Relationship between 1,5-anhydroglucitol and renal function assessed by dynamic renal scintigraphy in type 2 diabetes.

CONTEXT: The reliability of serum 1,5-anhydroglucitol (1,5-AG) in type 2 diabetic patients with renal insufficiency remains controversial. OBJECTIVE: To evaluate the relationship between renal function and serum 1,5-AG, and to assess the extent to which renal function influences 1,5-AG. METHODS: A total of 5337 participants with type 2 diabetes were enrolled. The measured glomerular filtration rate (mGFR) was assayed using 99mTc-DTPA dynamic renal scintigraphy. All subjects were stratified into five groups based on mGFR (≥ 120 [n = 507], 90-120 [n = 2015], 60-90 [n = 2178], 30-60 [n = 604], and < 30 mL/min/1.73 m2 [n = 33]). RESULTS: Overall, the serum 1,5-AG and mGFR levels were 3.3 (1.7-7.0) µg/mL and 88.6 ± 24.1 mL/min/1.73 m2, respectively. mGFR was found to be negatively correlated with 1,5-AG levels (r = -0.189, P < 0.001). Multiple linear regression revealed that mGFR was independently and negatively related to serum 1,5-AG after adjusting for covariates including HbA1c (P < 0.001). In subgroups with mGFR ≥ 30 mL/min/1.73 m2, the correlation coefficients between 1,5-AG and HbA1c, fasting plasma glucose, postprandial plasma glucose, and the differences between postprandial and fasting plasma glucose remained significant (range from -0.126 to -0.743, all P < 0.01). However, the link between 1,5-AG and traditional glycemic markers was attenuated in individuals with mGFR < 30 mL/min/1.73 m2. Sensitivity analysis after excluding anemic patients showed similar results regarding the relationship between serum 1,5-AG and HbA1c across the mGFR subgroups. CONCLUSIONS: Although we observed a weak inverse correlation (r = -0.189) between mGFR and serum 1,5-AG in type 2 diabetes, 1,5-AG remains a valid marker for assessing glucose control in subjects with mild or moderate renal dysfunction.

Real-time continuous glucose monitoring-guided glucose management in inpatients with diabetes receiving short-term continuous subcutaneous insulin infusion: a randomized clinical trial.

Background: The use of real-time continuous glucose monitoring (rtCGM) technology remains largely investigational in the hospital setting. The current study aimed to evaluate the effectiveness of rtCGM in inpatients with diabetes who were treated with short-term continuous subcutaneous insulin infusion (CSII). Methods: In this randomized, parallel controlled trial conducted on the endocrinology wards in a tertiary hospital located in Shanghai, adults with type 1 and type 2 diabetes who required short-term CSII during hospitalization were randomly assigned (1:1) to receive either rtCGM-based glucose monitoring and management program or point-of-care (POC) standard of care (8 times/day) with blinded CGM. Primary outcome measure was the difference in the percentage of time within the target glucose range of 3.9-10 mmol/L (TIR, %). This study was registered at www.chictr.org.cn (ChiCTR2300068933). Findings: Among the 475 randomized participants (237 in the rtCGM group and 238 in the POC group), the mean age of was 60 ± 13 years, and the mean baseline glycated hemoglobin level was 9.4 ± 1.8%. The CGM-recorded mean TIR was 71.1 ± 15.8% in the rtCGM group and 62.9 ± 18.9% in the POC group, with a mean difference of 8.2% (95% confidence interval [CI]: 5.1-11.4%, P < 0.001). The mean time above range >10 mmol/L was significantly lower in the rtCGM group than in the POC group (28.3 ± 15.8% vs. 36.6 ± 19.0%, P < 0.001), whereas there was no significant between-group difference in the time below range <3.9 mmol/L (P = 0.11). Moreover, the time to reach target glucose was significantly shorter in the rtCGM group than in the POC group (2.0 [1.0-4.0] days vs. 4.0 [2.0-5.0] days, P < 0.001). There were no serious adverse events in both groups. Interpretation: In patients with diabetes who received short-term CSII during hospitalization, the rtCGM program resulted in better glucose control than the POC standard of care, without increasing the risk of hypoglycemia. Funding: The Program of Shanghai Academic Research Leader (22XD1402300), Shanghai Oriental Talent Program (Youth Project) (No. NA), the Shanghai "Rising Stars of Medical Talent" Youth Development Program-Outstanding Youth Medical Talents (SHWSRS(2021)_099), and the Shanghai Research Center for Endocrine and Metabolic Diseases (2022ZZ01002).

Hybrid hair follicle stem cell extracellular vesicles co-delivering finasteride and gold nanoparticles for androgenetic alopecia treatment.

Androgenetic alopecia (AGA) is a non-fatal disease prevalent worldwide. However, mixed efficacy has been observed among different therapies for hair regrowth in AGA patients. Thus, a nano-platform with synergistic treatments based on a hybrid extracellular vesicle encapsulating gold nanoparticles (AuNPs) and finasteride (Hybrid/Au@Fi) was constructed through membrane fusion between hair follicle stem cell (HFSC)-derived extracellular vesicles and liposomes. These hybrid vesicles (HVs) not only fuel hair regrowth by providing cellular signals in extracellular vesicles, but also improve storage stability, follicle retention, and drug encapsulation efficiency (EE%) for finasteride inhibiting 5α-reductase, and nano-size AuNPs that simulate low-level laser therapy (LLLT) with similar photothermal effects in vitro. The EE% of finasteride in these HVs reached 45.33%. The dual administration of these extracellular vesicles and finasteride showed a strong synergistic effect on HFSCs in vitro. In an AGA mouse model, once-daily topical Hybrid/Au@Fi (115.07 ± 0.32 nm, -7.50 ± 1.68 mV) gel led to a faster transition of hair follicles (HFs) from the catagen to the anagen, increased hair regrowth coverage, and higher quality of regrowth hair, compared to once-daily 5% minoxidil treatment. Compared to topical minoxidil, the multifaceted synergistic therapy of Hybrid/Au@Fi through topical administration offers a new option for intractable AGA patients with low side effects.

Decreased complexity of glucose time series index associated with adverse pregnancy outcomes in gestational diabetes mellitus.

AIM: We investigated the relationship between the complexity of the glucose time series index (CGI) during pregnancy and adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM). MATERIALS AND METHODS: In this retrospective cohort study, 388 singleton pregnant women with GDM underwent continuous glucose monitoring (CGM) at a median of 26.86 gestational weeks. CGI was calculated using refined composite multiscale entropy based on CGM data. The participants were categorized into tertiles according to their baseline CGI (CGI <2.32, 2.32-3.10, ≥3.10). Logistic regression was used to assess the association between CGI and composite adverse outcomes or large for gestational age (LGA). The discrimination performance of CGI was estimated using receiver operating characteristic analysis. RESULTS: Of the 388 participants, 71 (18.3%) had LGA infants and 63 (16.2%) had composite adverse outcomes. After adjustments were made for confounders, compared with those with a high CGI (CGI ≥3.10), participants with a low CGI (CGI <2.32) had a higher risk of composite adverse outcomes (odds ratio: 12.10, 95% confidence interval: 4.41-33.18) and LGA (odds ratio: 12.68, 95% confidence interval: 4.04-39.75). According to the receiver operating characteristic analysis, CGI was significantly better than glycated haemoglobin and conventional CGM indicators for the prediction of adverse pregnancy outcomes (all p < .05). CONCLUSION: A lower CGI during pregnancy was associated with composite adverse outcomes and LGA. CGI, a novel glucose homeostasis predictor, seems to be superior to conventional glucose indicators for the prediction of adverse pregnancy outcomes in women with GDM.

Galloborates as ultraviolet nonlinear optical crystals: advances and perspectives.

Metal borates are excellent source materials for exploring short-wavelength nonlinear optical (NLO) crystals. Galloborates show rich structural chemistry with various coordination configurations of Ga cation and B-O anionic units and are suitable candidates as ultraviolet NLO crystals. Up to now, the shortest cut-off edge of galloborates was reported to be down to 190 nm in KCs2Ga(B5O10)(OH), while the largest second harmonic generation (SHG) effect of galloborates was reported to be up to 4.6 times that of KH2PO4 (KDP) in Na5Ga[B7O12(OH)]2·2B(OH)3. Herein, we give a detailed summary of the recent progress in NLO inorganic galloborates, where these galloborates are grouped into two types in terms of their compositions: (1) alkali/alkaline earth metal galloborates and (2) alkali/alkaline earth metal galloborate halides. We discuss their structural features, band gaps, and SHG intensities. Finally, we give future perspectives in this field.

Interplay among extracellular vesicles, cancer stemness and immune regulation in driving hepatocellular carcinoma progression.

The intricate interplay among extracellular vesicles, cancer stemness properties, and the immune system significantly impacts hepatocellular carcinoma (HCC) progression, treatment response, and patient prognosis. Extracellular vesicles (EVs), which are membrane-bound structures, play a pivotal role in conveying proteins, lipids, and nucleic acids between cells, thereby serving as essential mediators of intercellular communication. Since a lot of current research focuses on small extracellular vesicles (sEVs), with diameters ranging from 30 nm to 200 nm, this review emphasizes the role of sEVs in the context of interactions between HCC stemness-bearing cells and the immune cells. sEVs offer promising opportunities for the clinical application of innovative diagnostic and prognostic biomarkers in HCC. By specifically targeting sEVs, novel therapeutics aimed at cancer stemness can be developed. Ongoing investigations into the roles of sEVs in cancer stemness and immune regulation in HCC will broaden our understanding and ultimately pave the way for groundbreaking therapeutic interventions.

Transcriptome Analysis Reveals the Venom Genes of the Ectoparasitoid Habrobracon hebetor (Hymenoptera: Braconidae).

The ectoparasitoid Habrobracon hebetor (Hymenoptera: Braconidae) exhibits a broad parasitic capability towards various lepidopteran pests, with venom serving as a crucial virulent factor ensuring successful parasitization and subsequent host mortality. Analyzing the constituents of its venom is essential for elucidating the mechanisms underlying efficient host killing by this parasitoid and for exploring potentially functional venom proteins. Through a transcriptomic analysis, a total of 34 venom proteins were identified within the venom of H. hebetor, encompassing known components such as serine protease, metalloproteinase, esterase, and serine protease inhibitors commonly present in parasitoid venoms. Unique components like paralytic protein and ion transport peptide-like were identified, possibly specific to certain parasitoids, along with novel proteins with uncharacterized functions. Spatial gene expression profiling of the identified venom proteins using transcriptomic data, corroborated by quantitative PCR validation for 13 randomly selected proteins, revealed abundant expression levels in the venom apparatus, affirming them as genuine venom components. Notably, the paralytic protein exhibited prominent expression, with the highest FPKM (fragments per kilobase of transcript per million fragments mapped) value of 24,704.87 in the venom apparatus, indicative of its significant role in successful parasitism by H. hebetor. The identification of these venom proteins establishes a foundation for the further exploration of bioactive agents for pest management strategies.

Targeting the oncogenic m6A demethylase FTO suppresses tumourigenesis and potentiates immune response in hepatocellular carcinoma.

OBJECTIVE: Fat mass and obesity-associated protein (FTO), an eraser of N 6-methyadenosine (m6A), plays oncogenic roles in various cancers. However, its role in hepatocellular carcinoma (HCC) is unclear. Furthermore, small extracellular vesicles (sEVs, or exosomes) are critical mediators of tumourigenesis and metastasis, but the relationship between FTO-mediated m6A modification and sEVs in HCC is unknown. DESIGN: The functions and mechanisms of FTO and glycoprotein non-metastatic melanoma protein B (GPNMB) in HCC progression were investigated in vitro and in vivo. Neutralising antibody of syndecan-4 (SDC4) was used to assess the significance of sEV-GPNMB. FTO inhibitor CS2 was used to examine the effects on anti-PD-1 and sorafenib treatment. RESULTS: FTO expression was upregulated in patient HCC tumours. Functionally, FTO promoted HCC cell proliferation, migration and invasion in vitro, and tumour growth and metastasis in vivo. FTO knockdown enhanced the activation and recruitment of tumour-infiltrating CD8+ T cells. Furthermore, we identified GPNMB to be a downstream target of FTO, which reduced the m6A abundance of GPNMB, hence, stabilising it from degradation by YTH N 6-methyladenosine RNA binding protein F2. Of note, GPNMB was packaged into sEVs derived from HCC cells and bound to the surface receptor SDC4 of CD8+ T cells, resulting in the inhibition of CD8+ T cell activation. A potential FTO inhibitor, CS2, suppresses the oncogenic functions of HCC cells and enhances the sensitivity of anti-PD-1 and sorafenib treatment. CONCLUSION: Targeting the FTO/m6A/GPNMB axis could significantly suppress tumour growth and metastasis, and enhance immune activation, highlighting the potential of targeting FTO signalling with effective inhibitors for HCC therapy.

Habitual use of glucosamine and adverse liver outcomes among patients with type 2 diabetes and MASLD.

BACKGROUND: Glucosamine is a dietary supplement commonly used to support joint health. However, there has been interest in exploring other effects of glucosamine on health outcomes due to its ant-inflammation effect. OBJECTIVE: This study compared the risks of major adverse liver outcomes (MALOs) between regular users and non-users of glucosamine among patients with type 2 diabetes and metabolic dysfunction associated steatotic liver disease (MASLD) using the data from a large prospective cohort study. METHODS: Demographic, anthropometric, laboratory and medication prescription information among 18 753 patients with type 2 diabetes and MASLD was obtained from the UK Biobank. MASLD was identified based on hepatic steatosis defined by fatty liver index ≥60 plus the presence of any clues of metabolic dysregulation and cardio-metabolic risk factors, excluding patients with moderate to severe alcohol consumption. RESULTS: During a mean follow-up of 11.4 years, 826 incident MALOs events were recorded. Patients not regularly using glucosamine compared with patients using glucosamine showed a significantly higher risk of the composite MALOs (HR 1.36, 95% confidence interval [CI] 1.09-1.69) as well as most individual MALOs except for ascites. The multivariable-adjusted HRs of MALOs within 3, 5 and 10 years among non-users of glucosamine compared with regular users were 1.79 (95% CI .69-2.03), 1.88 (95% CI 1.21-2.54) and 1.32 (95% CI 1.05-1.72), respectively. Further subgroup analyses in participants with different baseline characteristics and sensitivity analyses excluding participants who regularly took any other supplements and participants who used self-reports to diagnose diabetes confirmed the findings. CONCLUSIONS: The present study indicated that habitual use of glucosamine was associated with a low risk of individual and composite MALOs among patients with type 2 diabetes and MASLD.

Self-Illuminating Nanoagonist Simultaneously Induces Dual Cell Death Pathways via Death Receptor Clustering for Cancer Therapy.

Inducing death receptor 5 (DR5) clustering holds particular promise in tumor-specific therapeutics because it could trigger an apoptotic cascade in cancerous cells. Herein, we present a tumor microenvironment H2O2-responsive self-illuminating nanoagonist, which could induce dual tumor cell death pathways through enhancing DR5 clustering. By conjugating DR5 ligand peptides onto the surfaces of self-illuminating nanoparticles with cross-linking capacity, this strategy not only provides scaffolds for ligands to bind receptors but also cross-links them through photo-cross-linking. This strategy allows for efficient activation of DR5 downstream signaling, initiating the extrinsic apoptosis pathway and immunogenic cell death of tumor cells, and contributes to improved tumor-specific immune responses, resulting in enhanced antitumor efficacy and minimized systemic adverse effects.

Hydronidone induces apoptosis in activated hepatic stellate cells through endoplasmic reticulum stress-associated mitochondrial apoptotic pathway.

BACKGROUND AND AIM: Hydronidone (HDD) is a novel pirfenidone derivative developed initially to reduce hepatotoxicity. Our previous studies in animals and humans have demonstrated that HDD treatment effectively attenuates liver fibrosis, yet the underlying mechanism remains unclear. This study aimed to investigate whether HDD exerts its anti-fibrotic effect by inducing apoptosis in activated hepatic stellate cells (aHSCs) through the endoplasmic reticulum stress (ERS)-associated mitochondrial apoptotic pathway. METHODS: The carbon tetrachloride (CCl4)- and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver fibrosis models were used for in vivo studies. In vitro studies were conducted using the human hepatic stellate cell line LX-2. The apoptotic effect of HDD on aHSCs was examined using TUNEL and flow cytometry assays. The small interfering RNA (siRNA) technique was employed to downregulate the expression of interest genes. RESULTS: HDD treatment significantly promoted apoptosis in aHSCs in both the CCl4- and DDC-induced liver fibrosis in mice and LX-2 cells. Mechanistic studies revealed that HDD triggered ERS and subsequently activated the IRE1α-ASK1-JNK pathway. Furthermore, the influx of cytochrome c from the mitochondria into the cytoplasm was increased, leading to mitochondrial dysfunction and ultimately triggering apoptosis in aHSCs. Notably, inhibition of IRE1α or ASK1 by siRNA partially abrogated the pro-apoptotic effect of HDD in aHSCs. CONCLUSIONS: The findings of both in vivo and in vitro studies suggest that HDD induces apoptosis in aHSCs via the ERS-associated mitochondrial apoptotic pathway, potentially contributing to the amelioration of liver fibrosis.

Establishment of a chip digital PCR detection method for canine circovirus.

Canine circovirus (CanineCV), which is a new mammalian circovirus first reported in the United States in 2012, mainly causes diarrhea and vomiting in dogs. As CanineCV evolves and new subtypes emerge, there is an urgent need for new detection technologies to improve the sensitivity and detection rates of viruses in complex scenarios. A chip digital PCR(cdPCR) assay was established for the detection of CanineCV in this study. The results showed good reproducibility, specificity and a linear relationship; the minimum detection limit of CanineCV by cdPCR was 6.62 copies/µL, which is 10 times more sensitive than quantitative real-time PCR (qPCR). The qPCR-positive detection rate was 1 %, while CanineCV cdPCR (2.1 %) exhibited a greater positive detection rate. Fifteen complete genomes were sequenced and subdivided into CanineCV-1 and CanineCV-3. In conclusion, we developed a rapid, reliable, and specific cdPCR method for screening and monitoring canine CV.

Optic Neuritis in a Pediatric Patient with Kikuchi-Fujimoto Disease: A Case Report and Review of the Literature.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare, benign, and self-limiting condition characterized by lymph node inflammation. While KFD is rarely associated with ocular manifestations, our case report highlights bilateral optic neuritis in a 13-year-old male patient with KFD. We also provide a comprehensive review of similar cases in the literature.

Severe dawn phenomenon predicts long-term risk of all-cause mortality in patients with type 2 diabetes.

AIMS: The dawn phenomenon (DP) is an abnormal early morning blood glucose rise without nocturnal hypoglycaemia, which can be more easily and precisely assessed with continuous glucose monitoring (CGM). This prospective study aimed to explore the association between DP and the risk of all-cause mortality in patients with type 2 diabetes. MATERIALS AND METHODS: A total of 5542 adult inpatients with type 2 diabetes in a single centre were analysed. The magnitude of DP (ΔG) was defined as the increment in the CGM-determined glucose value from nocturnal nadir (after 24:00) to prebreakfast. Participants were stratified into four groups by ΔG: ≤1.11, 1.12-3.33, 3.34-5.55, and >5.55 mmol/L. Cox proportional hazard regression models were used to evaluate the impact of DP on all-cause mortality risk. RESULTS: During a median follow-up of 9.4 years, 1083 deaths were identified. The restricted cubic spline revealed a nonlinear (p for nonlinearity = 0.002) relationship between ΔG and the risk of all-cause mortality. A multivariate-adjusted Cox regression model including glycated haemoglobin A1c (HbA1c) showed that ΔG > 5.55 mmol/L was associated with 30% (95% CI, 1.01-1.66) higher risk of all-cause mortality, as compared with ΔG 1.12-3.33 mmol/L. CONCLUSIONS: Higher ΔG is significantly related to an increased risk of all-cause mortality in type 2 diabetes, suggesting that severe DP should be given more attention as a part of glucose management to reduce the risk of long-term adverse outcomes.

The ESG performance influence mechanism analysis-based on empirical analysis.

ESG has emerged as a prominent method for evaluating enterprises, gaining increasing importance in recent years. It assesses a company's ability to promote sustainable economic development and fulfill its social responsibilities, encompassing three non-financial dimensions: environmental, social, and corporate governance. Regulatory authorities, industry associations, and investment institutions worldwide have placed growing emphasis on a company's ESG performance. From the perspective of career concern, this study conducted a multiple regression analysis using data from Chinese A-share companies listed in Shanghai and Shenzhen from 2011 to 2020. It used CEO shareholding and CEO political affiliation as moderating variables to examine the impact of CEO career concerns on the corporate environment, society, and corporate governance performance. Empirical testing of whether CEO career concerns promote or suppress the ESG performance in enterprises. The findings of this study reveal that CEOs with heightened career concerns tend to impede the ESG performance of their respective enterprises. Additionally, CEO shareholding and political affiliations exert a negative moderating influence on the relationship between CEO career concerns and ESG performance. This research significantly extends the investigation into factors influencing ESG performance, offering fresh perspectives that could inform improved CEO oversight, foster corporate transformation, and enhance ESG performance.

Continuous glucose monitoring profile in COVID-19 patients with and without diabetes receiving methylprednisolone.

PURPOSE: Methylprednisolone is widely used during the COVID-19 epidemic. We aimed to evaluate the glucose profile of COVID-19 patients with and without diabetes receiving methylprednisolone. METHODS: 36 patients with COVID-19 admitted to hospital were included: 17 with and 19 without diabetes. Methylprednisolone 40 mg was administered at about 9:00 a.m. Glucose levels were assessed by blinded intermittently scanned continuous glucose monitoring (isCGM) for an average of 6.8 ± 2.4 days. Excess hyperglycemia was defined as time above range (TAR) > 10.0 mmol/L (TAR>10.0) ≥ 25%, or TAR > 13.9 mmol/L (TAR>13.9) ≥ 10%. RESULTS: Glucose management indicator (GMI) was significantly higher than the admission glycated hemoglobin A1c (HbA1c) level in patients without diabetes [6.7 (6.1-7.0) % vs. 5.9 (5.9-6.1) %, P < 0.001], while no significant difference was found in patients with diabetes [9.0 (7.5-9.5) % vs. 8.9 (7.5-10.2) %, P > 0.05]. The difference between GMI and HbA1c (∆GMI-HbA1c) in patients without diabetes was significantly higher than in patients with diabetes [0.7 (0.2-1.0) % vs. -0.2 (-1.5-0.5) %, P = 0.005]. The circadian patterns of glucose were similar in the two groups. In patients without diabetes, excess hyperglycemia occurred in 31.6% (6/19) of participants, with 31.6% (6/19) having a TAR>10.0 ≥ 25%, while 21.1% (4/19) had a TAR>13.9 ≥ 10%. CONCLUSION: The impact of methylprednisolone on glycemia was more pronounced in COVID-19 patients without diabetes, compared to those with diabetes. A significant burden of methylprednisolone-induced hyperglycemia was observed in patients without diabetes.

The intrinsic substrate specificity of the human tyrosine kinome.

Phosphorylation of proteins on tyrosine (Tyr) residues evolved in metazoan organisms as a mechanism of coordinating tissue growth1. Multicellular eukaryotes typically have more than 50 distinct protein Tyr kinases that catalyse the phosphorylation of thousands of Tyr residues throughout the proteome1-3. How a given Tyr kinase can phosphorylate a specific subset of proteins at unique Tyr sites is only partially understood4-7. Here we used combinatorial peptide arrays to profile the substrate sequence specificity of all human Tyr kinases. Globally, the Tyr kinases demonstrate considerable diversity in optimal patterns of residues surrounding the site of phosphorylation, revealing the functional organization of the human Tyr kinome by substrate motif preference. Using this information, Tyr kinases that are most compatible with phosphorylating any Tyr site can be identified. Analysis of mass spectrometry phosphoproteomic datasets using this compendium of kinase specificities accurately identifies specific Tyr kinases that are dysregulated in cells after stimulation with growth factors, treatment with anti-cancer drugs or expression of oncogenic variants. Furthermore, the topology of known Tyr signalling networks naturally emerged from a comparison of the sequence specificities of the Tyr kinases and the SH2 phosphotyrosine (pTyr)-binding domains. Finally we show that the intrinsic substrate specificity of Tyr kinases has remained fundamentally unchanged from worms to humans, suggesting that the fidelity between Tyr kinases and their protein substrate sequences has been maintained across hundreds of millions of years of evolution.

DDLA: a double deep latent autoencoder for diabetic retinopathy diagnose based on continuous glucose sensors.

The current diagnosis of diabetic retinopathy is based on fundus images and clinical experience. However, considering the ineffectiveness and non-portability of medical devices, we aimed to develop a diagnostic model for diabetic retinopathy based on glucose series data from the wearable continuous glucose monitoring system. Therefore, this study developed a novel method, i.e., double deep latent autoencoder, for exploring glycemic variability influence from multi-day glucose data for diabetic retinopathy. Specifically, the model proposed in this research could encode continuous glucose sensor data with non-continuous and variable length via the integration of a data reorganization module and a novel encoding module with fragmented-missing-wise objective function. Additionally, the model implements a double deep autoencoder, which integrated convolutional neural network, long short-term memory, to jointly capturing the inter-day and intra-day glucose latent features from glucose series. The effectiveness of the proposed model is evaluated through a cross-validation method to clinical datasets of 765 type 2 diabetes patients. The proposed method achieves the highest accuracy value (0.89), precision value (0.88), and F1 score (0.73). The results suggest that our model can be used to remotely diagnose and screen for diabetic retinopathy by learning potential features of glucose series data collected by wearable continuous glucose monitoring systems.

Threshold of hyperglycaemia associated with mortality in critically ill patients: a multicentre, prospective, observational study using continuous glucose monitoring.

AIMS/HYPOTHESIS: Continuous glucose monitoring (CGM) provides comprehensive information on the exposure to dysglycaemia. This study aimed to investigate the threshold of hyperglycaemia related to mortality risk in critically ill patients using CGM technology. METHODS: A total of 293 adult critically ill patients admitted to intensive care units of five medical centres were prospectively included between May 2020 and November 2021. Participants wore intermittently scanned CGM for a median of 12.0 days. The relationships between different predefined time above ranges (TARs), with the thresholds of hyperglycaemia ranging from 7.8 to 13.9 mmol/l (140-250 mg/dl), and in-hospital mortality risk were assessed by multivariate Cox proportional regression analysis. Time in ranges (TIRs) of 3.9 mmol/l (70 mg/dl) to the predefined hyperglycaemic thresholds were also assessed. RESULTS: Overall, 66 (22.5%) in-hospital deaths were identified. Only TARs with a threshold of 10.5 mmol/l (190 mg/dl) or above were significantly associated with the risk of in-hospital mortality, after adjustment for covariates. Furthermore, as the thresholds for TAR increased from 10.5 mmol/l to 13.9 mmol/l (190 mg/dl to 250 mg/dl), the hazards of in-hospital mortality increased incrementally with every 10% increase in TARs. Similar results were observed concerning the associations between TIRs with various upper thresholds and in-hospital mortality risk. For per absolute 10% decrease in TIR 3.9-10.5 mmol/l (70-190 mg/dl), the risk of in-hospital mortality was increased by 12.1% (HR 1.121 [95% CI 1.003, 1.253]). CONCLUSIONS/INTERPRETATION: A glucose level exceeding 10.5 mmol/l (190 mg/dl) was significantly associated with higher risk of in-hospital mortality in critically ill patients.