Hypoglycemia In Diabetic Patients Research Articles

SAT149 In Vitro Characterization Of A Novel Long-acting Glucagon Analog (HM15136) And Its Potential Effect In Animal Models Of Chronic Hypoglycemic Diseases

Abstract Disclosure: J. Kim: Employee; Self; Hanmi Pharm. Co., Ltd. Y. Kim: Employee; Self; Hanmi Pharm. Co., Ltd. B. Ye: Employee; Self; Hanmi Pharm. Co., Ltd. W. Kim: Employee; Self; Hanmi Pharm. Co., Ltd. J. Kim: Employee; Self; Hanmi Pharm. Co., Ltd. S. Bae: Employee; Self; Hanmi Pharm. Co., Ltd. D. Kim: Employee; Self; Hanmi Pharm. Co., Ltd. S. Lee: Employee; Self; Hanmi Pharm. Co., Ltd. I. Choi: Employee; Self; Hanmi Pharm. Co., Ltd. Glucagon plays an essential role in glucose homeostasis, and has been used to treat acute hypoglycemia in diabetic patients. However, due to poor solubility and stability at physiological pH as well as short duration of action, its utility was hampered when managing chronic hypoglycemic diseases. One such example is congenital hyperinsulinism (CHI). CHI is a rare genetic disorder characterized by unregulated insulin secretion which leads to severe hypoglycemia especially during fasting condition. Another example is post-bariatric hypoglycemia (PBH) which can also lead to postprandial neuroglycopenia. Despite this life-threatening condition, no drugs are approved for CHI and/or PBH, and available glucagon therapies are very inefficient and inconvenient due to abovementioned limitations. Thus, to provide more optimal therapy for these chronic hypoglycemic diseases, a novel long-acting glucagon analog (HM15136) was developed. Here, we evaluated HM15136’s 1) solubility and stability at physiologic pH, 2) in vitro properties, and 3) potential therapeutic effect in animal models of CHI or PBH. First, we demonstrated improved solubility of HM15136 (≥150 vs. 0.03 mg/mL) at pH 7.0 and stability at day 20, compared to those of native glucagon. Next, in vitro cAMP assay was performed in CHO cells expressing human glucagon receptor (hGCGR), and HM15136 selectively activated hGCGR as a full agonist (EC50 = 0.024 vs. 0.003 nM; relative activity = ca.12.7%). In line with this, HM15136 promoted glycogenolysis and gluconeogenesis in rat primary hepatocytes in a dose dependent manner (relative potency = ca.20%), confirming glucose producing nature of HM15136. To investigate in vivo therapeutic effect on CHI and PBH, chronic hypoglycemia rats induced by SC infusion of insulin (CHI rats) and postprandial hypoglycemia rats induced by vertical sleeve gastrectomy (VSG rats) were established, respectively. Notably, HM15136 treatment significantly restored FBG by 37.3 ∼ 69.7% (p<0.05 ∼ 0.001) in CHI rats. Consistently, HM15136 treatment significantly prevented a massive BG reduction during MMTT in VSG rats (ΔBG between 0 and 45 min = +21 vs. -30 mg/dL, p<0.001). Furthermore, weekly dosing potential and BG elevation effect of HM15136 were also demonstrated in healthy human subjects (1). Based on these results, HM15136 could be a potential therapeutic option for chronic hypoglycemic diseases including CHI and PBH. Phase 2 clinical study in CHI subjects is on-going to assess the clinical relevance of these findings. Reference: (1) Diabetes Obes Metab. 2022 Mar; 23(3):411-20 Presentation: Saturday, June 17, 2023

Identification of Risk Factors and Development of a Predictive Model for Postoperative Hypoglycemia among Diabetic Patients during the Perioperative Period.

To explore the incidence and influencing factors of postoperative hypoglycemia in diabetic patients during the perioperative period and to construct a risk prediction model for postoperative hypoglycemia. Patients with T2DM admitted to the nonendocrinology department of Nanjing Drum Tower Hospital from December 2019 to January 2022 were included as research subjects. Basic information, hospital blood glucose management methods, laboratory indicators, and surgery-related indicators were collected. A risk prediction model and scoring table for postoperative hypoglycemia in patients with perioperative diabetes mellitus were established. A total of 440 patients were included, of which 109 had hypoglycemia, resulting in an incidence of postoperative hypoglycemia of 24.78%. The results show that preoperative C-peptide and operation duration were risk factors for postoperative hypoglycemia, while BMI and preoperative fasting blood glucose were protective factors. The model constructed in this study is a good method for evaluating the risk of postoperative hypoglycemia. The scoring table intuitively quantifies the risk of risk factors for outcome variables and has strong clinical practicability.

Hypoglycemia with Beta-Blocker in Patients with Type II Diabetes

Objective: To ascertain the frequency of hypoglycemia in diabetic patients using beta blockers.Study Design: A descriptive cross-sectional study.Place and Duration of Study: The study was conducted in the Department of Nephrology and Medicine, Lady Reading Hospital Peshawar, Pakistan, from 10th October 2021 to 10th April 2022.Materials and Methods: The total number of diabetic patients with hypoglycemia was 196, who were included in this study. The patients’ medical record was assessed, and the use of beta-blocker was noted and recorded.Results: This study included those patients whose ages ranged from 30 to 70 years, with a mean age of 51.964±6.38 years. The average duration of diabetes was 7.989±2.74 years, and an average weight of 87.178 kg. Male patients were 71.9%, and females were 28.1%, 43.9% of diabetic patients who had hypoglycemia used beta blockers. Conclusion:  According to this study, diabetic people who take oral beta-blockers have a higher risk of developing hypoglycemia. This research shows that Beta Blocker use causes increased chances of hypoglycemia in people with diabetes.

Patient Education to Prevent Hypoglycemia

Hypoglycemia in diabetic patients is an obstacle to self-management of diabetes. Severe hypoglycemia reduces quality of life and increases the risk of death in diabetic patients. Factors associated with hypoglycemia include older age, insulin use, inadequate diet, excessive exercise, and alcohol consumption. Patients who experience severe hypoglycemia may require adjustment of glycemic target and insulin dosage. Patients who frequently suffer from severe hypoglycemia may need to prepare glucagon in advance and use a continuous glucose monitor system or sensor augmented insulin pump. All diabetic patients should receive education on how to prevent and manage hypoglycemia. Healthcare professionals should identify the cause of hypoglycemia in patients visiting hospitals with severe hypoglycemia and provide appropriate patient education to prevent recurrence.

The association between hypoglycemia and mortality in sepsis and septic shock: A systematic review and meta-analysis.

Over 48 million cases of sepsis and 11 million sepsis-related deaths were reported in 2017, making it one of the leading causes of mortality. This meta-analysis compared mortality risk among patients with sepsis or septic shock and associated hypoglycemia or euglycemia on admission by searching for observational studies in PubMed, Embase and Scopus databases. The eligible studies included patients with sepsis and/or severe sepsis/septic shock and compared mortality rates between those with hypoglycemia on admission and those who were euglycemic. A stratified analysis based on sepsis or severe sepsis/septic shock and diabetes on admission included 14 studies. Patients with hypoglycemia had a significantly higher risk of in-hospital mortality and mortality during the 1st month after discharge. In addition, hypoglycemic patients with sepsis had a slightly increased risk of in-hospital mortality, but no increase in the mortality risk was observed within 1 month of follow-up. However, in patients with severe sepsis and/or septic shock, hypoglycemia was associated with a higher risk of both in-hospital mortality and mortality during 1 month of follow-up. In patients with diabetes, hypoglycemia was not associated with an increased risk of in-hospital mortality or mortality within 1 month of follow-up. Patients with sepsis or severe sepsis/septic shock and hypoglycemia had an increased mortality risk, and the association was stronger in cases of severe sepsis/septic shock. Hypoglycemia in diabetic patients did not correlate with increased mortality risk. Careful monitoring of blood glucose in sepsis and/or severe sepsis/septic shock patients is required.

Farmaci intranasali nel bambino: cosa devono sapere i pediatri

The use of the intranasal route of administration to deliver drugs in children became more and more popular in the last decades. Seizure, severe acute pain, and severe hypoglycemia in diabetic patients, may be managed with intranasal drugs. The intranasal administration is minimally invasive, not painful, needleless, and easy to learn and use. The evidence shows that it is a safe and effective way to deliver lipophilic drugs, that are quickly absorbed. This article is a practical guide that provides indications, dosages, and some “tricks” for this way of administration.

Prediction of Hypoglycemia in Diabetic Patients During Colonoscopy Preparation.

To explore the clinical outcomes and establish a predictive model of hypoglycemia during colonoscopy preparation for diabetic patients. Three-hundred ninety-four patients with diabetes who received colonoscopy were retrospectively enrolled in this study and assigned to hypoglycemia or non-hypoglycemia groups. Information about clinical characteristics and outcomes during colonoscopy preparation was collected and compared between the two groups. Logistic regression analysis was applied to identify the risk factors of hypoglycemia. These risk factors were used to construct a hypoglycemia predictive model verified by the receiver operating characteristic (ROC) curve and Hosmer-Lemeshow goodness fit test. Among 394 participants, 66 (16.8%) underwent a total of 88 hypoglycemia attacks during the bowel preparation. Grade 1 hypoglycemia (≤3.9 mmol/L) comprised 90.9% (80/88) of all hypoglycemia attacks and grade 2 hypoglycemia accounted for 9.1% (8/88), signifying that grade 1 hypoglycemia is the most common type. No severe hypoglycemia was identified. The incidence of nocturnal hypoglycemia was 15.9%. Logistic regression analyses revealed that the main risk factors of hypoglycemia during colonoscopy preparation were postprandial C-peptide, serum triglyceride, gender, type of diabetes mellitus, and insulin injection frequencies. The area under the ROC curve of the hypoglycemia prediction model was 0.777 (95% CI: 0.720-0.833). Diabetic patients are prone to develop mild to moderate hypoglycemia during colonoscopy preparation. This study proposes a predictive model that could provide a reference for identifying patients with a high risk of hypoglycemia during colonoscopy preparation.

Awareness Level of Hypoglycemia Among Diabetes Mellitus Type 2 Patients in Al Qassim Region.

Background Hypoglycemia has a major impact on patient health and glycemic management during insulin therapy for both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). It is the rate-limiting complication in diabetes management that prevents stringent glucose control. Objectives To assess the knowledge and awareness about hypoglycemia as a complication of T2D in adults in Al Qassim, Saudi Arabia. Methods This is a cross-sectional study done among type 2 diabetes patients in Al-Qassim, Kingdom of Saudi Arabia, from January to June 2022. A previously validated online questionnaire was disseminated through social media to gather information from respondents. Participants were chosen via a simple random sampling technique. Data analysis was completed using SPSS (version 23; IBM Corp., Armonk, NY). Results Overall, 213 respondents were included in our study. The majority of them were females (70.9%). The participants' average age was 35.9 + 13.0 years. Our results revealed that the average awareness score of the study population was found to be 3.6 ± 1.1 (by using the Clarke method) and 3.7 ± 2.1 (by using the Gold method). Moreover, we found that impaired awareness of hypoglycemia's prevalence by Clarke's questionnaire was 52.1% and 53.5%by using the Gold questionnaire. In addition, almost half of the respondents reported weakness as a symptom of hypoglycemia over the last six months and unconsciousness over the last 12 months. Hypertension was the most commonly reported chronic disease by our participants. Lastly, factors such as age, gender, educational level, geographic distribution, and history of chronic illness did not show any significant association with impaired awareness of the prevalence of hypoglycemia. Conclusion According to our research, we concluded that patients with type 2 diabetes mellitus in the region of Al-Qassim, Saudi Arabia, had insufficient knowledge about hypoglycemia as a complication of T2D. Moreover, the impaired awareness of hypoglycemia in diabetic patients was found to be high. Hence, there is a need for interventional programs to raise public awareness.

Clinical Evaluation of Predisposing Factors of Hypoglycaemia in Diabetic Patients

Background: Hypoglycemia is a common medical problem in diabetic patients, and the potential range of morbidity and mortality in diabetic patients exposed to hypoglycemia is significant. The study was conducted to evaluate the predisposing factors of hypoglycemia in diabetic populations.
 Methods: This is a descriptive cross-sectional study carried out in the indoor and outdoor patient department of BIRDEM hospital, Dhaka, Bangladesh, from July 2009 to December 2009 after ethical approval in conformity with the revised 1964 Helsinki declaration. Following informed written consent, a total of 50 diabetic patients having hypoglycemia were finally included. Data analysis was done using SPSS 17.
 Results: In the study population, significant members of hypoglycemic episodes were found in middle age (31-70) insulin-treated patients and poor diabetic education and in those who had other concomitant diseases. Poor dietary compliance (Reduced meal intake in 50% of cases and missed meal in 34% of cases) and lack of proper diabetic education about early recognition and treatment of hypoglycemia also appeared as important contributory factors. Noncompliance with regular exercise (40%) and unaccustomed exercise (4%) contribute to hypoglycemia. A significant number of hypoglycemic patients have chronic renal insufficiency (68%).
 Conclusion: Hypoglycemia is common in the diabetic population who have poor knowledge and practice about diet, drug exercise technique of, use of insulin devices, and have an underlying systemic illness. So more rational education system and appropriate management of systemic diseases regarding the prevention and treatment of hypoglycemia is demanded by our diabetic patients.
 TAJ 2022; 35: No-2: 143-149

Managing Severe Hypoglycaemia in Patients with Diabetes: Current Challenges and Emerging Therapies.

Hypoglycaemia is common in patients with diabetes mellitus and is a limiting factor for achieving adequate glycaemic control. In the vast majority of cases, hypoglycaemia develops due to the imbalance between food intake and insulin injections. As recurrent hypoglycaemia leads to significant morbidity and mortality, the recognition and immediate treatment of hypoglycaemia in diabetic patients is thus important. In the last 20 years, the introduction of improved insulin analogues, insulin pump therapy, continuous glucose monitoring (CGM), and sensor-augmented pump therapy have all made significant improvements in helping to reduce and prevent hypoglycaemia. In terms of treatment, the American Diabetes Association recommends oral glucose as the first-line treatment option for all conscious patients with hypoglycaemia. The second line of treatment (or first line in unconscious patients) is the use of glucagon. Novel formulations of glucagon include the nasal form, the Gvoke HypoPen which is a ready-to-deliver auto-injector packaged formulation and finally a glucagon analogue, Dasiglucagon. The Dasiglucagon formulation has recently been approved for the treatment of severe hypoglycaemia. It is a ready-to-use, similar to endogenous glucagon and its potency is also the same as native glucagon. It does not require reconstitution before injection and therefore ensures better compliance. Thus, significant improvements including development of newer insulin analogues, insulin pump therapy, continuous glucose monitoring (CGM), sensor-augmented pump therapy and novel formulations of glucagon have all contributed to reducing and preventing hypoglycaemia in diabetic individuals. However, considerable challenges remain as not all patients have access to diabetes technologies and to the newer glucagon formulations to help reduce and prevent hypoglycaemia.

Precipitating Factors of Hypoglycemia in Diabetic Patients Undergoing Treatment in Taksin Hospital

Background: Hypoglycemia is the most common complication and the most important obstacle to overcome to achieve good glycemic control in diabetic patients. It causes serious consequences, leading to increased morbidity and mortality. Objective: To identify the precipitating factors of hypoglycemia in diabetic patients undergoing treatment in Taksin hospital. Materials and Methods: A case-control study was conducted in 110 diabetic patients admitted due to hypoglycemia and 110 diabetic patients admitted for other reasons at Taksin Hospital, between October 2019 and September 2020. The sociodemographic information, clinical data, and precipitating causes of hypoglycemia were obtained from medical records. Logistic regression analysis was performed to identify the risk factor and reported as odds ratio (OR) with 95% confidence intervals (CI). Results: The multiple logistic regression analysis showed that the precipitating factors related to hypoglycemia among diabetic patients with a significant p-value (p<0.05) were poor self-care knowledge of hypoglycemia prevention (adjusted OR 14.37, 95% CI 5.75 to 35.89), insulin treatment in diabetic patients (adjusted OR 13.78, 95% CI 5.43 to 34.99), and intensive glycemic control HbA1c of less than 6% (adjusted OR 3.64, 95% CI 1.70 to 7.79). Furthermore, the result from the present study showed that individual factors were statistically significant and related to hypoglycemia. The factors included the age more than 60 years, low education level, functionally dependent patients, diabetes duration more than 10 years, hypertension, dyslipidemia, diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, and cognitive impairment. Conclusion: Poor self-care knowledge of hypoglycemia prevention, insulin treatment in diabetic patients, and intensive glycemic control were strong predictors of hypoglycemia in diabetic patients undergoing treatment in Taksin Hospital. Therefore, diabetes self-management education and tailoring diabetic therapy should be provided in diabetic patients to improve treatment and prevention of hospitalization due to hypoglycemia in diabetes. Keywords: Diabetes Mellitus; Hypoglycemia; Precipitating factor; Hospitalization

OR24-4 Targeting Hyperglucagonemia Reverses Glucagon Resistance

Abstract Elevation of glucagon levels and increase in alpha-cell mass are associated with states of hyperglycemia in diabetes. A better understanding of the molecular mechanisms governing glucagon secretion could have major implications in understanding abnormal responses to hypoglycemia in diabetic patients and provide novel avenues for diabetes management. Stimulation of glucagon secretion in hypoglycemia, or by amino acids, induces hepatic glucose production via cellular mechanisms including suppression of glycogenesis and glycolysis and stimulation of glycogenolysis and gluconeogenesis. The close link between amino acids and the alpha-cell is highlighted by the liver–alpha-cell axis. This axis was identified by the major increase in alpha-cell hyperplasia and hyperglucagonemia in models of reduced glucagon action in hepatocytes genetically or pharmacologically by treatment with glucagon receptor antagonists, which was subsequently attributed to the dramatic rise in amino acids. Induction of mTORC1 by constitutive genetic deletion of TSC2 in alpha-cells (aTSC2KO) recapitulated the effects of chronic hyperaminoacidemia with increases in alpha-cell mass and chronic hyperglucagonemia indicating that mTORC1 mediates amino acids signals in alpha-cells. However, the effects of acute versus chronic induction of alpha-cell mTORC1 signaling on these outcomes have not been explored. Using mice with doxycycline induction of Rheb (activator of mTORC1 signaling) (aRhebTg) and inducible Cre-mediated deletion of the mTORC1 inhibitor, TSC2, in alpha-cells (iaTSC2KO), we showed that induction of hyperglucagonemia is associated with two phases: Acute phase characterized by impaired glucose tolerance because of increased gluconeogenesis and glucose output by the liver. And a chronic phase, characterized by normalization of glucose tolerance due to downregulation of the hepatic glucagon receptor (Gcgr), Pepck, and some genes involved in amino acid metabolism and urea production. Importantly, the consequences of chronic hyperglucagonemia were reversible after normalization of glucagon levels by turning off alpha-cell Rheb expression. These studies uncovered the acute versus chronic effects of hyperglucagonemia on glucose homeostasis and further demonstrate that glucagon resistance is a reversible process. These observations provide insight into the impact of glucagon in the pathogenesis of hyperglycemia and the physiological effects of administration of dual GLP1/Glucagon receptor agonists. Presentation: Monday, June 13, 2022 11:45 a.m. - 12:00 p.m.

Classification and prediction of hypoglycemia in diabetic patients using machine learning techniques

Type 1 diabetics can lower their risk of microvascular and macrovascular problems by carefully regulating their blood glucose levels. The downside is that these measures are incredibly challenging because of the wide diversity across individuals, as well as other factors that affect glycemic management. Keeping glucose levels under control is difficult due to the possibility of severe hypoglycemia in patients receiving intensive insulin therapy. In people with diabetes, hypoglycemia is a common complication, which has a negative impact on overall health and well-being. Improving patient safety by anticipating unfavourable glycemic events has become a practical approach to enhanced patient safety using machine learning decision assistance. This paper suggests the use of three machine learning techniques to solve the problem of diabetic safety: (1) Random Forest for continuous glucose predictions, (2) support vector machines for postprandial period predictions, and (3)artificial neural networks for overnight hypoglycemic predictions. It has the two different categorization and prediction capabilities already established. A major system feature is the overall reduction in bouts of hypoglycemia, which results in an increase in patient safety and provides better confidence in treatment decisions.

IDF21-0623 Precipitating factors of hypoglycemia in diabetic patients undergoing treatment in Taksin hospital

Background: Hypoglycemia is the most common complication and also the most important obstacle to overcome in order to achieve good glycemic control in diabetic patients. It causes serious consequences, leading to increased morbidity and mortality.

POS0669 HYPOGLYCAEMIA FOLLOWING JAK INHIBITOR TREATMENT IN DIABETES MELLITUS PATIENTS WITH RHEUMATOID ARTHRITIS

Background:Janus kinase (JAK) inhibitors are effective small molecular drugs for rheumatoid arthritis (RA) and other immune mediated inflammatory diseases (IMIDs). JAK inhibitors exert their immunosuppressive effects by suppressing the action of JAK, an intracellular tyrosine. Although infections are the most reported side effects, potential glucose lowering effects in patients with diabetes mellitus (DM) have been described in literature and have also been reported as suspected adverse drug reactions (ADRs) to the National Pharmacovigilance Centre Lareb in the Netherlands (1).Objectives:To assess and describe suspected adverse effects of JAK inhibitors on glucose levels in diabetic patients with rheumatic diseases and other IMIDs, as reported in daily practice.Methods:We describe ADR reports of tofacitinib and baricitinib in the European pharmacovigilance Eudravigiliance (EV) database from initiation to 12 January 2021. All ADRs in EV are coded according to the Medical Dictionary for Regulatory Activities (MedDRA). We included all reports indicating hypoglycaemia in patients with reported DM type 1 and 2 or with antidiabetic drugs as concomitant medication. This could include oral antidiabetics as well as insulins.Results:On 12 January 2021 the EV database included 32 ADR reports, concerning 32 diabetic patients, indicating hypoglycaemia associated with the use of JAK inhibitors (15 tofacitinib, 17 baricitinib), out of 32,484 ADR reports in total concerning tofacitinib or baricitinb (Table 1). Most patients (25 patients, 78%) used the JAK inhibitor for rheumatoid arthritis. The suspected ADR with MedDRA Preferred Term ‘Hypoglycaemia’ was reported for 16 patients and MedDRA Preferred Term ‘Decreased blood glucose’ was reported for 15 patients. In one case, increased insulin sensitivity was described as suspected ADR of baricitinib. In this case, the insulin dose had to be reduced to prevent hypoglycaemia. Of note, the insulin dose had to be increased after temporary discontinuation of baricitinib and was reduced again after baricitinib was restarted. Additionally, in six cases improvements of glycaemic control were described after discontinuation or dose reduction of the JAK inhibitor or antidiabetic drug. Improvements were also described after unknown action or unchanged treatment with JAK inhibitor in eight cases.Conclusion:JAK inhibitors may induce hypoglycaemia by increasing insulin sensitivity, and consequently may reduce the need for antidiabetic medication (2-3). Healthcare professionals should be alert for these potential ADRs when starting a JAK inhibitor in patients with DM as comorbidity. More research is needed to support our findings and elucidate the underlying pharmacological mechanisms of this potentially beneficial effect of JAK inhibitors.Table 1.Suspected adverse drug reaction reports indicating hypoglycaemia in diabetic patients using tofacitinib or baricitinib in the Eudravigilance databaseTofacitinib N (%)Baricitinib N (%)No. of reports15 (100)17 (100)Mean age years (range)65 (56 - 78)62.2 (48 - 78)Female gender13 (87)13 (76)Indication for JAK inhibitor Rheumatoid arthritis11 (73)14 (82) Unknown3 (20)3 (18) Arthritis1 (7)Reported adverse drug reaction Hypoglycaemia6 (40)11 (65)a Decreased blood glucose9 (60)6 (35) aTime to onset after start JAK inhibitorb Within 1 month6 (40)3 (18) 2-6months2 (13)2 (12) More than 6 months1 (7)Improvement after action: Drug withdrawal3 (20)c1 (6)d Dose adjustments1 (6)e Other1 (7)fa.In one case of baricitinib hypoglycaemia as well as decreased blood glucose were reported as adverse drug reactions.b.Time to onset was unknown in 6 reports of tofacitinib and 12 reports of baricitinibc.Tofacitinib withdrawal: 1, sitagliptin withdrawal: 1, tofacitinib and insulin withdrawal: 1d.Baricitinib withdrawal: 1e.Baricitinib: after insulin dose adjustments: 1f.After tofacitinib withdrawal and insulin dose adjustments

Preparation of double-layer nanoemulsions with controlled release of glucose as prevention of hypoglycemia in diabetic patients

Encapsulation systems promote targeted delivery to the gastrointestinal tract. An oil-in-water (O/W) nanoemulsion was covered using new delivery system composition based on zein and sodium alginate. The impact of aqueous phase (distilled water and cooked pumpkin puree), pH (2–4), and zein-alginate concentration solution (0.05–0.20% w/v) was investigated on particle size, zeta potential, incorporation efficiency (IE), stability, viscosity, and glucose release from single-layer (SLN) and double-layer nanoemulsion (DLN). DLNs showed a larger droplet size and zeta potential. The slow gradual release of glucose proved effective application of zein/alginate as delivery system for nanoemulsion. Moreover, cooked pumpkin and 0.12% of zein exhibited more delayed release of glucose than distilled water as an aqueous phase of DLN and as a delivery system respectively. Up-to-49% IE, up-to-50% stability in a period of 7-day storage, and controlled-release glucose for 240 min under in vitro gastrointestinal conditions were obtained in DLN. The results of the current study revealed that SLN covered by zein at 0.12% of concentration can be an ideal delivery system composition for patients with hypoglycemia and clinical problems.

Sniffer dogs as a screening/diagnostic tool for COVID-19: a proof of concept study

BackgroundSniffer dogs are able to detect certain chemical particles and are suggest to be capable of helping diagnose some medical conditions and complications, such as colorectal cancer, melanoma, bladder cancer, and even critical states such as hypoglycemia in diabetic patients. With the global spread of COVID-19 throughout the world and the need to have a real-time screening of the population, especially in crowded places, this study aimed to investigate the applicability of sniffer dogs to carry out such a task.MethodsFirstly, three male and female dogs from German shepherd (Saray), German black (Kuzhi) and Labrador (Marco) breeds had been intensively trained throughout the classical conditioning method for 7 weeks. They were introduced to human specimens obtained from the throat and pharyngeal secretions of participants who were already reported positive or negative for SARS-COV-2 infection be RT-PCR. Each dog underwent the conditioning process for almost 1000 times. In the meantime another similar condition process was conducted on clothes and masks of COVID-19 patient using another three male and female dogs from Labrador (Lexi), Border gypsy (Sami), and Golden retriever (Zhico) breeds. In verification test for the first three dogs, 80 pharyngeal secretion samples consisting of 26 positive and 54 negative samples from different medical centers who underwent RT-PCR test were in a single-blind method. In the second verification test for the other three dogs, masks and clothes of 50 RT-PCR positive and 70 RT-PCR negative cases from different medical center were used.ResultsIn verification test using pharyngeal secretion, the sniffer dogs’ detection capability was associated with a 65% of sensitivity and 89% of specificity and they amanged to identify 17 out of the 26 positive and 48 out of the 54 true negative samples. In the next verification test using patients’ face masks and clothes, 43 out of the 50 positive samples were correctly identified by the dogs. Moreover, out of the 70 negative samples, 65 samples were correctly found to be negative. The sensitivity of this test was as high as 86% and its specificity was 92.9%. In addition, the positive and negative predictive values were 89.6 and 90.3%, respectively.ConclusionDogs are capable of being trained to identify COVID-19 cases by sniffing their odour, so they can be used as a reliable tool in limited screening.

The Effect of Peers Support on Fear of Hypoglycemia in Iranian Patients with Type 1 Diabetes: A Clinical Trial Study.

Background:Fear of hypoglycemia is a medical emergency which leads to disrupt individuals' normal lives. Peers support is a hopeful approach to improve diabetes self-care behaviors. This study was conducted to assess the effect of peers support on the fear of hypoglycemia in patients with type 1 diabetes.Materials and Methods:This randomized clinical trial study was performed among 60 patients with type 1 diabetes in Qazvin city from September 2019 to October 2020. Patients were assigned to control and intervention groups using a random method. The data collection tools included demographic characteristics and a standard questionnaire for Hypoglycemia Fear Survey (HFS). Patients in the intervention group were trained by skilled peers for 2 months, but those of the control group only received routine hospital training. The data were analyzed by SPSS version 16 and paired and independent t-test.Results:The scores of the fear of hypoglycemia in diabetic patients in the two groups had no significant statistical difference before intervention (t53 = 0.93, p = 0.94). But after the intervention, the independent t-test showed that there was a significant difference between the scores of the fear of hypoglycemia in both groups (t53 = -2.13, p = 0.03).Conclusions:Considering the results of the current study, peer support for diabetic patients is an effective way to reduce the fear of hypoglycemia. Therefore, it is recommended using this training method to train diabetic patients.

Hospital admissions trends for severe hypoglycemia in diabetes patients in Spain, 2005 to 2015

AimsTo analyze hospital admissions trends, inpatient mortality, and mean length of hospital stay due to hypoglycemia in patients with diabetes in Spain from 2005 to 2015. MethodsNational Institute of Statistics provided information on hospital discharge and mortality. Hospital admissions due to severe hypoglycemia were identified using ICD-9 codes. Age-adjusted admission and mortality rates were stratified by sex and year. Joinpoint regression models were used to estimate trends. ResultsAdmissions rates per 100,000 population were higher for men than women in 2005 (30.2, 95%CI:29.3, 31.0 versus 21.5, 95%CI:20.9, 22.1) and 2015 (23.7, 95%CI:23.0, 24.4 versus 13.2, 95%CI:12.7, 13.6). Mortality per 100,000 population was also higher for men in both years (2005: 9.4, 95%CI:7.8, 11.0 versus 8.6, 95%CI:7.4, 9.8; 2015: 6.4, 95%CI:5.3, 7.6 versus 4.1, 95%CI:3.3, 4.8). Mortality dropped 5.2 percentage points annually (95%CI:−8.4, −1.9) in men and 7.0 percentage points annually (95%CI:−8.7, −5.2) in women from 2005 to 2015. Mean length of hospital stay changed only for women: 7.8 days (95%CI:7.5, 8.0) to 6.7 days (95%CI:6.4, 6.9). ConclusionsHospital admissions and inpatient mortality due to hypoglycemia in diabetes patients decreased from 2005 to 2015. This trend was more pronounced in women. Mean length of hospital stay decreased in women.

Fasting-Evoked En Route Hypoglycemia in Diabetes (FEEHD): From Guidelines to Clinical Practice.

Lipid profiles have been used for the purposes of health screening and monitoring of the effects of lipid-lowering medications, especially in patients with diabetes who are prone to hyperlipidemia. Fasting for lipid profiles has been the norm for the past decades. This long-lasting tradition poses a risk of hypoglycemia, especially in patients with diabetes. Our aim is to review the overlooked occurrence of hypoglycemia in patients who fast for laboratory tests, especially lipid profile tests, and commute to the laboratory facility while fasting; a condition we titled "Fasting-Evoked En route Hypoglycemia in Diabetes patients" or "FEEHD". We also review its prevalence and clinical impact on patients with diabetes. We undertook an extensive literature search using search engines such as PubMed and Google Scholar. We used the following keywords for the search: Fasting, Non-fasting; Hypoglycemia; Hypoglycemic Agents; Laboratory Tests; Glucose, Hypoglycemia, Lipid Profiles, FEEHD. Our literature review has shown that the prevalence of FEEHD is alarmingly high (17-21% of patients at risk). This form of hypoglycemia is under recognized in the clinical practice despite its frequent occurrence. Recent changes in various international guidelines have uniformly endorsed the utilization of non-fasting lipid profiles as the new standard for obtaining lipid profiles with the exception of certain conditions. Multiple studies showed the efficacy of non-fasting lipid tests in comparison to fasting lipid tests, in routine clinical practice. We hope to increase awareness among clinicians about this overlooked and potentially harmful form of hypoglycemia in patients with diabetes, which can be easily avoided. We also hope to call upon clinicians to consider changing the habit of ordering lipid profiles in the fasting state, which has been recently shown to be largely unnecessary in routine clinical settings, with few exceptions in selected cases.