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Potential role of Drug Repositioning Strategy (DRS) for management of tauopathy.
Zaki, MO, Elsherbiny, DA, Salama, M, Azab, SS
Life sciences. 2022;:120267
Abstract
Tauopathy is a term that has been used to represent a pathological condition in which hyperphosphorylated tau protein aggregates in neurons and glia which results in neurodegeneration, synapse loss and dysfunction and cognitive impairments. Recently, drug repositioning strategy (DRS) becomes a promising field and an alternative approach to advancing new treatments from actually developed and FDA approved drugs for an indication other than the indication it was originally intended for. This paradigm provides an advantage because the safety of the candidate compound has already been established, which abolishes the need for further preclinical safety testing and thus substantially reduces the time and cost involved in progressing of clinical trials. In the present review, we focused on correlation between tauopathy and common diseases as type 2 diabetes mellitus and the global virus COVID-19 and how tau pathology can aggravate development of these diseases in addition to how these diseases can be a risk factor for development of tauopathy. Moreover, correlation between COVID-19 and type 2 diabetes mellitus was also discussed. Therefore, repositioning of a drug in the daily clinical practice of patients to manage or prevent two or more diseases at the same time with lower side effects and drug-drug interactions is a promising idea. This review concluded the results of pre-clinical and clinical studies applied on antidiabetics, COVID-19 medications, antihypertensives, antidepressants and cholesterol lowering drugs for possible drug repositioning for management of tauopathy.
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Diabetes Mellitus and COVID-19: Review Article.
Nassar, M, Daoud, A, Nso, N, Medina, L, Ghernautan, V, Bhangoo, H, Nyein, A, Mohamed, M, Alqassieh, A, Soliman, K, et al
Diabetes & metabolic syndrome. 2021;(6):102268
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BACKGROUND AND AIMS We aim to cover most of the current evidence on the mutual effect of diabetes & COVID-19 infection on each other and the management of the COVID-19 patients with diabetes. METHODS We utilized databases to review the current evidence related to diabetes mellitus and COVID-19. RESULTS We discussed the most recent evidence of diabetes milieus and COVID-19 regarding risk factors, management, complications, and telemedicine. CONCLUSION Diabetes mellitus is associated with a significant risk of complications, extended hospital stays, and mortality in COVID-19 infected patients.
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Pharmacotherapeutic considerations for the management of diabetes mellitus among hospitalized COVID-19 patients.
Hasan, SS, Kow, CS, Bain, A, Kavanagh, S, Merchant, HA, Hadi, MA
Expert opinion on pharmacotherapy. 2021;(2):229-240
Abstract
INTRODUCTION Diabetes mellitus is one of the most prevalent comorbidities identified in patients with coronavirus disease 2019 (COVID-19). This article aims to discuss the pharmacotherapeutic considerations for the management of diabetes in hospitalized patients with COVID-19. AREAS COVERED We discussed various aspects of pharmacotherapeutic management in hospitalized patients with COVID-19: (i) susceptibility and severity of COVID-19 among individuals with diabetes, (ii) glycemic goals for hospitalized patients with COVID-19 and concurrent diabetes, (iii) pharmacological treatment considerations for hospitalized patients with COVID-19 and concurrent diabetes. EXPERT OPINION The glycemic goals in patients with COVID-19 and concurrent type 1 (T1DM) or type 2 diabetes (T2DM) are to avoid disruption of stable metabolic state, maintain optimal glycemic control, and prevent adverse glycemic events. Patients with T1DM require insulin therapy at all times to prevent ketosis. The management strategies for patients with T2DM include temporary discontinuation of certain oral antidiabetic agents and consideration for insulin therapy. Patients with T2DM who are relatively stable and able to eat regularly may continue with oral antidiabetic agents if glycemic control is satisfactory. Hyperglycemia may develop in patients with systemic corticosteroid treatment and should be managed upon accordingly.
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Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19.
Lalau, JD, Al-Salameh, A, Hadjadj, S, Goronflot, T, Wiernsperger, N, Pichelin, M, Allix, I, Amadou, C, Bourron, O, Duriez, T, et al
Diabetes & metabolism. 2021;(5):101216
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AIMS: Metformin exerts anti-inflammatory and immunosuppressive effects. We addressed the impact of prior metformin use on prognosis in patients with type 2 diabetes hospitalised for COVID-19. METHODS CORONADO is a nationwide observational study that included patients with diabetes hospitalised for COVID-19 between March 10 and April 10, 2020 in 68 French centres. The primary outcome combined tracheal intubation and/or death within 7 days of admission. A Kaplan-Meier survival curve was reported for death up to day 28. The association between metformin use and outcomes was then estimated in a logistic regression analysis after applying a propensity score inverse probability of treatment weighting approach. RESULTS Among the 2449 patients included, 1496 were metformin users and 953 were not. Compared with non-users, metformin users were younger with a lower prevalence of diabetic complications, but had more severe features of COVID-19 on admission. The primary endpoint occurred in 28.0% of metformin users (vs 29.0% in non-users, P = 0.6134) on day 7 and in 32.6% (vs 38.7%, P = 0.0023) on day 28. The mortality rate was lower in metformin users on day 7 (8.2 vs 16.1%, P < 0.0001) and on day 28 (16.0 vs 28.6%, P < 0.0001). After propensity score weighting was applied, the odds ratios for primary outcome and death (OR [95%CI], metformin users vs non-users) were 0.838 [0.649-1.082] and 0.688 [0.470-1.007] on day 7, then 0.783 [0.615-0.996] and 0.710 [0.537-0.938] on day 28, respectively. CONCLUSION Metformin use appeared to be associated with a lower risk of death in patients with diabetes hospitalised for COVID-19.
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[The Management of Blood Glucose Should be Emphasized in the Treatment of COVID-19].
Ma, WX, Ran, XW
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition. 2020;(2):146-150
Abstract
Based on the higher mortality and the higher proportion of critically ill adults in coronavirus disease 2019 (COVID-19) patients with diabetes, good inpatient glycemic control is particularly important in the comprehensive treatment of COVID-19. Individualized blood glucose target goals and treatment strategies should be made according to specific circumstances of COVID-19 inpatients with diabetes. For mild patients, a strict glycemic control target (fasting plasma glucose (FPG) 4.4-6.1 mmol/L, 2-hour postprandial plasma glucose (2 h PG) 6.1-7.8 mmol/L) are recommended; a target for the glycemic control of common type patients (FPG 6.1-7.8 mmol/L, 2 h PG 7.8-10.0 mmol/L) and subcutaneous insulin deliver therapy are recommended; a target nonfasting blood glucose range of 10.0 mmol or less per liter for severe-type COVID-19 patients, a relatively Less stringent blood glucose control target (FPG 7.8-10.0 mmol/L, 2 h PG 7.8-13.9 mmol/L) for critically ill patients and intravenous insulin infusion therapy are recommended. Due to the rapid changes in the condition of some patients, the risk of diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar status (HHS) maybe occur during the treatment. Blood glucose monitoring, dynamic evaluation and timely adjustment of strategies should be strengthened to ensure patient safety and promote early recovery of patients.
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Metformin and COVID-19: From cellular mechanisms to reduced mortality.
Scheen, AJ
Diabetes & metabolism. 2020;(6):423-426
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Type 2 diabetes mellitus (T2DM) is associated with both poorer clinical outcomes during the COVID-19 pandemic and an increased risk of death in such hospitalized patients. While the role of glucose control has been emphasized to improve the prognosis, the impact of different glucose-lowering agents remains largely unknown. Metformin remains the first-line pharmacological choice for the management of hyperglycaemia in T2DM. Because metformin exerts various effects beyond its glucose-lowering action, among which are anti-inflammatory effects, it may be speculated that this biguanide might positively influence the prognosis of patients with T2DM hospitalized for COVID-19. The present concise review summarizes the available data from observational retrospective studies that have shown a reduction in mortality in metformin users compared with non-users, and briefly discusses the potential underlying mechanisms that might perhaps explain this favourable impact. However, given the potential confounders inherently found in observational studies, caution is required before drawing any firm conclusions in the absence of randomized controlled trials.
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Clinical considerations in patients with diabetes during times of COVID19: An update on lifestyle factors and antihyperglycemic drugs with focus on India.
Gupta, R, Misra, A
Diabetes & metabolic syndrome. 2020;(6):1777-1781
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BACKGROUND Diabetes is recognized as an important comorbidity in patients with COVID-19 and a large amount of literature has become available regarding this. The aim of this article is to review the literature regarding various aspects of association between diabetes and COVID-19 and to highlight clinically relevant points with focus on India. METHODS We searched Pubmed and Google Scholar databases for articles regarding diabetes and COVID-19 published between March 19, 2020 and August 30, 2020. RESULTS Diabetes and poor glycemic control are associated with increased severity and mortality in patients with COVID-19. Several clinical scenarios about hyperglycemia and COVID-19 are identified and each of these needs specific management strategies. CONCLUSION It is prudent to maintain good glycemic control in patients with diabetes in order to minimize the complications of COVID-19. There is a need for well conducted studies to asses the role of individual antihyperglycemic therapies in COVID-19 and also the behavior of new onset diabetes diagnosed either after COVID-19 infection or during this time.
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Anti-inflammatory properties of antidiabetic drugs: A "promised land" in the COVID-19 era?
Katsiki, N, Ferrannini, E
Journal of diabetes and its complications. 2020;(12):107723
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Inflammation is implicated in the development and severity of the coronavirus disease 2019 (COVID-19), as well as in the pathophysiology of diabetes. Diabetes, especially when uncontrolled, is also recognized as an important risk factor for COVID-19 morbidity and mortality. Furthermore, certain inflammatory markers [i.e. C-reactive protein (CRP), interleukin-6 (IL-6) and ferritin] were reported as strong predictors of worse outcomes in COVID-19 positive patients. The same biomarkers have been associated with poor glycemic control. Therefore, achieving euglycemia in patients with diabetes is even more important in the era of the COVID-19 pandemic. Based on the above, it is clinically interesting to elucidate whether antidiabetic drugs may reduce inflammation, thus possibly minimizing the risk for COVID-19 development and severity. The present narrative review discusses the potential anti-inflammatory properties of certain antidiabetic drugs (i.e. metformin, pioglitazone, sitagliptin, linagliptin, vildagliptin, alogliptin, saxagliptin, liraglutide, dulaglutide, exenatide, lixisenatide, semaglutide, empagliflozin, dapagliflozin, canagliflozin), with a focus on CRP, IL-6 and ferritin.
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Glycemic Control Improvement in Italian Children and Adolescents With Type 1 Diabetes Followed Through Telemedicine During Lockdown Due to the COVID-19 Pandemic.
Predieri, B, Leo, F, Candia, F, Lucaccioni, L, Madeo, SF, Pugliese, M, Vivaccia, V, Bruzzi, P, Iughetti, L
Frontiers in endocrinology. 2020;:595735
Abstract
BACKGROUND/OBJECTIVE To minimize the wide spread of coronavirus disease (COVID-19) pandemic, Italy was placed in an almost complete lockdown state that forced people to "stay at home". Aim of this study was to evaluate the effects of lockdown on glycemic control in children and adolescents with type 1 diabetes (T1D) followed through telemedicine. SUBJECTS/METHODS This observational study involved patients with T1D using the real-time continuous glucose monitoring (CGM) Dexcom G6®. Ambulatory glucose profile data from the 3-months before schools closure (November 26, 2019-February 23, 2020; T0) and from the 3-months of consecutive lockdown (February 24-May 18, 2020; T1) were compared. RESULTS Sixty-two children and adolescents (11.1 ± 4.37 years, 50% males) with T1D (median time disease 3.67 years) were enrolled in the study. Insulin total daily dose was unchanged, while time spent on physical activities was decreased (p<0.0001). Despite the lack of statistical significance, median value of the glucose management indicator decreased from 7.4% to 7.25%. Glucose standard deviation (p<0.0001) and coefficient of variation (p=0.001) improved across the study. Median time in range increased from 60.5% to 63.5% (p=0.008), time above range decreased from 37.3% to 34.1% (p=0.048), and time below range decreased from 1.85% to 1.45% (p=0.001). CONCLUSIONS Overall, in our children and adolescents with T1D glycemic control improved during lockdown. Despite patients were confined to their homes and limited to exercise, our data suggest that the use of real-time CGM, the continuous parental management, and the telemedicine can display beneficial effects on T1D care.
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The impact of strict COVID-19 lockdown in Spain on glycemic profiles in patients with type 1 Diabetes prone to hypoglycemia using standalone continuous glucose monitoring.
Mesa, A, Viñals, C, Pueyo, I, Roca, D, Vidal, M, Giménez, M, Conget, I
Diabetes research and clinical practice. 2020;:108354
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AIMS: Spain has been one of the worst affected countries by the COVID-19 pandemic. A very strict lockdown at home was imposed with a tough restriction of mobility. We aimed to evaluate the impact of this exceptional scenario on glucose profile of patients with T1D prone to hypoglycemia using standalone continuous glucose monitoring. METHODS Patients with T1D prone to hypoglycemia using multiple daily injections and either a Dexcom G5® or a Free Style Libre® CGM systems for at least 6 months under the funding of National Health Service were included in an observational, retrospective study. Data were collected in two periods: pre-lockdown (PL), February 23rd-March 7th and within lockdown (WL), April 1st-14th 2020. The primary outcome was the difference in the proportion of time in target glucose range of 70-180 mg/dL (TIR). Additional glucometric data were also analysed. RESULTS 92 patients were included: 40 women, age 42.8 ± 3.9 years, disease duration of 23.1 ± 12.6 years. Seventeen patients used Dexcom G5® and 75 Free Style Libre®. TIR 70-180 mg/dL (59.3 ± 16.2 vs 62.6 ± 15.2%), time > 180 (34.4 ± 18.0 vs 30.7 ± 16.9%), >250 (11.1 ± 10.6 vs 9.2 ± 9.7%) and Glucose Management Indicator (7.2 ± 0.8 vs 7.0 ± 0.8%) significantly improved (PL vs WL, respectively, p < 0.05). Time in hypoglycemia remained unchanged. CONCLUSIONS Lockdown conditions imposed by the COVID-19 pandemic may be managed successfully in terms of glycemic control by population with T1D prone to hypoglycemia using CGM. The strict daily routine at home could probably explain the improvement in the time in glycemic target without increasing the time in hypoglycemia.
