scholarly journals The Potential Role of Osteopontin and Furin in Worsening Disease Outcomes in COVID-19 Patients with Pre-Existing Diabetes

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2528
Author(s):  
Yvonne Adu-Agyeiwaah ◽  
Maria B. Grant ◽  
Alexander G. Obukhov

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the ongoing coronavirus disease 2019 (COVID-19) pandemic, with more than 50 million cases reported globally. Findings have consistently identified an increased severity of SARS-CoV-2 infection in individuals with diabetes. Osteopontin, a cytokine-like matrix-associated phosphoglycoprotein, is elevated in diabetes and drives the expression of furin, a proprotein convertase implicated in the proteolytic processing and activation of several precursors, including chemokines, growth factors, hormones, adhesion molecules, and receptors. Elevated serum furin is a signature of diabetes mellitus progression and is associated with a dysmetabolic phenotype and increased risk of diabetes-linked premature mortality. Additionally, furin plays an important role in enhancing the infectivity of SARS-CoV-2 by promoting its entry and replication in the host cell. Here, we hypothesize that diabetes-induced osteopontin and furin protein upregulation results in worse outcomes in diabetic patients with SARS-CoV-2 infection owing to the roles of these protein in promoting viral infection and increasing metabolic dysfunction. Thus, targeting the osteopontin-furin axis may be a plausible strategy for reducing mortality in SARS-CoV-2 patients with diabetes.

2010 ◽  
Vol 7 (2) ◽  
pp. 92
Author(s):  
Alberico L Catapano ◽  
Liliana Grigore ◽  
Angela Pirillo ◽  
◽  
◽  
...  

Diabetes increases the risk of developing cardiovascular disease (CVD), and several guidelines suggest that subjects with diabetes are at high risk of developing CVD. The increased risk can be attributed, at least in part, to associated risk factors, including hypertension and dyslipidaemia. The role of statins in primary and secondary prevention of CVD is well established, and the positive effect has been clearly demonstrated also in patients with type 2 diabetes. A number of studies have evaluated the effect of statin therapy on incident CVD and shown that statin therapy produces a great reduction in cardiovascular risk, but a recent meta-analysis revealed a slight increase in the risk of developing diabetes. Such risk is, however, low, especially when compared with the reduction in cardiovascular events and should not interfere with the choice of treating diabetic patients with a cholesterol-lowering therapy.


2021 ◽  
Vol 27 ◽  
Author(s):  
Reyhaneh Moradi-Marjaneh ◽  
Fereshteh Asgharzadeh ◽  
Elnaz Khordad ◽  
Mahdi Moradi Marjaneh

: Coronavirus disease 2019 (SARS-CoV-2) (COVID-19) has recently raised worldwide public health concerns. The available data on COVID-19 in patients with diabetes is limited but generally indicate that there is an increased risk of developing COVID-19 infection in diabetic patients, which ultimately impact the overall patient’s survival. Various aspects might be involved however, the exact mechanisms and interrelationships between diabetes and the novel COVID-19 have not yet been fully elucidated. This review summarizes the possible mechanisms by which present diabetes predispose individuals to COVID-19 infection, modulates the host-viral interactions and increases the risk of mortality. We hope this review can provide beneficial information for further studies and contribute for improved disease management of diabetic patients with COVID-19.


2021 ◽  
pp. svn-2020-000693
Author(s):  
Yanan Qiao ◽  
Siyuan Liu ◽  
Guochen Li ◽  
Yanqiang Lu ◽  
Ying Wu ◽  
...  

Background and purposeThe role of depression in the development and outcome of cardiometabolic diseases remains to be clarified. We aimed to examine the extent to which depressive symptoms affect the transitions from healthy to diabetes, stroke, heart disease and subsequent all-cause mortality in a middle-aged and elderly European population.MethodsA total of 78 212 individuals aged ≥50 years from the Survey of Health Ageing and Retirement in Europe were included. Participants with any baseline cardiometabolic diseases including diabetes, stroke and heart disease were excluded. Depressive symptoms were measured by the Euro-Depression scale at baseline. Participants were followed up to determine the occurrence of cardiometabolic diseases and all-cause mortality. We used multistate models to estimate the transition-specific HRs and 95% CIs after adjustment of confounders.ResultsDuring 500 711 person-years of follow-up, 4742 participants developed diabetes, 2173 had stroke, 5487 developed heart disease and 7182 died. Depressive symptoms were significantly associated with transitions from healthy to diabetes (HR: 1.12, 95% CI: 1.05 to 1.20), stroke (HR: 1.31, 95% CI: 1.18 to 1.44), heart disease (HR: 1.26, 95% CI: 1.18 to 1.34) and all-cause mortality (HR: 1.41, 95% CI: 1.34 to 1.49). After cardiometabolic diseases, depressive symptoms were associated with the increased risk of all-cause mortality in patients with diabetes (HR: 1.54, 95% CI: 1.25 to 1.89), patients who had stroke (HR: 1.29, 95% CI: 1.03 to 1.61) and patients with heart disease (HR: 1.21, 95% CI: 1.02 to 1.44).ConclusionsDepressive symptoms increase the risk of diabetes, stroke and heart disease, and affect the risk of mortality after the onset of these cardiometabolic conditions. Screening and treatment of depressive symptoms may have profound implications for the prevention and prognosis of cardiometabolic diseases.


2021 ◽  
Vol 17 ◽  
Author(s):  
Mehdi Kushkestani ◽  
Mohsen Parvani ◽  
Yaser Kazemzadeh

: SARS-COV-2 is the novel type of beta coronavirus that was first seen in December 2019 in Wuhan, China. Type 2 Diabetics are one of the groups most vulnerable to SARS-COV-2 and its associated complications. Many factors such as medication, pathophysiologic-induced compensatory mechanisms, and alterations in protein expression and immune system function can all contribute to severe outcomes in diabetics. In this review article, we first described the possible mechanisms of increased risk and more severe complications rate of SARS-COV-2 in diabetic patients. Secondly, we discussed the crucial roles of exercise in diabetic patients and in balancing of RAS system (ACE2/ACE). Finally, we showed the possible roles of acute and chronic exercise in reducing SARS-COV-2 severe outcomes in diabetics in accordance with the latest evidence. We concluded that regular exercise (especially moderate-intensity exercise) can play immune enhancing, anti-inflammatory, anti-oxidation roles and can balance ACE2/ACE ratio (decreasing ANG2 levels) in diabetic subjects.


Author(s):  
Hua Ma ◽  
QIng Gu ◽  
Huining Niu ◽  
Xiaohua Li ◽  
Rong Wang

Background: The use of Aspirin in the primary prevention of cardiovascular disease (CVD) is still a topic of debate, especially in patients with diabetes. The present meta-analysis aims to rule out the efficacy of Aspirin in patients with diabetes and to compare the effectiveness of Aspirin with a placebo (or no treatment) for the primary prevention of CVD and all-cause mortality events in people with diabetes. Materials and Methods: An extensive and systematic search was conducted in Medline (via PubMed), Cinahl (via Ebsco), Scopus, and Web of Sciences from 1988 to December 2020. A detailed literature search was conducted using Aspirin, cardiovascular disease (CVD), diabetes, and efficacy to identify trials of patients with diabetes who received Aspirin for primary prevention of CVD. Demographic details with the primary outcome of events and bleeding outcomes were analyzed. The risk of bias (RoB) in included studies was evaluated using the QUADAS-2 tool. Results: A total of 5 studies out of 13 were included with 23,570 diabetic patients; 11,738 allocated to Aspirin and 11,832 allocated to the placebo group. In patients with diabetes, there was no difference between Aspirin and placebo with respect to the risk of all-cause death with a confidence interval (CI) varying 0.63 to 1.17. In addition, there were no differences in the bleeding outcomes with an odds ratio of 1.4411 (CI 0.47 to 4.34). Conclusion: Aspirin has no significant risk on primary endpoints of cardiovascular events and the bleeding outcomes in diabetic patients compared to placebo. More research on the use of Aspirin alone or in combination with other antiplatelet drugs is required in patients with diabetes to supplement currently available research.


2021 ◽  
Vol 22 (19) ◽  
pp. 10643
Author(s):  
Lucia La Sala ◽  
Antonio E. Pontiroli

The goal of diabetes care is to achieve and maintain good glycemic control over time, so as to prevent or delay the development of micro- and macrovascular complications in type 1 (T1D) and type 2 diabetes (T2D). However, numerous barriers hinder the achievement of this goal, first of all the frequent episodes of hypoglycemia typical in patients treated with insulin as T1D patients, or sulphonylureas as T2D patients. The prevention strategy and treatment of hypoglycemia are important for the well-being of patients with diabetes. Hypoglycemia is strongly associated with an increased risk of cardiovascular disease in diabetic patients, due probably to the release of inflammatory markers and prothrombotic effects triggered by hypoglycemia. Treatment of hypoglycemia is traditionally based on administration of carbohydrates or of glucagon via intramuscular (IM) or subcutaneous injection (SC). The injection of traditional glucagon is cumbersome, such that glucagon is an under-utilized drug. In 1983, it was shown for the first time that intranasal (IN) glucagon increases blood glucose levels in healthy volunteers, and in 1989–1992 that IN glucagon is similar to IM glucagon in resolving hypoglycemia in normal volunteers and in patients with diabetes, both adults and children. IN glucagon was developed in 2010 and continued in 2015; in 2019 IN glucagon obtained approval in the US, Canada, and Europe for severe hypoglycemia in children and adults. In the 2010s, two ready-to-use injectable formulations, a stable non-aqueous glucagon solution and the glucagon analog dasiglucagon, were developed, showing an efficacy similar to traditional glucagon, and approved in the US in 2020 and in 2021, respectively, for severe hypoglycemia in adults and in children. Fast-acting glucagon (nasal administration and injected solutions) appears to represent a major breakthrough in the treatment of severe hypoglycemia in insulin-treated patients with diabetes, both adults and children. It is anticipated that the availability of fast-acting glucagon will expand the use of glucagon, improve overall metabolic control, and prevent hypoglycemia-related complications, in particular cardiovascular complications and cognitive impairment.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Lance S Longmore ◽  
Kimberly J Reid ◽  
Mikhail Kosiborod ◽  
Frederick A Masoudi ◽  
Verna Welch ◽  
...  

While diabetes is known to be associated with increased mortality after MI, whether these differences in outcome are due to patient characteristics, treatment, or other biological factors is unknown. We analyzed a contemporary cohort of MI survivors to comprehensively adjust for demographics, comorbidities, psychosocial, health status, clinical and treatment factors to determine if residual disparities in outcomes exist. We studied 2481 hospital survivors of MI in the prospective, 19-center PREMIER study (29% with diabetes). Multivariable models with sequential adjustment were employed to identify the extent to which variation in a wide range of patient characteristics (Figure ) accounted for differences in 3-year mortality in patients with and without diabetes. Unadjusted mortality was more than 2.5-fold greater for patients with diabetes (HR 2.55, 95% CI 2.08–3.14). Mortality was most attenuated by diabetes-related comorbidities (Figure ). The fully-adjusted model identified a significant, albeit attenuated, excess 3-year mortality among patients with diabetes (HR 1.57, 95% CI 1.22–1.99). Patients with diabetes experience a substantially increased risk for 3-year mortality after MI, even after accounting for a wide range of patient and treatment characteristics. This suggests that unmeasured, biologic variables associated with diabetes may mediate this difference. Further inquiry into the pathogenesis of diabetic cardiovascular disease is needed to identify new opportunities to improve the prognosis of patients with diabetes.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19519-e19519
Author(s):  
O. Yellin ◽  
J. Crowley ◽  
R. A. Swift ◽  
A. Makary ◽  
D. S. Gravenor ◽  
...  

e19519 Background: Although the overall survival of MM patients has improved with new treatment options, few studies have evaluated prognostic factors since these new therapies have become available. Monthly ZOL has been incorporated into many of these regimens to reduce skeletal complications. Side effects from ZOL have been reported but their frequency and outcomes have not been well-defined. This retrospective study aimed to identify key baseline and on-treatment prognostic factors among MM patients treated with ZOL. Methods: Three hundred patient charts were consecutively reviewed. Data was collected from the date of MM diagnosis to the date of chart review. Patient chart inclusion criteria required a diagnosis of MM and having received at least one dose of ZOL. Results: The median survival of among patients in this study was 131 months. Significant early risk factors for overall survival included skeletal-related events (SRE), increased serum creatinine, elevated serum calcium, and ISS Stage II or III at diagnosis. Fourteen patients (4.7%) developed osteonecrosis of the jaw (ONJ) after 9–96 months of ZOL treatment. Notably, there was a trend toward an increased risk of ONJ among diabetic patients. Thirteen patients with ONJ remain alive and currently are in remission or with stable disease. One patient with ONJ died while in remission from a myocardial infarction. Among the patients with a follow up of 4–49 months from the diagnosis of ONJ, 2 showed some worsening of this complication, 5 remained stable, while 7 improved or resolved. Patients with ONJ showed an improved overall survival using both landmark and time-dependent analysis. In addition, the overall skeletal morbidity rate (SMR; SREs/year) was 0.16. Notably, patients who developed ONJ had a lower SMR than among patients who did not develop ONJ. Conclusions: These results suggest that skeletal complications are an important prognostic factor for MM. Although ONJ occurs in MM patients, most patients show improvement with proper management and this complication appears to be associated with a reduced risk of SREs and improved overall survival. [Table: see text]


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Kevin R. Short ◽  
Dominic Frimberger

Children and adolescents who have decreased mobility due to spina bifida may be at increased risk for the components of metabolic syndrome, including abdominal obesity, insulin resistance, and dyslipidemia due to low physical activity. Like their nondisabled peers, adolescents with spina bifida that develop metabolic risk factors early in life have set the stage for adult disease. Exercise interventions can improve metabolic dysfunction in nondisabled youth, but the types of exercise programs that are most effective and the mechanisms involved are not known. This is especially true in adolescents with spina bifida, who have impaired mobility and physical function and with whom there have been few well-controlled studies. This paper highlights the current lack of knowledge about the role of physical activity and the need to develop exercise strategies targeting the reduction of cardiometabolic risk and improving quality of life in youth with spina bifida.


Sign in / Sign up

Export Citation Format

Share Document