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Introduction Pigment epithelium-derived factor (PEDF) may play a role in cardiometabolic disorders. The aim of this study was to investigate which biochemical and clinical parameters are independently associated with serum PEDF levels in patients with type 2 diabetes mellitus (T2DM). Methods We performed a cross-sectional analysis of 124 patients with T2DM who underwent continuous glucose monitoring (CGM) and blood chemistry analysis, including the diacron-reactive oxygen metabolites (d-ROMs) test and serum PEDF measurement (study 1). Then we investigated whether the changes in the studied biochemical and clinical parameters after 24 weeks of treatment (Δparameters) with anti-hyperglycemic agents, including sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and/or insulin and anti-hypertensive drugs and statins, were independently correlated with change in PEDF (ΔPEDF) in 52 of the patients with T2DM for whom there was sufficient serum samples to perform the post-treatment analysis (study 2). Serum levels of PEDF were measured with an enzyme-linked immunosorbent assay. CGM metrics were calculated on days 2 and 3. Oxidative stress was evaluated using the d-ROMs test. Results Body mass index (BMI), triglycerides, fasting C-peptide, mean amplitude of glycemic excursions (MAGE), urinary albumin-to-creatinine ratio (UACR), and d-ROMs were positively associated with serum PEDF level, and high-density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) were inversely associated with serum PEDF level. Because these parameters were correlated with each other, multivariate stepwise analysis was performed: eGFR, HDL-C, BMI, MAGE, and UACR remained significant (R2 = 0.452). Furthermore, ΔMAGE and Δd-ROMs were positively correlated with ΔPEDF in study 2. Conclusions The results of this study suggest that MAGE may be independently correlated with elevations in serum PEDF level in patients with T2DM.

Aims To date, no clinical studies have compared once-weekly dipeptidyl peptidase 4 (DPP-4) inhibitors with once-daily DPP-4 inhibitors in terms of glucose variability (GV) and oxidative stress (OS). Methods Thirty-six patients with type 2 diabetes mellitus (T2DM) treated with once-daily DPP-4 inhibitors for at least 12 weeks were randomized to either continue once-daily DPP-4 inhibitors or receive omarigliptin, a once-weekly DPP-4 inhibitor, for 24 weeks. The primary end points were changes in the diacron-reactive oxygen metabolite (d-ROMs) test, a marker of OS, and GV using flash glucose monitoring. The secondary end point was changes in the diabetes treatment satisfaction questionnaire (DTSQ) scores. Results There were no significant group differences in d-ROMs and DTSQ scores after 24 weeks of treatments. However, omarigliptin was superior to once-daily DPP-4 inhibitors in controlling fasting plasma glucose (FPG) and time in range (TIR). Although FPG and TIR were unchanged at 24 weeks after switching to omarigliptin, these parameters increased in the group receiving maintenance therapy with once-daily DPP-4 inhibitors. No statistically significant changes in hemoglobin A1c were observed between the two groups. Conclusions Our findings suggest that switching from once-daily DPP-4 inhibitors to omarigliptin may be efficacious for maintaining FPG and TIR in T2DM patients.

Aims: Standardized continuous glucose monitoring (CGM) metrics for clinical care were announced in 2019. There have been no reports, however, on the relationship between standardized CGM metrics and oxidative stress. We therefore decided to investigate the relationships between standardized CGM metrics, classical glycemic variability, and oxidative stress. Methods: This study was a cross-sectional analysis of 117 patients with type 2 diabetes mellitus (T2DM). Oxidative stress was estimated using the diacron-reactive oxygen metabolites (d-ROMs) test. The following parameters were used as CGM metrics: mean glucose level (MGL), percentage coefficient of variation for glucose (%CV), time above range (TAR), time in range (TIR), time below range (TBR), standard deviation (SD), and mean amplitude of glycemic excursions (MAGE), a classic index. Results: A total of 117 patients (mean age of 64.1 ± 12.6 years, mean disease duration of 13.1 ± 11.5 years, and HbA1c of 8.3 ± 1.5%) who met the study inclusion criteria were finally analyzed. The univariate analysis showed that age, triglyceride, HbA1c, MGL, %CV, SD, MAGE, and TAR were significantly correlated with d-ROMs. Further, a stepwise multiple regression analysis identified SD, MAGE, and sex as independent contributors to d-ROMs. Conclusions: Oxidative stress was associated with the SD and MAGE, two parameters affected by the mean glucose level, as CGM metrics in patients with T2DM. Disclosure Y. Kohata: None. M. Ohara: None. T. Fujikawa: None. H. Nagaike: None. H. Kushima: None. M. Hiromura: None. Y. Mori: Research Support; Self; Taisho Pharmaceutical Co., Ltd. T. Fukui: None. T. Hirano: None. S. Yamagishi: None.

Introduction Oxidative stress plays a central role in the development and progression of vascular complications in patients with type 2 diabetes mellitus (T2DM). We have previously shown that markers of glucose variability evaluated by continuous glucose monitoring (CGM) are positively associated with oxidative stress in patients with T2DM. However, the evaluation of the glycemic variability by CGM remains a time- and money-consuming procedure. Therefore, this study investigated the independent correlates of oxidative stress among various other clinical markers routinely measured in primary care. Methods This was a retrospective cross-sectional study with 234 T2DM patients to examine which clinical variables, including 1,5-anhydro-D-glucitol (1,5-AG) and glycated albumin (GA), were independently associated with oxidative stress. Oxidative stress was measured using the diacron-reactive oxygen metabolites (d-ROMs) test. The relationships between d–ROMs and clinical factors, such as blood glucose, glycated hemoglobin (HbA1c), 1,5-AG, GA, lipid parameters, and blood pressure, were examined. Results Multiple stepwise regression analysis revealed that 1,5-AG (inversely), GA, triglycerides, use of metformin and being female were independently associated with d-ROMs. When patients with T2DM were stratified into two groups with HbA1c

Aims To evaluate the clinical factors affecting daily and day-to-day glucose variability by using continuous glucose monitoring. Methods We performed a cross-sectional analysis of patients with type 2 diabetes mellitus (T2DM) who underwent a glucagon stimulation test (GST) with 72 h of continuous glucose monitoring. Daily glucose variability was evaluated by mean amplitude of glycemic excursions [MAGE], percentage coefficient of variation for glucose (%CV), and day-to-day glucose variability (mean of daily differences [MODD]) by using continuous glucose monitoring. Correlations of clinical factors, including insulin secretion ability by the GST with MAGE, %CV, and MODD, were analyzed. Results In 83 T2DM with insulin therapy, age and hemoglobin A1c (HbA1c) correlated with MAGE and %CV, fasting plasma glucose with MAGE and MODD, and increment of C-peptide immunoreactivity (ΔCPR) by GST correlated inversely with MAGE, %CV, and MODD. In 126 T2DM without insulin therapy, age, diastolic blood pressure, and triglycerides correlated with MODD, HbA1c with MAGE and MODD, and ΔCPR inversely correlated with %CV. Use of α-glucosidase inhibitors inversely correlated with %CV, whereas that of sulfonylurea was associated with MAGE and %CV. Conclusions These results suggest that ΔCPR correlated with stability of glycemic control, whereas poorly controlled diabetes is associated with increase in glucose variability. α-glucosidase inhibitors may be superior to sulfonylureas in reducing the glucose variability in T2DM.

This paper presents simple analytical models of hybrid TCP congestion controls, which switch loss-based mode and delay-based mode adaptively, and tries their performance tuning. We firstly present ideal behavior models of three kinds of TCP congestion controls (loss-based, delay-based and hybrid). We then give abstracted models of the actual hybrid TCP s and consider their performance tuning. Finally, experiments validate analytical expectations and effectiveness of the hybrid TCP.

This paper presents a hybrid congestion control algorithm supporting throughput efficiency, TCP friendliness and RTT fairness, in order to provide highly smart multimedia streaming over the Internet. Recent studies on TCP and TFRC are evolving to achieve better throughput efficiency and RTT fairness. Examples are Hybrid TCP congestion control, VTP and TCP-Libra, where the former two improve throughput efficiency of TCP and TFRC, respectively, and the last one improves RTT fairness of TCP. This paper integrates these ideas and propose a new congestion control algorithm, called Hybrid TFRC, for multimedia streaming. Experiments are carried out and effectiveness of our proposal is verified.

This paper presents TCP-Fusion supporting RTT (Round Trip Time) fairness in addition to throughput efficiency and friendliness to TCP-Reno. When multiple TCP flows having different RTT values compete, more bandwidth is unfairly allocated to the flow having smaller RTT. This means that a user with longer RTT may not be able to obtain sufficient bandwidth by the current methods. On the other hand, recent studies on the TCP congestion control to achieve RTT fairness and throughput efficiency are evolving actively. An example for RTT fairness is TCP-Libra and an example for throughput efficiency is Hybrid TCP congestion control. This paper focuses on Hybrid TCP (exploiting residual link capacity when TCP-Reno drops its rate) and improves its RTT fairness by incorporating the ideas of TCP-Libra (congestion window increase in proportion to square of RTT) to its loss mode. Experiments are carried out to validate the proposed method and much better performances in RTT fairness and throughput are provided against conventional methods.