ObjectiveHypoglycemia represents a serious acute complication in individuals with type 1 diabetes mellitus (T1DM). In order to more effectively identify and discriminate the occurrence of hypoglycemic events in patients with T1DM, this study aims to evaluate the impact of two distinct glucose monitoring systems—Flash Glucose Monitoring (FGM) and Continuous Glucose Monitoring (CGM)—on the management of blood glucose levels and the emotional responses associated with hypoglycemic episodes in individuals with T1DM.MethodIn this study, a total of 113 patients with type 1 diabetes mellitus were enrolled and allocated to two groups for the implementation of Glucose Monitoring Systems (GMS). The groups consisted of the FreeStyle Libre group (FGM, n=56) and the ipro2 group (CGM, n=57). Participants in both groups utilized GMS at least biannually and completed a set of three questionnaires: the Diabetes Monitoring and Treatment Satisfaction Questionnaire (DMTSQ), the Diabetes Specific Quality of Life (DQOL), and the Chinese Version of the Hypoglycemia Fear Survey II (CFHSII). Clinical data, CGM metrics, and questionnaire scores were collected at the initial visit and after a one-year follow-up period.ResultsThe glucose coefficient of variation (GCV) and the standard deviation of blood glucose (SDBG) were independently associated with Time Below Range (TBR). Specifically, GCV could predict TBR ≥12%, with a cut-off point of 40.55. This yielded a specificity of 88.10% and a sensitivity of 68.18% in the overall patient population. For the FreeStyle Libre group and the iPro2 group, the cut-off points were 38.69 and 40.55, respectively, with specificities of 0.74 and 0.92, and sensitivities of 0.73 and 0.86, respectively. In the FreeStyle Libre group, where the frequency of use was greater than or equal to five times per year, the hypoglycemic episodes (time/month) and CHFSII-B scores were significantly reduced at follow-up compared to baseline (7.80 ± 10.25 vs 13.95 ± 14.87; 27.37 ± 11.05 vs 38.90 ± 21.61, respectively, all P <0.05).ConclusionThe utilization of multiple Flash Glucose Monitoring (FGM) implementations proved to be valuable in discriminating the occurrence of hypoglycemia and mitigating the fear of hypoglycemic episodes in patients with type 1 diabetes. Within the parameters of Glucose Monitoring Systems (GMS), the glucose glycemic variability (GCV) was identified as a predictive factor for the risk of severe hypoglycemia (TBR > 12%). The optimal cut-off point for GCV was determined to be 40.55.

BACKGROUND:Diabetes mellitus (DM) is a clinical condition that affects gait performance and control in millions of individuals worldwide. Contrary to basic spatiotemporal parameters, gait-based spectral analysis may provide useful insights into gait neuromotor control. Hence, this study was set to investigate the spectral content of gait at the preferred speed in patients with DM. METHODS:Total 1117 individuals [658 DM and 649 healthy adults (HA)] performed a 10 m walk while wearing an inertial measurement unit over the fourth lumbar vertebra. Mann-Whitney-U test was used for between-group gait parameters comparisons. RESULTS:DM group had a slower step time (1.2%, p < 0.05) and gait speed (2.4%, p < 0.05) than HA. Additionally, DM individuals showed reduced dominant frequency (DM:0.24 Hz vs HA:0.25 Hz on average, p < 0.05). Increased antero-posterior and vertical dominant frequency width (DM:1.73 Hz vs HA:1.76 Hz on average, p < 0.05) and medio-lateral relative power spectral density at the dominant frequency (DM:6.19% vs HA:5.96%, p < 0.05). CONCLUSIONS:It was demonstrated for the first time that the gait spectral content, not only corroborates spatiotemporal characteristics, but also provides further insight into their neuromotor control deficits in diabetic patients. Ultimately, this type of analysis in the diabetic population can help guide the therapeutic interventions to prevent diabetic foot.

Interleukin (IL)‐17 is associated with autoimmunity. This study aimed to affirm the role of IL‐17A, IL‐17F and single nucleotide polymorphisms (SNPs) in genes related to them and their receptors in autoimmune type 1 diabetes (T1D) for Chinese population.

Objective This study was to assess the alteration of circulating complement factor Ba (CFBa) within 11 to 17 weeks of gestation and its association with subsequent gestational diabetes mellitus (GDM) and its delivery outcome. Methods Biochemical parameters and blood samples were collected from 399 pregnant women within 11 to 17 weeks of gestation. At 24 to 28 weeks of gestation, all participants underwent 75-g oral glucose tolerance test and were assigned to GDM group (n = 80) and normal control group (n = 319). Perinatal data were collected after delivery. A propensity score-matched (PSM) analysis was performed to reduce the impact of confounding factors on glucose metabolism during pregnancy between the two groups. Results Two groups of 74 well-matched patients who maintained balance in terms of baseline characteristics. The levels of CFBa in pregnant women who later developed GDM were significantly higher than those in healthy pregnant women [0.4(0.1-0.8) vs. 0.2(0.2-0.3), p = 0.024]. Logistic regression analysis results confirmed that the level of CFBa was an independent impact factor for the occurrence of GDM (OR = 1.57, 95% CI: 1.118-2.210, p = 0.009). Further grouping according to the median level of CFBa, it was found that the incidence of GDM in category two (>0.23 ng/ml, n = 74) was markedly higher than that in the first category (<= 0.23 ng/ml, n = 74) (p = 0.021). Conclusions High level of the CFBa within 11 to 17 weeks of gestation increases the risk of subsequent GDM, and maybe a biomarker for predicting GDM.

AbstractBackgroundComplement factor H (CFH) has been found to be associated with insulin resistance. This study assessed the correlation between CFH and other clinical parameters, and determined whether CFH played a role in gestational diabetes mellitus (GDM) and adverse pregnancy outcomes.MethodsA total of 397 pregnant women were included for analysis in this nested case-control study. Clinical parameters and serum were collected within the 11-17th gestational age at the first prenatal visit. At 24–28 weeks of gestation, a 75 g oral glucose tolerance test was performed and subjects were divided into a GDM (n = 80) and a non-GDM control group (n = 317). The delivery data were also followed. The serum CFH level was assayed by ELISA.ResultsCFH was higher in GDM than in non-GDM controls (280.02 [58.60] vs. 264.20 [68.77];P = 0.014). CFH level was moderately associated with pre-pregnancy body mass index (BMI), BMI and total triglycerides (TG), and slightly associated with gestational age, low density lipoprotein cholesterol (LDL-C), total cholesterol (TC) in GDM and non-GDM (allP < 0.05). Moreover, CFH level was moderately correlated with alkaline phosphatase (ALP) and slightly correlated with age, uric acid (UA) and total bilirubin (TB) in non-GDM (allP < 0.05). After adjustment for clinical confounding factors, BMI, TG, gestational age, ALP, TB, age and UA were independent risk factors for log10CFH levels (allP < 0.05) in all subjects. In addition, overweight or obese pregnant women, women with hypertriglyceridemia and women in the second trimester had significantly higher CFH levels than normal weight and underweight group (P < 0.001), the non-hypertriglyceridemia group (P < 0.001) and women in the first trimester group (P < 0.05) in all pregnant women respectively. Following binary logistic regression, CFH was not independently associated with GDM and related pregnant outcomes.ConclusionsThe CFH in 11-17th weeks of gestation might be affected by many factors, including BMI, TG, gestational age, ALP, TB, age and UA. CFH was not an independent risk factor for GDM and avderse pregnancy outcomes.

Aims: Hypoglycemia is an acute complication of patients with type 1 diabetes. This study investigated flash glucose monitoring in hypoglycemia monitor in patients with type 1 diabetes. Methods: A total of 120 patients with type 1 diabetes were recruited and randomly divided to implement FreeStyle LibreTM as flash glucose monitoring group (n=60) and retrospective continuous glucose monitoring system (CGMS) as control group (n=60). Both groups carried out CGMS at least two times a year and filled three questionnaires including Diabetes Monitoring and Treatment Satisfaction Questionnaire (DMTSQ), Diabetes Specific Quality of Life (DQoL) and Chinese Version Hypoglycemia Fear Survey II (CFH II). Clinical Data, CGM metrics and Questionnaire scores were collected at first visit and one year follow up. Results: The result showed that the time below range (TBR) and the glucose coefficient of variation (CV) were significantly higher in flash glucose monitoring group than control group (all P <0.05). TBR was prolonged with the increase of CV (P <0.05) and low blood glucose index (LBGI) (P <0.05) in both two groups. After multiple stepwise linear regression, CV and LBGI were independent risk factors for TBR (Standardized Coefficients β=0.665, β=0.762, respectively, All P<0.001 ). After one year followed up, the scores of DQoL and DMTSQ had no significant difference, but number of hypoglycemia times per month and scores of behavior part of CFH II significantly decreased in flash glucose monitoring group compared with a year ago (all P<0.05). Conclusions: Glucose CV and LBGI were independent risk factors for TBR. And Flash glucose monitoring decreased number of hypoglycemia times per month and fear behavior of hypoglycemia in patients with type 1 diabetes after one year. Disclosure J. Li: None. F. Liu: None. Funding National Key Research and Development Program of China (2017YFC1309601)

Background: Several studies have shown that the over activation of complement factor B(CFB) was related to obesity, insulin resistance(IR) and type 2 diabetes mellitus. This study was to assess whether circulating complement factor Ba (CFBa) within 11 to 17 weeks of gestation is associated with subsequent gestational diabetes mellitus (GDM) or not. Methods: Biochemical parameters and blood samples were collected from 399 pregnant women within 11 to 17 weeks of gestation. At 24 to 28 weeks of pregnancy, all participants underwent 75-g oral glucose tolerance test (fasting for more than 8 hours before blood sampling) and were assigned to GDM group(n=80) and normal control group(n=319). Perinatal data were collected after delivery. A propensity score-matched (PSM) analysis was performed to reduce the impact of confounding factors on glucose metabolism during pregnancy between the two groups. Results: Two groups of 74 well-matched patients who maintained balance in terms of baseline characteristics. The levels of CFBa in pregnant women who later developed GDM were significantly higher than those in healthy pregnant women [0.4(0.1-0.8) vs. 0.2(0.2-0.3), P =0.031]. Logistic regression results confirmed that the level of CFBa was an independent influencing factor for the occurrence of GDM (OR=1.52, 95% CI: 1.25-1.85, P =0.000). Further grouping according to the quartile of CFBa level, it was found that the incidence of GDM in category 3 was markedly higher than that in the first and the second categories. Conclusions: High level of the CFBa within 11 to 17 weeks of gestation increased the risk of subsequent GDM, and maybe a biomarker for predicting GDM.

Purpose: To explore a new mechanism of improving glucose homeostasis in pregnancy through activation of Takeda G protein-coupled receptor 5 (TGR5) in bone marrow derived macrophages (BMDM) from gestational diabetes mellitus (GDM) model mouse and observation the changes of macrophages migration, inflammatory factors and chemokines expression and secretion, and the expression of Proprotein Convertase 1/3 (PC1/3). Methods: INT-777 was used as TGR5 agonist and LPS was used as inducer for macrophage polarization to M1. Primary bone marrow cells were extracted from GDM model mouse and were induced into macrophages. The macrophages activity and migration were detected by cck-8 tests and Transwell assay respectively when macrophages were treated with INT-777. The expression and secretion levels of inflammatory factors and chemokines in macrophages were detected by real-time PCR, cytometric bead array and ELISA, and the expression levels of PC1/3 was detected by Western blot when macrophages were treated both with INT-777 and lipopolysaccharide (LPS). Results: TGR5 activation of macrophages by INT-777 increased cell activity (P < 0.01) and decreased cell migration (P < 0.001). Moreover, the mRNA levels of inflammatory cytokines and chemokines including IL-1β, IL-6, TNF-α, CCL2, CCL4, CCL5 and CCL7 mRNA were significantly decreased (All P < 0.05), the secretion levels of inflammatory cytokines and chemokines including IL-6, TNF-α, MCP-1, CCL2, CCL3 and CCL4 were significantly decreased (All P < 0.05) and the expression of PC1/3 was increased (P < 0.05) in INT-777 + LPS treated macrophages, compared with LPS treated macrophages only. Conclusions: Activation of TGR5 in BMDM can effectively inhibit the macrophage polarization to M1, including inhibiting inflammatory factors expression and secretion. Moreover, activation of TGR5 can inhibit macrophage chemokine expression and secretion, cell migration and can upregulate PC1/3 expression. Disclosure J. Li: None. F. Liu: None. Funding National Natural Science Foundation of China (81770802)

Background Mesenchymal stem cell (MSC)-derived exosomes emerge as promising candidates for treating delayed wound healing in diabetes due to the promotion of angiogenesis. Preconditioned MSC with chemical or biological factors could possibly enhance the biological activities of MSC-derived exosomes. The purpose of this research focused on whether exosomes derived from the bone marrow MSC (BMSC) pretreated with atorvastatin (ATV), could exhibit better pro-angiogenic ability in diabetic wound healing or not and its underlying molecular mechanism. Methods We isolated exosomes from non-pretreated BMSC (Exos) and ATV pretreated BMSC (ATV-Exos) and evaluated their characterization by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and Western blotting. In vivo, we made full-thickness skin defects in streptozotocin (STZ)-induced diabetic rats and the defects received multiple-point injection with PBS, Exos, or ATV-Exos. Two weeks later, histological analysis was conducted to evaluate the impact of different treatments on wound healing and the neovascularization was measured by micro-CT. In vitro, cell proliferation, migration, tube formation, and vascular endothelial growth factor (VEGF) secretion were measured in human umbilical vein endothelial cells (HUVEC). The role of miRNAs and AKT/eNOS signaling pathway in the promoted angiogenesis of ATV-Exos were assessed with their inhibitors. Results No significant difference in morphology, structure, and concentration was observed between ATV-Exos and Exos. In STZ-induced diabetic rats, ATV-Exos exhibited excellent abilities in facilitating the wound regeneration by promoting the formation of blood vessels compared with Exos without influencing liver and kidney function. Meanwhile, ATV-Exos promoted the proliferation, migration, tube formation, and VEGF level of endothelial cells in vitro. And AKT/eNOS pathway was activated by ATV-Exos and the pro-angiogenic effects of ATV-Exo were attenuated after the pathway being blocked. MiR-221-3p was upregulated by ATV-Exos stimulation, and miR-221-3p inhibitor suppressed the pro-angiogenesis effect of ATV-Exos. Conclusions Exosomes originated from ATV-pretreated MSCs might serve as a potential strategy for the treatment of diabetic skin defects through enhancing the biological function of endothelial cells via AKT/eNOS pathway by upregulating the miR-221-3p.