The Influence of Smoking, Cessation Measures, and Other Substances on Progression of Diabetic Retinopathy in Type 2 Diabetes.

The risk of having microvascular complication is high among Type 2 Diabetes Mellitus (T2DM) patients. However, factors associated with the glycemic control and progression of diabetic retinopathy (DR) in T2DM patients is limited. This study aims to determine association between anti-diabetic agents, glycemic control and progression of diabetic retinopathy in a Malaysian population. A retrospective study conducted in a tertiary teaching hospital in Malaysia, from January 2009 until March 2014. This study enrolled 104 patients aged 40-84 years, with a mean age 63.12 ± 9.18 years. patients had non-proliferative diabetic retinopathy (NPDR, 77%) and 35% had proliferative diabetic retinopathy (PDR). Diabetic macula edema (DME) was present in 20% of NPDR patients, compared with 7% in PDR. Alpha-glucosidase inhibitor (p=0.012), age (p=0.014) and number of antidiabetic agents used (p=0.015) were significantly associated with stages of diabetic retinopathy. Family history of T2DM (p=0.039) was associated with DME. Identifying factors influencing the progression of diabetic retinopathy may aid in optimizing the therapeutic effects of anti-diabetic agents in T2DM patients.

SUMMARYOBJECTIVE:Diabetic retinopathy exhibits a higher risk of atherosclerotic cardiovascular disease-related complications. Proliferative diabetic retinopathy is the most serious complication of diabetic retinopathy and can lead to total visual loss. Given that inflammation plays a key role in diabetic retinopathy, using blood-derived indexes could be a feasible way to predict the proliferative diabetic retinopathy. The aim of this study was to assess the effectiveness of pan-immune-inflammation value in predicting proliferative diabetic retinopathy in type 2 diabetes mellitus patients and atherosclerotic cardiovascular disease.METHODS:This retrospective study included 234 patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. The study population was classified into three groups according to severity of diabetic retinopathy: no-diabetic retinopathy, non-proliferative diabetic retinopathy, and proliferative diabetic retinopathy groups. Complete blood counts were obtained, and neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and pan-immune-inflammation value ([neutrophils×platelets×monocytes]÷lymphocytes) were calculated. A receiver operating characteristic curve was performed to analyze the ability of inflammatory markers for proliferative diabetic retinopathy.RESULTS:The mean age was 56.6±7.8 years, and there were 109 men and 125 women. The median (interquartile range) pan-immune-inflammation value levels in the no-diabetic retinopathy, non-proliferative diabetic retinopathy, and proliferative diabetic retinopathy groups were 213 (137–325), 240 (157–297), and 375 (318–540), respectively (p<0.001). Multivariate analysis revealed that the pan-immune-inflammation value (OR 1.066; 95%CI 1.051–1.072; p=0.001), total cholesterol (OR 1.055; p=0.018), and hemoglobin (OR 0.145; p=0.036) were independent risk factors of proliferative diabetic retinopathy in patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease.CONCLUSION:Our study revealed a significant association between increased pan-immune-inflammation value levels and high proliferative diabetic retinopathy risk in type 2 diabetes mellitus patients and atherosclerotic cardiovascular disease.

Актуальність. За прогнозами Міжнародної федерації діабету (IDF), до 2030 року кількість хворих на цукровий діабет (ЦД) зросте з 366 до 552 мільйонів. В Україні зареєстровано понад 1,5 мільйона хворих на цукровий діабет, із яких 84–95 % — хворі на діабет 2-го типу (ЦД2). Одним із важливих ускладнень цукрового діабету є діабетична ретинопатія (ДР), що залишається однією з причин сліпоти і слабкозорості, в тому числі в осіб працездатного віку. В патогенезі ДР важлива роль належить метаболічним порушенням, в тому числі активації поліолового шляху утилізації глюкози, ключову роль у чому відіграє альдозоредуктаза, активність якої пов’язують з поліморфізмом її гена — AKR1B1. Вивчення нових метаболічних і генетичних механізмів розвитку і прогресування ДР при ЦД2 у пацієнтів української популяції є актуальним завданням сучасної офтальмології. Мета: дослідити та узагальнити нові дані про генетично детерміновані фактори ризику діабетичної ретинопатії при цукровому діабеті 2-го типу. Матеріали та методи. У дослідження було залучено 409 осіб, які були розподілені на чотири групи: 1-ша — пацієнти когорти порівняння (98 осіб без ЦД2); 2-га — 76 пацієнтів (I стадія ДР, без змін на очному дні); 3-тя — 64 пацієнти (непроліферативна ДР (НПДР)); 4-та — 64 пацієнти (проліферативна ДР); контрольну групу для генетичних досліджень становили 107 офтальмологічно здорових обстежених пацієнтів. Всім пацієнтам виконували забір крові для молекулярно-генетичних досліджень шляхом пункції ліктьової вени і забору 2,5 мл крові через одноразовий шприц (Hemoplast, Etalon+, Україна) об’ємом 5,0 мл із голкою діаметром 23G з подальшим випусканням до контейнера (Vacuette K3E K3EDTA, Greiner bio-one, Австрія) об’ємом 3,0 мл. Досліджували розподіл поліморфних алелей і генотипів rs759853 та rs9640883 гена AKR1B1 у пацієнтів з НПДР та ПДР і ЦД2 та в контрольній групі та їх асоціацію з захворюванням і впливом на виникнення, механізми розвитку і прогресування ДР. На підставі проведених досліджень було розроблено модель прогнозування розвитку ДР шляхом побудови множинної регресії з достатньою надійністю ступеня впливу незалежних змінних на розрахунковий показник. Результати. В результаті проведених нами досліджень були встановлені нові, генетично детерміновані, фактори ризику розвитку та прогресування різних стадій ДР у пацієнтів із ЦД2, а саме роль поліморфних алелей і генотипів rs759853 та rs9640883 гена AKR1B1. Розроблені логістичні моделі регресії встановили, що ризик розвитку ДР у п’ять разів менший у носіїв генотипів G/G і G/A порівняно з носіями генотипу A/A поліморфізму rs759853 (p &lt; 0,001). Встановлено, що ризик у два рази більший (p = 0,01) у носіїв генотипу G/G rs9640883 порівняно з генотипами A/A + G/A. Ризик розвитку ПДР у 3,3 раза менший у носіїв генотипу G/G та в 2,5 раза — у носіїв генотипу G/A порівняно з носіями генотипу А/А rs759853. Висновки. Отже, на підставі проведених нами клінічних, офтальмологічних і молекулярно-генетичних та статистичних досліджень були встановлені нові фактори ризику розвитку та прогресування різних стадій ДР у пацієнтів із ЦД2. Були побудовані математичні моделі розвитку та прогресування різних стадій ДР у пацієнтів із ЦД2.

Insulin lispro and the development of proliferative diabetic retinopathy during pregnancy

Purpose. Tissue inhibitor of metalloproteinase-3 (TIMP-3) is a member of the TIMP family of proteins, playing a significant role in the control of extracellular matrix remodelling. TIMP-3 might play a role in the regulation of retinal neovascularization during progression of diabetic retinopathy. Recently, three novel polymorphisms (-899T/A, -915A/G and -1296T/C) in the promoter region of the TIMP-3 gene have been identified. The aim of the study was to investigate a possible association of these polymorphisms with proliferative diabetic retinopathy (PDR) in type 2 diabetes mellitus (T2DM). Methods. Genotypes were detected by polymerase chain reaction and subsequent restriction with specific endonucleases. Allele frequencies were determined in an association study comprising three groups of subjects (n = 371). Results. Linkage disequilibrium was found among the three polymorphisms (P = 0.01). Allele frequencies did not differ between neither T2DM + PDR and T2DM non-PDR subjects (P > 0.05) nor between all T2DM versus non-diabetic subjects (P > 0.05). Conclusions. Polymorphisms in the promoter region of the TIMP-3 gene were not associated with the PDR in the Caucasian T2DM patients.

Purpose:The objective of this study is to evaluate pattern of diabetic retinopathy (DR) during pregnancy in females with pregestational diabetes mellitus (DM).Methods:This is an ambispective observational cohort study conducted at an Indian tertiary care centre. A total of 50 pregnant females with pregestational DM were included while those with gestational DM were excluded from the study. Ocular examination (inclusive of fundus photography) was conducted and systemic parameters (inclusive of Glycated hemoglobin) were assessed during each of the 3 trimesters and 3 months postpartum. The prevalence and progression of DR during pregnancy in the study cohort were the main outcome measures.Results:Three of the 50 patients had type 1 DM while 47 had type II DM. All the patients with type I DM were insulin dependent while 19 patients with type II DM were insulin dependent. Overall prevalence of DR was 8% (4/50); 2 cases had nonproliferative DR (NPDR), and 2 had proliferative DR (PDR). During the study period, worsening was seen in both the patients with PDR and one required vitrectomy. Mean visual acuity in patients with PDR decreased from 0.77 logMAR units at presentation to 1.23 logMAR at final follow-up. There was no change in the mean visual acuity of patients with NPDR. None of the patients with NPDR converted to PDR. There was no new onset DR in the patients without DR at presentation. Assessment of risk factors for DR revealed significantly higher duration of DM (14 ± 6.32 years vs. 3.43 ± 1.43 years, P = 0.0008). The median age was also higher in the DR patients (31 years vs. 29 years, P = 0.32).Conclusion:No new onset cases were seen during the course of pregnancy and no conversion from NPDR to PDR was seen; however, a worsening of the two PDR cases was observed. No cases of DR were seen in noninsulin-dependent DM. None of the four participants with DR showed a spontaneous resolution of DR postpartum. Patients with PDR and long-standing DM require careful observation during pregnancy. A registry of diabetic mothers should be set up for development of guidelines for managing such cases.

Correlation of various serum biomarkers with the severity of diabetic retinopathy

Efficacy of artificial intelligence-based screening for diabetic retinopathy in type 2 diabetes mellitus patients

Background and Objectives: The global epidemic of diabetes, especially type 2 (DM2), is related to lifestyle changes, obesity, and the process of population aging. Diabetic retinopathy (DR) is the most serious complication of the eye caused by diabetes. The aim of this research was to assess the prevalence of diabetic retinopathy in type 1 and type 2 diabetes mellitus patients in north-east Poland. Materials and Methods: The eye fundus was assessed on the basis of two-field 50 degrees color fundus photographs that showed the optic nerve and macula in the center after the pupil was dilated with 1% tropicamide. Results: The experimental group included 315 (26%) patients with type 1 diabetes mellitus (DM1) and 894 (74%) patients with DM2. DM1 patients were diagnosed with DR in 32.58% of cases, with non-proliferative diabetic retinopathy (NPDR) in 24.44% of cases, proliferative diabetic retinopathy (PDR) in 1.59% of cases, diabetic macular edema (DME) in 5.40% of cases, and PDR with DME in 0.95% of cases. DR was found in DM2 patients in 23.04% of cases, NPDR in 17.11% of cases, PDR in 1.01% of cases, DME in 4.81% of cases, and PDR with DME in 0.11% of cases. Conclusions: The presented study is the first Polish study on the prevalence of diabetic retinopathy presenting a large group of patients, and its results could be extrapolated to the whole country. Diabetic retinopathy was found in 25.48% of patients in the whole experimental group. The above results place Poland within the European average, indicating the quality of diabetic care offered in Poland, based on the number of observed complications.

Dear Editor, We read with interest the article by Halilovic et al. regarding the influence of diabetes mellitus (DM) type on the glaucoma development (1). Similar to the results of previous studies, the authors found that the individuals with DM have an increased risk of developing primary open-angle glaucoma (POAG) (2) and neovascular glaucoma (NVG) (3). Glaucoma is a type of optic neuropathy and DM alone could cause optic neuropathy (by accelerated apoptosis of ganglion and retinal inner neurons, altered metabolism of astrocytes and compromised neuro-glial function) with a complex relation between the two of them (2, 3). Longer DM duration is associated with the increased risk of having POAG (2), while use of systemic medications such as statins, systemic β-blockers and nitrates is associated with lower intraocular pressure (IOP) (3). On the other hand, DM is the major etiologic factor for NVG, with majority of cases seen in proliferative diabetic retinopathy (PDR) (3). Poor metabolic control is a good marker for development and progression of diabetic retinopathy (DR), referring to duration and control of DM which is related to hyperglycemia, hypertension, hyperlipidemia, pregnancy, nephropathy and anemia (3, 4). It is important to note that the DM patients have increased risk of cataracts that can significantly influence the visual acuity (VA) too (4, 5). Other risk factors that predict the development of POAG include: family history, older age, male gender, higher intraocular pressure, longer axial length, thinner central cornea, higher waist to hip ratio, higher cup-to-disk ratios of the optic disc, and higher pattern standard deviation values on the Humphrey automated perimeter at baseline examination (6). It should be noted that central corneal thickness is found to be thicker in patients with DM, which could also cause higher IOP readings (3, 6). For these reasons, we would kindly ask the authors to perform the correlations for age, gender, BMI, DM duration and regimen of therapy, HbA1C, patient follow up time, the use of other systemic drugs, VA, family history of POAG, IOP changes and type of therapy, presence and grade of the lens opacification, axial length, stage of DR, cup-disc ratio and deviation values on the automated perimeter between the groups. Without these information’s it would be difficult to hypothesize the direct influence of DM on glaucoma development, especially in patients without PDR. In these patients, glaucoma development could be consequent to summation of more risk factors, including poor metabolic control, rather than DM type. These findings will significantly contribute to the papers scientific value and contribution. Overall we agree with Halilovic et al. that DM remains important risk factor for glaucoma development and all diabetic patients should have regular ophthalmological control examinations. Other systemic and ocular risk factors such as DM duration, glycemic control together with use of other systemic drugs, IOP values and DR progression should be carefully monitored too.

To investigate the redox state of human serum albumin concerning cysteine-34 as a possible systemic redox marker in patients with different eye diseases with and without complications and with consideration of possible effects of age. Cataract (CAT), glaucoma, age-related macular degeneration (AMD), diabetes mellitus (DM), diabetic retinopathy and hypertension were the pathologies investigated. Albumin redox state concerning cysteine-34 was measured by high-performance liquid chromatography with fluorescence detection. The separation gives three fractions: the fully reduced form containing a thiol group, the disulphide form and a higher oxidized form. Statistical analysis was done by Student's t-test, analysis of variance and stepwise regression analysis. Albumin as a systemic marker for oxidative stress was shifted to a more oxidized state by DM. An even stronger shift to the oxidized form was observed in patients with proliferative diabetic retinopathy. Notably, these effects were independent from age. In contrast, CAT and AMD had no influence on serum albumin redox state. Serum albumin is not shifted to more oxidized forms by localized oxidative stress, but it is in systemic diseases like DM.

Arterial stiffness has been associated with diabetic retinopathy; however, the information is limited in Asians. We aim to examine the association of central arterial stiffness with the presence and severity of diabetic retinopathy in type 2 diabetes mellitus patients in Singapore. Arterial stiffness was estimated by carotid-femoral pulse wave velocity and augmentation index using applanation tonometry method. Digital colour fundus photographs from 1,203 patients were assessed for diabetic retinopathy. Diabetic retinopathy severity was categorized into non-proliferative diabetic retinopathy and proliferative diabetic retinopathy. Logistic regression model was used to evaluate the associations of diabetic retinopathy with pulse wave velocity and augmentation index. Diabetic retinopathy was diagnosed in 391 (32.5%) patients, including 271 non-proliferative diabetic retinopathy and 108 proliferative diabetic retinopathy. Diabetic retinopathy have higher pulse wave velocity (11.2 ± 3.3 vs 9.5 ± 2.6 m/s, p < 0.001) and augmentation index (28.4 ± 9.4 vs 26.1 ± 10.6%, p < 0.001) than non-diabetic retinopathy. After multivariable adjustment, pulse wave velocity [odds ratio = 1.11 (95% confidence interval = 1.05-1.17), p < 0.001] and augmentation index [odds ratio = 1.03 (95% confidence interval = 1.01-1.04), p = 0.009] was associated with diabetic retinopathy. In severity analyses, pulse wave velocity was associated with non-proliferative diabetic retinopathy [odds ratio = 1.10 (95% confidence interval = 1.03-1.17), p = 0.002] and proliferative diabetic retinopathy [odds ratio = 1.15 (95% confidence interval = 1.06-1.25), p = 0.001] (p-trend < 0.001). Augmentation index showed significant associations with non-proliferative diabetic retinopathy [odds ratio = 1.02 (95% confidence interval = 1.01-1.04), p = 0.008], but not with proliferative diabetic retinopathy [odds ratio = 1.01 (95% confidence interval = 0.98-1.04), p = 0.36] (p-trend = 0.03). Central arterial stiffness was associated with the presence and severity of diabetic retinopathy in type 2 diabetes mellitus patients, suggesting its etiologic implication in diabetic retinopathy.

Prognostic factors for the development and progression of proliferative diabetic retinopathy in people with diabetic retinopathy (Protocol).

Background: Diabetic retinopathy (DR) is a leading cause of blindness in patients with type 2 diabetes mellitus (T2DM). Cardiovascular risk factors, such as hypertension, obesity, and dyslipidemia, may play a crucial role in the development and progression of DR, though the evidence remains mixed. This study aimed to assess cardiovascular risk factors as independent predictors of DR and to develop a predictive model for DR progression in T2DM patients. Methods: A retrospective cross-sectional study was conducted on 377 patients with T2DM who underwent a comprehensive eye exam. Clinical data, including blood pressure, lipid profile, BMI, and smoking status, were collected. DR staging was determined through fundus photography and classified as No DR, Non-Proliferative DR (NPDR), and Mild, Moderate, Severe, or Proliferative DR (PDR). A Multivariate Logistic Regression was used to evaluate the association between cardiovascular risk factors and DR presence. Several machine learning models, including Random Forest, XGBoost, and Support Vector Machines, were applied to assess the predictive value of cardiovascular risk factors and identify key predictors. Model performance was evaluated using accuracy, precision, recall, and ROC-AUC. Results: The prevalence of DR in the cohort was 41.6%, with 34.5% having NPDR and 7.1% having PDR. A multivariate analysis identified systolic blood pressure (SBP), LDL cholesterol, and body mass index (BMI) as independent predictors of DR progression (p < 0.05). The Random Forest model showed a moderate predictive ability, with an AUC of 0.62 for distinguishing between the presence and absence of DR XGBoost showing a better performance, featuring a ROC-AUC of 0.68, while SBP, HDL cholesterol, and BMI were consistently identified as the most important predictors across models. After tuning, the XGBoost model showed a notable improvement, with an ROC-AUC of 0.72. Conclusions: Cardiovascular risk factors, particularly BP and BMI, play a significant role in the progression of DR in patients with T2DM. The predictive models, especially XGBoost, showed moderate accuracy in identifying DR stages, suggesting that integrating these risk factors into clinical practice may improve early detection and intervention strategies for DR.

Background: Diabetic retinopathy is the primary ocular outcome of diabetes mellitus, a serious disease that significantly impacts global health. Microvascular complications arise from damage to small blood vessels, including retinopathy, nephropathy, cardiomyopathy, and neuropathy. Inconsistent findings exist in epidemiological research that specifically examines lipid levels and diabetic retinopathy. The small, dense Low-Density Lipoprotein particles are a specific subset of Low-Density Lipoprotein that possesses several pro-atherogenic characteristics.Objectives: to evaluate the usefulness of serum small dense low-density lipoprotein level as a biomarker for predicting patients with type II diabetes mellitus who suffer from proliferative and non-proliferative diabetic retinopathy. Methods: The study involved 160 individuals divided into four groups: 40 patients with non-proliferative diabetic retinopathy, 40 patients with proliferative diabetic retinopathy, 40 controlled diabetic patients without diabetic retinopathy, and 40 healthy controls. Student’s t-test and ANOVA were employed to compare the means between the groups.Results: The study revealed that small dense low-density lipoprotein levels in the proliferative diabetic retinopathy group were significantly higher than those in the non-proliferative diabetic retinopathy, diabetic without retinopathy, and healthy control groups. The mean and standard deviation in patients with proliferative diabetic retinopathy were 4.70±1.96 µmol/L, in non-proliferative diabetic retinopathy, it was 3.00±0.90 µmol/L, in diabetic patients without retinopathy, it was 2.51±0.53 µmol/L, and in healthy controls, it was 2.45± 0.48 µmol/L.Conclusion: Small, dense, low-density lipoprotein and triglycerides play roles in the progression of diabetic retinopathy in patients with type II diabetes mellitus. The small, dense, low-density lipoprotein and triglyceride levels were highest in the proliferative diabetic retinopathy and lowest in the healthy control.