XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

Blood glucose concentration is a key indicator of patients' health, particularly for symptoms associated with diabetes mellitus. Because of the large number of diabetic patients, many approaches for glucose measurement have been studied to enable continuous and accurate glucose level monitoring. Among them, electrochemical analysis is prominent because it is simple and quantitative. This technology has been incorporated into commercialized and research-level devices from simple test strips to wearable devices and implantable systems. Although directly monitoring blood glucose assures accurate information, the invasive needle-pinching step to collect blood often results in patients (particularly young patients) being reluctant to adopt the process. An implantable glucose sensor may avoid the burden of repeated blood collections, but it is quite invasive and requires periodic replacement of the sensor owing to biofouling and its short lifetime. Therefore, noninvasive methods to estimate blood glucose levels from tears, saliva, interstitial fluid (ISF), and sweat are currently being studied. This review discusses the evolution of enzyme-based electrochemical glucose sensors, including materials, device structures, fabrication processes, and system engineering. Furthermore, invasive and noninvasive blood glucose monitoring methods using various biofluids or blood are described, highlighting the recent progress in the development of enzyme-based glucose sensors and their integrated systems.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/adhm.201701150

Enzyme-Based Glucose Sensor: From Invasive to Wearable Device.

EMT, cancer stem cells and autophagy; The three main axes of metastasis.

It has been reported that there are multiple mechanisms by which bufalin could exert its antimetastatic effect. HIF-1α has been reported to be involved in tumor migration and invasion by regulating EMT. However, it is not known whether bufalin could exert the antimetastatic effect by modulating HIF-1α expression in hepatocellular carcinoma. In the present study, we aimed to evaluate the antimetastatic potential of bufalin in vivo and in vitro. Our results demonstrated that the liver/lung metastases were significantly reduced in bufalin-treated mice, as tested in the orthotopic transplanted and tail vein injection tumor models. Furthermore, the epithelial-to-mesenchymal transition (EMT) was inhibited in bufalin-treated tumors, as reflected the upregulation of E-cadherin, and downregulation of N-cadherin, vimentin, Snail. Similar results were observed in SMMC7721 cells treated with bufalin. Moreover, the transforming growth factor-β1 (TGF-β1)-induced EMT was also abrogated by bufalin. Mechanistically, our study demonstrated that hypoxia-inducible factor-1α (HIF-1α) played an important role in the antimetastatic effect of bufalin in hepatocellular carcinoma. Importantly, HIF-1α expression may be regulated through the inhibition of the PI3K/AKT/mTOR pathway. Taken together, our results suggest that bufalin suppresses hepatic tumor invasion and metastasis and that this process may be related to the PI3K/AKT/mTOR/ HIF-1α axis.

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Bufalin suppresses hepatocellular carcinoma invasion and metastasis by targeting HIF-1α via the PI3K/AKT/mTOR pathway

Skin injury affects millions of people via the uncontrolled inflammation and infection. Many cellular components including fibroblasts and signaling pathways such as transforming growth factor-β (TGF-β) were activated to facilitate the wound healing to repair injured tissues. C57BL/6 female mice were divided into control and ozone oil treated groups. Excisional wounds were made on the dorsal skin and the fibroblasts were isolated from granulation tissues. The skin injured mouse model revealed that ozone oil could significantly decrease the wound area and accelerate wound healing compared with control group. QPCR and Western blotting assays showed that ozone oil up-regulated collagen I, α-SMA, and TGF-β1 mRNA and protein levels in fibroblasts. Wound healing assay demonstrated that ozone oil could increase the migration of fibroblasts. Western blotting assay demonstrated that ozone oil increased the epithelial-mesenchymal transition (EMT) process in fibroblasts via up-regulating fibronectin, vimentin, N-cadherin, MMP-2, MMP-9, insulin-like growth factor binding protein (IGFBP)-3, IGFBP5, and IGFBP6, and decreasing epithelial protein E-cadherin and cellular senescence marker p16 expression. Mechanistically, Western blotting assay revealed that ozone oil increased the phosphorylation of PI3K, Akt, and mTOR to regulate the EMT process, while inhibition of PI3K reversed this effect of ozone oil. At last, the results from Cytometric Bead Array (CBA) demonstrated ozone oil significantly decreased the inflammation in fibroblasts. Our results demonstrated that ozone oil facilitated the wound healing via increasing fibroblast migration and EMT process via PI3K/Akt/mTOR signaling pathway in vivo and in vitro The cellular and molecular mechanisms we found here may provide new therapeutic targets for the treatment of skin injury.

Ozone oil promotes wound healing by increasing the migration of fibroblasts via PI3K/Akt/mTOR signaling pathway.

Aim To develop a deep learning (DL) model that predicts age from fundus images (retinal age) and to investigate the association between retinal age gap (retinal age predicted by DL model minus chronological age) and mortality risk. Methods A total of 80 169 fundus images taken from 46 969 participants in the UK Biobank with reasonable quality were included in this study. Of these, 19 200 fundus images from 11 052 participants without prior medical history at the baseline examination were used to train and validate the DL model for age prediction using fivefold cross-validation. A total of 35 913 of the remaining 35 917 participants had available mortality data and were used to investigate the association between retinal age gap and mortality. Results The DL model achieved a strong correlation of 0.81 (p<0·001) between retinal age and chronological age, and an overall mean absolute error of 3.55 years. Cox regression models showed that each 1 year increase in the retinal age gap was associated with a 2% increase in risk of all-cause mortality (hazard ratio (HR)=1.02, 95% CI 1.00 to 1.03, p=0.020) and a 3% increase in risk of cause-specific mortality attributable to non-cardiovascular and non-cancer disease (HR=1.03, 95% CI 1.00 to 1.05, p=0.041) after multivariable adjustments. No significant association was identified between retinal age gap and cardiovascular- or cancer-related mortality. Conclusions Our findings indicate that retinal age gap might be a potential biomarker of ageing that is closely related to risk of mortality, implying the potential of retinal image as a screening tool for risk stratification and delivery of tailored interventions.

Retinal age gap as a predictive biomarker for mortality risk

To assess the prevalence and causes of low vision and blindness in type 2 diabetes patients, a population-based cross-sectional study including 8952 rural-dwelling residents aged 40 years or older from Hengli Town in Southern China was conducted. Participants underwent standard interviews, physical measurements, laboratory tests, and comprehensive eye examinations. Low vision and blindness were defined based on WHO criteria. Visual acuity data were available for 1348 (89.9%) of the 1500 subjects with type 2 diabetes. Age-standardized prevalence of bilateral low vision and blindness assessed in the better-seeing eye was 2.9% (95% confidence interval [CI]: 2.0–3.8) and 0.7% (95% CI: 0.2–1.1) based on best-corrected visual acuity (BCVA). Cataracts were the primary cause of low vision and blindness. Visual impairment was associated with age (odds ratio [OR]: 3.73, 95% CI: 2.39–5.83), education level (OR: 3.21, 95% CI: 1.63–6.29), duration of diabetes (OR: 1.14, 95% CI: 1.04–1.25) and body mass index (OR: 0.86, 95% CI: 0.77–0.95). Our data suggest that approximately 70% of visual impairment in this diabetic population could be eliminated with appropriate cataract surgery or spectacle correction. Greater consideration should be given to older type 2 diabetes patients with a level of lower education.

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Prevalence and causes of low vision and blindness in a Chinese population with type 2 diabetes: the Dongguan Eye Study.

The present study aimed to investigate whether the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway is involved in the transforming growth factor β2 (TGF-β2)-induced epithelial-mesenchymal transition (EMT) in human lens epithelial (HLE) cells. HLEB-3 cells were cultured and stimulated with 10 ng/ml TGF-β2 for 24 h. Western blotting was then performed to analyze the expression levels of connexin 43 and fibronectin, and the activities of Akt and mTOR. Confocal cell immunofluorescence was used to observe the expression of phosphorylated (p)-Akt. The toxicity of 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) was assessed using a Cell Counting Kit-8 assay, and inhibition investigations were performed using a PI3K inhibitor. The expression of connexin 43 was suppressed and the expression of fibronectin was increased when the cells were stimulated with 10 ng/ml TGF-β2 for 24 h. In addition, Akt and mTOR were activated during TGF-β2-induced EMT. Treatment of with LY294002 (20 µM) inhibited the activation of Akt and mTOR and effectively prevented TGF-β2-induced EMT in the HLECs. Therefore, the results of the present study indicated that TGF-β2 induces EMT by activating the PI3K/Akt/mTOR signaling pathway in cultured HLECs.

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TGF-β2 induces epithelial-mesenchymal transition in cultured human lens epithelial cells through activation of the PI3K/Akt/mTOR signaling pathway.

Predictive role of corneal Q-value differences between nasal-temporal and superior-inferior quadrants in orthokeratology lens decentration.

Abstract Introduction retinal age derived from fundus images using deep learning has been verified as a novel biomarker of ageing. We aim to investigate the association between retinal age gap (retinal age–chronological age) and incident Parkinson’s disease (PD). Methods a deep learning (DL) model trained on 19,200 fundus images of 11,052 chronic disease-free participants was used to predict retinal age. Retinal age gap was generated by the trained DL model for the remaining 35,834 participants free of PD at the baseline assessment. Cox proportional hazards regression models were utilised to investigate the association between retinal age gap and incident PD. Multivariable logistic model was applied for prediction of 5-year PD risk and area under the receiver operator characteristic curves (AUC) was used to estimate the predictive value. Results a total of 35,834 participants (56.7 ± 8.04 years, 55.7% female) free of PD at baseline were included in the present analysis. After adjustment of confounding factors, 1-year increase in retinal age gap was associated with a 10% increase in risk of PD (hazard ratio [HR] = 1.10, 95% confidence interval [CI]: 1.01–1.20, P = 0.023). Compared with the lowest quartile of the retinal age gap, the risk of PD was significantly increased in the third and fourth quartiles (HR = 2.66, 95% CI: 1.13–6.22, P = 0.024; HR = 4.86, 95% CI: 1.59–14.8, P = 0.005, respectively). The predictive value of retinal age and established risk factors for 5-year PD risk were comparable (AUC = 0.708 and 0.717, P = 0.821). Conclusion retinal age gap demonstrated a potential for identifying individuals at a high risk of developing future PD.

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Xiaohong Yang

Papers

Retinal age gap as a predictive biomarker for mortality risk

Prevalence and causes of low vision and blindness in a Chinese population with type 2 diabetes: the Dongguan Eye Study.

TGF-β2 induces epithelial-mesenchymal transition in cultured human lens epithelial cells through activation of the PI3K/Akt/mTOR signaling pathway.

Predictive role of corneal Q-value differences between nasal-temporal and superior-inferior quadrants in orthokeratology lens decentration.

Retinal age gap as a predictive biomarker of future risk of Parkinson’s disease