Atherothrombotic disease is a well-recognized complication of diabetes and is a major contributor to the high morbidity and mortality associated with diabetes. Although there is substantial evidence ...linking diabetes with cardiovascular disease, the specific effect of hyper- (or hypo-) glycaemia is less well understood. The present review focuses on the impact that glycaemic dysregulation has on respiratory function and ROS (reactive oxygen species) generation in the endothelial cells that are critical in preventing several key steps in the atherothrombotic process. Endothelial cells are particularly susceptible to ROS-mediated dysfunction not only because of reduced cell viability and increased senescence, but also because one of the major endothelium-derived factors that help to protect against atherosclerosis, nitric oxide, is rapidly deactivated by superoxide radicals.
Meta-analyses have indicated that individuals with type 1 or type 2 diabetes are at increased risk of suffering a severe form of COVID-19 and have a higher mortality rate than the non-diabetic ...population. Patients with diabetes have chronic, low-level systemic inflammation, which results in global cellular dysfunction underlying the wide variety of symptoms associated with the disease, including an increased risk of respiratory infection. While the increased severity of COVID-19 amongst patients with diabetes is not yet fully understood, the common features associated with both diseases are dysregulated immune and inflammatory responses. An additional key player in COVID-19 is the enzyme, angiotensin-converting enzyme 2 (ACE2), which is essential for adhesion and uptake of virus into cells prior to replication. Changes to the expression of ACE2 in diabetes have been documented, but they vary across different organs and the importance of such changes on COVID-19 severity are still under investigation. This review will examine and summarise existing data on how immune and inflammatory processes interplay with the pathogenesis of COVID-19, with a particular focus on the impacts that diabetes, endothelial dysfunction and the expression dynamics of ACE2 have on the disease severity.
Platelet hyperaggregability is a pro-thrombotic feature of type-2 diabetes, associated with low levels of the antioxidant glutathione (GSH). Clinical delivery of N-acetylcysteine (NAC), a ...biosynthetic precursor of GSH, may help redress a GSH shortfall in platelets, thereby reducing thrombotic risk in type-2 diabetes patients. We investigated the effect of NAC in vitro, at concentrations attainable with tolerable oral dosing, on platelet GSH concentrations and aggregation propensity in blood from patients with type-2 diabetes.
Blood samples (n = 13) were incubated (2 h, 37°C) with NAC (10-100 micromolar) in vitro. Platelet aggregation in response to thrombin and ADP (whole blood aggregometry) was assessed, together with platelet GSH concentration (reduced and oxidized), antioxidant status, reactive oxygen species (ROS) generation, and plasma NOx (a surrogate measure of platelet-derived nitric oxide; NO).
At therapeutically relevant concentrations (10-100 micromolar), NAC increased intraplatelet GSH levels, enhanced the antioxidant effects of platelets, and reduced ROS generation in blood from type-2 diabetes patients. Critically, NAC inhibited thrombin- and ADP-induced platelet aggregation in vitro. Plasma NOx was enhanced by 30 micromolar NAC.
Our results suggest that NAC reduces thrombotic propensity in type-2 diabetes patients by increasing platelet antioxidant status as a result of elevated GSH synthesis, thereby lowering platelet-derived ROS. This may increase bioavailability of protective NO in a narrow therapeutic range. Therefore, NAC might represent an alternative or additional therapy to aspirin that could reduce thrombotic risk in type-2 diabetes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study investigated the impact of either type 2 diabetes or obesity, separately or in combination, on the absolute amounts of microparticles (MP) and the pathways by which these are associated ...with either condition. The concentrations of circulating MP derived from platelets (PMP), leukocytes (LMP) and monocytes (MMP), together with their specific activation markers, were compared in 30 subjects who were characterised across 4 cohorts as obese or type 2 diabetes. The subjects with type 2 diabetes had elevated concentrations of total PMP (
P
= 0.003), and PMP that were fibrinogen-positive (
P
= 0.04), tissue factor-positive (
P
< 0.001), P-selectin-positive (
P
= 0.03). Type 2 diabetes did not alter either total or activated LMP or MMP. Obesity per se did not impact on any MP measurement. Elevated concentrations of plasma PMP occurred in subjects with type 2 diabetes, whether they were obese or non-obese. In contrast, obesity in the absence of type 2 diabetes had no effect. The increased concentrations of specific marker-positive PMP in the subjects with diabetes might reflect potential pathways by which PMP may contribute to the pathogenesis of atherosclerosis and type 2 diabetes.
People with diabetes often have difficulty maintaining optimal blood-glucose levels, risking progressive complications that can lead to unscheduled care. Unscheduled care can include attending ...emergency departments, ambulance call outs, out-of-hours care and non-elective hospital admissions. A large proportion of non-elective hospital admissions involve people with diabetes, with significant health and economic burden.
To identify precipitating factors influencing diabetes-related unscheduled hospital admissions, exploring potential preventative strategies to reduce admissions.
Thirty-six people with type 1 (n=11) or type 2 (n=25) diabetes, admitted to hospital for unscheduled diabetes-related care across three hospitals in Scotland, Northern Ireland and the Republic of Ireland were interviewed. Participants were admitted for peripheral limb complications (n=17), hypoglycaemia (n=5), hyperglycaemia (n=6), or for comorbidities presenting with erratic blood glucose levels (n=8).
Factors precipitating admissions were examined using Framework analysis.
Three aspects of care influenced unscheduled admissions: inadequate knowledge; restricted provision; and complexities in engagement. Limited specialist professional knowledge of diabetes by staff in primary and community care, alongside inadequate patient self-management knowledge, led to inappropriate treatment and significant delays. This was compounded by restricted provision of care, characterised by poor access to services, in time and proximity, and poor continuity of care. Complexities in patient engagement, help-seeking, and illness-beliefs, further complicated the progression to unscheduled admissions.
Dedicated investment in primary care is needed to enhance provision of and access to services, promoting increased and earlier diabetes specialist team involvement, alongside training and use of technology and telemedicine to enhance existing care.
SCOPE: Inflammatory status can increase the risk of adverse cardiovascular events linked to platelet activity and involvement of microparticles (MP) released from platelets (PMP), leukocytes (LMP), ...and monocytes (MMP). These MP carry host cell‐derived antigens that may act as markers of metabolic health. Subjects newly diagnosed with type 2 diabetes are offered appropriate standard dietary advice (SDA) but this may not be optimal as specific inclusion of other nutrients, such as oats, may add benefit. The effectiveness of such interventions can be tested by examination of MP activation markers. METHODS AND RESULTS: Subjects (n = 22) with type 2 diabetes participated in a randomized cross‐over trial involving 8 wk interventions with either an oat‐enriched diet (OAT) or following reinforced SDA. Responses were also compared with preintervention habitual (HAB) intake. OAT reduced the concentrations and proportions of fibrinogen‐ and tissue factor‐related PMP and MMP_11b. The main effect of SDA was to reduce fibrinogen‐activated PMP. Regardless of chronic intake, a healthy test meal led to postprandial declines in total PMP as well as tissue factor‐, fibrinogen‐, and P‐selectin‐positive PMP. CONCLUSION: OAT improved risk factors assessed by MP status, even in subjects with type 2 diabetes already well‐controlled by diet and life‐style alone.
N-Acetylcysteine (NAC) is a frequently used “antioxidant” in vitro, but the concentrations applied rarely correlate with those encountered with oral dosing in vivo. Here, we investigated the in vitro ...antioxidant and antiplatelet properties of NAC at concentrations (10-100 μM) that are achievable in plasma with tolerable oral dosing. The impact of NAC pretreatment (2 hours) on aggregation of platelets from healthy volunteers in response to thrombin and adenosine diphosphate and on platelet-derived nitric oxide (NO) was examined. NAC was found to be a weak reducing agent and a poor antioxidant compared with glutathione (reduced form) (GSH). However, platelets treated with NAC showed enhanced antioxidant activity and depression of reactive oxygen species generation associated with increases in intraplatelet GSH levels. An approximately 2-fold increase in NO synthase-derived nitrite was observed with 10 μM NAC treatment, but the effect was not concentration dependent. Finally, NAC significantly reduced both thrombin-induced and adenosine diphosphate-induced platelet aggregation. NAC should be considered a weak antioxidant that requires prior conversion to GSH to convey antioxidant and antithrombotic benefit at therapeutically relevant concentrations. Our results suggest that NAC might be an effective antiplatelet agent in conditions where increased oxidative stress contributes to heightened risk of thrombosis but only if the intraplatelet machinery to convert it to GSH is functional.
Digital games are an important class of eHealth interventions in diabetes, made possible by the Internet and a good range of affordable mobile devices (eg, mobile phones and tablets) available to ...consumers these days. Gamifying disease management can help children, adolescents, and adults with diabetes to better cope with their lifelong condition. Gamification and social in-game components are used to motivate players/patients and positively change their behavior and lifestyle. In this paper, we start by presenting the main challenges facing people with diabetes-children/adolescents and adults-from a clinical perspective, followed by three short illustrative examples of mobile and desktop game apps and platforms designed by Ayogo Health, Inc. (Vancouver, BC, Canada) for type 1 diabetes (one example) and type 2 diabetes (two examples). The games target different age groups with different needs-children with type 1 diabetes versus adults with type 2 diabetes. The paper is not meant to be an exhaustive review of all digital game offerings available for people with type 1 and type 2 diabetes, but rather to serve as a taster of a few of the game genres on offer today for both types of diabetes, with a brief discussion of (1) some of the underpinning psychological mechanisms of gamified digital interventions and platforms as self-management adherence tools, and more, in diabetes, and (2) some of the hypothesized potential benefits that might be gained from their routine use by people with diabetes. More research evidence from full-scale evaluation studies is needed and expected in the near future that will quantify, qualify, and establish the evidence base concerning this gamification potential, such as what works in each age group/patient type, what does not, and under which settings and criteria.
Background: Oxidative stress is a detrimental feature of diabetes implicated in the progression of the disease and its complications. The relationship between insulin therapy and oxidative stress is ...complex. This study tested the hypothesis that improved glucose control, rather than insulin dose, is central to reduced oxidative stress in patients with type 2 diabetes following continuous subcutaneous insulin infusion (CSII). Methods: In this 16-week, multicenter study, 54 CSII-naïve patients with type 2 diabetes (age 57 ± 10 years, HbA1c 69 ± 15 mmol/mol 8.5 ± 1.4%, diabetes duration 13 ± 6 years) treated with either oral antidiabetic agents (OAD) alone (n = 17), basal insulin ± OAD (n = 17), or multiple daily injections (MDI) ± OAD (n = 20) were the evaluable group. Diabetes medications except metformin were discontinued, and 16 weeks of CSII was initiated. Insulin dose was titrated to achieve optimal glycemic control. A plasma marker of oxidative stress relevant to cardiovascular disease (oxidized low density lipoprotein ox-LDL) was assessed at baseline and week 16. Results: CSII improved glycemic control (HbA1c −13 ± 2 mmol/mol −1.2 ± 0.2%; fasting glucose −36.6 ± 8.4 mg/dL; mean glucose excursion −23.2 ± 6.5 mg/dL, mean ± SE; all P < .001) and reduced ox-LDL (–10.5%; P < .05). The antioxidant effect was cohort-independent (P > .05), but was significantly more pronounced in patients on statins (P = .019). The effect of CSII was more closely correlated to improvements in glucose excursion (P = .013) than to insulin dose (P > .05) or reduction in HbA1c (P > .05). Conclusions: CSII induces depression of plasma ox-LDL associated with change in glucose control, rather than with change in insulin dose. The effect is augmented in patients receiving statins.
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