Fulminant type 1 diabetes: Focusing on triggering factors.

Fulminant type 1 diabetes (FT1D) is a novel type of type 1 diabetes that is caused by extremely rapid destruction of the pancreatic ß cells. Early diagnosis or prediction of FT1D is critical for the prevention or timely treatment of diabetes ketoacidosis, which can be life-threatening. Understanding its triggers or promoting factors plays an important role in the prevention and treatment of FT1D. In this review, we summarised the various triggering factors of FT1D, including susceptibility genes, immunological factors (cellular and humoural immunity), immune checkpoint inhibitor therapies, drug reactions with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome, pregnancy, viral infections, and vaccine inoculation. This review provides the basis for future research into the pathogenetic mechanisms that regulate FT1D development and progression to further improve the prognosis and clinical management of patients with FT1D.

Hsa_circRNA_405498 and hsa_circRNA_100033 serve as potential biomarkers for differential diagnosis of type 1 diabetes.

PURPOSE: The role of circular RNAs (circRNAs) in type 1 diabetes (T1D) is largely unknown. We aimed to identify some circRNAs as differential diagnostic biomarkers for T1D to discriminate patients with latent autoimmune diabetes in adults (LADA), and type 2 diabetes (T2D). METHODS: The circRNA expression profiles were determined by Arraystar human circRNA microarray in T1D compared to controls (n = 6 each). The differentially expressed circRNAs were validated by RT-qPCR using a validation cohort with 20 T1D and 20 controls. The diagnostic performances of the candidate circRNAs and the clinical parameters were assessed using the logistic least absolute shrinkage and selection operator (LASSO) regression model in a larger cohort with 457 subjects including patients with T1D, T2D and LADA, and controls. RESULTS: We identified 110 differentially expressed circular transcripts (53 upregulated and 57 downregulated) in T1D patients compared with controls. Further analysis showed that the levels of hsa_circRNA_405498 and hsa_circRNA_100033 were significantly downregulated in T1D compared to controls (both P < 0.05). Moreover, the expression levels of these two circRNAs showed sequential downregulation from controls, patients with T2D, LADA, to T1D (P < 0.05). The area under the curve (AUC) of receiver operating characteristic (ROC) plots in logistic LASSO regression model showed high diagnostic accuracy for combination model with the two circRNAs and some clinical parameters in discriminating T1D from LADA (AUC = 0.915), T2D (AUC = 0.993), and controls (AUC = 0.992). CONCLUSIONS: Our study demonstrated that hsa_circRNA_405498 and hsa_circRNA_100033 are promising novel differential diagnostic biomarkers for T1D.

Association of the rs1990760, rs3747517, and rs10930046 polymorphisms in the IFIH1 gene with susceptibility to autoimmune diseases: a meta-analysis.

Objective: Interferon induced with helicase C domain 1 (IFIH1) single-nucleotide polymorphisms (SNP) rs1990760, rs3747517, and rs10930046 have been shown to be closely related to the risk of autoimmune diseases. The aim of this study was firstly to examine the association of the rs1990760 with type 1 diabetes (T1D) in a Chinese population. Secondly, to assess the association of SNP rs1990760, rs3747517, and rs10930046 with autoimmune diseases susceptibility. Methods: A total of 1,273 T1D patients and 1,010 healthy control subjects in a Chinese population were enrolled in this case-control study. Subsequently, we performed a meta-analysis on the association of the SNP rs1990760, rs3747517, and rs10930046 in the IFIH1 gene with susceptibility to autoimmune diseases. The random and fixed genetic effects models were used to evaluate the association and the effect sizes, including odds ratios (OR) and 95% confidence intervals (CI). Stratification analyses based on ethnicity and the type of autoimmune diseases were performed. Results: IFIH1 SNP rs1990760 was not associated with a significant risk of T1D in the Chinese population in the case-control study. A total of 35 studies including 70,966 patients and 124,509 controls were identified and included in the meta-analysis. The results displayed significant associations between IFIH1 rs1990760 A allele and rs3747517 C allele and autoimmune diseases risk (OR=1.09, 95% CI: 1.01~1.17; OR=1.24, 95% CI: 1.15~1.25, respectively). Stratified analysis indicated a significant association rs1990760 and rs3747517 with autoimmune diseases risk in the Caucasian population (OR=1.11, 95% CI: 1.02~1.20, OR=1.29, 95% CI: 1.18~1.41, respectively). Conclusions: This study revealed no association between IFIH1 SNP rs1990760 and T1D in Chinese. Furthermore, the meta-analysis indicated that rs1990760 and rs3747517 polymorphisms, confer susceptibility to autoimmune diseases, especially in the Caucasian population.

Identification of hsa_circRNA_100632 as a novel molecular biomarker for fulminant type 1 diabetes.

Objective: Circular RNAs (circRNAs) are associated with diabetes, but their role in fulminant type 1 diabetes (FT1D) is unclear. Thus, we characterized the role of circRNAs in FT1D. Research design and methods: CircRNA expression profiles were detected in peripheral blood mononuclear cells (PBMCs) of five FT1D patients and five controls using a circRNA microarray. An independent cohort comprised of 40 FT1D cases, 75 type 1 diabetes (T1D) cases, and 115 controls was used to verify the circRNAs using quantitative real-time polymerase chain reaction (qRT-PCR). Spearman's correlation analysis and receiver operating characteristic (ROC) curve analysis were performed to determine the clinical diagnostic capability of circRNAs. Bioinformatics was used to identify potential biological functions and circRNA-miRNA-mRNA interactions. Results: There were 13 upregulated and 13 downregulated circRNAs in PBMCs of patients with FT1D. Five circRNAs were further verified in a second cohort. Hsa_circRNA_100632 was significantly upregulated in the FT1D and T1D groups. Hsa_circRNA_100632 was differentiated between patients with FT1D and controls [area under the curve (AUC) 0.846; 95% CI 0.776-0.916; P<0.0001] as well as between patients with FT1D and patients with T1D (AUC 0.726; 95% CI 0.633-0.820; P<0.0001). Bioinformatics analysis showed that hsa_circRNA_100632 may be involved in 47 circRNA-miRNA-mRNA signaling pathways associated with diabetes. Conclusions: CircRNAs were aberrantly expressed in PBMCs of patients with FT1D, and hsa_circRNA_100632 may be a diagnostic marker of FT1D.

Clinical and immunological characteristics of PD-1 associated fulminant type 1 diabetes mellitus. / PD-1ç›¸å ³æ€§æš´å‘æ€§1åž‹ç³–å°¿ç— çš„ä¸´åºŠä¸Žå ç–«ç‰¹å¾.

OBJECTIVES: Programmed death 1 (PD-1) associated fulminant type 1 diabetes (PFD) is a rare acute and critical in internal medicine, and its clinical characteristics are still unclear. This study aims to analyze the clinical characteristics of PFD patients to improve clinical diagnosis and treatment. METHODS: We retrospectively analyzed the clinical data of 10 patients with PFD admitted to the Second Xiangya Hospital of Central South University, combined with the data of 66 patients reported in the relevant literature, analyzed and summarized their clinical and immunological characteristics, and compared the patients with PFD with different islet autoantibody status. RESULTS: Combined with our hospital and literature data, a total of 76 patients with PFD were reported, with the age of (60.9±12.1) years old, 60.0% male and body mass index of (22.1±5.2) kg/m2. In 76 patients, the most common tumors were lung cancer (43.4%) and melanoma (22.4%). Among PD-1 inhibitors, the most common drugs are nivolumab (37.5%) and pembrolizumab (38.9%). 82.2% of PFD patients developed diabetes ketoacidosis. The median onset time from PD-1 related inhibitor treatment to hyperglycemia was 95 (36.0, 164.5) d, and the median treatment cycle before the onset of diabetes was 6 (2.3, 8.0) cycles. 26% (19/73) of PFD patients had positive islet autoantibodies, and the proportion of ketoacidosis in the positive group was significantly higher than that in the negative group (100.0% vs 75.0%, P<0.05). The onset time and infusion times of diabetes after PD-1 inhibitor treatment in the autoantibody positive group were significantly lower than those in the autoantibody negative group (28.5 d vs 120.0 d; 2 cycles vs 7 cycles, both P<0.001). CONCLUSIONS: After initiation of tumor immunotherapy, it is necessary to be alert to the occurrence of adverse reactions of PFD, and the onset of PFD with islet autoantibody positive is faster and more serious than that of patients with autoantibodies negative. Detection of islet autoantibodies and blood glucose before and after treatment with PD-1 inhibitors is of great value for early warning and prediction of PFD.

Characterization of immune checkpoint inhibitor-associated fulminant type 1 diabetes associated with autoantibody status and ethnic origin.

Objective: Fulminant type 1 diabetes may uniquely occur as a fatal adverse event during immune checkpoint inhibitor (ICI) therapy. We investigated the clinical and immunological characteristics of ICI-associated fulminant type 1 diabetes (IFD). Research design and methods: We enrolled 80 patients with IFD (77 cases from the literature), 56 patients with ICI-associated type 1 diabetes (IT1D) (55 cases from the literature), 45 patients with traditional fulminant type 1 diabetes (TFD), and 43 patients with acute-onset type 1 diabetes for comprehensive analysis including islet autoantibodies and subgroup analysis based on ethnic origin. Results: Patients with IFD accounted for 58.8% (80/136) of patients with ICI-related diabetes. IFD had a more rapid onset than IT1D after ICI therapy (90.5 days vs. 120 days, p <0.05). The onset time and number of infusions after ICI therapy initiation were lower in the antibody-positive IFD group than that in the antibody-negative IFD group (both p <0.001). IFD had a more rapid onset and more serious among Caucasians than that among Asians (p <0.01, p <0.05, respectively), and the prevalence of islet autoantibody positivity in the Caucasian IFD were prominently higher than those in the Asian IFD (p <0.05). Onset age and plasma glucose levels were significantly higher in the IFD group than those in the TFD and acute-onset type 1 diabetes groups. HbA1c levels were slightly higher in patients with IFD than those with TFD. Conclusions: IFD is relatively common in Caucasian population where TFD is very rare or almost absent. IFD occurrence is significantly related to islet autoantibody status and ethnic origin.

Circular RNAs in diabetes and its complications: Current knowledge and future prospects.

A novel class of non-coding RNA transcripts called circular RNAs (circRNAs) have been the subject of significant recent studies. Accumulating evidence points that circRNAs play an important role in the cellular processes, inflammatory expression, and immune responses through sponging miRNA, binding, or translating in proteins. Studies have found that circRNAs are involved in the physiologic and pathologic processes of diabetes. There has been an increased focus on the relevance of between abnormal circRNA expression and the development and progression of various types of diabetes and diabetes-related diseases. These circRNAs not only serve as promising diagnostic and prognostic molecular biomarkers, but also have important biological roles in islet cells, diabetes, and its complications. In addition, many circRNA signaling pathways have been found to regulate the occurrence and development of diabetes. Here we comprehensively review and discuss recent advances in our understanding of the physiologic function and regulatory mechanisms of circRNAs on pancreatic islet cells, different subtypes in diabetes, and diabetic complications.

Latent autoimmune diabetes in adults: a focus on ß-cell protection and therapy.

Latent autoimmune diabetes in adults (LADA) is a heterogeneous disease sharing some phenotypic, genetic, and immunological features with both type 1 and 2 diabetes. Patients with LADA have a relatively slow autoimmune process and more residual islet ß-cell function at onset, allowing a time window to protect residual islet ß cells and delay or inhibit disease progression. It is crucial to discover various heterogeneous factors affecting islet ß-cell function for precise LADA therapy. In this review, we first describe the natural history of LADA. Thereafter, we summarize ß-cell function-related heterogeneous factors in LADA, including the age of onset, body mass index, genetic background, and immune, lifestyle, and environmental factors. In parallel, we evaluate the impact of current hypoglycemic agents and immune intervention therapies for islet ß-cell protection. Finally, we discuss the opportunities and challenges of LADA treatment from the perspective of islet ß-cell function protection.

HEAR: Approach for Heartbeat Monitoring with Body Movement Compensation by IR-UWB Radar.

Further applications of impulse radio ultra-wideband radar in mobile health are hindered by the difficulty in extracting such vital signals as heartbeats from moving targets. Although the empirical mode decomposition based method is applied in recovering waveforms of heartbeats and estimating heart rates, the instantaneous heart rate is not achievable. This paper proposes a Heartbeat Estimation And Recovery (HEAR) approach to expand the application to mobile scenarios and extract instantaneous heartbeats. Firstly, the HEAR approach acquires vital signals by mapping maximum echo amplitudes to the fast time delay and compensating large body movements. Secondly, HEAR adopts the variational nonlinear chirp mode decomposition in extracting instantaneous frequencies of heartbeats. Thirdly, HEAR extends the clutter removal method based on the wavelet decomposition with a two-parameter exponential threshold. Compared to heart rates simultaneously collected by electrocardiograms (ECG), HEAR achieves a minimum error rate 4.6% in moving state and 2.25% in resting state. The Bland⁻Altman analysis verifies the consistency of beat-to-beat intervals in ECG and extracted heartbeat signals with the mean deviation smaller than 0.1 s. It indicates that HEAR is practical in offering clinical diagnoses such as the heart rate variability analysis in mobile monitoring.

[A quantitative detection of Poincare scatter for T-wave alternans].

To study the quantitative detection method of T-wave alternans (TWA), we analyzed the relationship between the graphic mode of Poincare scatter and TWA, and proposed 'horizontal search algorithm' to complete graphic processing. Then, based on the shape of Poincare scatter, we took Axial_ratio as the final index. Through Matlab simulation, Axial_ratio was compared with the results of spectral method (SM) and appropriate threshold value was selected to recognize the TWA. The results showed that Axial_ratio could accurately detect the TWA.

[Shock shape representation of sinus heart rate based on cloud model].

The present paper is to analyze the trend of sinus heart rate RR interphase sequence after a single ventricular premature beat and to compare it with the two parameters, turbulence onset (TO) and turbulence slope (TS). Based on the acquisition of sinus rhythm concussion sample, we in this paper use a piecewise linearization method to extract its linear characteristics, following which we describe shock form with natural language through cloud model. In the process of acquisition, we use the exponential smoothing method to forecast the position where QRS wave may appear to assist QRS wave detection, and use template to judge whether current cardiac is sinus rhythm. And we choose some signals from MIT-BIH Arrhythmia Database to detect whether the algorithm is effective in Matlab. The results show that our method can correctly detect the changing trend of sinus heart rate. The proposed method can achieve real-time detection of sinus rhythm shocks, which is simple and easily implemented, so that it is effective as a supplementary method.