneic (deceased donor) pancreatic islet cell therapy, lantidra (donislecel), was approved by the FDA Centre for Biologics Evaluation and Research (CBER) on June 28, 2023. It is intended to treat adults with type 1 diabetes who, despite current management, do not achieve target glycosylated hemoglobin levels due to recurrent episodes of severe hypoglycemia. The editorial’s goal is to draw attention to the growing impact of type 1 diabetes on the world’s health, discuss earlier attempts at pancreatic transplant techniques, and announces the first regulatory approval of a revolutionary transplant strategy called allogeneic pancreatic islet beta cell infusion.

Safety of Options to "Boost" (Enhancing Insulin Infusion Rates) and "Ease-Off" (Reducing Insulin Infusion Rates) in CamAPS FX Hybrid Closed-Loop System: A Real-World Analysis.

The usage and safety of the Boost and Ease-off features in the CamAPS FX hybrid closed-loop system were analyzed in a retrospective analysis of real-world data from 7,464 users over a 12-month period. Boost was used more frequently than Ease-off, but for a shorter duration per use. Mean starting glucose was above range for Boost (229 ± 51 mg/dL), and within range for Ease-off (114 ± 29 mg/dL). Time spent below 70 mg/dL was low during Boost periods [median (interquartile range; IQR) 0.0% (0.0, 0.5%)], and lower than during no Boost periods [2.1% (1.2, 3.4%)], while time spent above 180 mg/dL was lower during Ease-off periods (15 ± 14%) compared with no Ease-off periods (25 ± 12%). There were no episodes of severe hypoglycemia or diabetic ketoacidosis attributed to Boost or Ease-off use. Boost and Ease-off allow users to engage safely with CamAPS FX to manage their glucose levels during periods of more-than-usual and less-than-usual insulin needs.

Initiation or switch to insulin degludec/insulin aspart in adults with type 2 diabetes in India: Results from a prospective, non-interventional, real-world study.

To investigate clinical outcomes in adults with type 2 diabetes (T2D) after insulin degludec/insulin aspart (IDegAsp) treatment in a real-world setting. The 26 weeks study involved 1102 adults with T2D who were either initiated with or switched to IDegAsp according to local practice in six countries. It was an open-label, non-interventional study. The primary endpoint was the change in glycosylated haemoglobin (HbA1c) levels from baseline to the end of study (EOS). From India, 185 adults participated in this study with mean age of 58.1 (10.3) years and 14.4 (8.1) years of mean duration of T2D. Mean HbA1c decreased from 9.8% (1.8) at baseline to 8.2% (0.1) at the EOS; change in HbA1c from baseline [95% CI]: -1.6% (0.1) [-1.8; -1.4], P < 0.0001. There was a significant reduction in mean fasting plasma glucose (FPG) level from 190.0 (65.8) mg/dl at baseline to 141.9 (4.3) mg/dl at EOS; change in FPG from baseline [95% CI]: -52.2 (4.3) mg/dl [-60.7; -43.7], P < 0.0001. There was a numerical reduction in resource utilization related to diabetes and its complications and hypoglycaemic episodes. From baseline to EOS, the participants with outpatient visits (72 to 32) and workdays missed (2 to 0) decreased. Additionally, the number of patient-reported non-severe hypoglycaemic (47 to 8) and severe hypoglycaemic (4 to 1) episodes decreased as well. Initiation or switching to IDegAsp led to improvement in glycaemic control in real-world population of Indian adults with T2D. This was accompanied by a numerical reduction in resource utilization and patient-reported hypoglycaemia. Clinical trial registration: NCT04042441.

Optimizing Physical Activity for Glycemic Control in Type 1 Diabetes: Strategies and Risks

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune condition characterized by the destruction of insulin-producing beta cells in the pancreas, necessitating lifelong insulin therapy. This study explores the impact of physical activity on glycemic control and overall health in individuals with T1DM. Despite its proven benefits, including improved cardiovascular health, lower HbA1c levels, and reduced insulin requirements, over 60% of T1DM patients do not engage in regular exercise. Different types of physical activities—such as aerobic, anaerobic, and high-intensity interval training (HIIT)—affect metabolic responses differently. Aerobic exercises and HIIT have shown significant improvements in health-related quality of life (HRQoL) and reduced incidence of severe complications, such as diabetic ketoacidosis. However, exercise-induced hypoglycemia remains a significant risk, especially if exercise follows recent severe hypoglycemic episodes. Proper management strategies include adjusting insulin doses, monitoring glucose levels, and carbohydrate intake. The study highlights the importance of tailored exercise plans and preventive measures to mitigate risks such as nocturnal hypoglycemia and elevated ketones. Ultimately, effective integration of physical activity into diabetes management can lead to enhanced overall health and quality of life for individuals with T1DM.

Insulin-Related Suicide Attempt in Non-Diabetic Pediatric Patient

Insulin analogs are basic drugs that are widely used in the treatment of diabetes around the world. Suicides with their use are described as rare, occurring mainly in the population of diabetic patients due to their easy access to the drug and knowledge of its properties. Among non-diabetic people, insulin is used for suicidal purposes mainly by adults with medical education. A case of a 15-year-old girl found unconscious by her mother at night was described. The patient was immediately transported to the hospital, where she was diagnosed with her first severe hypoglycemic episode of unknown origin. Once conscious and in a better state, the patient admitted to having taken insulin, which she had stolen from her diabetic mother, for suicidal purposes. The patient had no history of mental illness or self-destructive behavior. The patient was referred to psychiatric care. Suicides and suicide attempts involving insulin are usually observed among people with chronic diabetes. Moreover, such attempts are made by adults who know the mechanism of action of the drug. In the pediatric group without diabetes, such cases are extremely rare. Additionally, the issue of similar behaviors becomes very important due to the increasing popularity and availability of insulin therapy and the possibilities of obtaining information about using it to commit suicide from the Internet. Particular vigilance is required in pediatric emergency departments when a patient is identified as having a first episode of severe hypoglycemia of unknown origin.

A case study on the implementation of quality and comprehensive indicators set in routine diabetes care

IntroductionType 2 diabetes is a major public health issue in Mexico due to its high prevalence and its projection for the coming years for this disease. Findings on multidisciplinary care related to chronic diseases have proven effective, based on measurement of patient-centered outcomes, The Center of Comprehensive Care for Patients with Diabetes (CAIPaDi) is a multidisciplinary program focused on reducing diabetes complications. This case study aims to illustrate the results of implementing health outcomes measurements and demonstrate the beneficial effects of establishing a comprehensive model of care through a patient-centered approach.MethodsA descriptive analysis of the comprehensive care indicators of patients with type 2 diabetes treated in the CAIPaDi program between 2013 and 2023 was conducted. The results were structured according to the standard set of outcomes for diabetes proposed by the International Consortium for Health Outcomes Measurements (ICHOM).ResultsThe baseline and prospective registration of consultations was completed for five years, complying with 25 of the 26 indicators of the ICHOM set. In diabetes control, 56.5% of patients had A1c ≤ 7%, 87.9% had BP ≤ 130/80 mmHg, 60.9% had LDL-cholesterol < 100 mg/dl, and obesity rates decreased from 42.19% to 30.6% during annual consultations. Fewer years of diagnosis before the first visit is key to overall improvement in program adherence (P = 0.02).In acute events, a hyperglycemic crisis occurred in only two cases and severe hypoglycemia episodes in 8 patients. For chronic complications, no lower limb amputations occurred. Cardiovascular outcomes occurred in < 1%. Periodontal disease was analyzed, and periodontitis decreased from 82.9% to 78.7%. Mortality reports were low, with COVID-19 being the main cause of death. Patient-reported outcomes demonstrated reductions in anxiety, depression, and diabetes distress during follow-up.ConclusionRegistering quality-of-care indicators is feasible in a comprehensive care program. It allows improving the medical, mental health, and lifestyle outcomes of patients with type 2 diabetes and provides relevant data for planning health programs. A quick diagnosis before program adherence is crucial for overall improvement in patients.

Diabetes Stigma and Clinical Outcomes: An International Review.

Diabetes stigma is the social burden of living with diabetes. People with diabetes may experience or perceive an adverse social judgment, prejudice, or stereotype about living with diabetes at work, school, in healthcare settings, popular culture, or relationships. This review describes the methods that have been used to assess diabetes stigma, and explores the prevalence of diabetes stigma, associated sociodemographic and socioeconomic factors, cultural factors, and how diabetes stigma is associated with clinical outcomes, including HbA1c levels, diabetic ketoacidosis, severe hypoglycemia, and chronic complications, in addition to psychosocial complications in youth, adolescents, and adults with type 1 diabetes (T1D) and type 2 diabetes (T2D). The prevalence of diabetes stigma has been reported as high as 78% in adults with T1D, 70% in adults with T2D, 98% in youth and adolescents with T1D, and is unknown in youth and adolescents with T2D. Diabetes stigma has been associated with lower psychosocial functioning, decreased self-care behaviors, higher HbA1c levels, and higher frequency of diabetes complications in adults with T1D and T2D. In adolescents and young adults with T1D, diabetes stigma is associated with lower psychosocial functioning, higher HbA1c levels, and higher frequency of diabetic ketoacidosis and severe hypoglycemia episodes in addition to chronic complications. In youth and adolescents with T2D, one study demonstrated an association of diabetes stigma with lower psychosocial functioning, higher HbA1c levels, and presence of retinopathy. Gaps exist in our understanding of the mechanisms of diabetes stigma, particularly in youth and adolescents with T2D.

Effect of recurrent severe insulin-induced hypoglycemia on the cognitive function and brain oxidative status in the rats

BackgroundEpisodes of recurrent or severe hypoglycemia can occur in patients with diabetes mellitus, insulinoma, neonatal hypoglycemia, and medication errors. However, little is known about the short-term and long-term effects of repeated episodes of acute severe hypoglycemia on the brain, particularly in relation to hippocampal damage and cognitive dysfunction.MethodsThirty-six wistar rats were randomly assigned to either the experimental or control group. The rats were exposed to severe hypoglycemia, and assessments were conducted to evaluate oxidative stress in brain tissue, cognitive function using the Morris water maze test, as well as histopathology and immunohistochemistry studies. The clinical and histopathological evaluations were conducted in the short-term and long-term.ResultsThe mortality rate attributed to hypoglycemia was 34%, occurring either during hypoglycemia or within 24 h after induction. Out of the 14 rats monitored for 7 to 90 days following severe/recurrent hypoglycemia, all exhibited clinical symptoms, which mostly resolved within three days after the last hypoglycemic episode, except for three rats. Despite the decrease in catalase activity in the brain, the total antioxidant capacity following severe insulin-induced hypoglycemia increased. The histopathology findings revealed that the severity of the hippocampal damage was higher compared to the brain cortex 90 days after hypoglycemia. Memory impairments with neuron loss particularly pronounced in the dentate gyrus region of the hippocampus were observed in the rats with severe hypoglycemia. Additionally, there was an increase in reactive astrocytes indicated by GFAP immunoreactivity in the brain cortex and hippocampus.ConclusionRecurrent episodes of severe hypoglycemia can lead to high mortality rates, memory impairments, and severe histopathological changes in the brain. While many histopathological and clinical changes improved after three months, it seems that the vulnerability of the hippocampus and the development of sustained changes in the hippocampus were greater and more severe compared to the brain cortex following severe and recurrent hypoglycemia. Furthermore, it does not appear that oxidative stress plays a central role in neuronal damage following severe insulin-induced hypoglycemia. Further research is necessary to assess the consequences of repeated hypoglycemic episodes on sustained damage across various brain regions.

Once-weekly insulin icodec compared with daily basal insulin analogues in type 2 diabetes: Participant-level meta-analysis of the ONWARDS 1-5 trials.

To perform a participant-level post hoc meta-analysis of Phase 3a trials in type 2 diabetes (T2D) to characterize the hypoglycaemia safety and glycaemic efficacy of once-weekly insulin icodec (icodec). All ONWARDS 1-5 randomized participants were pooled as overall T2D, insulin-naive, an insulin-experienced subgroups, and by once-daily trial comparator (degludec or glargine U100). The main outcomes included incidence and rates of clinically significant and severe hypoglycaemia. Additional endpoints included change in glycated haemoglobin (HbA1c) from baseline and HbA1c target achievement without clinically significant or severe hypoglycaemia. The meta-analysis comprised 3765 participants (1882 icodec vs. 1883 comparators). In the overall T2D pool, clinically significant hypoglycaemia incidence was similar in the icodec group versus the comparator group (17.9% vs. 16.2%, odds ratio [OR] 1.14, 95% confidence interval [CI] 0.94, 1.38); however, rates were low but significantly higher in the icodec group (1.15 vs. 1.00 episodes/participant-year of exposure, estimated rate ratio 1.51 [95% CI 1.24, 1.85]). Fewer severe hypoglycaemic episodes occurred with icodec than with comparators (8 vs. 18). A greater reduction in HbA1c occurred with icodec versus comparators, irrespective of subgroup (estimated treatment difference range [-0.10 to -0.29%]; all p < 0.05). Across subgroups, except for the insulin-experienced subgroup, the odds of achieving HbA1c <53 mmol/mol (7.0%) without clinically significant or severe hypoglycaemia were greater with icodec than with comparators (OR range 1.30-1.55; all p < 0.05). Icodec was associated with a similar incidence but higher rates of clinically significant hypoglycaemia (equating to one additional hypoglycaemic episode every 6 years) and fewer severe hypoglycaemic episodes versus comparators. Our findings also confirmed the greater efficacy of icodec that was demonstrated in the ONWARDS trial programme.

Immunoprotection Strategies in β-Cell Replacement Therapy: A Closer Look at Porcine Islet Xenotransplantation.

Type 1 diabetes mellitus (T1DM) is characterized by absolute insulin deficiency primarily due to autoimmune destruction of pancreatic β-cells. The prevailing treatment for T1DM involves daily subcutaneous insulin injections, but a substantial proportion of patients face challenges such as severe hypoglycemic episodes and poorly controlled hyperglycemia. For T1DM patients, a more effective therapeutic option involves the replacement of β-cells through allogeneic transplantation of either the entire pancreas or isolated pancreatic islets. Unfortunately, the scarcity of transplantable human organs has led to a growing list of patients waiting for an islet transplant. One potential alternative is xenotransplantation of porcine pancreatic islets. However, due to inter-species molecular incompatibilities, porcine tissues trigger a robust immune response in humans, leading to xenograft rejection. Several promising strategies aim to overcome this challenge and enhance the long-term survival and functionality of xenogeneic islet grafts. These strategies include the use of islets derived from genetically modified pigs, immunoisolation of islets by encapsulation in biocompatible materials, and the creation of an immunomodulatory microenvironment by co-transplanting islets with accessory cells or utilizing immunomodulatory biomaterials. This review concentrates on delineating the primary obstacles in islet xenotransplantation and elucidates the fundamental principles and recent breakthroughs aimed at addressing these challenges.

A cross-sectional questionnaire study: Impaired awareness of hypoglycaemia remains prevalent in adults with type 1 diabetes and is associated with the risk of severe hypoglycaemia.

Impaired awareness of hypoglycaemia (IAH) is a risk factor for severe hypoglycaemia (SH) in type 1 diabetes (T1D). Much of the IAH prevalence data comes from older studies where participants did not have the benefit of the latest insulins and technologies. This study surveyed the prevalence of IAH and SH in a tertiary adult clinic population and investigated the associated factors. Adults (≥18 years) attending a tertiary T1D clinic completed a questionnaire, including a Gold and Clarke score. Background information was collected from health records. 189 people (56.1% female) with T1D (median [IQR] disease duration 19.3 [11.5, 29.1] years and age of 41.0 [29.0, 52.0] years) participated. 17.5% had IAH and 16.0% reported ≥1 episode of SH in the previous 12 months. Those with IAH were more likely to report SH (37.5% versus 11.7%, p = 0.001) a greater number of SH episodes per person (median [IQR] 0 [0,2] versus 0 [0,0] P<0.001) and be female (72.7% versus 52.6%, p = 0.036). Socio-economic deprivation was associated with IAH (p = 0.032) and SH (p = 0.005). Use of technology was the same between IAH vs aware groups, however, participants reporting SH were more likely to use multiple daily injections (p = 0.026). Higher detectable C-peptide concentrations were associated with a reduced risk of SH (p = 0.04). Insulin pump and continuous glucose monitor use was comparable in IAH versus aware groups. Despite this, IAH remains a risk factor for SH and is prevalent in females and in older people. Socioeconomic deprivation was associated with IAH and SH, making this an important population to target for interventions.

Efficacy and Safety of Oral Semaglutide in the Treatment of Type 2 Diabetes: A Meta-Analysis.

This study aims to systematically review the efficacy and safety of oral semaglutide in the treatment of type 2 diabetes mellitus (T2DM) and provide a basis for the rational use of the drug in clinical practice. From the database's inception until February 2023, a systematic search was conducted in PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, and China Science and Technology Journal Database to identify randomized controlled trials (RCTs) comparing the efficacy of oral semaglutide at dosages of 3, 7, and 14 mg (trial group) against placebo or other positive control drugs (control group) for the treatment of T2DM. Following literature screening and data extraction, the bias risk assessment tool in the Cochrane reviewer handbook 5.1.0 was used to evaluate the literature quality. Meta-analysis was carried out with RevMan 5.4 software. A total of 10 RCTs with 9541 patients were included. The meta-analysis results revealed that compared with placebo or positive control drugs (empagliflozin, sitagliptin, liraglutide, and dulaglutide), oral semaglutide significantly reduced the hemoglobin A1c (HbA1c) in patients (compared to placebo, 3 mg [MD = -0.61%, 95% CI (-0.89, -0.34)], 7 mg [MD = -1.12%, 95% CI (-1.45, -0.79)], 14 mg [MD = -1.08%, 95% CI (-1.32, -0.85)]; compared to positive control drugs (7 mg [MD = -0.26%, 95% CI (-0.38, -0.15)], 14 mg [MD = -0.37%, 95% CI (-0.52, -0.23)]). Oral semaglutide also showed certain advantages over placebo or positive control drugs in terms of weight loss, HbA1c reduction achievement rate, fasting plasma glucose level, and body mass index with overall dose-dependent efficacy. The incidence of nausea, diarrhea, and vomiting caused by oral semaglutide was higher than that of the placebo or positive control drugs, and the incidence of appetite decrease or constipation was higher than that of the placebo. Severe or symptomatic hypoglycemic episodes were reduced compared to positive control drugs. Oral semaglutide has definite clinical benefits of reducing blood glucose, body weight, reducing the risk of hypoglycemia, and with good safety.

Glycemia control after total pancreatoduodenectomy

Aim. To study the features of correction of carbohydrate metabolism disorders and nutritional deficiency in patients after total pancreatoduodenectomy; to develop a unified protocol for managing patients after total pancreatoduodenectomy. Materials and methods. From 2007 to 2022, 62 patients underwent total pancreatoduodenectomy in the Hepatopancreatic Surgery Unit of the Botkin Hospital. The patients were divided into two groups, comparable in terms of basic parameters. The first group included patients (n = 32) who underwent “classical” total pancreatoduodenectomy with gastric resection and splenectomy. The second group consisted of patients (n = 30) who underwent total pancreatoduodenectomy in the modification of Botkin Hospital. In the perioperative period, patients of both groups were examined for carbohydrate metabolism with the selection and assessment of the average daily dose of short-acting and long-acting insulin, assessment of enzyme and protein deficiency with the selection of enzyme replacement therapy and nutritional support. For a more accurate assessment of carbohydrate metabolism disorders, all patients underwent continuous monitoring of the level of glycemia intraoperatively and in the early postoperative period (FreeStyle Libre flash monitoring system, Abbott). The glycated hemoglobin level was assessed on day 90 and body mass index – on days 30, 60 and 90 after surgery. Results. The mean level of glycemia in patients after total pancreatoduodenectomy in the modification of the Botkin Hospital accounted for 8.0 mmol/l and the variability (daily fluctuations in glycemia) comprised 39 %, which was significantly lower compared to the group of “classical” total pancreatoduodenectomy with 7.6 mmol/l and 48 %, respectively. Seven patients (21.9 %) after total pancreatoduodenectomy in the modification of the Botkin Hospital experienced a severe hypoglycemic episode, while a similar severe hypoglycemic episode was noted in 25 patients (80.6 %) after pancreatectomy in its “classical” variant, of which 18 patients (60 %) required hospitalization in the endocrinology unit in order to correct the sugar-lowering therapy. In turn, only three patients (9.4 %) after total pancreatoduodenectomy modified by the Botkin Hospital required hospitalization due to severe hypoglycemia. The mean level of glycated hemoglobin in patients of the first and second groups on day 90 accounted for 7.2 % and 7.7 %, respectively (p = 0.789). The average body mass index on day 90 after surgery was higher in the group of organ-preserving total pancreatoduodenectomy: 24 kg/m2, compared to the “classical” pancreatectomy with 21.2 kg/m2 (p = 0.001). The daily dose of both short-acting and long-acting insulin was higher in the organ-preserving total pancreatoduodenectomy group of 17.4 ± 5.6 U/day and 12 ± 4.6 U/day, respectively, compared to the group of “classical” total pancreatoduodenectomy of 13.8 ± 4.6 U/day and 10.8 ± 2.7 U/day, respectively. This can be attributed to the faster normalization of the patient's body weight and the preserved function of physiological digestion due to the pylorus-preserving variant of total pancreatoduodenectomy. Conclusion. Management of patients after total pancreatoduodenectomy is claimed to be an extremely complex task that requires a multidisciplinary approach involving surgeons, intensivists, endocrinologists and gastroenterologists at all stages of patient management. Organ-preserving modification of total pancreatoduodenectomy with preservation of the stomach, spleen and splenic vessels in the modification of the Botkin Hospital improves treatment results and simplifies the selection of insulin therapy for this group of patients.

Pharmacist consult to prevent hypoglycemia in adult inpatients with renal dysfunction.

The objective of this study was to evaluate the impact of a pharmacist consult service on rates of hypoglycemia in adult inpatients with renal dysfunction receiving antidiabetic medications. This was a single-center, institutional review board-approved, quasi-experimental, 2-phase prospective study. Adult inpatients admitted within 48 to 96 hours of hospitalization with a creatine clearance of less than 30 mL/min or estimated glomerular filtration rate of less than 30 mL/min/1.73 m2 and an active antidiabetic medication order were included. Patients located in a critical care unit or with a previous or planned transplantation were excluded. Each phase was conducted over 4 months. The primary endpoint was the change in the incidence of hypoglycemic episodes (blood glucose [BG] of <70 mg/dL) per 100 patient days when comparing the cohorts. Secondary endpoints included the incidence of recurrent and severe (BG of <40 mg/dL) episodes of hypoglycemia per 100 patient days, occurrence of a BG concentration of higher than 300 mg/dL, and length of stay. Overall, 150 patients were included in the retrospective preimplementation phase and 172 were included in the prospective postimplementation phase. In the postimplementation group, there was a significant decrease in the rate of hypoglycemia per 100 patient days when compared to the retrospective group (5.8 vs 9.0; incidence rate ratio, 1.55; 95% confidence interval, 1.2-2.0; P < 0.05). There was no difference in secondary endpoints between the groups. The implementation of a pharmacy consult service resulted in lower rates of hypoglycemic events, which supports pharmacist involvement to prevent hypoglycemia in this at-risk population. Additional studies involving pharmacists working under collaborative practice agreements may reinforce the results.

Effectiveness of the flash glucose monitoring system in preventing severe hypoglycemic episodes and in improving glucose metrics and quality of life in subjects with type 1 diabetes at high risk of acute diabetes complications

AimsTo assess the effectiveness of the intermittent-scanned continuous glucose monitoring (isCGM) system in preventing severe hypoglycemic episodes and in improving glucose parameters and quality of life.MethodsFour hundred T1D individuals were enrolled in a prospective real-word study with an intermittently scanned continuous glucose monitoring device during the 12-months follow-up. The primary endpoint was the incidence of severe hypoglycemic events.Results82% of subjects were naïve to the use of the device (group A) and 18% were already wearing the system (group B). The cumulative incidence of severe hypoglycemia (SH) at 12 months was 12.06 per 100 person-year (95% CI: 8.35–16.85) in group A and 10.14 (95% CI: 4.08–20.90) in group B without inter-group differences. In group A there was a significant decrease in SH at 12 months compared to 3 months period (p = 0.005). Time in glucose range significantly increased in both groups accompanied with a significant decrease in glucose variability. HbA1c showed a progressive significant time-dependent decrease in group A. The use of the device significantly improved the perceived quality of life.ConclusionThis study confirmed the effectiveness of the isCGM in reducing hypoglycemic risk without glucose deterioration, with potential benefits on adverse outcomes in T1D individuals.Trial registration: ClinicalTrials.gov registration no. NCT04060732.

Efficacy and safety of advanced hybrid closed loop systems in children with type 1 diabetes younger than 6 years.

Tight glycemic control is essential for the normal growth and development of preschool children. The aim of our study was to evaluate the impact of advanced hybrid closed loop (AHCL) systems in a real-life setting in children younger than 6 years. We conducted a two-center prospective study. We enrolled 19 patients with a median age at disease onset of 2.6 years [interquartile range (IQR) 1.6; 4.4] and a median disease duration of 1.4 years (IQR 0.9; 2.8) who were switched to AHCL from multiple daily injections or open-loop insulin therapy and with a 6-month follow-up. Clinical data, sensor glycemic metrics, and pump settings were collected and analyzed. After 6 months of follow-up, there was a significant reduction in median HbA1c (p = 0.0007) and glucose management indicator (p = 0.03). A reduction in both mild (>180 mg/dL) (p = 0.04) and severe (>250 mg/dL) (p = 0.01) hyperglycemia was observed after 1 month of auto mode, and in mild hyperglycemia, it persisted up to 6 months (p = 0.02). A small increase in time below range (<70 mg/dL) was observed (p = 0.04) without a significant difference in time <54 mg/dL (p = 0.73). Time in range increased significantly, reaching a 10% increment (p = 0.03) compared with baseline. A significant reduction in the average sensor glucose was observed (p = 0.01) while coefficient of glucose variability (CV%) remained stable (p = 0.12). No episodes of ketoacidosis or severe hypoglycemia have been recorded. AHCL systems are effective and safe for children younger than 6 years and should be considered as a valid therapeutic option from diabetes onset.