Search

Diabetes mellitus (DM) and arginine vasopressin deficiency (AVP‐D) are characterized by polyuria. Marfan syndrome is an autosomal dominant disorder caused by pathogenetic variants in FBN1. Here, we report a patient with type 2 diabetes mellitus, AVP‐D, and Marfan syndrome. Although the coexistence of type 2 diabetes mellitus and AVP‐D is rare, for those patients with type 2 diabetes mellitus, the existence of AVP‐D should be considered when polyuria is not in accordance with the blood glucose levels, especially for those with a low urine specific gravity. Specific symptoms or signs help to identify Marfan syndrome early, and genetic testing of the FBN1 pathogenetic variant helps to make a definitive diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to investigate whether treatment with exenatide could increase time in range (TIR) and decrease glycemic variability, and to evaluate the association between TIR and endothelial injury in patients with type 2 diabetes mellitus (T2DM). Methods: Two-hundred patients with T2DM treated with exenatide for 16 weeks were included in this study. Seven-point fingerstick blood glucose was used to evaluate derived TIR and glycemic variability. The serum levels of soluble endothelial cell protein C receptor (sEPCR) and von Willebrand factor (vWF) were measured. Ninety-three patients having the data of endothelial injury markers were categorized as derived TIR > 70% or ≤ 70% after the treatment and the association between TIR and endothelial injury were evaluated. Results: Treatment with exenatide for 16 weeks resulted in a significant reduction in fasting blood glucose, postprandial 2 h blood glucose, and glycated hemoglobin A1c (HbA1c) levels in patients with T2DM. Compared with baseline, derived TIR value was significantly increased [85.7 (57.1, 100.0) % vs. 42.9 (14.9, 71.4) %, P < 0.001], and the parameters of glycemic variability were remarkably decreased after the treatment. After the treatment, serum sEPCR level was significantly decreased from baseline in patients with TIR > 70% [74.5 (32.8, 122.5) ng/mL vs. 96.9 (48.5, 150.9) ng/mL, P = 0.006] but not in those with TIR ≤ 70%; serum vWF level was remarkably decreased in patients with TIR > 70% [from 1166.2 (848.1, 1335.5) mIU/mL to 907.4 (674.3, 1335.1) mIU/mL, P = 0.001] while this effect was modest in those with TIR ≤ 70%. Conclusions: Treatment with exenatide increases TIR and decreases glycemic variability in patients with T2DM. Moreover, the amelioration of endothelial injury is more pronounced in patients with TIR > 70% after the treatment. Trial Registration: ChiCTR-IPR-15006558 (registered, 27 May 2015). [ABSTRACT FROM AUTHOR]

Aims: We aimed to investigate whether treatment with exenatide could ameliorate endothelial injury in patients with type 2 diabetes mellitus (T2DM), and to identify biomarkers for predicting amelioration of the endothelial injury induced by the treatment.Methods: Ninety-three patients with T2DM were recruited and treated with exenatide for 16 weeks. Enzyme-linked immunosorbent assays were performed at baseline and after the treatment to measure serum levels of endothelial injury markers, including soluble thrombomodulin (sTM). Patients were categorized as responders (n = 47) or non-responders (n = 46) based on median changes in their sTM levels. Serum levels of metabolites at baseline were measured with non-targeted liquid chromatography-mass spectrometry. The results obtained were evaluated with multivariate analysis.Results: Treatment with exenatide for 16 weeks resulted in reduced body weight and improved levels of fasting plasma glucose, 2-hour postprandial plasma glucose, and HbA1c in patients with T2DM (all P < 0.05). Compared with baseline, serum levels of endothelial injury markers including sTM were significantly lowered after the treatment. Metabolites presented at significantly different levels in responders versus non-responders were considered as biomarkers for a therapeutic response of sTM to the exenatide treatment. Among those identified, 4-hydroxyproline and 12-oxo-9(Z)-dodecenoic acid were found to correlate most closely with the exenatide-induced endothelial protection response. The specificity and sensitivity of the multi-metabolite signature model contained higher 4-hydroxyproline and lower 12-oxo-9(Z)-dodecenoic acid were 53.3% and 92.3%, respectively, and the area under receiver operating characteristic curve was 69.2% (P < 0.001).Conclusions: Treatment with exenatide for 16 weeks ameliorates endothelial injury in patients with T2DM. Endothelial protection benefit from exenatide treatment was effectively predicted by the specific metabolomic combination of higher 4-hydroxyproline and lower 12-oxo-9(Z)-dodecenoic acid. [ABSTRACT FROM AUTHOR]

• PA induces oxidative stress, apoptosis and endothelin-1 secretion dysfunction in MS-1 cells. • Liraglutide ameliorates oxidative injury and endothelin-1 secretion dysfunction induced by PA. • GLP-1R/PKA and GTPCH1/eNOS signaling pathways are involved in the effects of liraglutide. In type 2 diabetes, lipotoxicity damages islet microvascular endothelial cells (IMECs), leading to pancreatic islet β cell dysfunction directly or indirectly. Glucagon-like peptide-1 (GLP-1) and its analogs have beneficial roles in endothelial cells. However, the protective effects of GLP-1 agents on IMECs and their potential mechanism remained obscure. In this study, exposure of MS-1 (a cell line derived from mouse IMECs) to different concentrations of palmitic acid (PA) was used to establish an injury model. The cells exposed to PA (0.25 mmol/L) were treated with a GLP-1 analog liraglutide (3, 10, 30, and 100 nmol/L). Reactive oxygen species (ROS) generation, apoptosis-related protein level, and endothelin-1 production were detected. The protein levels of signaling molecules were analyzed and specific inhibitors or blockers were used to identify involvement of signaling pathways in the effects of liraglutide. Results showed that PA significantly increased ROS generation and the levels of pro-apoptotic protein Bax, and decreased the levels of anti-apoptotic protein Bcl-2 and the mRNA expression and secretion of endothelin-1. Meanwhile, PA downregulated the protein levels of GLP-1 receptor (GLP-1R), phosphorylated protein kinase A (PKA), guanosine 5′-triphosphate cyclohydrolase 1 (GTPCH1), and endothelial nitric oxide synthase (eNOS). Furthermore, liraglutide ameliorated all these effects of PA in a dose-dependent manner. Importantly, GLP-1R antagonist exendin (9–39), PKA inhibitor H89, GTPCH1 inhibitor 2,4-diamino-6-hydroxypyrimidine, or NOS inhibitor N-nitro- l -arginine-methyl ester abolished the liraglutide-mediated amelioration in PA-impaired MS-1 cells. In conclusion, liraglutide ameliorates the PA-induced oxidative stress, apoptosis, and endothelin-1 secretion dysfunction in mouse IMECs through GLP-1R/PKA and GTPCH1/eNOS signaling pathways. [ABSTRACT FROM AUTHOR]

Background Potentially inappropriate medications (PIMs) are frequently prescribed to older people with diabetes. This study aimed to assess the prevalence of PIM use in older people with diabetes and identify potential risk factors influencing the development of PIM use. Methods This was a cross-sectional study conducted in an outpatient setting in Beijing, China, using Chinese criteria. The prevalence of PIM use, polypharmacy, and comorbidities in older adults with diabetes in an outpatient setting was measured. Logistic models were employed to investigate the association among polypharmacy, comorbidities, and PIM use. Results The prevalence of PIM use and polypharmacy was 50.1% and 70.8%, respectively. The most common comorbidities were hypertension (68.0%), hyperlipemia (56.6%), and stroke (36.3%), and the top three inappropriately used medications were insulin (22.0%), clopidogrel (11.9%), and eszopiclone (9.81%). Age (OR 1.025; 95% CI 1.009, 1.042), the number of diagnoses (OR 1.172; 95% CI 1.114, 1.232), coronary heart disease (OR 1.557; 95% CI 1.207, 2.009), and polypharmacy (OR 1.697; 95% CI 1.252, 2.301) were associated with PIM use. Conclusions Given the higher rate of PIM use among older adults with diabetes, strategies and interventions targeting this population are needed to minimize PIM use. [ABSTRACT FROM AUTHOR]

Background: Diabetes is associated with poor coronavirus disease 2019 (COVID-19) outcomes. However, little is known on the impact of undiagnosed diabetes in the COVID-19 population. We investigated whether diabetes, particularly undiagnosed diabetes, was associated with an increased risk of death from COVID-19. Methods: This retrospective study identified adult patients with COVID-19 admitted to Tongji Hospital (Wuhan) from January 28 to April 4, 2020. Diabetes was determined using patients' past history (diagnosed) or was newly defined if the hemoglobin A1c (HbA1c) level at admission was ≥6.5% (48 mmol/mol) (undiagnosed). The in-hospital mortality rate and survival probability were compared between the non-diabetes and diabetes (overall, diagnosed, and undiagnosed diabetes) groups. Risk factors of mortality were explored using Cox regression analysis. Results: Of 373 patients, 233 were included in the final analysis, among whom 80 (34.3%) had diabetes: 44 (55.0%) reported a diabetes history, and 36 (45.0%) were newly defined as having undiagnosed diabetes by HbA1c testing at admission. Compared with the non-diabetes group, the overall diabetes group had a significantly increased mortality rate (22.5% vs. 5.9%, p < 0.001). Moreover, the overall, diagnosed, and undiagnosed diabetes groups displayed lower survival probability in the Kaplan-Meier survival analysis (all p < 0.01). Using multivariate Cox regression, diabetes, age, quick sequential organ failure assessment score, and D-dimer ≥1.0 μg/mL were identified as independent risk factors for in-hospital death in patients with COVID-19. Conclusions: The prevalence of undiagnosed pre-existing diabetes among patients with COVID-19 is high in China. Diabetes, even newly defined by HbA1c testing at admission, is associated with increased mortality in patients with COVID-19. Screening for undiagnosed diabetes by HbA1c measurement should be considered in adult Chinese inpatients with COVID-19. [ABSTRACT FROM AUTHOR]

The level of serum angiopoietin-like protein 8 (ANGPTL8), a novel hepatokine, is associated with obesity and type 2 diabetes mellitus (T2DM). The aims of this study were to investigate whether serum ANGPTL8 level in patients with T2DM was affected by treatment with exenatide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, and to determine whether and how GLP-1R agonists regulated ANGPTL8 production in hepatocytes. A multiple-center trial was conducted in China. Among 240 patients with T2DM enrolled in this trial, 195 patients adhered to a 16-week exenatide treatment and follow-up. Human liver cell line HepG2 cells were incubated for 24 h with either exendin-4 (a native form of exenatide) or liraglutide in the presence or absence of GLP-1R antagonist exendin (9–39) and PI3K inhibitor LY294002. Change of serum ANGPTL8 level in patients with T2DM and regulation of ANGPTL8 production by the GLP-1R agonists in HepG2 cells were evaluated. Results showed that compared with baseline, exenatide treatment significantly increased serum ANGPTL8 level, and lowered body weight, fasting blood glucose (FBG) and glycated hemoglobin A1c (HbA1c) in patients with T2DM (all P  <  0.05). The exenatide treatment-mediated upregulation of serum ANGPTL8 level was not associated with the levels of its lowering effects on body weight, FBG and HbA1c stratified by the median. Moreover, exendin-4 or liraglutide dose-dependently upregulated the level of ANGPTL8 expression and secretion in HepG2 cells, which was eliminated by adding exendin (9–39) and LY294002. In conclusion, GLP-1R agonists enhance ANGPTL8 production in vivo and in vitro , which is mediated via the PI3K/Akt pathway in a GLP-1R-dependent manner. [ABSTRACT FROM AUTHOR]