Comparing the glycaemic outcomes between real-time continuous glucose monitoring (rt-CGM) and intermittently scanned continuous glucose monitoring (isCGM) among adults and children with type 1 diabetes: A systematic review and meta-analysis of randomized controlled trials.

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.

Effects of intermittently scanned continuous glucose monitoring in adult type 1 diabetes patients with suboptimal glycaemic control: A multi-centre randomized controlled trial.

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).

Nanotechnology translation in vascular diseases: From design to the bench.

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.

The relationship between humeral head angulation and bone void within the humeral head in proximal humerus fractures.

Background: The variability of humeral head angulation in proximal humerus fractures (PHFs) is a noteworthy observation. The purpose of this study was to investigate the potential association between humeral head angulation and bone void within the humeral head in PHFs. Methods: We used the reconstruction function in Mimics software to generate three-dimensional models of fractures. Bony landmarks were employed to accurately define the calcar and humeral head zone. Boolean subtraction was performed to calculate the volume of head bone void. Results: The cohort consisted of 60 (74.1 %) varus, 21 (25.9 %) valgus, and 23 (22.1 %) neutral angulated PHFs. The mean percentage of humeral head bone void was 38.5 ± 17.8 in varus, 36.3 ± 15.7 in valgus, and 30.1 ± 10.6 in neutral angulated PHFs. A significant difference was observed between the varus and neutral groups (P = 0.035). In addition, an analysis of humeral head bone void was conducted among patients aged over 65 years old, revealing a mean percentage of 42.7 ± 16.4 in varus (27 cases), 34.8 ± 14.5 in valgus (13 cases), and 28.1 ± 11.8 in neutral (8 cases) angulated PHFs. The difference between the varus and neutral groups was also significant (P = 0.023). Conclusion: All types of angulation patterns exhibited humeral head bone void to some extent, with the varus-displaced PHFs demonstrating more obvious defects in comparison to the neutral angulated type.

Factors influencing further vertebral height loss following percutaneous vertebroplasty in osteoporotic vertebral compression fractures: A 1-year follow-up study.

BACKGROUND: Osteoporotic vertebral compression fractures (OVCFs) contribute to back pain and functional limitations in older individuals, with percutaneous vertebroplasty (PVP) emerging as a minimally invasive treatment. However, further height loss post-PVP prompts investigation into contributing factors. AIM: To investigate the factors associated with further height loss following PVP with cement augmentation in OVCF patients. METHODS: A total of 200 OVCF patients who underwent successful PVP between January 2021 and December 2022 were included in this study. "Further height loss" during 1 year of follow-up in OVCF patients with bone edema was defined as a vertical height loss of ≥ 4 mm. The study population was divided into two groups for analysis: The "No Further Height Loss group (n = 179)" and the "Further Height Loss group (n = 21)." RESULTS: In comparing two distinct groups of patients, significant differences existed in bone mineral density (BMD), vertebral compression degree, prevalence of intravertebral cleft (IVF), type of bone cement used, and cement distribution patterns. Results from binary univariate regression analysis revealed that lower BMD, the presence of IVF, cleft distribution of bone cement, and higher vertebral compression degree were all significantly associated with further height loss. Notably, the use of mineralized collagen modified-poly(methyl methacrylate) bone cement was associated with a significant reduction in the risk of further height loss. In multivariate regression analysis, lower BMD and the presence of IVF remained significantly associated with further height loss. CONCLUSION: Further height loss following PVP in OVCF patients is influenced by a complex interplay of factors, especially lower BMD and the presence of IVF. These findings underscore the importance of assessing and managing these factors when addressing height loss following PVP in OVCF patients.

Protocol for a prospective, multicenter, parallel-group, open-label randomized controlled trial comparing standard care with Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control: the CO-PILOT trial.

Purpose: Advanced hybrid closed loop (AHCL) systems have the potential to improve glycemia and reduce burden for people with type 1 diabetes (T1D). Children and youth, who are at particular risk for out-of-target glycemia, may have the most to gain from AHCL. However, no randomized controlled trial (RCT) specifically targeting this age group with very high HbA1c has previously been attempted. Therefore, the CO-PILOT trial (Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control) aims to evaluate the efficacy and safety of AHCL in this group. Methods: A prospective, multicenter, parallel-group, open-label RCT, comparing MiniMed™ 780G AHCL to standard care (multiple daily injections or continuous subcutaneous insulin infusion). Eighty participants aged 7-25 years with T1D, a current HbA1c ≥ 8.5% (69 mmol/mol), and naïve to automated insulin delivery will be randomly allocated to AHCL or control (standard care) for 13 weeks. The primary outcome is change in HbA1c between baseline and 13 weeks. Secondary outcomes include standard continuous glucose monitor glycemic metrics, psychosocial factors, sleep, platform performance, safety, and user experience. This RCT will be followed by a continuation phase where the control arm crosses over to AHCL and all participants use AHCL for a further 39 weeks to assess longer term outcomes. Conclusion: This study will evaluate the efficacy and safety of AHCL in this population and has the potential to demonstrate that AHCL is the gold standard for children and youth with T1D experiencing out-of-target glucose control and considerable diabetes burden. Trial registration: This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry on 14 November 2022 (ACTRN12622001454763) and the World Health Organization International Clinical Trials Registry Platform (Universal Trial Number U1111-1284-8452). Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01397-4.

Relative contributions of fasting and postprandial glucose increments, glycemic variability, and non-glycemic factors to HbA1c in individuals with type 1 diabetes.

AIM: Evidence for contribution of basal and postprandial glucose increment, and glycemic variability to glycated hemoglobin (HbA1c) among adults with type 1 diabetes (T1D) is limited. This study aimed to capture glycemic fluctuation patterns and quantify contributions of these factors to HbA1c levels among adults with T1D. METHODS: HbA1c, continuous glucose monitoring (CGM), and diet diaries were collected and pooled from two clinical trials. Available data sets were divided into HbA1c quartiles: group 1 (≤6.7%), group 2 (6.7%-7.3%), group 3 (7.3%-7.8%), and group 4 (≥7.8%). Area under curve above 110 mg/dL (AUC>110mg/dL ) in 24-h profile was defined as overall hyperglycemia and stratified with postprandial hyperglycemia (PHG, AUC>110mg/dL in 3-h period after meals) and basal hyperglycemia (BHG, AUC>110mg/dL in remaining period). Linear regression analysis was used to estimate the proportion of variance in HbA1c explained by BHG, preprandial glucose, PHG, glycemic variability, and non-glycemic factors (age, body mass index, hemoglobin, and duration). RESULTS: A total of 169 550 glucose data in 2409 meals recorded from 102 patients (male/female, 34/68) were included. Age and duration were 35.2 ± 12.6 and 8.9 (2.9, 13.0) years, with 51.0% using pumps. Overall, BHG was four times higher than PHG (p all <.05) and between-group comparisons showed BHG exhibited a progressive increase (group 1 vs. 2, 3, 4, p = .053, .086, .006) with fasting contribution of 76.1%, 82.6%, 81.5%, and 84.3% from group 1 to 4. The increment was not significant among groups 2, 3, and 4 (p > .05). Factors included in analysis explained a total of 74% of the variance in HbA1c, in which BHG accounted for 32.1% of variance whereas PHG accounted for 24.4%. In group with HbA1c >7.3%, BHG accounted for a higher percentage with 33.8% of the variance in HbA1c. CONCLUSIONS: In our study, basal hyperglycemia better predicts overall glycemic control than postprandial hyperglycemia among adults with T1D. The relative contribution of basal hyperglycemia increased gradually with HbA1c increasing and predominant strategy for insulin titration among T1D is different among different levels of glycemic control.

Discrepancies in glycemic metrics derived from different continuous glucose monitoring systems in adult patients with type 1 diabetes mellitus.

BACKGROUND: Continuous glucose monitoring systems have been widely used but discrepancies among various brands of devices are rarely discussed. This study aimed to explore differences in glycemic metrics between FreeStyle Libre (FSL) and iPro2 among adults with type 1 diabetes mellitus (T1DM). METHODS: Participants with T1DM and glycosylated hemoglobin of 7%-10% were included and wore FSL and iPro2 for 2 weeks simultaneously. Datasets collected on the insertion and detachment day, and those with insufficient quantity (<90%) were excluded. Agreements of measurement accuracy and glycemic metrics were evaluated. RESULTS: A total of 40 498 paired data were included. Compared with the values from FSL, significantly higher median value was observed in iPro2 (147.6 [106.2, 192.6] vs. 144.0 [100.8, 192.6] mg/dl, p < 0.001) and the largest discordance was observed in hypoglycemic range (median absolute relative difference with iPro2 as reference value: 25.8% [10.8%, 42.1%]). Furthermore, significant differences in glycemic metrics between iPro2 and FSL were also observed in time in range (TIR) 70-180 mg/dl (TIR, 62.8 ± 12.4% vs. 58.8 ± 12.3%, p = 0.004), time spent below 70 mg/dl (4.4 [1.8, 10.9]% vs. 7.2 [5.4, 13.3]%, p < 0.001), time spent below 54 mg/dl (0.9 [0.3, 4.0]% vs. 2.6 [1.3, 5.6]%, p = 0.011), and coefficient of variation (CV, 38.7 ± 8.5% vs. 40.9 ± 9.3%, p = 0.017). CONCLUSIONS: During 14 days of use, FSL and iPro2 provided different estimations on TIR, CV, and hypoglycemia-related parameters, which needs to be considered when making clinical decisions and clinical trial designs.

Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis.

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.

Metformin in cardiovascular diabetology: a focused review of its impact on endothelial function.

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.

Effects of novel flash glucose monitoring system on glycaemic control in adult patients with type 1 diabetes mellitus: protocol of a multicentre randomised controlled trial.

INTRODUCTION: Optimal 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 ANALYSIS: This 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 DISSEMINATION: This 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 NUMBER: NCT03522870.

Impacts of glycemic variability on the relationship between glucose management indicator from iPro™2 and laboratory hemoglobin A1c in adult patients with type 1 diabetes mellitus.

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 ß = 0.83, p < 0.001). Further adjustment for SD or MAGE reduced the standardized ß for laboratory HbA1c from 0.83 to 0.71 and 0.73, respectively (both p < 0.001). In contrast, the ß 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.

Clinical Characteristics of Fulminant Type 1 Diabetes Compared with Typical Type 1 Diabetes: One-Year Follow-Up Study from the Guangdong T1DM Translational Medicine Study.

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). FT1DM patients had higher plasma glucose levels and higher percentage of diabetes ketoacidosis (P < 0.001). FT1DM patients had higher plasma glucose levels and higher percentage of diabetes ketoacidosis (P < 0.001). FT1DM patients had higher plasma glucose levels and higher percentage of diabetes ketoacidosis (P < 0.001). FT1DM patients had higher plasma glucose levels and higher percentage of diabetes ketoacidosis (P < 0.001). FT1DM patients had higher plasma glucose levels and higher percentage of diabetes ketoacidosis (P < 0.001). FT1DM patients had higher plasma glucose levels and higher percentage of diabetes ketoacidosis (P < 0.001). FT1DM patients had higher plasma glucose levels and higher percentage of diabetes ketoacidosis (. 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.