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Personalized cytomic assessment of vascular health: Evaluation of the vascular health profile in diabetes mellitus.

ABSTRACT: An inexpensive and accurate blood test does not currently exist that can evaluate the cardiovascular health of a patient. This study evaluated a novel high dimensional flow cytometry approach in combination with cytometric fingerprinting (CF), to comprehensively enumerate differentially expressed subsets of pro-angiogenic circulating progenitor cells (CPCs), involved in the repair of vasculature, and microparticles (MPs), frequently involved in inflammation and thrombosis. CF enabled discovery of a unique pattern, involving both MPs and CPCs and generated a personalized signature of vascular health, the vascular health profile (VHP).Levels of CPCs and MPs were measured with a broad panel of cell surface markers in a population with atherosclerosis and type 2 diabetes mellitus (DM) and age-similar Healthy controls (HC) using an unbiased computational approach, termed CF.Circulating hematopoietic stem and progenitor cell (CHSPCAng) levels were detected at significantly lower concentrations in DM (P < 0.001), whereas levels of seven phenotypically distinct MPs were present at significantly higher concentrations in DM patients and one MP subset was present at significantly lower concentration in DM patients. Collectively, the combination of CHSPC(Ang) and MP levels was more informative than any one measure alone.This work provides the basis for a personalized cytomic vascular health profile that may be useful for a variety of applications including drug development, clinical risk assessment and companion diagnostics.

SUBMITTER: Kurtzman N

PROVIDER: S-EPMC3812912 | biostudies-literature | 2013 Jul-Aug

REPOSITORIES: biostudies-literature

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Personalized cytomic assessment of vascular health: Evaluation of the vascular health profile in diabetes mellitus.

Kurtzman Nicholas N Zhang Lifeng L French Benjamin B Jonas Rebecca R Bantly Andrew A Rogers Wade T WT Moore Jonni S JS Rickels Michael R MR Mohler Emile R ER

Cytometry. Part B, Clinical cytometry 20130605 4

<h4>Background</h4>An inexpensive and accurate blood test does not currently exist that can evaluate the cardiovascular health of a patient. This study evaluated a novel high dimensional flow cytometry approach in combination with cytometric fingerprinting (CF), to comprehensively enumerate differentially expressed subsets of pro-angiogenic circulating progenitor cells (CPCs), involved in the repair of vasculature, and microparticles (MPs), frequently involved in inflammation and thrombosis. CF ...[more]

PMID: 23740755

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Project description:BackgroundPersonalized blood glucose (BG) prediction for diabetes patients is an important goal that is pursued by many researchers worldwide. Despite many proposals, only a few projects are dedicated to the development of complete recommender system infrastructures that incorporate BG prediction algorithms for diabetes patients. The development and implementation of such a system aided by mobile technology is of particular interest to patients with gestational diabetes mellitus (GDM), especially considering the significant importance of quickly achieving adequate BG control for these patients in a short period (ie, during pregnancy) and a typically higher acceptance rate for mobile health (mHealth) solutions for short- to midterm usage.ObjectiveThis study was conducted with the objective of developing infrastructure comprising data processing algorithms, BG prediction models, and an appropriate mobile app for patients' electronic record management to guide BG prediction-based personalized recommendations for patients with GDM.MethodsA mobile app for electronic diary management was developed along with data exchange and continuous BG signal processing software. Both components were coupled to obtain the necessary data for use in the personalized BG prediction system. Necessary data on meals, BG measurements, and other events were collected via the implemented mobile app and continuous glucose monitoring (CGM) system processing software. These data were used to tune and evaluate the BG prediction model, which included an algorithm for dynamic coefficients tuning. In the clinical study, 62 participants (GDM: n=49; control: n=13) took part in a 1-week monitoring trial during which they used the mobile app to track their meals and self-measurements of BG and CGM system for continuous BG monitoring. The data on 909 food intakes and corresponding postprandial BG curves as well as the set of patients' characteristics (eg, glycated hemoglobin, body mass index [BMI], age, and lifestyle parameters) were selected as inputs for the BG prediction models.ResultsThe prediction results by the models for BG levels 1 hour after food intake were root mean square error=0.87 mmol/L, mean absolute error=0.69 mmol/L, and mean absolute percentage error=12.8%, which correspond to an adequate prediction accuracy for BG control decisions.ConclusionsThe mobile app for the collection and processing of relevant data, appropriate software for CGM system signals processing, and BG prediction models were developed for a recommender system. The developed system may help improve BG control in patients with GDM; this will be the subject of evaluation in a subsequent study.

Project description:Mothers with a history of gestational diabetes mellitus (GDM) have an increased risk of developing diabetes in the future and a lifelong cardiovascular risk. Postpartal expression profile of cardiovascular/cerebrovascular disease associated microRNAs was assessed 3-11 years after the delivery in whole peripheral blood of young and middle-aged mothers with a prior exposure to GDM with the aim to identify a high-risk group of mothers at risk of later development of diabetes mellitus and cardiovascular/cerebrovascular diseases who would benefit from implementation of early primary prevention strategies and long-term follow-up. The hypothesis of the assessment of cardiovascular risk in women was based on the knowledge that a series of microRNAs play a role in the pathogenesis of diabetes mellitus and cardiovascular/cerebrovascular diseases. Abnormal expression profile of multiple microRNAs was found in women with a prior exposure to GDM (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-342-3p, miR-499a-5p, and-miR-574-3p). Postpartal combined screening of miR-1-3p, miR-16-5p, miR-17-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-26a-5p, miR-29a-3p, miR-103a-3p, miR-133a-3p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p showed the highest accuracy for the identification of mothers with a prior exposure to GDM at a higher risk of later development of cardiovascular/cerebrovascular diseases (AUC 0.900, p 0.001, sensitivity 77.48%, specificity 93.26%, cut off >0.611270413). It was able to identify 77.48% mothers with an increased cardiovascular risk at 10.0% FPR. Any of changes in epigenome (upregulation of miR-16-5p, miR-17-5p, miR-29a-3p, and miR-195-5p) that were induced by GDM-complicated pregnancy are long-acting and may predispose mothers affected with GDM to later development of diabetes mellitus and cardiovascular/cerebrovascular diseases. In addition, novel epigenetic changes (upregulation of serious of microRNAs) appeared in a proportion of women that were exposed to GDM throughout the postpartal life. Likewise, a previous occurrence of either GH, PE, and/or FGR, as well as a previous occurrence of GDM, is associated with the upregulation of miR-1-3p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-29a-3p, miR-100-5p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-199a-5p, miR-221-3p, and miR-499a-5p. On the other hand, upregulation of miR-16-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-103a-3p, miR-195-5p, miR-342-3p, and miR-574-3p represents a unique feature of aberrant expression profile of women with a prior exposure to GDM. Screening of particular microRNAs may stratify a high-risk group of mothers with a history of GDM who might benefit from implementation of early primary prevention strategies.

Project description:BackgroundCardiovascular disease is the leading cause of mortality in type 1 diabetes mellitus (T1DM) and relates strongly to insulin resistance (IR). Lean and obese adolescents with T1DM have marked IR. Metformin improves surrogate markers of IR in T1DM, but its effect on directly measured IR and vascular health in youth with T1DM is unclear. We hypothesized that adolescents with T1DM have impaired vascular function and that metformin improves this IR and vascular dysfunction.MethodsAdolescents with T1DM and control participants underwent magnetic resonance imaging of the ascending (AA) and descending aorta to assess pulse wave velocity, relative area change, and maximal (WSSMAX) and time-averaged (WSSTA) wall shear stress. Participants with T1DM also underwent assessment of carotid intima-media thickness by ultrasound, brachial distensibility by DynaPulse, fat and lean mass by dual-energy x-ray absorptiometry, fasting laboratories after overnight glycemic control, and insulin sensitivity by hyperinsulinemic-euglycemic clamp (glucose infusion rate/insulin). Adolescents with T1DM were randomized 1:1 to 3 months of 2000 mg metformin or placebo daily, after which baseline measures were repeated.ResultsForty-eight adolescents with T1DM who were 12 to 21 years of age (40% body mass index [BMI] ≥90th percentile; 56% female) and 24 nondiabetic control participants of similar age, BMI, and sex distribution were enrolled. Adolescents with T1DM demonstrated impaired aortic health compared with control participants, including elevated AA and descending aorta pulse wave velocity, reduced AA and descending aorta relative area change, and elevated AA and descending aorta WSSMAX and WSSTA. Adolescents with T1DM in the metformin versus placebo group had improved glucose infusion rate/insulin (12.2±3.2 [mg·kg-1·min-1]/μIU/μL versus -2.4±3.6 [mg·kg-1·min-1]/μIU/μL, P=0.005; 18.6±4.8 [mg·lean kg-1·min-1]/μIU/μL versus -3.4±5.6 [mg·lean kg-1·min-1]/μIU/μL, P=0.005) and reduced weight (-0.5±0.5 kg versus 1.6±0.5 kg; P=0.004), BMI (-0.2±0.15 kg/m2 versus 0.4±0.15 kg/m2; P=0.005), and fat mass (-0.7±0.3 kg versus 0.6±0.4 kg; P=0.01). Glucose infusion rate/insulin also improved in normal-weight participants (11.8±4.4 [mg·kg-1·min-1]/μIU/μL versus -4.5±4.4 [mg·kg-1·min-1]/μIU/μL, P=0.02; 17.6±6.7 [mg·lean kg-1·min-1]/μIU/μL versus -7.0±6.7 [mg·lean kg-1·min-1]/μIU/μL, P=0.02). The metformin group had reduced AA WSSMAX (-0.3±0.4 dyne/cm2 versus 1.5±0.5 dyne/cm2; P=0.03), AA pulse wave velocity (-1.1±1.20 m/s versus 4.1±1.6 m/s; P=0.04), and far-wall diastolic carotid intima-media thickness (-0.04±0.01 mm versus -0.00±0.01 mm; P=0.049) versus placebo.ConclusionsAdolescents with T1DM demonstrate IR and impaired vascular health compared with control participants. Metformin improves IR, regardless of baseline BMI, and BMI, weight, fat mass, insulin dose, and aortic and carotid health in adolescents with T1DM. Metformin may hold promise as a cardioprotective intervention in T1DM.Clinical trial registrationURL: https://www.clinicaltrials.gov . Unique identifier: NCT01808690.

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Personalized cytomic assessment of vascular health: Evaluation of the vascular health profile in diabetes mellitus.

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Personalized cytomic assessment of vascular health: Evaluation of the vascular health profile in diabetes mellitus.

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