Hypoglycemia Research Articles

Efficacy and safety of basal insulin degludec 100 IU/mL versus glargine 300 IU/mL for type 1 diabetes: The single-center INEOX randomized controlled trial

AimsTo compare efficacy and safety of degludec 100 IU/mL (Deg-100) and glargine 300 IU/mL (Gla-300) in adults with type 1 diabetes. MethodsOpen-label, single-center, randomized, parallel-group, 24-week trial in adults with type 1 diabetes, on basal-bolus insulin therapy, HbA1c ≤ 10%, using self-monitoring blood glucose. Participants were randomized 1:1 to a basal-bolus insulin regimen with Deg-100 (N = 129) or Gla-300 (N = 131). Primary efficacy endpoint: mean change in HbA1c from baseline to week-24. Main safety outcome: incidence rate of hypoglycemia during the study. Quality of life (DQOL) and satisfaction with diabetes treatment (DTSQ) were assessed. ResultsAt week 24, after adjusting for baseline HbA1c, the decrease in HbA1c did not differ between groups: Deg-100 (−0.07 ± 0.7%) and Gla-300 (−0.16 ± 0.77%) (P = 0.320). There were no significant differences between groups in HbA1c, nocturnal hypoglycemia, severe hypoglycemia, DQOL, or DTSQ scores. The incidence rates of hypoglycemia < 3.9 mmol/L (Deg-100: 115.24 events/person-year vs Gla-300: 99.01 events/person-year, p < 0.001); and < 3.0 mmol/L (Deg-100: 41.17 events/person-year vs Gla-300: 34.29 events/person-year, p < 0.001) were different between groups. ConclusionsDeg-100 and Gla-300 have similar metabolic efficacy, incidence ratio of nocturnal and severe hypoglycemia, DQOL and DTSQ scores. Differences in the incidence rate of hypoglycemia < 3.9 mmol/L and < 3.0 mmol/L should be confirmed.

The comparative analysis of efficacy and safety parameters of Insulin Degludec versus Insulin Glargine: A Narrative Review

Background and aim: Insulin degludec and insuline glargine are the two long-acting insulins most commonly prescribed for the treatment of Diabetes Type 1 as well as Diabetes Type 2. Both insulins were generated to address a clinical need for the basal insulin which produces a more even and flat activity profile and reduces the number of hypoglycemia- a dangerous side effect of insulin therapy. Although glargine and degludec confirmed their superiority in terms of reduced rate of hypoglycemia, especially in comparison with first generations, several studies revealed that degludec is associated with less glycemic variability. Moreover, degludec is more effective in reaching better fasting plasma glucose levels without increasing a risk of nocturnal hypoglycemia. The aim of this study is to compare the five most essential efficacy and safety parameters of insulin degludec versus insulin glargine. Methods: This study used a narrative synthesis of the research findings. The search for existing narrative and systematic reviews on the research topic was conducted through PubMed, Embase, and Google Scholar electronic databases. Reviews were selected according to a study design and methodological quality of the included studies. The reviews published within 2015-2023 period were included. The data on five safety and efficacy parameters (the reduction of fasting plasma glucose level, HbA1c levels, overall and nocturnal hypoglycemia episodes, body weight gain) were retrieved for the analysis. Findings: The analysis of data retrieved out of 10 systematic reviews confirmed superiority of insulin degludec in comparison with insulin glargine in terms of four safety and efficacy parameters. The treatment with degludec was associated with fewer overall and nocturnal hypoglycemia episodes, a better reduction of fasting plasma glucose levels in both Diabetes Type 1 and Diabetes Type 2 groups (insulin naïve and experienced) patients, less weight gain in Diabetes Type 2 insulin experienced group and Diabetes Type 1 groups. Both insulins provided a similar reduction of HbA1c levels among patients with Diabetes Type 1 and Diabetes Type 2. Conclusion: In conclusion, this narrative review revealed that insulin degludec is superior to insulin glargine in terms of four safety and efficacy parameters such as change in fasting plasma glucose, body weight gain, nocturnal and overall hypoglycemia episodes. Degludec and glargine produced similar changes in HbA1c levels. The most pronounced differences in almost all the examined reviews were detected in the variables indicating nocturnal and overall hypoglycemia. The treatment with degludec also resulted in less hypoglycemia, accompanied with a better reduction of fasting plasma glucose levels. This characteristic confirms that degludec produces less glycemic variability and a close to physiological activity profile.

Continuous Glucose Monitoring and Other Wearable Devices to Assess Hypoglycemia among Older Adult Outpatients with Diabetes Mellitus.

Hypoglycemia (HG) causes symptoms that can be fatal, and confers risk of dementia. Wearable devices can improve measurement and feedback to patients and clinicians about HG events and risk. The aim of the study is to determine whether vulnerable older adults could use wearables, and explore HG frequency over 2 weeks. First, 10 participants with diabetes mellitus piloted a continuous glucometer, physical activity monitor, electronic medication bottles, and smartphones facilitating prompts about medications, behaviors, and symptoms. They reviewed graphs of glucose values, and were asked about the monitoring experience. Next, a larger sample (N = 70) wore glucometers and activity monitors, and used the smartphone and bottles, for 2 weeks. Participants provided feedback about the devices. Descriptive statistics summarized demographics, baseline experiences, behaviors, and HG. In the initial pilot, 10 patients aged 50 to 85 participated. Problems addressed included failure of the glucometer adhesive. Patients sought understanding of graphs, often requiring some assistance with interpretation. Among 70 patients in subsequent testing, 67% were African-American, 59% were women. Nearly one-fourth (23%) indicated that they never check their blood sugars. Previous HG was reported by 67%. In 2 weeks of monitoring, 73% had HG (glucose ≤70 mg/dL), and 42% had serious, clinically significant HG (glucose under 54 mg/dL). Eight patients with HG also had HG by home-based blood glucometry. Nearly a third of daytime prompts were unanswered. In 24% of participants, continuous glucometers became detached. Continuous glucometry occurred for 2 weeks in an older vulnerable population, but devices posed wearability challenges. Most patients experienced HG, often serious in magnitude. This suggests important opportunities to improve wearability and decrease HG frequency among this population.

Nighttime hypoglycemia in Japanese children with type 1 diabetes mellitus treated with multiple daily injection insulin therapy.

Prevention of hypoglycemia is an important strategy for glycemic management in patients with type 1 diabetes mellitus (T1D). Hypoglycemia is difficult to recognize at night while sleeping, particularly when using multiple daily injection (MDI) insulin therapy rather than sensor-augmented insulin-pump therapy. Therefore, it is possible that patients with T1D are at higher risk of nocturnal hypoglycemia when insulin is administered using an MDI regimen. We investigated nocturnal hypoglycemia in 50 pediatric patients with T1D on MDI insulin therapy using data from an intermittently scanned continuous glucose monitoring (isCGM) system. Hypoglycemia was observed on 446 of the 1,270 nights studied. Most of the hypoglycemic episodes were severe (blood glucose <54 mg/dL). On nights when hypoglycemia occurred, the blood glucose concentrations measured using finger-stick blood glucose monitoring (FSGM) before sleep and the next morning were lower than nights when hypoglycemia did not occur. However, few values were below the normal blood glucose range, suggesting that FSGM alone may be insufficient to detect nocturnal hypoglycemia. Approximately 7% of time was spent below the normal glucose range during the 10 hours from 21:00 to 7:00 the next morning. This result suggests that the patients on MDI insulin therapy could end up spending more time in hypoglycemia than is recommended by the American Diabetes Association (time below range <4.0% of time per day). Monitoring glucose levels overnight using an isCGM sensor may improve glycemic management via automatic detection of blood glucose peaks and troughs.

The behaviour change behind a successful pilot of hypoglycaemia reduction with HYPO-CHEAT.

Children with hypoglycaemia disorders, such as congenital hyperinsulinism (CHI), are at constant risk of hypoglycaemia (low blood sugars) with the attendant risk of brain injury. Current approaches to hypoglycaemia detection and prevention vary from fingerprick glucose testing to the provision of continuous glucose monitoring (CGM) to machine learning (ML) driven glucose forecasting. Recent trends for ML have had limited success in preventing free-living hypoglycaemia, due to a focus on increasingly accurate glucose forecasts and a failure to acknowledge the human in the loop and the essential step of changing behaviour. The wealth of evidence from the fields of behaviour change and persuasive technology (PT) allows for the creation of a theory-informed and technologically considered approach. We aimed to create a PT that would overcome the identified barriers to hypoglycaemia prevention for those with CHI to focus on proactive prevention rather than commonly used reactive approaches. We used the behaviour change technique taxonomy and persuasive systems design models to create HYPO-CHEAT (HYpoglycaemia-Prevention-thrOugh-Cgm-HEatmap-Assisted-Technology): a novel approach that presents aggregated CGM data in simple visualisations. The resultant ease of data interpretation is intended to facilitate behaviour change and subsequently reduce hypoglycaemia. HYPO-CHEAT was piloted in 10 patients with CHI over 12 weeks and successfully identified weekly patterns of hypoglycaemia. These patterns consistently correlated with identifiable behaviours and were translated into both a change in proximal fingerprick behaviour and ultimately, a significant reduction in aggregated hypoglycaemia from 7.1% to 5.4% with four out of five patients showing clinically meaningful reductions in hypoglycaemia. We have provided pilot data of a new approach to hypoglycaemia prevention that focuses on proactive prevention and behaviour change. This approach is personalised for individual patients with CHI and is a first step in changing our approach to hypoglycaemia prevention in this group.

Bilateral Asymmetric Fracture Dislocation of Shoulder after Hypoglycemic Shock

Bilateral Asymmetric Fracture Dislocation of Shoulder after Hypoglycemic Shock

An Analysis of Health Factors Affecting Employees’ Absenteeism: Influences of HDL Cholesterol and Blood Sugar Levels

Background: Workers’ health condition is an important issue. It affects not only the well-being of workers but also the firms and society as a whole through medical costs and productivity losses due to absenteeism and presenteeism. Data and Methods: Data were obtained from 1136 employees at an operational site of a large corporation. The dataset contained both medical checkups and working record information. Health factors affecting long-term absence (over three days in three months) were analyzed. Logistic regression models and the procedure for selecting proper covariates based on likelihood test statistics and the Akaike information criterion were used. Results: Among health factors, high-density lipoprotein cholesterol (HDL-C) and blood sugar levels were important in the selected model. For HDL-C, the odds ratio (OR) based on one standard deviation difference was 0.75 with a 95% confidence interval (CI) of 0.59 - 0.95. For blood sugar, the OR was 1.20 with a 95% CI of 1.01 - 1.42. Improving HDL-C and blood sugar levels would reduce long-term absence by 25% and 20%, respectively. Conclusion: Controlling HDL-C and blood sugar levels is important to reduce long-term absenteeism. These factors can be improved by modifying eating habits. Since the operational site has its own company cafeterias, which most employees use, nutritional intervention is relatively easy with little or no cost. It may be worthwhile to implement nutritional intervention, especially for patients with low HDL-C or high blood sugar levels. Limitations: The results of this study were based on one operational site of a corporation. The employees were mainly operators working inside the building. The results may be different from other types of jobs and working conditions, such as fieldwork. Analyses of different types of jobs and working conditions are necessary.

Research progress on the hypoglycemic effect of mulberry leaves

Mulberry leaf, as a traditional Chinese medicine with medicinal and food values, is nowadays widely used in the clinical treatment of diabetes and hyperlipidemia. Its active ingredients are mainly flavonoids, polysaccharides, alkaloids and other substances, which have good efficacy in regulating insulin secretion, hypoglycemia and lipid lowering. In recent years, a large number of experimental studies and some clinical studies have proved that mulberry leaf does have hypoglycemic effect, and it is widely available, easy to obtain and low in price. In this paper, we review the research progress on the mechanisms of mulberry leaf inhibition of α-glucosidase activity, promotion of insulin secretion, improvement of pancreatic islet function, promotion of glucose utilization by peripheral tissues, and enhancement of hepatic glycogen. It is expected to provide guidelines for in-depth research on the mechanism of action of mulberry leaves in regulating blood glucose and preventing diabetic complications, and to provide a basis and reference for the development and utilization of mulberry leaf resources.

EFFECT OF HEALTH ANXIETY ON GLYCEMIC CONTROL IN PATIENTS WITH TYPE II DIABETES MELLITUS: A SINGLE CENTER, CROSS SECTIONAL STUDY.

Health anxiety was rarely investigated in Type II Diabetes Mellitus (T2DM). The present study examines the effect of health anxiety on glycemic control and evaluates factors associated with health anxiety in patients with T2DM according to HbA1c level. Cross-sectional. Socio Demographic Data Form (SDVF), Health Anxiety Inventory-Short Form(SHAI), The Hospital Anxiety and Depression Scale (HADS) were administered to 185 patients with Type II DM . Patients were divided into two groups according to HbA1 c level (HbA1c levels below 7 (Group 1, n=69) and above 7 (Group 2, n=185)). We analyzed prevalence of health anxiety, factors associated with health anxiety between poor and good glycemic control and evaluated of T2DM patients according to health anxiety scale scores. SHAI scale scores were low in 52 (28%), intermediate in 58 (31.2%) and high in 76 (40.8%) of the patients. We found the severity of depressive symptoms was positively correlated with health anxiety in both groups. As a result of this study, there was a relationship between high education and low socioeconomic level, having a job, exercise and anxiety level and low SHAI score in T2DM patients. Depression, stressful life events in the last 6 months were related with high health anxiety. Although the level of health anxiety was not different between groups, low blood sugar levels were related with high health anxiety. This study found that the prevalence of health anxiety in T2DM patients was higher than expected irrespective to poor or good glycemic control, but level of health anxiety in patients with T2DM is not a good predictor for the HbA1c level.

Green synthesis for the treatment of type-II diabetes

Type-II diabetes mellitus (T2DM) is a serious threat to human life as till the year 2019, approximately 463 million individuals of age between 20-79 years are suffering with diabetes and it will rise to 700 million by the year 2045. For the testing and diagnosis of diabetes, The WHO and the ADA are using various clinical and laboratory characteristics. Diabetes is a silent killer which cannot be cured, however by changing the lifestyle, losing fat, using low blood sugar medications, and using metformin (biguanide) which helps in reducing insulin resistance, one can control diabetes to an extent. Metformin is widely used medicine to treat obesity. Various short- and long-term problems including premature death occurs in type-II diabetic patients. Due to the late diagnosis and poor medical facilities for type-II diabetes in countries like Africa, they are susceptible to developing diseases that lead to death. This article mainly discusses type-II diabetes mellitus (T2DM) and the drugs used for its cure. It also gives a green synthesis of one of the diabetes drug done in our lab.

Effects of Physical Activity Timing and Intensity on the Occurrence and Risk of Nocturnal Hypoglycemia in Adolescents With Type 1 Diabetes

Clinical Scenario: Athletic trainers should be aware of how physical activity may influence the risk of nocturnal hypoglycemia in adolescents with type 1 diabetes (T1D). Clinical Question: Does the timing and intensity of physical activity affect the occurrence and risk of nocturnal hypoglycemia in adolescents with T1D? Results of the Search: Four studies meeting the inclusion criteria were found and included in the appraisal. Three studies were prospective observational cohorts, and one was a randomized case-crossover study. Clinical Bottom Line: Adolescents with T1D may be at greater risk of nocturnal hypoglycemia after performing 30–60 minutes of moderate-to-vigorous physical activity during the late afternoon or evening. Implications: Athletic trainers should educate adolescents with T1D and their parents about the risk of nocturnal hypoglycemia after MVPA, and work in collaboration with the diabetes care physician to ensure prevention techniques are included in the patient'’s diabetes care plan. Level of Evidence: Strength of Recommendation Taxonomy Grade B.

Effect of Borneol to Enhance Topical Drug Penetration for Lipophilic Drug

Abstract: Progesterone is a C21-steroid hormone, lipophilic, having log P of 3.56 and therefore, poor permeation of active moiety in the skin is a major challenge of transdermal delivery. There are many strategies to overcome the permeation of drugs through the skin, such as using nanocarriers, applying physical and chemical permeation enhancers and others. Penetration enhancers act by modifying the hydration properties of stratum corneum and altering the structure of lipids and proteins in the intercellular channels carrier mechanism. The present work estimates the in-vitro permeation of progesterone from microemulsionbased transdermal formulations containing Borneol as penetration enhancers. Progesterone was taken as a model drug. The microemulsion was formulated by a simple stirring method, followed by adding Myritol as oil, Tween 80 as a surfactant, and + PEG 400 as a co-surfactant. The globule size of the final microemulsion formulation was found to be in the range of 200- 394 nm with PDI 0.123, and Zeta potential study indicated -23.1 mV showing good stability. TEM images showed that the F14 batch is spherical, and its size was identical to that obtained from laser diffraction. For ease of application, microemulsion was converted to gel using Carbopol 980. Borneol with a concentration of 4% showed a drug release of 83% after 9hrs. The formulation's viscosity, pH and texture profile was found to be optimum. The final formulation follows Korsmeyer-Peppas release kinetics. A stability study of microemulsion gel was performed for 180 days at refrigerated temperature and room temperature. The formulation showed better storage via stability study with good spreadability. Thus, developed Borneol containing microemulsion-based transdermal formulation can be a promising alternative to deliver progesterone for hormone replacement therapy in any indication such as breast tenderness, infertility, lumpy (fibrocystic) breasts, low blood sugar, increased blood clotting etc.

Hypoglycemia and cardiac arrhythmias in diabetes mellitus

The article provides an assessment of cardiovascular risks associated with episodes of hypoglycemia in patients with diabetes mellitus. The analysis has been performed for the experimental and clinical data on cardiac arrhythmias during induced hypoglycemia in animal models and in patients with diabetes. The pathogenetic mechanisms of the development of life‑threatening heart rhythm disorders during hypoglycemic states (in particular, changes in autonomic nervous system activation and in the serum level of potassium) have been considered. The nature of electrocardiographic changes preceding the development of arrhythmias during hypoglycemia is described and factors affecting QT interval duration during hypoglycemia are given. The authors highlight the results of clinical studies of spontaneous hypoglycemia in terms of the arrhythmias’ specific features in daytime and nocturnal hypoglycemia, and different mechanisms of the cardiac arrhythmias’ development at different periods of the day. Clinical data have been presented as regards the drug‑induced hypoglycemia during administration beta‑adrenergic receptor blockers, angiotensin‑converting enzyme inhibitors, fluoroquinolones, as well as mechanisms of dysglycemic effects of these drugs. It has been noted that β‑blockers can mask symptoms of catecholamine‑mediated hypoglycemia. It has been established that among hypoglycemic agents, insulin secretion stimulators (sulfonylureas, meglinides) and insulin have the highest risk of serious hypoglycemia. However, the use of basal and prandial insulin analogues was associated with a lower frequency of hypoglycemia compared to human insulin. It was emphasized that hypoglycemia should be avoided in clinical practice to improve prognosis and prevent arrhythmias. For this, it is necessary to individualize target glycemic values with their mitigation in high‑risk patients, to use the safest insulin and non‑insulin hypoglycemic agents, and to implement new technologies (pumps, continuous glucose monitoring) more widely. It is extremely important to take into account comorbidity and the effects on hypoglycemia risk of drugs used for the treatment of concomitant diseases.

Association between the severity of nocturnal asymptomatic hypoglycemia and heart rate variability change in patients with type 2 diabetes

Association between the severity of nocturnal asymptomatic hypoglycemia and heart rate variability change in patients with type 2 diabetes

Assessment and comparison of IVth and Vth year dentistry students' knowledge of the impact systemic diseases have on dental extraction procedures

Radvilė Raubaitė1, Rūta Rastenienė1 1Vilnius University, Faculty of Medicine, Institute of Odontology, Vilnius, Lithuania Abstract Background. Dentistry students lack confidence to treat patients with systemic diseases. Many referrals to oral surgery departments are considered as routine procedures, which may cause a delay of service to more critical patients. Reluctance to perform dental extraction procedures on patients with systemic diseases may be due to lack of knowledge in managing potential postoperative complications (e.g. postoperative bleeding, delayed wound healing, hypoglycaemic shock). Aim. To assess and compare the knowledge of 4th– and 5th-year Lithuanian dentistry students on the influence systemic diseases have on dental extraction procedures, determine factors leading to one’s better knowledge and assess the need for practical guidelines. Methods. An anonymous survey was presented electronically to 4th– and 5th– year Lithuanian dentistry students. Statistical data analysis was performed with program R. Results. On average, 40.3 percent of answers to theoretical questions were correct. 5th year students’ knowledge on hypertension and diabetes was significantly better than 4th year students (p < 0.05). The knowledge of students, who expressed further interest in minimal surgical interventions, was significantly more extensive (p = 0.02). Most respondents (96.2 percent) indicated the need for practical guidelines on the topic. Conclusions. Although being a final-year student was a significant factor in deeper understanding of the effect diabetes and hypertension have on dental extraction procedures, all students generally may lack expertise in this field. Further interest in surgical interventions, including attending conferences, courses or reading scientific literature contribute to ones’ better knowledge. The need for practical guidelines on this topic is significant. Keywords: systemic diseases, tooth extraction, complications after tooth extraction.

ASSOCIATION OF HBA1C WITH BEHAVIORAL SYMPTOMS OF DEMENTIA IN VA NURSING HOME RESIDENTS WITH DIABETES (2013–2019)

Abstract For people with dementia, behavioral symptoms of dementia are often signs of distress and may be caused by pain, confusion, agitation, or negative moods. In people with diabetes, pain, confusion, and agitation may result from aspects of diabetes management, including poor glycemic control, episodes of very low or high blood sugar (hypo- and hyper-glycemia), insulin injections, or fingerstick pricks to check blood glucose. Few studies have examined how diabetes control contributes to behavioral symptoms of dementia. We conducted a retrospective study in VA nursing home (NH) residents aged 65+ with both dementia and diabetes, and a NH stay&amp;gt;45 days. We used the second assessment of the Minimum Dataset (MDS 3.0) to identify behavioral symptoms of verbal or physical outbursts during the prior 7 days. We conducted mixed-effects logistic regression, with clustering by NH facility. The 5060 residents were overwhelmingly male (99%), had an average age of 78, with mean HbA1c was 7.1 (standard deviation 1.6). The overall prevalence of any behavioral symptoms was 16.7%. Compared to residents with HbA1c &amp;lt; 6%, behavioral symptoms were slightly more common among residents with HbA1c 6-7%, 7-8%, and &amp;gt;9%, but not statistically significantly different. Behavioral symptoms were significantly more common in residents with HbA1c 8-9% (prevalence 19.6%) than in residents with HbA1c &amp;lt; 6% (prevalence 15.5%; odd ratios adjusted for NH facility: 1.35, 95% confidence interval: 1.05-1.75). Additional research is needed to determine which aspects of diabetes management may be contributing to excess risk of behavioral symptoms of dementia.

Severe Recurrent Nocturnal Hypoglycemia During Chemotherapy With 6-mercaptopurine in 2 Children With Acute Lymphoblastic Leukemia.

Mercaptopurine (6MP) and methotrexate are the cornerstones of maintenance therapy in pediatric patients with acute lymphoblastic leukemia. However, although bone marrow suppression and liver dysfunction are common side effects of these antimetabolites, 6MP-induced hypoglycemia during the maintenance phase is rare. Guidelines and international protocols are well established for the management of bone marrow suppression and liver dysfunction, but promptly identifying 6MP-induced hypoglycemia is the key to its control. Here we report 2 cases of leukemia that developed hypoglycemia during the maintenance phase. Both patients were boys younger than 6 years of age and both suffered symptomatic morning hypoglycemia induced by 6MP (which was diagnosed after excluding all other possible causes). Successful management included changing the time of 6MP administration from evening to morning. Other management options are also discussed.

Bedtime Prediction of Nocturnal Hypoglycemia in Insulin-Treated Type 2 Diabetes Patients.

Hypoglycemia may lead to anxiety, poor adherence, and hypoglycemia unawareness and is especially a threat during the night in patients with insulin-treated type 2 diabetes (T2D). It would therefore be beneficial to warn patients at risk of hypoglycemia at bedtime so they can react accordingly and avoid the episode. Hence, the aim of the present study was to develop a model for predicting nocturnal hypoglycemia. Continuous glucose monitoring (CGM), mealtime, and insulin data were collected from 67 insulin-treated patients with T2D (NCT01819129). Data were structured into 24-hour periods and labeled as nocturnal hypoglycemia or not depending on whether 15 consecutive minutes were spent below 3.0 mmol/L (54 mg/dL) during the following night. Each period was divided into "last night," "morning," "day," and "evening" for feature extraction purposes, and 72 potential features were extracted for every period. A five-fold cross-validation was used to select features by forward selection and for training and validating a model based on logistic regression. The prediction model was based on 30 patients with 60/496 periods resulting in nocturnal hypoglycemia. Forward selection revealed that the best features were based on CGM and involved the last value and mean value during the evening, as well as the relative difference in maximum value during the day between the present period and previous periods. The model obtained a mean area under the receiver operating characteristics curve (AUC) of 0.82 with an accuracy of 0.79. The model was able to predict nocturnal hypoglycemia with an acceptable accuracy and could therefore prevent such cases.

Acute effects of insulin and insulin-induced hypoglycaemia on carotid body chemoreceptor activity and cardiorespiratory responses in dogs.

What is the central question of this study? What are the effects of insulin and insulin-induced hypoglycaemia on carotid body chemoreceptor activity in vivo and how do carotid body chemoreceptor stimulation-mediated cardiorespiratory responses in beagle dogs compare during euglycaemia and insulin-induced hypoglycaemia? What is the main finding and its importance? Intracarotid insulin administration leads to sustained increase in carotid body chemoreceptor activity and respiratory response with significant cardiovascular effects. Insulin-induced hypoglycaemia exacerbated NaCN-mediated carotid body chemoreceptor activity and respiratory response with enhanced cardiovascular reflex response. These findings suggest that insulin-induced hypoglycaemia augments the carotid body chemoreceptors to initiate the adaptive counter-regulatory responses to restore the normoglycaemic condition. The carotid body chemoreceptors (CBC) play an important role in the adaptive counter-regulatory response to hypoglycaemia by evoking the CBC-mediated sympathetic neuronal system to restore normoglycaemia. Ex vivo studies have shown varied responses of insulin-induced hypoglycaemia on CBC function, and several in vivo studies have indirectly established the role of CBCs in restoring normoglycaemia in both animals and humans. However, a direct effect of insulin and/or insulin-induced hypoglycaemia on CBC activity is not established in animal models. Therefore, the aim of this study was to evaluate in vivo effects of insulin and insulin-induced hypoglycaemia on CBC activity and cardiorespiration in a preclinical large animal model. The carotid sinus nerve (CSN) activity and cardiorespiratory responses to sodium cyanide (NaCN; 25µg/kg) were compared before (euglycaemic) and after (hypoglycaemic) intracarotid administration of insulin (12.5-100µU/dogs) in beagle dogs. Insulin administration increased CSN activity and minute ventilation ( E ) with significant (P<0.0001) effects on heart rate and blood pressure. Insulin-mediated effects on CSN and cardiorespiration were sustained and the change in E was driven by tidal volume only. Insulin significantly (P<0.0001) lowered blood glucose level. NaCN-mediated CSN activity and E were significantly (P<0.0001) augmented during insulin-induced hypoglycaemia. The augmented E was primarily driven by respiratory frequency and partially by tidal volume. The cardiovascular reflex response mediated through CBC stimulation was significantly (P<0.0001) exacerbated during insulin-induced hypoglycaemia. Collectively, these results demonstrate direct effects of insulin and insulin-induced hypoglycaemia on CBC chemosensitivity to potentiate CBC-mediated neuroregulatory pathways to initiate adaptive neuroendocrine and cardiorespiratory counter-regulatory responses to restore normoglycaemia.

EE507 Insulin Degludec/Insulin Aspart Versus Basal+Bolus Insulin Treatment (Insulin Glargine U100 & Insulin Aspart) in T2D in India: A Short-Term Cost-Effectiveness Analysis Based on the Step-By-Step Clinical Trial

The Step-by-step clinical trial (NCT02906917) in basal insulin ± oral antidiabetic drugs treated people with type 2 diabetes (T2D) confirmed a similar glycemic effect for insulin degludec/insulin aspart (IDegAsp) versus basal+bolus insulin treatment (BB) of IGlar U100 + IAsp that was consistent over 38-weeks period with a significantly lower risk of nocturnal hypoglycemia. The aim of the present analysis was to assess the short-term cost-effectiveness of IDegAsp vs BB in Indian setting.