Dataset Information

Uncontrolled Diabetes Mellitus Has No Major Influence on the Platelet Transcriptome.

ABSTRACT: Background:Diabetes mellitus (DM) has been associated with increased platelet reactivity as well as increased levels of platelet RNAs in plasma. Here, we sought to evaluate whether the platelet transcriptome is altered in the presence of uncontrolled DM. Methods:Next-generation sequencing (NGS) was performed on platelet RNA for 5 patients with uncontrolled DM (HbA1c 9.0%) and 5 control patients (HbA1c 5.5%) with otherwise similar clinical characteristics. RNA was isolated from leucocyte-depleted platelet-rich plasma. Libraries of platelet RNAs were created separately for long RNAs after ribosomal depletion and for small RNAs from total RNA, followed by next-generation sequencing. Results:Platelets in both groups demonstrated RNA expression profiles characterized by absence of leukocyte-specific transcripts, high expression of well-known platelet transcripts, and in total 6,343 consistently detectable transcripts. Extensive statistical bioinformatic analysis yielded 12 genes with consistently differential expression at a lenient FDR < 0.1, thereof 8 protein-coding genes and 2 genes with known expression in platelets (MACF1 and ITGB3BP). Three of the four differentially expressed noncoding genes were YRNAs (RNY1, RNY3, and RNY4) which were all downregulated in DM. 23 miRNAs were differentially expressed between the two groups. Of the 13 miRNAs with decreased expression in the diabetic group, 8 belonged to the DLK1-DIO3 gene region on chromosome 14q32.2. Conclusions:In this study, uncontrolled DM had a remote impact on different components of the platelet transcriptome. Increased expression of MACF1, together with supporting predicted mRNA-miRNA interactions as well as reduced expression of RNYs in platelets, may reflect subclinical platelet activation in uncontrolled DM.

SUBMITTER: Nuhrenberg TG

PROVIDER: S-EPMC6241365 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Uncontrolled Diabetes Mellitus Has No Major Influence on the Platelet Transcriptome.

Nührenberg Thomas G TG Cederqvist Marco M Marini Federico F Stratz Christian C Grüning Björn A BA Trenk Dietmar D Binder Harald H Gilsbach Ralf R Neumann Franz-Josef FJ Hein Lutz L

BioMed research international 20181101

<h4>Background</h4>Diabetes mellitus (DM) has been associated with increased platelet reactivity as well as increased levels of platelet RNAs in plasma. Here, we sought to evaluate whether the platelet transcriptome is altered in the presence of uncontrolled DM.<h4>Methods</h4>Next-generation sequencing (NGS) was performed on platelet RNA for 5 patients with uncontrolled DM (HbA1c 9.0%) and 5 control patients (HbA1c 5.5%) with otherwise similar clinical characteristics. RNA was isolated from leu ...[more]

PMID: 30519591

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Project description:BackgroundManaging hypertension (HT) and diabetes mellitus (DM) is crucial to preventing cardiovascular diseases. Few studies have investigated the incidence and risk of cardiovascular diseases or mortality in uncontrolled HT or DM in the Asian population. Epidemiological studies of cardiovascular disease should be conducted with continuous consideration of the changing disease risk profiles, lifestyles, and socioeconomic status over time.ObjectiveWe aimed to examine the association of uncontrolled HT or DM with the incidence of cardiovascular events or deaths from any cause.MethodsThis population-based retrospective study was conducted using data from the Korean National Health Insurance Service-National Health Screening Cohort, including patients aged 40-79 years who participated in national screening from 2002 to 2003 and were followed up until 2015. The health screening period from 2002 to 2013 was stratified into 6 index periods in 2-year cycles, and the follow-up period from 2004 to 2015 was stratified accordingly into 6 subsequent 2-year periods. The incidence rates and hazard ratio (HR) for major adverse cardiovascular events (MACE) and death from any cause were estimated according to HT or DM control status. Extended Cox models with time-dependent variables updated every 2 years, including sociodemographic characteristics, blood pressure (BP), fasting blood glucose (FBG), medication prescription, and adherence, were used.ResultsAmong the total cohort of 440,249 patients, 155,765 (35.38%) were in the uncontrolled HT or DM group. More than 60% of the patients with HT or DM who were prescribed medications did not achieve the target BP or FBG. The incidence of MACE was 10.8-15.5 and 9.6-13.3 per 1000 person-years in the uncontrolled DM and uncontrolled HT groups, respectively, and increased with age. In the uncontrolled HT and DM group, the incidence of MACE was high (15.2-17.5 per 1000 person-years) at a relatively young age and showed no age-related trend. Adjusted HR for MACE were 1.28 (95% CI 1.23-1.32) for the uncontrolled DM group, 1.32 (95% CI 1.29-1.35) for the uncontrolled HT group, and 1.54 (95% CI 1.47-1.60) for the uncontrolled HT and DM group. Adjusted HR for death from any cause were 1.05 (95% CI 1.01-1.10) for the uncontrolled DM group, 1.13 (95% CI 1.10-1.16) for the uncontrolled HT group, and 1.17 (95% CI 1.12-1.23) for the uncontrolled HT and DM group.ConclusionsThis up-to-date evidence of cardiovascular epidemiology in South Korea serves as the basis for planning public health policies to prevent cardiovascular diseases. The high uncontrolled rates of HT or DM, regardless of medication prescription, have led us to suggest the need for a novel system for effective BP or glycemic control, such as a community-wide management program using mobile health technology.

Project description:BackgroundBetter medication adherence among people with diabetes mellitus was found to be associated with improved glycaemic control. However, medication non-adherence is a significant concern in older people with uncontrolled type 2 diabetes mellitus.PurposeTo explore the perspectives of older people with uncontrolled type 2 diabetes mellitus towards medication adherence.DesignA qualitative descriptive exploratory study.MethodologyA purposive sample of older people with uncontrolled type 2 diabetes mellitus living in the community was recruited. Snowball sampling was applied in community recruitment. In-depth telephone interviews were conducted using a semi-structured interview guide. Interviews were transcribed verbatim. Thematic analysis was used in data analysis. The consolidated criteria for reporting qualitative research (COREQ) guidelines were followed.ResultsThe emerged six themes were: (a) impact of knowledge, attitudes and practices on medication adherence, (b) treatment-related barriers to medication adherence, (c) impact of age-related changes on medication adherence, (d) person-related barriers to medication adherence, (e) impact of COVID-19 on medication adherence and, (f) role of support systems in medication adherence. Knowledge of the disease process and medications, attitudes towards medication adherence, the practice of different treatment approaches, self-medication and dosing, negative experiences related to medications, polypharmacy, changes in lifestyle and roles, the influence of work-life, motivation, negligence, family support, support received from health workers, facilities available and financial capability are the main factors influence medication adherence. Age-related memory impairment, visual disturbances and physical weaknesses affect medication adherence in older people. Additionally, COVID-19-related guidelines imposed by the government and healthcare system-related issues during the COVID-19 pandemic also affected medication adherence.ConclusionAdherence to medications among older people is hampered by a variety of factors, including their knowledge, attitudes and practices, person and treatment-related factors and age-related changes. The COVID-19 pandemic has brought additional challenges. Individualised patient care for older people with uncontrolled type 2 diabetes mellitus to improve medication adherence is timely. Strengthening support mechanisms for the above population is essential.

Project description:Platelets affect myocardial damage from ischemia/reperfusion. Redox-dependent sphingosine-1-phosphate production and release are altered in diabetic platelets. Sphingosine-1-phosphate is a double-edged sword for ischemia/reperfusion injury. Therefore, we aimed to verify whether: (1) human healthy- or diabetic-platelets are cardioprotective, (2) sphingosine-1-phosphate receptors and downstream kinases play a role in platelet-induced cardioprotection, and (3) a correlation between platelet redox status and myocardial ischemia/reperfusion injury exists. Isolated rat hearts were subjected to 30-min ischemia and 1-h reperfusion. Infarct size was studied in hearts pretreated with healthy- or diabetic-platelets. Healthy-platelets were co-infused with sphingosine-1-phosphate receptor blocker, ERK-1/2 inhibitor, PI3K antagonist or PKC inhibitor to ascertain the cardioprotective mechanisms. In platelets we assessed (i) aggregation response to ADP, collagen, and arachidonic-acid, (ii) cyclooxygenase-1 levels, and (iii) AKT and ERK-phosphorylation. Platelet sphingosine-1-phosphate production and platelet levels of reactive oxygen species (ROS) were quantified and correlated to infarct size. Infarct size was reduced by about 22% in healthy-platelets pretreated hearts only. This cardioprotective effect was abrogated by either sphingosine-1-phosphate receptors or ERK/PI3K/PKC pathway blockade. Cyclooxygenase-1 levels and aggregation indices were higher in diabetic-platelets than healthy-platelets. Diabetic-platelets released less sphingosine-1-phosphate than healthy-platelets when mechanical or chemically stimulated in vitro. Yet, ROS levels were higher in diabetic-platelets and correlated with infarct size. Cardioprotective effects of healthy-platelet depend on the platelet's capacity to activate cardiac sphingosine-1-phosphate receptors and ERK/PI3K/PKC pathways. However, diabetic-platelets release less S1P and lose cardioprotective effects. Platelet ROS levels correlate with infarct size. Whether these redox alterations are responsible for sphingosine-1-phosphate dysfunction in diabetic-platelets remains to be ascertained.

Dataset Information

Uncontrolled Diabetes Mellitus Has No Major Influence on the Platelet Transcriptome.

Publications

Uncontrolled Diabetes Mellitus Has No Major Influence on the Platelet Transcriptome.

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