Clinical characteristics and complication risks in data-driven clusters among Chinese community diabetes populations.

BACKGROUND: Novel diabetes phenotypes were proposed by the Europeans through cluster analysis, but Chinese community diabetes populations might exhibit different characteristics. This study aims to explore the clinical characteristics of novel diabetes subgroups under data-driven analysis in Chinese community diabetes populations. METHODS: We used K-means cluster analysis in 6369 newly diagnosed diabetic patients from eight centers of the REACTION (Risk Evaluation of cAncers in Chinese diabeTic Individuals) study. The cluster analysis was performed based on age, body mass index, glycosylated hemoglobin, homeostatic modeled insulin resistance index, and homeostatic modeled pancreatic ß-cell functionality index. The clinical features were evaluated with the analysis of variance (ANOVA) and chi-square test. Logistic regression analysis was done to compare chronic kidney disease and cardiovascular disease risks between subgroups. RESULTS: Overall, 2063 (32.39%), 658 (10.33%), 1769 (27.78%), and 1879 (29.50%) populations were assigned to severe obesity-related and insulin-resistant diabetes (SOIRD), severe insulin-deficient diabetes (SIDD), mild age-associated diabetes mellitus (MARD), and mild insulin-deficient diabetes (MIDD) subgroups, respectively. Individuals in the MIDD subgroup had a low risk burden equivalent to prediabetes, but with reduced insulin secretion. Individuals in the SOIRD subgroup were obese, had insulin resistance, and a high prevalence of fatty liver, tumors, family history of diabetes, and tumors. Individuals in the SIDD subgroup had severe insulin deficiency, the poorest glycemic control, and the highest prevalence of dyslipidemia and diabetic nephropathy. Individuals in MARD subgroup were the oldest, had moderate metabolic dysregulation and the highest risk of cardiovascular disease. CONCLUSION: The data-driven approach to differentiating the status of new-onset diabetes in the Chinese community was feasible. Patients in different clusters presented different characteristics and risks of complications.

M2 macrophage infusion ameliorates diabetic glomerulopathy via the JAK2/STAT3 pathway in db/db mice.

Objectives: To explore the therapeutic effects of M2 macrophages in diabetic nephropathy (DN) and their mechanism.Methods: We infused M2 macrophages stimulated with IL-4 into 10-week-old db/db mice once a week for 4 weeks through the tail vein as M2 group. Then we investigated the role of M2 macrophages in alleviating the infammation of DN and explored the mechanism.Results: M2 macrophages hindered the progression of DN, reduced the levels of IL-1ß (DN group was 34%, M2 group was 13%, p < 0.01) and MCP-1 (DN group was 49%, M2 group was 16%, p < 0.01) in the glomeruli. It was also proven that M2 macrophages alleviate mesangial cell injury caused by a high glucose environment. M2 macrophage tracking showed that the infused M2 macrophages migrated to the kidney, and the number of M2 macrophages in the kidney reached a maximum on day 3. Moreover, the ratio of M2 to M1 macrophages was 2.3 in the M2 infusion group, while 0.4 in the DN group (p < 0.01). Mechanistically, M2 macrophages downregulated Janus kinase (JAK) 2 and signal transducer and activator of transcription (STAT) 3 in mesangial cells.Conclusions: Multiple infusions of M2 macrophages significantly alleviated inflammation in the kidney and hindered the progression of DN at least partially by abrogating the M1/M2 homeostasis disturbances and suppressing the JAK2/STAT3 pathway in glomerular mesangial cells. M2 macrophage infusion may be a new therapeutic strategy for DN treatment.

Small interfering RNA (siRNA) as a potential gene silencing strategy for diabetes and associated complications: challenges and future perspectives.

Objective: This article critically reviews the recent search on the use of Small Interfering RNA (siRNA) in the process of gene regulation that has been harnessed to silence specific genes in various cell types, including those involved in diabetes complications. Significance: Diabetes, a prevalent and severe condition, poses life-threatening risks due to elevated blood glucose levels. It results from inadequate insulin production by the pancreas or ineffective insulin utilization by the body. Recent research suggests siRNA could hold promise in addressing diabetes complications. Methods: In this review, we discussed several subjects, including diabetes; its function, and common treatment options. An in-depth analysis of gene silencing method for siRNA and role of siRNA in diabetes, focusing on its impact on glucose homeostasis, diabetic retinopathy, wound healing, diabetic nephropathy and peripheral neuropathy, diabetic foot ulcers, diabetic atherosclerosis, and diabetic cardiomyopathy. Result: siRNA-based treatment has the potential to target specific genes without disrupting several other endogenous pathways, which decreases the risk of off-target effects. In addition, siRNA has the capability to provide long-term efficacy with a single dose which will reduce treatment options and enhance patient compliance. Conclusion: In the context of diabetic complications, siRNA has been explored as a potential therapeutic tool to modulate the expression of genes involved in various processes associated with diabetes-related issues such as Diabetic Retinopathy, Neuropathy, Nephropathy, wound healing. The use of siRNA in these contexts is still largely experimental, and challenges such as delivery to specific tissues, potential off-target effects, and long-term safety need to be addressed. Additionally, the development of siRNA-based therapies for clinical use in diabetic complications is an active area of research. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01405-7.

Syndecans and diabetic complications: A narrative review.

Syndecan (SDC) is a member of the heparan sulfate proteoglycan (HSPG) family. It appears to play a role in the aetiology of diabetic complications, with decreased levels of SDCs being reported in the kidney, retina, and cardiac muscle in models of diabetes mellitus (DM). The reduced levels of SDCs may play an important role in the development of albuminuria in DM. Some studies have provided the evidence supporting the mechanisms underlying the role of SDCs in DM. However, SDCs and the molecular mechanisms involved are complex and need to be further elucidated. This review focuses on the underlying molecular mechanisms of SDCs that are involved in the development and progression of the complications of DM, which may help in developing new strategies to prevent and treat these complications.

Survival, incidence, and predictors of diabetic neuropathy among type 2 diabetic patients in hospitals of Addis Ababa.

Background: Diabetic neuropathy is a very common complication of diabetes mellitus. Thus, measuring the incidence of diabetic neuropathy is a key element in tracking the progress of epidemics of diabetes mellitus and an indication of early accessibility for healthcare in terms of type 2 diabetic patients. Objective: To assess survival, incidence, and predictors of diabetic neuropathy among type 2 diabetic patients in hospitals of Addis Ababa from June 25 to August 25, 2023. Methods: An institutional-based retrospective follow-up study design was used among newly diagnosed type 2 diabetic patients at hospitals of Addis Ababa. A chart review tool that contains socio-demographic, clinical, and comorbidity characteristics, biochemical characteristics, and the status of type 2 patients was used. A cleaned data was exported from Epi-data manager 4.6 version to SPSS version 25 for analysis. Bivariate Cox regression analysis was done to identify predictors of diabetic neuropathy at a 95% confidence level. Result: A total of 414 type 2 diabetic patients were included in the study. Of these, 97 (23.4%) developed diabetic neuropathy. Variables like having hypertension (AHR 11.25, 95% CI 3.73-33.93), anemia (AHR 4.18, 95% CI 1.78-9.82), high-density lipoprotein < 40 mg/dl (AHR 5.07, 95% CI 1.38-18.67), high creatinine level (AHR 14.67, 95% CI 4.27-50.40), diabetic retinopathy (AHR 4.32, 95% CI 1.32-14.18), and diabetic nephropathy (AHR 2.50, 95% CI 1.09-6.57) were associated with the incidence of diabetic neuropathy. The mean time to develop diabetic neuropathy was 4.94 years, CI (4.50-5.38), and the mean survival time was 6.61 years. Conclusion: The incidence of diabetic neuropathy was high relative to other studies. Variables like having hypertension, anemia, high-density lipoprotein, high creatinine level, diabetic retinopathy, and diabetic nephropathy were predictors of diabetic neuropathy. The mean time to develop diabetic neuropathy was 5 years, with a survival mean time of 7 years.

Advances in the study of microparticles in diabetic retinopathy.

Diabetic retinopathy (DR) is one of the common diabetic microangiopathies, which severely impairs vision in diabetic population. The underlying mechanisms regarding the development of DR are not fully understood, and there is a lack of biomarkers to guide clinical, assessment of disease progression. Recently researchers have found that microparticles (MP) and its bioactive molecules are involved in the development of DR. MP is widely distributed in the circulation and can exert autocrine and paracrine benefits in intercellular signalling, provide a catalytic platform for the thrombospondin complex to promote coagulation, and promote the accumulation of reactive oxygen species to cause endothelial damage. MP interacts with advanced glycosylation end products (AGE) and AGE receptor (RAGE) to activate inflammatory pathways. MP carries a variety of miRNAs that regulate the vascular endothelial growth factor generation pathway. MP has also been applied to the exploration of mesenchymal stromal cell replacement therapy to treat DR. In a word, MP provides new ideas for the study of DR. MP has emerged as a marker to assess the progression of DR. As a potential therapeutic target, MP also has considerable research value.

Care, control and complications of hospitalised patients with type 1 diabetes in China: A nationwide-based registry study.

AIMS: To evaluate the status quo of type 1 diabetes (T1D) management and characteristics of hospitalised patients with T1D in China through a nationwide multicentre registry study, the China Diabetes Type 1 Study (CD1S). MATERIALS AND METHODS: Clinical data from the electronic hospital records of all people with T1D were retrospectively collected in 13 tertiary hospitals across 7 regions of China from January 2016 to December 2021. Patients were defined as newly diagnosed who received a diagnosis of diabetes for less than 3 months. RESULTS: Among the 4993 people with T1D, the median age (range) at diagnosis was 23.0 (1.0-87.0) years and the median disease duration was 2.0 years. The median haemoglobin A1c (HbA1c) level was 10.7%. The prevalence of obesity, overweight, dyslipidemia, and hypertension were 2.5%, 10.8%, 62.5% and 25.9%, respectively. The incidence rate of diabetic ketoacidosis at disease onset was 41.1%, with the highest in children <10 years of age (50.6%). In patients not newly diagnosed, 60.7% were diagnosed with at least one chronic diabetic complication, with the highest proportion (45.3%) of diabetic peripheral neuropathy. Chronic complications were detected in 79.2% of people with T1D duration ≥10 years. CONCLUSIONS: In the most recent years, there were still unsatisfactory metabolic control and high incidence of diabetic ketoacidosis as well as chronic diabetic complications among inpatients with T1D in China. The ongoing CD1S prospective study aims to improve the quality of T1D management nationally.

Development of Machine Learning Models for the Identification of Elevated Ketone Bodies During Hyperglycemia in Patients with Type 1 Diabetes.

Aims: Diabetic ketoacidosis (DKA) is a serious life-threatening condition caused by a lack of insulin, which leads to elevated plasma glucose and metabolic acidosis. Early identification of developing DKA is important to start treatment and minimize complications and risk of death. The aim of the present study is to develop and test prediction model(s) that gives an alarm about their risk of developing elevated ketone bodies during hyperglycemia. Methods: We analyzed data from 138 type 1 diabetes patients with measurements of ketone bodies and continuous glucose monitoring (CGM) data from over 30,000 days of wear time. We utilized a supervised binary classification machine learning approach to identify elevated levels of ketone bodies (≥0.6 mmol/L). Data material was randomly divided at patient level in 70%/30% (training/test) dataset. Logistic regression (LR) and random forest (RF) classifier were compared. Results: Among included patients, 913 ketone samples were eligible for modeling, including 273 event samples with ketone levels ≥0.6 mmol/L. An area under the receiver operating characteristic curve from the RF classifier was 0.836 (confidence interval [CI] 90%, 0.783-0.886) and 0.710 (CI 90%, 0.646-0.77) for the LR classifier. Conclusions: The novel approach for identifying elevated ketone levels in patients with type 1 diabetes utilized in this study indicates that CGM could be a valuable resource for the early prediction of patients at risk of developing DKA. Future studies are needed to validate the results.

Novel spiroindoline derivatives targeting aldose reductase against diabetic complications: Bioactivity, cytotoxicity, and molecular modeling studies.

Despite significant developments in therapeutic strategies, Diabetes Mellitus remains an increasing concern, leading to various complications, e.g., cataracts, neuropathy, retinopathy, nephropathy, and several cardiovascular diseases. The polyol pathway, which involves Aldose reductase (AR) as a critical enzyme, has been focused on by many researchers as a target for intervention. On the other hand, spiroindoline-based compounds possess remarkable biological properties. This guided us to synthesize novel spiroindoline oxadiazolyl-based acetate derivatives and investigate their biological activities. The synthesized molecules' structures were confirmed herein, using IR, NMR (1H and 13C), and Mass spectroscopy. All compounds were potent inhibitors with KI constants spanning from 0.186 ± 0.020 µM to 0.662 ± 0.042 µM versus AR and appeared as better inhibitors than the clinically used drug, Epalrestat (EPR, KI: 0.841 ± 0.051 µM). Besides its remarkable inhibitory profile compared to EPR, compound 6k (KI: 0.186 ± 0.020 µM) was also determined to have an unusual pharmacokinetic profile. The results showed that 6k had less cytotoxic effect on normal mouse fibroblast (L929) cells (IC50 of 569.58 ± 0.80 µM) and reduced the viability of human breast adenocarcinoma (MCF-7) cells (IC50 of 110.87 ± 0.42 µM) more than the reference drug Doxorubicin (IC50s of 98.26 ± 0.45 µM and 158.49 ± 2.73 µM, respectively), thus exhibiting more potent anticancer activity. Moreover, molecular dynamic simulations for 200 ns were conducted to predict the docked complex's stability and reveal significant amino acid residues that 6k interacts with throughout the simulation.

Diabetic Keratopathy: Redox Signaling Pathways and Therapeutic Prospects.

Diabetes mellitus, the most prevalent endocrine disorder, not only impacts the retina but also significantly involves the ocular surface. Diabetes contributes to the development of dry eye disease and induces morphological and functional corneal alterations, particularly affecting nerves and epithelial cells. These changes manifest as epithelial defects, reduced sensitivity, and delayed wound healing, collectively encapsulated in the context of diabetic keratopathy. In advanced stages of this condition, the progression to corneal ulcers and scarring further unfolds, eventually leading to corneal opacities. This critical complication hampers vision and carries the potential for irreversible visual loss. The primary objective of this review article is to offer a comprehensive overview of the pathomechanisms underlying diabetic keratopathy. Emphasis is placed on exploring the redox molecular pathways responsible for the aberrant structural changes observed in the cornea and tear film during diabetes. Additionally, we provide insights into the latest experimental findings concerning potential treatments targeting oxidative stress. This endeavor aims to enhance our understanding of the intricate interplay between diabetes and ocular complications, offering valuable perspectives for future therapeutic interventions.

The vascular complications of diabetes: a review of their management, pathogenesis, and prevention.

INTRODUCTION: This review highlights the pathogenesis of both microvascular and macrovascular complications of diabetes and how these mechanisms influence both the management and preventative strategies of these complications. The cumulative data shown in this review suggest hyperglycemic and blood pressure control remain central to this intricate process. AREAS COVERED: We reviewed the literature including retrospective, prospective trials as well as meta-analysis, and post hoc analysis of randomized trials on microvascular andmacrovascular complications. EXPERT OPINION: Further research is needed to explore the ideal intervention targets and preventative strategies needed to prevent macrovascular complications. Furthermore, as the data for trials looking at microvascular complications lengthen more long-term data will further elucidate the role that the duration of diabetes has on these complications. Additionally, trials looking to maximize hyperglycemic control with multiple agents in diabetes, such as metformin, SGL2isand GLP-1 receptor agonists are currently in process, which will have implications for rates of microvascular as well as macrovascular complications.

The level of serum retinol-binding protein is associated with diabetic mild cognitive impairment.

BACKGROUND: Several studies have shown that retinol-binding protein (RBP) is linked to diabetes and neurodegenerative diseases. However, no studies have elucidated the relationship between RBP and diabetic cognitive disorders. OBJECTIVE: To determine whether the change characteristics of serum RBP are associated with alterations in cognitive functioning in type 2 diabetes mellitus (T2DM). METHODS: In this study, 252 patients with T2DM and 34 people as healthy controls were included. According to the Montreal Cognitive Assessment (MoCA), the diabetic subjects were divided into the mild cognitive impairment (MCI) group and the Non-MCI group. Demographic characteristics and clinical indicators as well as serum RBP levels were analyzed. RESULTS: The serum RBP levels in the MCI group were lower compared with the Non-MCI group (P = 0.02). The level of RBP was higher in the diabetes without MCI group than in the healthy control (P < 0.001). Serum RBP levels were positively correlated with MoCA scores (r = 0.178, P = 0.003). Binary Logistic regression model analysis showed that low RBP [odds ratio (OR) = 0.936], old age (OR = 1.074), high fasting blood glucose (OR = 1.164), and low fasting C-peptide (OR = 0.722) may be independent risk factors for diabetic MCI. The ROC curve of serum RBP for predicting diabetic MCI showed that the area under the curve was 0.630. CONCLUSIONS: Our study revealed an association between serum RBP and diabetic MCI. Serum RBP levels in diabetic MCI are lower and correlated with cognitive function.

Antibiotic-loaded bone cement enhances ability of tibial cortex transverse transport for treating infected wounds / 中国组织工程研究

BACKGROUND:Diabetic foot patients with wound infections constitute a large patient population,and there is currently no satisfactory treatment approach. OBJECTIVE:To investigate the clinical efficacy of a modified tibial cortex transverse transport combined with antibiotic-loaded bone cement for treating refractory diabetic foot ulcers. METHODS:A total of 46 diabetic foot ulcers patients,27 males and 19 females,with an average age of 64.37 years,were selected from Beijing Chaoyang Hospital,Capital Medical University and Beijing Chaoyang Integrative Medicine Rescue and First Aid Hospital from January 2020 to January 2023.All of them underwent the modified tibial cortex transverse transport combined with antibiotic-loaded bone cement treatment.Ankle-brachial index,WIFi(Wound/Ischemia/Foot infection)classification,pain visual analog scale score,and ulcer area were recorded before and 3 months after surgery. RESULTS AND CONCLUSION:(1)The mean ulcer healing time for the 46 patients was(58.07±24.82)days.At 3 months postoperatively,there were significant improvements in ankle-brachial index,pain visual analog scale score,ulcer area,and WIFi classification in 46 patients,as compared to the preoperative values,with statistically significant differences(P<0.05).Two patients experienced pin-tract infections,without infection or ulcer recurrence during the follow-up period.(2)These findings indicate that the modified tibial cortex transverse transport combined with antibiotic-loaded bone cement effectively alleviates patients'pain,improves lower limb circulation,controls infections,and promotes ulcer healing.

Evaluation of Trace Elements Levels and Construction of Auxiliary Prediction Model in Patients with Diabetes Ketoacidosis in Type 1 Diabetes.

Background: Trace elements play an important role in reflecting physical metabolic status, but have been rarely evaluated in diabetes ketoacidosis (DKA). Since clinical biochemical parameters are the first-line diagnostic data mastered by clinical doctors and DKA has a rapid progression, it is crucial to fully utilize clinical data and combine innovative parameters to assist in assessing disease progression. The aim of this study was to evaluate the levels of trace elements in DKA patients, followed by construction of predictive models combined with the laboratory parameters. Methods: A total of 96 T1D individuals (48 DKA patients) were collected from the First Hospital of Jilin University. Serum calcium (Ca), magnesium (Mg), zinc (Zn), copper (Cu), iron (Fe) and selenium (Se) were measured by Inductively Coupled Plasma Mass Spectrometry, and the data of biochemical parameters were collected from the laboratory information system. Training and validation sets were used to construct the model and examine the efficiency of the model. The lambda-mu-sigma method was used to evaluate the changes in the model prediction efficiency as the severity of the patient's condition increases. Results: Lower levels of serum Mg, Ca and Zn, but higher levels of serum Fe, Cu and Se were found in DKA patients. Low levels of total protein (TP), Zn and high levels of lipase would be an efficient combination for the prediction of DKA (Area under curves for training set and validation set were 0.867 and 0.961, respectively). The examination test confirmed the clinical applicability of the constructed models. The increasing predictive efficiency of the model was found with NACP. Conclusion: More severe oxidative stress in DKA led to further imbalance of trace elements. The combination of TP, lipase and Zn could predict DKA efficiently, which would benefit the early identification and prevention of DKA to improve prognosis.

Tetrahedral Framework Nucleic Acids Based Small Interfering RNA Targeting Receptor for Advanced Glycation End Products for Diabetic Complications Treatment.

Complications arising from diabetes can threaten multiple organs. Advanced glycation end products (AGEs) play a significant role in inducing these complications. Highly processed diets and hyperglycemia facilitate the accumulation of AGEs in the body. Interaction between AGEs and their main receptor (RAGE) initiates the transmission of intracellular inflammatory and cell death signals, which ultimately lead to complications. To counter AGEs-induced damage, we developed an siRNA-binding tetrahedral framework nucleic acids (TDN) system, termed Tsi, which combines the potent cell membrane penetrability and serum stability of TDN with the gene-targeting specificity of siRNA-RAGE. Tsi effectively and persistently downregulates the expression of RAGE, thereby suppressing inflammation by blocking the NF-κB pathway as well as exhibiting antioxidant functions. Furthermore, Tsi regulates the pyroptosis state of macrophages via the NLRP3/caspase-1 axis, which inhibits the spread of cell death signals and maintains homeostasis. This is of great significance for the synergistic treatment strategy for systemic complications in patients with refractory hyperglycemia. In summary, this study describes a nanomedicine that targets the RAGE and suppresses AGE-induced inflammation. This nucleic acid drug holds long-lasting efficacy and is independent of lowering hyperglycemia, which provides a strategy for the treatment of diabetic complications and age-related diseases.

The role of miRNAs carried by extracellular vesicles in type 2 diabetes and its complications.

Diabetes poses severe global public health problems and places heavy burdens on the medical and economic systems of society. Type 2 diabetes (T2D) accounts for 90% of these cases. Diabetes also often accompanies serious complications that threaten multiple organs such as the brain, eyes, kidneys, and the cardiovascular system. MicroRNAs (miRNAs) carried by extracellular vesicles (EV-miRNAs) are considered to mediate cross-organ and cross-cellular communication and have a vital role in the pathophysiology of T2D. They also offer promising sources of diabetes-related biomarkers and serve as effective therapeutic targets. Here, we briefly reviewed studies of EV-miRNAs in T2D and related complications. Specially, we innovatively explore the targeting nature of miRNA action due to the target specificity of vesicle binding, aiding mechanism understanding as well as the detection and treatment of diseases.

Plasma proteins and onset of type 2 diabetes and diabetic complications: Proteome-wide Mendelian randomization and colocalization analyses.

We conduct proteome-wide Mendelian randomization and colocalization analyses to decipher the associations of blood proteins with the risk of type 2 diabetes and diabetic complications. Genetic data on plasma proteome are obtained from 54,306 UK Biobank participants and 35,559 Icelanders. Summary-level data on type 2 diabetes are obtained from the DIAGRAM (DIAbetes Genetics Replication And Meta-analysis consortium) consortium (74,124 cases) and FinnGen study (33,043 cases). Data on 10 diabetic complications are obtained from FinnGen and corresponding studies. Among 1,886 proteins, genetically predicted levels of 47 plasma proteins are associated with type 2 diabetes. Eleven of these proteins have strong support of colocalization. Seventeen proteins are associated with at least one diabetic complication, although a few have colocalization support. HLA-DRA, AGER, HSPA1A, and HSPA1B are associated with most microvascular complications. This study reveals causal proteins for the onset of type 2 diabetes and diabetic complications, which enhances the understanding of molecular etiology and development of therapeutics.

VEGFR-2 adhesive nanoprobes reveal early diabetic retinopathy in vivo.

Diabetic retinopathy (DR) is a debilitating organ manifestation of diabetes. Absent of early diagnosis and intervention, vision tends to drastically and irreversibly decline. Previously, we showed higher vascular endothelial growth factor receptor 2 (VEGFR-2) expression in diabetic microvessels, and the suitability of this molecule as a biomarker for early DR diagnosis. However, a hurdle to translation remained generation of biodegradable nanoprobes that are sufficiently bright for in vivo detection. Here, an adhesive fluorescent nanoprobe with high brightness was developed using biodegradable materials. To achieve that, a fluorophore with bulky hydrophobic groups was encapsulated in the nanoparticles to minimize fluorophore π-π stacking, which diminishes brightness at higher loading contents. The nanoprobe selectively targeted the VEGFR-2 under dynamic flow conditions. Upon systemic injection, the nanoprobes adhered in the retinal microvessels of diabetic mice and were visualized as bright spots in live retinal microscopy. Histology validated the in vivo results and showed binding of the nanoprobes to the microvascular endothelium and firmly adhering leukocytes. Leukocytes were found laden with nanoprobes, indicating the potential for payload transport across the blood-retinal barrier. Our results establish the translational potential of these newly generated nanoprobes in early diagnosis of DR.

Preserved Ratio Impaired Spirometry and Risks of Macrovascular, Microvascular Complications and Mortality Among Individuals With Type 2 Diabetes.

BACKGROUND: The prospective associations of preserved ratio impaired spirometry (PRISm) with new-onset macrovascular and microvascular complications and mortality among individuals with type 2 diabetes (T2D) and whether PRISm enhances the prediction ability of an established office-based risk score remain to be elucidated. RESEARCH QUESTION: Can PRISm be used as a predictor of poor prognosis in individuals with T2D? STUDY DESIGN AND METHODS: We included 20,047 study participants with T2D and complete data on spirometry at recruitment from the UK Biobank cohort. Multivariable Cox proportional hazards models were used to assess the associations of baseline PRISm (FEV1 to FVC ratio, ≥ 0.70; FEV1, < 80% predicted) with subsequent risks of incident stroke (any type), ischemic stroke, myocardial infarction, unstable angina, coronary heart disease, diabetic retinopathy, diabetic kidney disease, all-cause mortality, cardiovascular mortality, and respiratory mortality. RESULTS: For this cohort analysis, 4,521 patients (22.55% of participants with T2D) showed comorbid PRISm at baseline. Over a median follow-up of 11.52 to 11.87 years, patients with T2D with PRISm at baseline showed higher risks than those with normal spirometry findings of various T2D complications developing and mortality; the adjusted hazard ratios for PRISm were 1.413 (95% CI, 1.187-1.681) for stroke (any type), 1.382 (95% CI, 1.129-1.690) for ischemic stroke, 1.253 (95% CI, 1.045-1.503) for myocardial infarction, 1.206 (95% CI, 1.086-1.339) for coronary heart disease, 1.311 (95% CI, 1.141-1.506) for diabetic retinopathy, 1.384 (95% CI, 1.190-1.610) for diabetic kidney disease, 1.337 (95% CI, 1.213-1.474) for all-cause mortality, 1.597 (95% CI, 1.296-1.967) for cardiovascular mortality, and 1.559 (95% CI, 1.189-2.044) for respiratory mortality, respectively. The addition of PRISm significantly improved the reclassification ability, based on the net reclassification index, of an office-based risk score by 15.53% (95% CI, 10.14%-19.63%) to 33.60% (95% CI, 20.90%-45.79%). INTERPRETATION: Individuals with T2D with comorbid PRISm, accounting for a considerable proportion of the population with T2D, showed significantly increased risks of adverse macrovascular and microvascular complications and mortality.