Atherosclerosis is an immuno-metabolic disease involving chronic inflammation, oxidative stress, epigenetics, and metabolic dysfunction. There is compelling evidence suggesting numerous modifications ...including the change of the size, density, and biochemical properties in the low-density lipoprotein (LDL) within the vascular wall. These modifications of LDL, in addition to LDL transcytosis and retention, contribute to the initiation, development and clinical consequences of atherosclerosis. Among different atherogenic modifications of LDL, oxidation represents a primary modification. A series of pathophysiological changes caused by oxidized LDL (oxLDL) enhance the formation of foam cells and atherosclerotic plaques. OxLDL also promotes the development of fatty streaks and atherogenesis through induction of endothelial dysfunction, formation of foam cells, monocyte chemotaxis, proliferation and migration of SMCs, and platelet activation, which culminate in plaque instability and ultimately rupture. This article provides a concise review of the formation of oxLDL, enzymes mediating LDL oxidation, and the receptors and pro-atherogenic signaling pathways of oxLDL in vascular cells. The review also explores how oxLDL functions in different stages of endothelial dysfunction and atherosclerosis. Future targeted pathways and therapies aiming at reducing LDL oxidation and/or lowering oxLDL levels and oxLDL-mediated pro-inflammatory responses are also discussed.
IntroductionOptimal glycaemic control is beneficial to prevent and delay microvascular complications in patients with type 1 diabetes mellitus (T1DM). The benefits of flash glucose monitoring (FGM) ...have been proved among well-controlled adults with T1DM, but evidence for FGM in adults with T1DM who have suboptimal glycaemic control is limited. This study aims to evaluate the effect of FGM in suboptimally controlled adult patients with T1DM .Methods and analysisThis open-label, multicentre, randomised trial will be conducted at eight tertiary hospitals and recruit 104 adult participants (≥18 years old) with T1DM diagnosed for at least 1 year and with suboptimal glycaemic control (glycated haemoglobin (HbA1c) ranging from 7.0% to 10.0%). After a run-in period (baseline, 0–2 weeks), eligible participants will be randomised 1:1 to either use FGM or self-monitoring of blood glucose alone consequently for the next 24 weeks. At baseline, 12–14 weeks and 24–26 weeks, retrospective continuous glucose monitoring (CGM) systems will be used in both groups for device-related data collection. Biological metrics, including HbA1c, blood routine, lipid profiles, liver enzymes, questionnaires and adverse events, will be assessed at baseline, week 14 and week 26. All analyses will be conducted on the intent-to-treat population. Efficacy endpoint analyses will also be repeated on the per-protocol population. The primary outcome is the change of HbA1c from baseline to week 26. The secondary outcomes are the changes of CGM metrics, including time spent in range, time spent in target, time spent below range, time spent above range, SD, coefficient of variation, mean amplitude of glucose excursions, high or low blood glucose index, mean of daily differences, percentage of HbA1c in target (<7%), frequency of FGM use, total daily insulin dose and the scores of questionnaires including Diabetes Distress Scale, Hypoglycemia Fear Scale and European Quality of Life Scale.Ethics and disseminationThis study was approved by the Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University in January 2017. Ethical approval has been obtained at all centres. All participants will be provided with oral and written information about the trial. The study will be disseminated by peer-review publications and conference presentations.Trial registration numberNCT03522870.
Aims:
Our aim was to investigate the impact of glycemic variability (GV) on the relationship between glucose management indicator (GMI) and laboratory glycated hemoglobin A1c (HbA1c).
Methods:
Adult ...patients with type 1 diabetes mellitus (T1D) were enrolled from five hospitals in China. All subjects wore the iPro™2 system for 14 days before HbA1c was measured at baseline, 3 months and 6 months. Data derived from iPro™2 sensor was used to calculate GMI and GV parameters standard deviation (SD), glucose coefficient of variation (CV), and mean amplitude of glycemic excursions (MAGE). Differences between GMI and laboratory HbA1c were assessed by the absolute value of the hemoglobin glycation index (HGI).
Results:
A total of 91 sensor data and corresponding laboratory HbA1c, as well as demographic and clinical characteristics were analyzed. GMI and HbA1c were 7.20 ± 0.67% and 7.52 ± 0.73%, respectively. The percentage of subjects with absolute HGI 0 to lower than 0.1% was 21%. GMI was significantly associated with laboratory HbA1c after basic adjustment (standardized β = 0.83, p < 0.001). Further adjustment for SD or MAGE reduced the standardized β for laboratory HbA1c from 0.83 to 0.71 and 0.73, respectively (both p < 0.001). In contrast, the β remained relatively constant when further adjusting for CV. Spearman correlation analysis showed that GMI and laboratory HbA1c were correlated for each quartile of SD and MAGE (all p < 0.05), with the corresponding correlation coefficients decreased across ascending quartiles.
Conclusions:
This study validated the GMI formula using the iPro™2 sensor in adult patients with T1D. GV influenced the relationship between GMI and laboratory HbA1c.
Aims: Our aim was to investigate the impact of glycemic variability (GV) on the relationship between glucose management indicator (GMI) and laboratory glycated hemoglobin A1c (HbA1c). Methods: Adult ...patients with type 1 diabetes mellitus (T1D) were enrolled from five hospitals in China. All subjects wore the iPro ™ 2 system for 14 days before HbA1c was measured at baseline, 3 months and 6 months. Data derived from iPro ™ 2 sensor was used to calculate GMI and GV parameters standard deviation (SD), glucose coefficient of variation (CV), and mean amplitude of glycemic excursions (MAGE). Differences between GMI and laboratory HbA1c were assessed by the absolute value of the hemoglobin glycation index (HGI). Results: A total of 91 sensor data and corresponding laboratory HbA1c, as well as demographic and clinical characteristics were analyzed. GMI and HbA1c were 7.20 ± 0.67% and 7.52 ± 0.73%, respectively. The percentage of subjects with absolute HGI 0 to lower than 0.1% was 21%. GMI was significantly associated with laboratory HbA1c after basic adjustment (standardized β = 0.83, p < 0.001). Further adjustment for SD or MAGE reduced the standardized β for laboratory HbA1c from 0.83 to 0.71 and 0.73, respectively (both p < 0.001). In contrast, the β remained relatively constant when further adjusting for CV. Spearman correlation analysis showed that GMI and laboratory HbA1c were correlated for each quartile of SD and MAGE (all p < 0.05), with the corresponding correlation coefficients decreased across ascending quartiles. Conclusions: This study validated the GMI formula using the iPro ™ 2 sensor in adult patients with T1D. GV influenced the relationship between GMI and laboratory HbA1c.
Background. Fulminant type l diabetes mellitus (FT1DM) is a subtype of type 1 diabetes mellitus (T1DM) with abrupt onset, but data on its progression was limited. This study was aimed at exploring ...the clinical features through one-year follow-up. Methods and Materials. Patients with T1DM finishing at least one-year follow-up from June 2011 to July 2018 were enrolled from Guangdong Type 1 Diabetes Translational Medicine Study. Patients who fulfilled the respective criteria were categorized as an FT1DM group and a typical T1DM group (TT1DM). The 1 : 4 propensity score matching based on onset age, duration, and gender was performed between the FT1DM and TT1DM groups. Characteristics at the onset and after one-year follow-up were compared between the two groups. Results. A total of 53 patients with FT1DM and 212 matched patients with TT1DM were included. At the onset, there was a shorter duration of symptomatic period before diagnosis observed in the FT1DM group than in the TT1DM group (2 1, 7 vs. 30 10, 60 days, P<0.001). FT1DM patients had higher plasma glucose levels and higher percentage of diabetes ketoacidosis (P<0.001, respectively). Both fasting and postprandial C-peptide levels (FCP and PCP, respectively) in FT1DM were significantly lower (P<0.001). At enrollment, the duration of diabetes was 0.03 (0.00, 0.81) and 0.07 (0.00, 1.11) years and the level of HbA1c was 7.21±1.56% and 10.06±3.23% (P<0.001) in the FT1DM and TT1DM groups, respectively. After one year, both FCP and PCP were still significantly lower in the FT1DM group (P<0.001, 0.022) and the HbA1c level was similar between the two groups (P=0.128). The level of HDL-C in FT1DM was significantly higher than that in the TT1DM group at enrollment (P=0.019), and the change from enrollment was significantly greater than that in the FT1DM group (P=0.042). Conclusion. Patients with FT1DM had more severe metabolic derangement and deficiency of insulin secretion than patients with TT1DM at the onset, but glycaemic and metabolic control was not worse than that in TT1DM.
Atherosclerosis is a systemic pathophysiological condition contributing to the development of majority of polyvascular diseases. Nanomedicine is a novel and rapidly developing science. Due to their ...small size, nanoparticles are freely transported in vasculature, and have been widely employed as tools in analytical imaging techniques. Furthermore, the application of nanoparticles also allows target intervention, such as drug delivery and tissue engineering regenerative methods, in the management of major vascular diseases. Therefore, by summarizing the physical and chemical characteristics of common nanoparticles used in diagnosis and treatment of vascular diseases, we discuss the details of these applications from cellular, molecular, and in vivo perspectives in this review. Furthermore, we also summarize the status and challenges of the application of nanoparticles in clinical translation.
This article is categorized under:
Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease
Implantable Materials and Surgical Technologies > Nanomaterials and Implants
Therapeutic Approaches and Drug Discovery > Emerging Technologies
Nanomedicine‐based strategies to diagnose and treat vascular disease.
Aims
To investigate whether intermittently scanned continuous glucose monitoring without alarms (intermittently scanned CGM (isCGM)) improves glycaemic control over capillary blood glucose monitoring ...(BGM) among adult type 1 diabetes mellitus (T1DM) patients with suboptimal control.
Materials and Methods
Adults with T1DM and HbA1c between 7% and 10% were 1:1 randomized to use isCGM or BGM for 24 weeks. The primary outcome was the change in HbA1c levels after intervention. The secondary outcomes were the changes in sensor‐derived metrics.
Results
A total of 104 adults with T1DM (34.2 ± 12.2 years; M/F, 38/66) were randomized to the isCGM group (n = 54) and the BGM group (n = 50). After 24 weeks, HbA1c significantly decreased in the isCGM group (8.1 ± 0.7% to 7.5 ± 1.0%) and the BGM group (8.0 ± 0.8% to 7.7 ± 1.0%) with between‐group differences of 0.3% (95% coefficient intervals, 0.0%–0.6%; P = 0.04). The percentage of HbA1c reduction over 1.0% and 1.5% was significantly higher in the isCGM group with adjusted odds ratios of 2.5 (95% CI: 1.1–5.5; P = 0.03) and 3.2 (95% CI: 1.1–9.0; P = 0.03). Mean time‐in‐range 70–180 mg/dl (TIR) in the isCGM group significantly increased (from 58.5 ± 13.0% to 63.0 ± 12.6%), whereas mean TIR was similar in the BGM group (from 58.0 ± 14.6% to 57.5 ± 14.5%). Time spent in hyperglycemia reduced more in the isCGM group and time spent in hypoglycemia did not change significantly in both groups.
Conclusions
Among adult T1DM patients with suboptimal glycaemic control, compared with BGM, isCGM use resulted in a statistically significant improvement in glycaemic control after 24‐week intervention.
Trial Registration
Clinicaltrials.gov Identifier (NCT03522870)
As a first-line treatment for diabetes, the insulin-sensitizing biguanide, metformin, regulates glucose levels and positively affects cardiovascular function in patients with diabetes and ...cardiovascular complications. Endothelial dysfunction (ED) represents the primary pathological change of multiple vascular diseases, because it causes decreased arterial plasticity, increased vascular resistance, reduced tissue perfusion and atherosclerosis. Caused by "biochemical injury", ED is also an independent predictor of cardiovascular events. Accumulating evidence shows that metformin improves ED through liver kinase B1 (LKB1)/5'-adenosine monophosphat-activated protein kinase (AMPK) and AMPK-independent targets, including nuclear factor-kappa B (NF-κB), phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), endothelial nitric oxide synthase (eNOS), sirtuin 1 (SIRT1), forkhead box O1 (FOXO1), krüppel-like factor 4 (KLF4) and krüppel-like factor 2 (KLF2). Evaluating the effects of metformin on endothelial cell functions would facilitate our understanding of the therapeutic potential of metformin in cardiovascular diabetology (including diabetes and its cardiovascular complications). This article reviews the physiological and pathological functions of endothelial cells and the intact endothelium, reviews the latest research of metformin in the treatment of diabetes and related cardiovascular complications, and focuses on the mechanism of action of metformin in regulating endothelial cell functions.
Aim
To conduct a systematic review and meta‐analysis of randomized controlled trials (RCTs) comparing the effectiveness of real‐time continuous glucose monitoring (rtCGM) versus intermittently ...scanned continuous glucose monitoring (isCGM) on key glycaemic metrics (co‐primary outcomes HbA1c and time‐in‐range TIR 70–180 mg/dL, 3.9–10.0 mmol/L) among people with type 1 diabetes (T1D).
Methods
Medline, PubMed, Scopus, Web of Science and Cochrane Central Register of clinical trials were searched. Inclusion criteria were RCTs; T1D populations of any age and insulin regimen; comparing any type of rtCGM with isCGM (only the first generation had been compared to date); and reporting the glycaemic outcomes. Glycaemic outcomes were extracted post‐intervention and expressed as mean differences and 95% CIs between the two comparators. Results were pooled using a random‐effect meta‐analysis. The risk of bias was assessed using the Cochrane RoB2 tool. The quality of evidence was assessed by the GRADE approach.
Results
Five RCTs met the inclusion criteria (4 parallel and 1 crossover design; 4 with CGM use <8 weeks), involving 446 participants (354 adults; 92 children and adolescents). Overall, meta‐analysis showed rtCGM compared to isCGM improved absolute TIR by +7.0% (95% CI: 5.8%–8.3%, I2 = 0%, p < 0.01) accompanied by a favorable effect on time‐below‐range <70 mg/dL (3.9 mmol/L) – 1.7% (95%CI: −3.0% to −0.4%; p = 0.03). No differences were seen regarding HbA1c.
Conclusions
This meta‐analysis highlights that for people with T1D, rtCGM confers benefits over isCGM primarily related to increased TIR, with improvements in hypo‐ and hyperglycaemia.
Background: The relation of CGM derived parameters and adverse pregnancy outcomes (APOs) in pregnant women with type 1 diabetes (T1D) is not completely clear.
Methods: During 2015 - 2018, data were ...prospectively collected from pregnancies of women with pregestational T1D receiving intermittent CGM in 11 centers in China. Characteristics and CGM derived parameters were compared between the women who had severe APOs and those who did not. Severe APOs were defined as maternal death, neonatal death, congenital anomaly, pregnancy loss in 2nd/3rd trimester and neonatal admission to intensive care unit.
Results: Data of 84 pregnant women with pregestational T1D were collected. Among them, 56 had received CGM in the 1st trimester, 55 in the 2nd trimester, and 59 in the 3rd trimester. 30 of these 84 women had severe APOs. Compared with women without severe APOs, women who had severe APOs had lower age at diagnosis, longer diabetes duration at conception. For CGM derived parameters, women who had severe APOs had significantly higher mean glucose (MG), MG at wake, MG at night, and time above range (TAR, >7.8mmol/L) throughout all 3 trimesters, compared with women who did not have. Details see Table.
Conclusions: Higher MG, MG at wake, MG at night, and TAR throughout pregnancy were associated with the presence of severe APOs in women with T1D. These parameters should be closely monitored.
Disclosure
S. Luo: None. P. Ling: None. Y. Ding: None. X. Zheng: None. D. Yang: None. Y. Zhou: None. J. Yan: None. J. Weng: None.
Funding
National Health and Family Planning Commission of the People’s Republic of China; Foundation for Public Welfare Industry Research Project (201502011)
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