New-Onset Diabetes Mellitus in COVID-19: A Scoping Review.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic became superimposed on the pre-existing obesity and diabetes mellitus (DM) pandemics. Since COVID-19 infection alters the metabolic equilibrium, it may induce pathophysiologic mechanisms that potentiate new-onset DM, and we evaluated this issue. METHOD: A systematic review of the literature published from the 1 January 2020 until the 20 July 2023 was performed (PROSPERO registration number CRD42022341638). We included only full-text articles of both human clinical and randomized controlled trials published in English and enrolling adults (age > 18 years old) with ongoing or preceding COVID-19 in whom hyperglycemia was detected. The search was based on the following criteria: "(new-onset diabetes mellitus OR new-onset DM) AND (COVID-19) AND adults". RESULTS: Articles on MEDLINE (n = 70) and the Web of Science database (n = 16) were included and analyzed by two researchers who selected 20 relevant articles. We found evidence of a bidirectional relationship between COVID-19 and DM. CONCLUSIONS: This link operates as a pathophysiological mechanism supported by epidemiological data and also by the clinical and biological findings obtained from the affected individuals. The COVID-19 pandemic raised the incidence of DM through different pathophysiological and psychosocial factors.

Telemedicine for diabetes management during COVID-19: what we have learnt, what and how to implement.

The past two decades have witnessed telemedicine becoming a crucial part of health care as a method to facilitate doctor-patient interaction. Due to technological developments and the incremental acquisition of experience in its use, telemedicine's advantages and cost-effectiveness has led to it being recognised as specifically relevant to diabetology. However, the pandemic created new challenges for healthcare systems and the rate of development of digital services started to grow exponentially. It was soon discovered that COVID-19-infected patients with diabetes had an increased risk of both mortality and debilitating sequelae. In addition, it was observed that this higher risk could be attenuated primarily by maintaining optimal control of the patient's glucose metabolism. As opportunities for actual physical doctor-patient visits became restricted, telemedicine provided the most convenient opportunity to communicate with patients and maintain delivery of care. The wide range of experiences of health care provision during the pandemic has led to the development of several excellent strategies regarding the applicability of telemedicine across the whole spectrum of diabetes care. The continuation of these strategies is likely to benefit clinical practice even after the pandemic crisis is over.

Glucometabolic Perturbations in Type 2 Diabetes Mellitus and Coronavirus Disease 2019: Causes, Consequences, and How to Counter Them Using Novel Antidiabetic Drugs - The CAPISCO International Expert Panel.

The growing amount of evidence suggests the existence of a bidirectional relation between coronavirus disease 2019 (COVID-19) and type 2 diabetes mellitus (T2DM), as these two conditions exacerbate each other, causing a significant healthcare and socioeconomic burden. The alterations in innate and adaptive cellular immunity, adipose tissue, alveolar and endothelial dysfunction, hypercoagulation, the propensity to an increased viral load, and chronic diabetic complications are all associated with glucometabolic perturbations of T2DM patients that predispose them to severe forms of COVID-19 and mortality. Severe acute respiratory syndrome coronavirus 2 infection negatively impacts glucose homeostasis due to its effects on insulin sensitivity and ß-cell function, further aggravating the preexisting glucometabolic perturbations in individuals with T2DM. Thus, the most effective ways are urgently needed for countering these glucometabolic disturbances occurring during acute COVID-19 illness in T2DM patients. The novel classes of antidiabetic medications (dipeptidyl peptidase 4 inhibitors (DPP-4is), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are considered candidate drugs for this purpose. This review article summarizes current knowledge regarding glucometabolic disturbances during acute COVID-19 illness in T2DM patients and the potential ways to tackle them using novel antidiabetic medications. Recent observational data suggest that preadmission use of GLP-1 RAs and SGLT-2is are associated with decreased patient mortality, while DPP-4is is associated with increased in-hospital mortality of T2DM patients with COVID-19. Although these results provide further evidence for the widespread use of these two classes of medications in this COVID-19 era, dedicated randomized controlled trials analyzing the effects of in-hospital use of novel antidiabetic agents in T2DM patients with COVID-19 are needed.

Post-COVID syndrome, inflammation, and diabetes.

The raging COVID-19 pandemic is in its third year of global impact. The SARS CoV 2 virus has a high rate of spread, protean manifestations, and a high morbidity and mortality in individuals with predisposing risk factors. The pathophysiologic mechanisms involve a heightened systemic inflammatory state, cardiometabolic derangements, and varying degrees of glucose intolerance. The latter can be evident as significant hyperglycemia leading to new-onset diabetes or worsening of preexisting disease. Unfortunately, the clinical course beyond the acute phase of the illness may persist in the form of a variety of symptoms that together form the so-called "Long COVID" or "Post-COVID Syndrome". It is thought that a chronic, low-grade inflammatory and immunologic state persists during this phase, which may last for weeks or months. Although numerous insights have been gained into COVID-related hyperglycemia and diabetes, its prediction, course, and management remain to be fully elucidated.

Molecular and pro-inflammatory aspects of COVID-19: The impact on cardiometabolic health.

Obesity, type 2 diabetes (T2DM), hypertension (HTN), and Cardiovascular Disease (CVD) often cluster together as "Cardiometabolic Disease" (CMD). Just under 50% of patients with CMD increased the risk of morbidity and mortality right from the beginning of the COVID-19 pandemic as it has been reported in most countries affected by the SARS-CoV2 virus. One of the pathophysiological hallmarks of COVID-19 is the overactivation of the immune system with a prominent IL-6 response, resulting in severe and systemic damage involving also cytokines such as IL2, IL4, IL8, IL10, and interferon-gamma were considered strong predictors of COVID-19 severity. Thus, in this mini-review, we try to describe the inflammatory state, the alteration of the adipokine profile, and cytokine production in the obese state of infected and not infected patients by SARS-CoV2 with the final aim to find possible influences of COVID-19 on CMD and CVD. The immunological-based discussion of the molecular processes could inspire the study of promising targets for managing CMD patients and its complications during COVID-19.

The Dual Pandemics of COVID-19 and Obesity: Bidirectional Impact.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, has been shown to disrupt many organ systems in the human body. Though several medical disorders have been affected by this infection, a few illnesses in addition may also play a role in determining the outcome of COVID-19. Obesity is one such disease which is not only affected by the occurrence of COVID-19 but can also result in a worse clinical outcome of COVID-19 infection. This manuscript summarizes the most recent evidence supporting the bidirectional impact of COVID-19 and obesity. It highlights how the presence of obesity can be detrimental to the outcome of COVID-19 in a given patient because of the mechanical limitations in lung compliance and also by the activation of several thrombo-inflammatory pathways. The sociodemographic changes brought about by the pandemic in turn have facilitated the already increasing prevalence of obesity. This manuscript highlights the importance of recognizing these pathways which may further help in policy changes that facilitate appropriate measures to prevent the further worsening of these two pandemics.

Current and emerging drugs for the treatment of atherosclerosis: the evidence to date.

INTRODUCTION: Atherosclerosis can be considered a chronic inflammatory process that stands out as a dominant cause of cardiovascular disease (CVD). Since blood lipids are the leading risk factor for atherosclerosis development, lowering low-density lipoprotein cholesterol (LDL-C) and other apolipoprotein B-containing lipoproteins reduces the risk of future cardiovascular events. However, there has been significant progress in developing lipid-lowering drugs for aggressive management of dyslipidemia, the rates of CVD events remain unacceptably high, so there is great need to identify novel therapeutic pathways targeting the atherosclerosis process. AREAS COVERED: We discussed the current guidelines on CVD prevention, the role of novel lipid-lowering drugs, as well as emerging drugs for atherosclerosis, emphasizing the current data on compounds targeting inflammatory and oxidant pathways. EXPERT OPINION: Although novel lipid-lowering drugs all showed their therapeutic efficacy in LDL-C lowering, data regarding their impact on cardiovascular outcomes is still inconclusive. On the other hand, some of the agents targeting inflammatory pathways, especially colchicine, showed promising results in terms of reducing CVD events. In contrast, those pointed at oxidant pathways failed to do so. Finally, exploring ways of targeting new therapeutic venues, such as adaptive immunity and clonal hematopoiesis, is a goal in the future.

The Relationship between COVID-19 and Hypothalamic-Pituitary-Adrenal Axis: A Large Spectrum from Glucocorticoid Insufficiency to Excess-The CAPISCO International Expert Panel.

Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding severity, vulnerability to infection due to comorbidities, and treatment approaches. The hypothalamic-pituitary-adrenal (HPA) axis has been identified as one of the most critical endocrine targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that might significantly impact outcomes after infection. Herein we review the rationale for glucocorticoid use in the setting of COVID-19 and emphasize the need to have a low index of suspicion for glucocorticoid-induced adrenal insufficiency, adjusting for the glucocorticoid formulation used, dose, treatment duration, and underlying health problems. We also address several additional mechanisms that may cause HPA axis dysfunction, including critical illness-related corticosteroid insufficiency, the direct cytopathic impacts of SARS-CoV-2 infection on the adrenals, pituitary, and hypothalamus, immune-mediated inflammations, small vessel vasculitis, microthrombotic events, the resistance of cortisol receptors, and impaired post-receptor signaling, as well as the dissociation of ACTH and cortisol regulation. We also discuss the increased risk of infection and more severe illness in COVID-19 patients with pre-existing disorders of the HPA axis, from insufficiency to excess. These insights into the complex regulation of the HPA axis reveal how well the body performs in its adaptive survival mechanism during a severe infection, such as SARS-CoV-2, and how many parameters might disbalance the outcomes of this adaptation.

Safety and Outcomes of Intravitreal Aflibercept in Diabetic Macular Edema - A Systematic Review.

BACKGROUND: Recent evidence on the role of vascular endothelial growth factor (VEGF) in the pathogenesis of ischemia and microvascular hyperpermeability leading to macular edema has brought anti-VEGF intravitreal therapy into the limelight. OBJECTIVE: We performed a systematic literature review focusing on the outcomes and safety of the intravitreal use of aflibercept in diabetic macular edema. METHODS: The studies documented cases with at least three consecutive intravitreal injections of aflibercept (IVA) repeated monthly with a follow-up period of at least one year. The outcomes were evaluated in terms of reported functional and anatomical improvement of the macula, as reflected by changes in visual acuity and macular thickness measured by Optical Coherence Tomography (OCT). In addition, for safety assessment, all reported local and general adverse effects were analyzed. RESULTS: All studies showed an overall significant anatomical and functional improvement. In patients with the 5 IVA monthly at the beginning of the therapy, the visual gain at 52 weeks varied widely between 5 and 18.9 EDRS letters, with a mean value of 9.48 letters. The higher gain was obtained in treatment naïve patients, with worse VA and increased CST at baseline. The lower gain was obtained in patients previously treated with anti- VEGF. Anti-Platelet Trialists' Collaboration-defined arterial thromboembolic events were not statistically different between the aflibercept group and the laser group. CONCLUSION: Intravitreal aflibercept therapy provides significant improvement in visual acuity and a good safety profile. Randomized studies are needed to document the optimal frequency of intravitreal injections for optimal treatment.

The Emerging Role of Dual GLP-1 and GIP Receptor Agonists in Glycemic Management and Cardiovascular Risk Reduction.

The incretin pathway is a self-regulating feedback system connecting the gut with the brain, pancreas, and liver. Its predominant action is on the postprandial glucose levels, with extraglycemic effects on fat metabolism and endovascular function. Of the two main incretin hormones released with food ingestion, the actions of glucagon-like peptide-1 (GLP-1) have been exploited for therapeutic benefit. However, little attention has been paid to glucose-dependent insulinotropic polypeptide (GIP) until the recent experimental introduction of dual agonists, or "twincretins". Interestingly, simultaneous activation of both receptors is not only replicative of normal physiology, it seems to be an innovative way to enhance their mutual salubrious actions. In patients with type 2 diabetes, dual agonists can have powerful benefits for glucose control and weight reduction. Additionally, there is mounting evidence of their favorable cardiovascular impact, making them potentially appealing pharmacologic agents of choice in the future. Although we seem to be poised on the horizons of exciting new breakthroughs, much knowledge has yet to be gained before these novel agents are ready for prime time.

Liraglutide Improved Cardiometabolic Parameters More in Obese than in Non-obese Patients with Type 2 Diabetes: A Real-World 18-Month Prospective Study.

INTRODUCTION: The glucagon-like peptide-1 agonist (GLP1-RA) liraglutide is currently approved for the treatment of both obesity and type 2 diabetes (T2DM). We investigated whether the effect of this agent on cardiometabolic parameters in subjects with T2DM varied in relation to the concomitant presence of obesity. METHODS: One hundred thirty-five subjects (78 men and 57 women; age: 62 ± 10 years) naïve to incretin-based therapies were treated with low-dose liraglutide (1.2 mg/day) as an add-on to metformin for 18 months. Patients were divided into two subgroups based on their body-mass index (BMI): (a) obese (BMI ≥ 30) and (b) non-obese (BMI < 30). Clinical and laboratory analyses were assessed at baseline and every 6 months. RESULTS: During follow-up, significant improvements were seen in both groups in fasting glycemia, glycated hemoglobin, waist circumference, and carotid intima-media thickness (cIMT), while body weight, BMI, total cholesterol, and low-density lipoprotein cholesterol decreased significantly in obese subjects only. Correlation analysis revealed that changes in subclinical atherosclerosis (assessed by cIMT) were associated with changes in triglycerides (r = 0.488, p < 0.0001) in the obese group only. CONCLUSION: Liraglutide had beneficial actions on glycemic parameters and cardiometabolic risk factors in both non-obese and obese patients with T2DM, with a greater efficacy in the latter. These findings reinforce the benefits of liraglutide for the cardiometabolic outcomes of obese patients with T2DM in the real-world setting. This has critical importance during the current pandemic, since patients with diabetes and obesity are exposed globally to the most severe forms of COVID-19, related complications, and death. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01715428.

Experimental and Emerging Free Fatty Acid Receptor Agonists for the Treatment of Type 2 Diabetes.

The current management of Type 2 Diabetes Mellitus (T2DM) includes incretin-based treatments able to enhance insulin secretion and peripheral insulin sensitivity as well as improve body mass, inflammation, plasma lipids, blood pressure, and cardiovascular outcomes. Dietary Free Fatty Acids (FFA) regulate metabolic and anti-inflammatory processes through their action on incretins. Selective synthetic ligands for FFA1-4 receptors have been developed as potential treatments for T2DM. To comprehensively review the available evidence for the potential role of FFA receptor agonists in the treatment of T2DM, we performed an electronic database search assessing the association between FFAs, T2DM, inflammation, and incretins. Evidence indicates that FFA1-4 agonism increases insulin sensitivity, induces body mass loss, reduces inflammation, and has beneficial metabolic effects. There is a strong inter-relationship between FFAs and incretins. FFA receptor agonism represents a potential target for the treatment of T2DM and may provide an avenue for the management of cardiometabolic risk in susceptible individuals. Further research promises to shed more light on this emerging topic.

Correlations between Diabetes Mellitus Self-Care Activities and Glycaemic Control in the Adult Population: A Cross-Sectional Study.

Although it is well known that lifestyle changes can affect plasma glucose levels, there is little formal evidence for the sustained effectiveness of exercise and diet in diabetes mellitus (DM) management. Self-care in DM refers to the real-life application of the knowledge that the patient gained during the education programmes. The goals are to bring about changes in the patient's behaviour, thus improving glycaemic control. We evaluated the influence of DM self-care activities (SCA) on glycaemic control in a total of 159 patients with DM. Plasma glycated haemoglobin (HbA1c) levels were used to monitor glycaemic control, while SCA were assessed using the standardised Diabetes Self-Management Questionnaire (DSMQ). In our study, 53% of the patients had a HbA1c ≥ 7%. In univariate linear regression models, a statistically significant inverse association was observed between the HbA1c (the dependent variable) and both the DSMQ Dietary Control Score (R2 = 0.037, p = 0.0145) and the DSMQ Sum Score (R2 = 0.06, p = 0.0014). The mean absolute change in the HbA1c% associated with one standard deviation (SD) change in the DSMQ Sum Score, independent of the other significant variables retained in the compacted multivariate regression model, was -0.419% (confidence interval: 95%: from -0.18 to -0.65). Although the impact of the DSMQ Score was modest when compared to the other independent variables in the multivariate model, the findings emphasise the importance of maintaining optimal lifestyle changes to avoid hyperglycaemia and its complications. In conclusion, enhanced self-management of DM is associated with improved glucose control. In patients with chronic diseases such as DM, the role of streamlining SCA encompassing physical activity and proper dietary choices is imperative because of a significantly reduced access to healthcare globally as a result of the COVID-19 pandemic.

Inclisiran: a small interfering RNA strategy targeting PCSK9 to treat hypercholesterolemia.

INTRODUCTION: Inclisiran is a novel posttranscriptional gene silencing therapy that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) synthesis by RNA interference and has a potent, dose-dependent, durable effect in lowering LDL-C, and therefore is an effective drug to treat dyslipidemia, reducing the risk for acute cardiovascular (CV) events. It is safe and well-tolerated. AREAS COVERED: This paper aims to review the mechanism of action of inclisiran while evaluating its efficacy and safety in the treatment of dyslipidemia from data of the clinical trials in the ORION program. EXPERT OPINION: Data from the clinical trials in the ORION program demonstrated efficacy and safety of inclisiran in patients with dyslipidemia. Adverse events were similar in the inclisiran and placebo groups in the clinical trials, although injection-site reactions were more frequent with inclisiran than with placebo. Although the combination of efficacy and safety makes inclisiran a good option for the treatment of dyslipidemia compared to other PCSK9 targeting therapeutic strategies, however, further studies should exclude the possibility that inclisiran, through lower-affinity interactions, may influence other mRNAs in the physiological milieu.

Diabetes and COVID-19: What 2 Years of the Pandemic Has Taught Us.

As the world enters its third year of the COVID-19 pandemic, individuals with diabetes have faced particular challenges from the virus. A deleterious bidirectional relationship exists between the two disorders, with heightened inflammatory, immunologic, and cellular mechanisms leading to a more severe illness and increased morbidity and mortality. Tight glucose control, though necessary, is hampered by physical restrictions and difficulty accessing health care. Novel glucose-lowering medications may provide unique benefits in this regard. It is imperative that multi-pronged efforts be prioritized in order to reduce adverse outcomes in patients with diabetes at risk for COVID-19.

Associations between Periodontitis, COVID-19, and Cardiometabolic Complications: Molecular Mechanisms and Clinical Evidence.

Periodontitis is a microbially driven, host-mediated disease that leads to loss of periodontal attachment and resorption of bone. It is associated with the elevation of systemic inflammatory markers and with the presence of systemic comorbidities. Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the majority of patients have mild symptoms, others experience important complications that can lead to death. After the spread of the COVID-19 pandemic, several investigations demonstrating the possible relationship between periodontitis and COVID-19 have been reported. In addition, both periodontal disease and COVID-19 seem to provoke and/or impair several cardiometabolic complications such as cardiovascular disease, type 2 diabetes, metabolic syndrome, dyslipidemia, insulin resistance, obesity, non-alcoholic fatty liver disease, and neurological and neuropsychiatric complications. Therefore, due to the increasing number of investigations focusing on the periodontitis-COVID-19 relationship and considering the severe complications that such an association might cause, this review aims to summarize all existing emerging evidence regarding the link between the periodontitis-COVID-19 axis and consequent cardiometabolic impairments.

Cardiometabolic Alterations in the Interplay of COVID-19 and Diabetes: Current Knowledge and Future Avenues.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019 [COVID-19]) pandemic has raged for almost two years, with few signs of a sustained abatement or remission [...].