2型糖尿病性视网膜病变临床因素分析

目的:探讨影响2型糖尿病视网膜病变(DR)发病的相关临床因素。方法:回顾性分析483例2型糖尿病患者的临床资料。结果:2型糖尿痛DR患病率为35%(169/483),其中非增殖型视网膜病变(NPDR)73.4%(124/169),增殖型视网膜病变(PDR)26.6% (45/169)。DR患者的病程、SBP、合并肾脏病变、合并心脏病变、HbA1c、TC、TG、LDL-c、BUN和Cr均显著高于NDR患者(P<0.05);Logistic回归分析显示病程、年龄、SBP、TC、LDL-c、合并心脏病变和/或肾脏病变是DR发病的危险因素。结论:DM病程、患病年龄、SBP、HbA1c、TC、LDL-c、合并心脏病变和/或肾脏病变、肾功能是DR发生发展的危险因素。     

Endothelial nitric oxide synthase genotype and haplotype are not associated with diabetic retinopathy in diabetes type 2 patients

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene have been associated with the development of diabetic retinopathy (DR) in patients with type 1 diabetes mellitus (T1DM), but not with T2DM. However, no previous study has analyzed combinations of genetic markers (haplotypes), which can be more informative. We studied three eNOS genetic polymorphisms: a single nucleotide polymorphism in the promoter region (T(-786)C), in exon 7 (Glu298Asp), and a variable number of tandem repeats in intron 4 (b/a) in 103 healthy controls, and in 170 patients with T2DM (without DR, N=114; with DR, N=56). We also examined the association of eNOS gene haplotypes with T2DM and with DR. No differences were found in the frequencies of genotypes and alleles of the three polymorphisms among the three groups of subjects. However, the "C-Glu-b" haplotype was more common in healthy controls (24%) than in T2DM patients (7%) (P=0.0001). Finally, no significant difference in the distribution of eNOS haplotypes frequencies was found when T2DM patients with or without DR were compared (P=0.7372). These findings suggest no association between DR and individual eNOS haplotypes in T2DM patients. The "C-Glu-b" haplotype, however, may have a protective effect against T2DM. Further studies should be conducted to address the molecular basis for such an effect.     

The role of oxidative stress after retinal laser photocoagulation in nonproliferative diabetic retinopathy

Diabetic retinopathy (DR) represents the most common chronic complication of diabetes, and it is the leading cause of new cases of blindness in patients between 20-74 years old in developed countries. Laser photocoagulation (LF) represents an efficacious approach to the treatment of DR. Oxidative factors, such as free radicals (FR), are continuously generated in aerobic organisms as a result of different metabolic processes. It is well known that oxidative stress plays a role in the development of DR. The aim of this study was to evaluate the thermal effects of the scatter retinal laser photocoagulation technique on the production of FR. A total of 90 patients were enrolled in this study. They were divided in 3 groups: 30 diabetic patients with DR, 30 diabetic patients without DR, and 30 control individuals without diabetes mellitus (DM). Full scatter retinal LF was performed in all patients with DR. We measured the concentrations of superoxide dismutase (SOD), glutathione peroxidase (GPOD), catalase, and total antioxidative status (TAS). Of the 30 DR patients, 13 showed the appearance or worsening of macular edema after LEF, whereas the other 17 patients showed no change. Thirty days after LF, improvement in visual acuity was observed, but this change was not statistically significant. The mean plasma or erythrocyte lysate concentrations of various antioxidants were significantly lower in the diabetic patients without DR compared to the individuals without DM and in the diabetic patients with DR compared to the individuals without DM; the diabetic patients with DR did not show lower concentrations of the antioxidants compared to the diabetic patients without DR. The concentrations of SOD, GPOD, catalase, and TAS were significantly lower in the diabetic patients with DR after retinal scatter LF, which could be the consequence of retinal oxidative stress caused by the LF thermal effect.     

HbA1c和FPG水平与2型糖尿病患者视网膜病变的相关性分析

目的：探讨糖化血红蛋（HbA1c）、空腹血糖（FPG）与2型糖尿病患者视网膜病变（DR）的相关性。方法：对我院2010年1月-2012年12月住院或门诊的336例2型糖尿病（T2DM）患者进行眼底检查或眼底血管荧光素造影检测,按有无视网膜病变分为视网膜病变（DR）组和无视网膜病变（NDR）组,并对HbA1c、FBG水平进行检测。结果：DR组较NDR组HbA1c水平高,差异有统计学意义（P〈0．05）,HbA1c水平和DR分期呈正相关（I=0．526,P〈0．001）,而DR组和NDR组FPG水平差异无无统计学意义（P〉0．05）。结论：可将HbA1c作为2型糖尿病患者视网膜病变发生和发展的监测指标之一。     

Chronic Kidney Disease and Diabetic Retinopathy in Patients with Type 2 Diabetes

Purpose

To explore the relationship between chronic kidney disease (CKD) and diabetic retinopathy (DR) in a representative population of type 2 diabetes mellitus (DM2) patients in Catalonia (Spain).

Methods

This was a population-based, cross-sectional study. A total of 28,344 patients diagnosed with DM2 who had recorded ophthalmologic and renal functional examinations were evaluated. Data were obtained from a primary healthcare electronic database of medical records. CKD was defined as an estimated glomerular filtration ratio (eGFR) of <60 ml/min/1.73m² and/or urine albumin to creatinine ratio (UACR) ≥30 mg/g. DR was categorized as non-vision threatening diabetic retinopathy and vision threatening diabetic retinopathy.

Results

CKD was associated with a higher rate of DR [OR], 95% confidence interval [CI], 1.5 (1.4–1.7). When we analyzed the association between different levels of UACR and DR prevalence observed that DR prevalence rose with the increase of UACR levels, and this association was significant from UACR values ≥10 mg/g, and increased considerably with UACR values ≥300mg/g (Odds ratio [OR], 95% confidence interval [CI], 2.0 (1.6–2.5). This association was lower in patients with eGFR levels 44 to 30 mL/min/1.73m² [OR], 95% confidence interval [CI], 1.3 (1.1–1.6).

Conclusions

These results show that CKD, high UACR and/or low eGFR, appear to be associated with DR in this DM2 population.     

Association of RAGE gene polymorphisms with type 2 diabetes mellitus,diabetic retinopathy and diabetic nephropathy

A meta-analysis was performed to assess the associations of the receptor for advanced glycation end products (RAGE) gene polymorphisms [Gly82Ser (rs2070600), 1704 G/T (rs184003), 429 T/C (rs1800625)] with type 2 diabetes mellitus (T2DM), diabetic retinopathy (DR) and diabetic nephropathy (DN). A comprehensive research was conducted to identify all case-control or cohort studies. The fixed or random effect pooled measure was selected based on the homogeneity test among studies that was evaluated with I². Meta-regression was used to explore the potential sources of between-study heterogeneity. Publication bias was estimated using Peters test. Twenty-nine articles were included. Overall, after excluding articles deviating from Hardy–Weinberg equilibrium in controls and sensitive analysis, no significant association was found between RAGE gene polymorphisms (Gly82Ser, 1704 G/T, 429 T/C) and any of T2DM, DR and DN risk, respectively. Subgroup analysis stratified by ethnicity (Asian and Caucasian) also found no significant association between the above-mentioned three polymorphisms and T2DM risk, respectively. This meta-analysis suggested that there might be no association of RAGE gene polymorphisms (Gly82Ser, 1704 G/T, 429 T/C) with T2DM, DR and DN risk.     

Investigation of Variants in UCP2 in Chinese Type 2 Diabetes and Diabetic Retinopathy

Purpose

The aim of this study was to investigate variants in UCP2 genes in type 2 diabetes mellitus (DM) and diabetic retinopathy (DR) in Chinese population.

Materials and Methods

We conducted a single nucleotide polymorphism-based and haplotype-based case-control study between the variants of UCP2 and DM and between the variants of UCP2 and DR in 479 Chinese patients with type 2 DM and 479 control subjects without DM. Two SNPs (rs660339 and rs659366) were selected as genetic markers.

Results

The risk allele C at UCP2 rs660339 was closely associated with DM in Chinese population. There was significant difference in rs660339 between DM and controls (P = 0.0016; OR [95%CI]  = 1.37 (1.14–1.65)). Subjects who were homozygous of the C allele were more likely to develop DM. The frequency of C allele was higher in DM (58%) than in control (51%). But this locus didn''t have a definite effect on the onset of non-proliferative diabetic retinopathy (NPDR) (P = 0.44; OR [95%CI]  = 0.80 (0.56–1.14)) and proliferative diabetic retinopathy (PDR) (P = 1.00; OR [95%CI]  = 0.99 (0.74–1.34)) comparing to subjects with DM without retinopathy (DWR), respectively. Moreover, the UCP2 rs659366 polymorphism showed no significant difference between DM and control (P = 0.66; OR [95%CI]  = 1.10 (0.91–1.32)). However, there was a significant difference between PDR and DWR (P = 0.016; OR [95%CI]  = 0.66 (0.49–0.90)), but there was no difference between NPDR and DWR (P = 1.00; OR [95%CI]  = 0.96 (0.67–1.37)). Participants who carried the G allele at rs659366 were more likely to develop PDR. For the haplotype, C-A was present more frequently in DM than in control (16% vs 7%), indicating that it was risky, and T-A was present less in DM than in control (29% vs 35%). Haplotype frequencies in DR and DWR showed no significant difference (P = 0.068).

Conclusion

It was indicated that UCP2 may be implicated in the pathogenesis of type 2 DM and DR in Chinese population.     

维生素D缺乏和2型糖尿病视网膜病变风险度的相关性研究

摘要 目的：是探讨维生素D缺乏与2型糖尿病（T2DM）患者视网膜病变（DR）发生风险度的关系。方法：选取2020年12月至2022年8月在新疆医科大学第二附属医院内分泌科住院的2型糖尿病患者作为研究对象。将209名患者根据眼底检查分为DR组（n=50）和正常眼底（NDR）组（n=159）。比较各组患者一般资料、实验室检查指标;采用Spearman分析法分析病程、FBG、HbAlC、25(OH)D与DR的相关性,采用Pearson分析居住地（城镇）、与维生素D缺乏、SBP与DR的相关性,采用Logistics回归分析DR发生的影响因素,比较各组患者维生素D缺乏、病程、FBG、HbA1c及25(OH)D对DR的预测价值。结果：DR组的居住地（农村）、FBG、HbA1c、病程等均大于NDR组,25(OH)D水平低于NDR组,DR组维生素D缺乏率大于NDR组,差异有统计学意义（P＜0.05）。Pearson相关性分析结果表明DR与居住地（城镇）呈负相关（P＜0.05）,与SBP、维生素D缺乏呈正相关（P＜0.05）;Spearman相关分析表明DR与25(OH)D呈负相关（P＜0.05）,与病程、空腹血糖和糖化血红蛋白等呈正相关（P＜0.05）。Logistic回归分析结果显示,维生素D缺乏、病程、FBG、HbA1c为DR的独立危险因素（P＜0.05）,维生素D缺乏的T2DM患者DR发病风险是维生素D不缺乏者的22.019倍（OR=22.019,95%CL 2.119~228.771,P＜0.05）。受试者工作特征（ROC）曲线分析显示,病程、FBG、HbA1c、25(OH)D作为联合变量可有效预测DR,ROC曲线下面积为0.924。结论：25(OH)D与DR呈负相关,维生素D缺乏可能与T2DM患者DR的发生有关。     

PAI-1 -675 4G/5G Polymorphism in Association with Diabetes and Diabetic Complications Susceptibility: a Meta-Analysis Study

A meta-analysis was performed to assess the association between the PAI-1 -675 4G/5G polymorphism and susceptibility to diabetes mellitus (DM), diabetic nephropathy (DN), diabetic retinopathy (DR) and diabetic coronary artery disease (CAD). A literature-based search was conducted to identify all relevant studies. The fixed or random effect pooled measure was calculated mainly at the allele level to determine heterogeneity bias among studies. Further stratified analyses and sensitivity analyses were also performed. Publication bias was examined by the modified Begg’s and Egger’s test. Twenty published articles with twenty-seven outcomes were included in the meta-analysis: 6 studies with a total of 1,333 cases and 3,011 controls were analyzed for the PAI-1 -675 4G/5G polymorphism with diabetes risk, 7 studies with 1,060 cases and 1,139 controls for DN risk, 10 studies with 1,327 cases and 1,557 controls for DR and 4 studies with 610 cases and 1,042 controls for diabetic CAD risk respectively. Using allelic comparison (4G vs. 5G), the PAI-1 -675 4G/5G polymorphism was observed to have no significant association with diabetes (REM OR 1.07, 95% CI 0.96, 1.20), DN (REM OR 1.10, 95% CI 0.98, 1.25), DR (REM OR 1.09, 95% CI 0.97, 1.22) or diabetic CAD risk (REM OR 1.07, 95% CI 0.81, 1.42), and similar results were obtained in the dominant, recessive and co-dominant models. Our meta-analyses suggest that the PAI-1 -675 4G/5G polymorphism might not be a risk factor for DM, DN, DR or diabetic CAD risk in the populations investigated. This conclusion warrants confirmation by further studies.     

NAD(P)H oxidase-stimulating activity of serum from type 2 diabetic patients with retinopathy mediates enhanced endothelial expression of E-selectin

Endothelial expression of E-selectin is enhanced in diabetic patients with retinopathy, however, the underlying mechanisms are unclear. Therefore, this study was aimed to determine if endothelial expression of E-selectin is stimulated with serum from type 2 diabetic patients with retinopathy, and whether this process is related to NAD(P)H oxidase-derived oxidative stress. Serum was obtained from type 2 diabetic patients with (T2DR) or without (T2DM) retinopathy, and age-matched non-diabetic healthy person (Control). Serum was added to in vitro-grown human coronary artery endothelial cells (HCAEC), after which E-selectin expression, reactive oxygen species (ROS) production, and NAD(P)H oxidase activity were measured. Serum from T2DR induced a significantly higher expression of E-selectin than serum from T2DM and control in association with an enhanced production of ROS in HCAEC. T2DR serum enhanced E-selectin expression in a ROS-dependent manner since this process was significantly attenuated not only by tiron (1 mM), a superoxide scavenger, but also by DPI (10 micromol/L) and apocynin (100 micromol/L), inhibitors of NAD(P)H oxidase. Furthermore, the activity of NADH oxidase was markedly increased by T2DR serum, and this was accompanied by the enhanced membrane translocation of p47phox, a cytosolic subunit of NAD(P)H oxidase. These findings suggest that serum from T2DR induced up-regulation of E-selectin expression in HCAEC, and this process might be dependent on activation of endothelial NADH oxidase via an enhanced membrane translocation of p47phox.     

吡格列酮治疗STZ诱导糖尿病大鼠视网膜中TSP-1的变化

观察吡格列酮在治疗STZ诱导糖尿病大鼠视网膜中血小板反应素Ⅰ(thmmbospondin-1,TSP-1)的变化,探讨噻唑烷二酮类药物在糖尿病视网膜病变中的影响和可能作用机制。用链脲佐菌素(STZ)腹腔注射建立大鼠糖尿病模型,随机分正常对照组(C组),糖尿病安慰剂组(D组)和糖尿病吡格列酮治疗组(DP组),8周后取视网膜组织行免疫组织化学、RT-PCR半定量检测TSP- 1mRNA水平的变化,结果显示在糖尿病早期视网膜神经节细胞层、内核层中均有明显的TSP1表达,对比于糖尿病对照组,糖尿病治疗组视网膜单位面积表达TSP1的细胞数量要较二组对照组高;糖尿病治疗组、糖尿病对照组和正常对照组间TSP-1的荧光灰度值分别为528.2±47.78、493.4±39.36和417.7±28.74:内参照GAPDH的荧光灰度值分别为796.4±21.18、811.2±36.80和832.4±43.18,各组间TSP-1 mRNA表达有显著性差异,提示吡格列酮对糖尿病早期视网膜中TSP-1的表达变化有影响,吡格列酮可能在延缓糖尿病视网膜病变的发生发展中起一定的作用。     

Class I and II HLA genes are associated with susceptibility and age at onset in Finnish families with type 1 diabetes

OBJECTIVES: We explored the properties of the long-term survivor model (LTS) in the genetic association studies and studied allelic and haplotypic associations between the age at onset and partially latent susceptibility of type 1 diabetes (T1DM) and Human Leucocyte Antigen (HLA) A, B and DR loci. METHODS: The authors applied the long-term survivor model (LTS) for sibships collected in a population-based registry during a calendar time period. The method uses sibs that could not become probands and includes the proband's age at onset during the recruitment period. Association between the candidate gene and the partially latent susceptibility is modeled with logistic regression and the age at onset with a two-parameter gamma distribution, where a scale parameter depends on the candidate genotypes. We also performed a simulation study of nuclear families to compare the power of the likelihood ratio tests of the genetic association based on the LTS model with those obtained using family-based association method (FBAT) and bias of the case-pseudo control design. In addition, we analysed allele and haplotype associations between HLA A, B and DR loci (IDDM1) with T1DM, using population-based ascertainment of 705 sibships with complete HLA information. RESULTS: A simulation study showed that the estimates of the genetic association using an ascertainment-corrected LTS model are virtually unbiased and that the relative risk estimates obtained from case-pseudo control design (TDT) are negatively biased. In the analysis of the Finnish T1DM families we found that only B62 (p < 0.05) is positively significantly associated with susceptibility after adjusting for the haplotype effects. Five alleles were significantly associated with age at onset (B8 and DR3, p < 0.01; A2, B60 and DR6, p < 0.05). No significant three-locus haplotype associations with the susceptibility were found, but A3B18DR4 (p < 0.001) haplotype was associated with older age at onset than average. CONCLUSIONS: Estimates of genetic relative risk obtained from the case-pseudo control design are negatively biased and the prospective LTS model is an appropriate choice, when there are non-susceptible subjects in the population with variable age at onset. Based on the analysis of T1DM, we conclude that there are gene(s) in the HLA region that are associated with susceptibility and/or age at onset of T1DM, and this should be taken into account in future studies.     

Diabetic retinopathy in the Eastern Morocco: Different stage frequencies and associated risk factors

Diabetes is a major cause of morbidity and mortality worldwide. It can affect many organs and, over time, leads to serious complications. Diabetic retinopathy (DR), a specific ocular complication of diabetes, remains the leading cause of vision loss and vision impairment in adults. This work is the first in Eastern Morocco aimed at identifying the different stages of DR and to determine their frequencies and associated risk factors. It is a case-control study conducted from December 2018 to July 2019 at the ophthalmology department of Al-Irfane Clinic (Oujda). Data were obtained from a specific questionnaire involving 244 diabetic patients (122 cases with retinopathy vs 122 controls without retinopathy). All results were analyzed by the EPI-Info software. This study shows a predominance of proliferative diabetic retinopathy (PDR) with 57.4% of cases (uncomplicated proliferative diabetic retinopathy (UPDR): 23.8%; complicated proliferative diabetic retinopathy (CPDR): 33.6%). The non-proliferative diabetic retinopathy (NPDR) represents 42.6% (minimal NPDR: 8.2%; moderate NPDR: 26.2%; severe NPDR: 8.2%). The determinants of DR were insulin therapy, high blood pressure, poor glycemic control and duration of diabetes. Regarding the chronological evolution, retinopathy precedes nephropathy. Diabetic nephropathy (DN) was present in 10.6% of cases especially in patients with PDR. In summary, the frequency of PDR was higher than that of NPDR. DR appears before DN with a high frequency of DN in patients with PDR. Good glycemic control and blood pressure control, as well as early diagnosis are the major preventive measures against DR.     

Status of B-vitamins and homocysteine in diabetic retinopathy: association with vitamin-B12 deficiency and hyperhomocysteinemia

Diabetic retinopathy (DR) is a common cause of blindness. Although many studies have indicated an association between homocysteine and DR, the results so far have been equivocal. Amongst the many determinants of homocysteine, B-vitamin status was shown to be a major confounding factor, yet very little is known about its relationship to DR. In the present study, we, therefore, investigated the status of B-vitamins and homocysteine in DR. A cross-sectional case-control study was conducted with 100 normal control (CN) subjects and 300 subjects with type-2 diabetes (T2D). Of the 300 subjects with T2D, 200 had retinopathy (DR) and 100 did not (DNR). After a complete ophthalmic examination including fundus fluorescein angiography, the clinical profile and the blood levels of all B-vitamins and homocysteine were analyzed. While mean plasma homocysteine levels were found to be higher in T2D patients compared with CN subjects, homocysteine levels were particularly high in the DR group. There were no group differences in the blood levels of vitamins B1 and B2. Although the plasma vitamin-B6 and folic acid levels were significantly lower in the DNR and DR groups compared with the CN group, there were no significant differences between the diabetes groups. Interestingly, plasma vitamin-B12 levels were found to be significantly lower in the diabetes groups compared with the CN group; further, the levels were significantly lower in the DR group compared with the DNR group. Higher homocysteine levels were significantly associated with lower vitamin-B12 and folic acid but not with other B-vitamins. Additionally, hyperhomocysteinemia and vitamin-B12 deficiency did not seem to be related to subjects' age, body mass index, or duration of diabetes. These results thus suggest a possible association between vitamin-B12 deficiency and hyperhomocysteinemia in DR. Further, the data indicate that vitamin-B12 deficiency could be an independent risk factor for DR.     

Proteomic analysis and identification of aqueous humor proteins with a pathophysiological role in diabetic retinopathy

Diabetic retinopathy (DR) can cause irreversible blindness and is the severest microvascular complication in the eyes of patients with diabetic mellitus (DM). The identification of susceptibility factors contributing to development of DR is helpful for identifying predisposed patients and improving treatment efficacy. Although proteomics analysis is useful for identifying protein markers related to diseases, it has never been used to explore DR-associated susceptibility factors in the aqueous humor (AH). To better understand the pathophysiology of DR and to identify DR-associated risk factors, a gel-based proteomics analysis was performed to compare AH protein profiles of DM patients with and without development of DR. MALDI-TOF MS was then performed to identify protein spots that were differentially expressed between the two groups and western blot analysis was used to validate the expressional change of protein demonstrated by proteomics. Our proteomics and bioinformatics analysis identified 11 proteins differentially expressed between DR and control groups. These proteins are linked to biological networks associated with nutrition transport, microstructure reorganization, angiogenesis, anti-oxidation, and neuroprotection. The data may provide potential AH biomarkers and susceptibility factors for predicting DR development, and provide an insight into the underlying pathophysiological mechanisms of DR. This article is part of a Special Issue entitled: Proteomics: The clinical link.     

Berberine improves insulin-induced diabetic retinopathy through exclusively suppressing Akt/mTOR-mediated HIF-1α/VEGF activation in retina endothelial cells

Background: Insulin therapy is the major treatment of glycaemic control in type I diabetes mellitus (DM) and advanced type II DM patients who fail to respond to oral hypoglycemic agents. Nonetheless, insulin therapy is deemed unsuccessful in controlling the incidence of diabetic retinopathy (DR) and is likely a risk factor. Berberine, an isoquinoline alkaloid, has caught great attention towards its anti-diabetic mechanisms. This study aims to investigate the effect of berberine in decelerating DR progression in insulin-treated DM.Methods: To better understand the therapeutic potential of berberine in the presence of insulin, we elaborated the action of mechanism whether berberine inhibited retinal expression of HIF-1α and VEGF through regulating AKT/mTOR pathway. Suppression of insulin-induced neovasculature of retina endothelial cells by berberine was also studied. Lastly, the in vivo efficacy and safety of berberine as adjuvant therapy for the treatment of DR were systemically investigated in experimental type I and type II DM mice with insulin treatment.Results: Among various types of retinal cells, the activity of HIF-1α and VEGF in retinal endothelial cells could be particularly and exclusively stimulated by insulin intervention, which could be inhibited by berberine treatment in a dose- and time-dependent manner. Berberine suppressed Akt/mTOR activity in these cells, and restoration of Akt/mTOR signalling attenuated berberine''s inhibition on HIF-1α and VEGF expression. Berberine suppressed the progression of DR in experimental type I and type II diabetic mice receiving insulin therapy.Conclusion: Berberine improves insulin-induced diabetic retinopathy in type I and II diabetes through inhibiting insulin-induced activation of retinal endotheliocytes via Akt/mTOR/ HIF-1α/VEGF pathway.     

Identification of an anti-aldolase autoantibody as a diagnostic marker for diabetic retinopathy by immunoproteomic analysis

Circulating autoantibodies specific for retinal proteins are associated with retinal destruction in patients with diabetic retinopathy (DR). In this study, we screened diabetic sera for the presence of anti-retinal autoantibodies with an aim of developing diagnostic markers for DR. Immunoblot analysis of DR patients' sera with human retinal cytosolic proteins revealed a higher incidence of anti-retinal autoantibodies, compared to normal blood donors or diabetic patients without DR. Anti-retinal protein autoantibody profiles of DR patient sera were obtained by 2-DE immunoblot analysis. Specifically, 20 protein spots reactive with DR patient sera were identified by ESI-MS/MS. Of these spots, 14 were specific for DR patients, and 4 reacted with both non-proliferative DR (non-PDR) and PDR sera. The anti-aldolase autoantibody was selected as a DR marker candidate, and specific reactivity of DR patient sera was confirmed by immunoblot analysis with rabbit aldolase. The serum anti-aldolase autoantibody level was measured by ELISA. DR patients showed significantly higher autoantibody levels than normal donors or diabetic patients without retinopathy. However, no significant differences were observed between non-PDR and PDR patients, suggesting that the level of anti-aldolase autoantibody is not determined by the severity of retinopathy in diabetic patients. Our data collectively demonstrate that the anti-aldolase autoantibody serves as a useful marker for DR diagnosis.     

The APOE4 allele is associated with a decreased risk of retinopathy in type 2 diabetics

Background

Common polymorphisms within the apolipoprotein E (APOE) gene are suggested to be associated with the development of type 2 diabetes mellitus (T2DM), but the potential association with T2DM complications (nephropathy, neuropathy and retinopathy) remains unclear. We perform the case–control study to analyse the association between the APOE polymorphism and risk of T2DM and to analysed the potential relationship between the APOE and T2DM complications.

Methods and results

APOE variants (rs429358 and rs7412) were genotyped by TaqMan assay in T2DM patients (N?=?1274; N?=?829 with complications including retinopathy, neuropathy and nephropathy status) and with PCR–RFLP in healthy nondiabetic controls (N?=?2055). The comparison of subjects with genotypes associated with low plasma cholesterol (APOE2/E2 and APOE2/E3 carriers vs. others) did not show an association with T2DM (OR [95% CI]?=?0.88 [0.71–1.08). The differences remained insignificant after adjusting for diabetes duration, sex and BMI. Carriers of at least one APOE4 allele (rs429358) are protected against T2DM related retinopathy (OR [95% CI]?=?0.65 [0.42–0.99]. Protection against retinopathy is driven mostly by females (OR [95% CI]?=?0.50 [0.25–0.99]); and remains significant (P?=?0.044) after adjustment for diabetes duration and BMI.

Conclusion

Common APOE polymorphism was not associated with T2DM in the Czech population. Yet, APOE4 allele revealed an association with retinopathy. In particular, female T2DM patients with at least one APOE4 allele exhibit lower prevalence of retinopathy in our study subjects.

     

上海市杨浦区社区2型糖尿病患者周围神经病变患病率调查及其影响因素分析

摘要 目的：调查上海市杨浦区社区2型糖尿病（T2DM）患者周围神经病变（DPN）患病率,并分析其影响因素。方法：于2019年3月~2020年3月在上海市杨浦区所辖社区中随机选取5个社区,采用分层随机抽样法从每个社区选取100例T2DM患者进行调查,统计T2DM患者DPN患病率,采用多因素Logistic回归分析DPN发生的影响因素。结果：本次研究共发放500份调查问卷,回收498份,回收率为99.60%（498/500）,其中DPN患者222例,DPN发生率为44.58%（222/498）,纳为DPN组,276例未发生DPN纳为非DPN组。单因素分析结果显示：DPN组与非DPN组在腰围、合并糖尿病视网膜病变（DR）、合并下肢血管病变（PVD）、吸烟史、高血压、脑梗死病史、文化程度、婚姻状况、收缩压（SBP）、空腹血糖（FPG）、葡萄糖达标时间百分比（TIR）、载脂蛋白B、尿酸方面比较有差异（P<0.05）。进一步多因素Logistic回归分析结果显示：合并DR、合并PVD、有吸烟史、有脑梗死病史、婚姻状况为未婚/离异/丧偶、FPG水平较高是T2DM患者发生DPN的危险因素（P<0.05）。结论：T2DM患者中DPN的患病率较高,合并DR、PVD、吸烟史、脑梗死病史以及婚姻状况是DPN发生的影响因素,应重视DPN筛查并进行干预,针对上述影响因素对T2DM患者开展健康宣教,减少DPN的发生。     

A Multi-Branch Convolutional Neural Network for Screening and Staging of Diabetic Retinopathy Based on Wide-Field Optical Coherence Tomography Angiography

BackgroundDiabetic retinopathy (DR) is one of the major causes of blindness in adults suffering from diabetes. With the development of wide-field optical coherence tomography angiography (WF-OCTA), it is to become a gold standard for diagnosing DR. The demand for automated DR diagnosis system based on OCTA images have been fostered due to large diabetic population and pervasiveness of retinopathy cases.Materials and methodsIn this study, 288 diabetic patients and 97 healthy people were imaged by the swept-source optical coherence tomography (SS-OCT) with 12 mm × 12 mm single scan centered on the fovea. A multi-branch convolutional neural network (CNN) was proposed to classify WF-OCTA images into four grades: no DR, mild non-proliferative diabetic retinopathy (NPDR), moderate to severe NPDR, and proliferative diabetic retinopathy (PDR).ResultsThe proposed model achieved a classification accuracy of 96.11%, sensitivity of 98.08% and specificity of 89.43% in detecting DR. The accuracy of the model for DR staging is 90.56%, which is higher than that of other mainstream convolution neural network models.ConclusionThis technology enables early diagnosis and objective tracking of disease progression, which may be useful for optimal treatment to reduce vision loss.