Vessels In Diabetic Patients Research Articles

Efficacy of retrograde revascularization in diabetic patients with chronic limb-threatening ischemia after a failed antegrade approach.

Chronic limb-threatening ischemia is the end stage of peripheral arterial disease. The revascularization of patients suffering from diabetes mellitus who present chronic total occlusions of below-the-knee vessels can be technically very difficult and sometimes impossible to achieve by performing only an antegrade approach. As regards retrograde recanalization, several studies have investigated the efficacy and safety of this technique in the femoropopliteal axis or in the infrageniculate arterial vessels in patients with advanced atherosclerotic disease. Currently in the literature there are still few studies analyzing the effectiveness of the retrograde approach in the treatment of occlusions of below-the-knee vessels in patients suffering from diabetes mellitus. The purpose of the study was to retrospectively evaluate safety, technical success, and clinical outcome of retrograde transpedal/transtibial recanalization in patients suffering from diabetes mellitus. This is a retrospective observational monocentric study. We retrospectively analyzed data over a three-year period (August 2019-September 2022) of patients that underwent revascularization of one or more below-the-knee vessels for chronic limb-threatening ischemia and had a retrograde transpedal/transtibial approach after a failed antegrade transfemoral revascularization. We identified and included in the study 28 out of 352 patients. We evaluated clinical comorbidities, Rutherford-Becker classification, Texas classification, and the occluded vessels (only below-the-knee or multi-level occlusions); we then analyzed technical, procedural and clinical success, survival rate, and procedural complications. All patients included in the study underwent a 6 months follow-up. Patients belonged to Rutherford-Becker stage V (18) or VI (10), Texas wound classification IIC: 7 IID: 8 IIIC: 4 IIID: 9, all suffering from diabetes, and five were on dialysis. Treatment of a femoropopliteal lesion was performed during the same procedure in 6 of 28 patients (28.6%). Technical success was obtained in 25 out of 28 patients (89.3%), and procedural success was achieved in 23 of 28 patients (82.1%). No complications occurred at the pedal/tibial access. One minor complication at the femoral access was observed. The cure rate 6 months after the procedure was 57.1% (16/28 patients), and the 6-month survival rate was 96.4%. Three major amputations (10.7%) and four minor amputations (14.2%) were performed after revascularization procedures. Two patients were readmitted for vascular causes (7.1%). Retrograde approach for revascularization of below-the-knee vessels in diabetic patients is safe and effective with high procedural and clinical success rates in the absence of significant complications. It should be considered when revascularization cannot be achieved with an antegrade transfemoral approach.

High Glucose Levels Promote Switch to Synthetic Vascular Smooth Muscle Cells via Lactate/GPR81.

Hyperglycemia, lipotoxicity, and insulin resistance are known to increase the secretion of extracellular matrix from cardiac fibroblasts as well as the activation of paracrine signaling from cardiomyocytes, immune cells, and vascular cells, which release fibroblast-activating mediators. However, their influences on vascular smooth muscle cells (vSMCs) have not been well examined. This study aimed to investigate whether contractile vascular vSMCs could develop a more synthetic phenotype in response to hyperglycemia. The results showed that contractile and synthetic vSMCs consumed high glucose in different ways. Lactate/GPR81 promotes the synthetic phenotype in vSMCs in response to high glucose levels. The stimulation of high glucose was associated with a significant increase in fibroblast-like features: synthetic vSMC marker expression, collagen 1 production, proliferation, and migration. GPR81 expression is higher in blood vessels in diabetic patients and in the high-glucose, high-lipid diet mouse. The results demonstrate that vSMCs assume a more synthetic phenotype when cultured in the presence of high glucose and, consequently, that the high glucose could trigger a vSMC-dependent cardiovascular disease mechanism in diabetes via lactate/GPR81.

Stem Cell Therapy in Critical Limb Ischemia.

Critical limb ischemia (CLI), a serious outcome of peripheral artery disease, is frequently associated with morbid outcomes. The available treatment modalities do not provide satisfactory results, leading to marked morbidities such as joint contracture and amputations, resulting in a high economic burden. The peripheral vascular disease tends to cause more morbidity in patients with diabetes and atherosclerosis, given the pre-existing compromised perfusion of medium and small vessels in diabetic patients. With surgical procedures, the chance of vascular compromise further increases, inducing a significantly greater rate of amputation. Hence, the need for nonsurgical treatment modalities such as stem cell therapy (SCT), which promotes angiogenesis, is warranted. In CLI, SCT acts through neovascularization and the development of collateral arteries, which increases blood supply to the soft tissues of the ischemic limb, providing satisfactory outcomes. An electronic database search was performed in PubMed, SCOPUS, EMBASE, and ScienceDirect to identify published clinical trial data, research studies, and review articles on stem cell therapy in critical limb ischemia. The search resulted in a total of 2391 results. Duplicate articles screening resulted in 565 articles. In-depth screening of abstracts and research titles excluded 520 articles, yielding 45 articles suitable for full-text review. On review of full text, articles with overlapping and similar results were filtered, ending in 25 articles. SCT promotes arteriogenesis, and bone marrow-derived mesenchymal stromal cells produce significant effects like reduced morbidity, improved amputation-free survival (AFS ) rate, and improved distal perfusion even in "no-option" CLI patients. SCT is a promising treatment modality for CLI patients, even in those in whom endovascular and revascularization procedures are impossible. SCT assures a prolonged AFS rate, improved distal perfusion, improved walking distances, reduced amputation rates, and increased survival ratio, and is well-tolerated.

A Diabetic Retinopathy Detection Using Customized Convolutional Neural Network

The disease, Diabetic Retinopathy (DR) causes due to damage to retinal blood vessels in diabetic patients. DR occurs if you have type 1 or 2 diabetes along with high blood sugar. When the retinal blood vessels are damaged, they can become clogged, some of which can block the blood supply to the retina leading to blood loss, these new blood vessels may leak, and the creation of scar tissue can lead to loss of vision. It takes a lot of time and effort to examine and analyse fundus images the old-fashioned way to find differences in how the eyes are shaped. In this modern era, technology has evolved so fleet which has the solution to every problem. In this paper, we have proposed a Customized Convolutional Neural Network (CCNN) deep learning technique for Diabetic Retinopathy Detection. We have clung to traditional strategies mainly containing input Data retrieval, pre-processing of data, segmentation, trait measurement, feature extraction, model creation, model training, model testing, consequence, and interpretation of the model. Performance evaluation is done on standard MESSIDOR Dataset in which 560 images for training phase whereas 163 images for testing phase. The experiment results achieved the highest test accuracy of 97.24% which is effectively higher than that of existing algorithms.

Dapagliflozin restores diabetes-associated decline in vasculogenic capacity of endothelial progenitor cells via activating AMPK-mediated inhibition of inflammation and oxidative stress

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) provide added vascular protection beyond glucose lowering to patients with type 2 diabetes mellitus (T2DM). Endothelial progenitor cells (EPCs) are an important endogenous repair mechanism for diabetic vascular complications. Yet, whether SGLT2i protect vessels in diabetic patients by improving the function of EPCs remains to be elucidated. Here we enrolled Sixty-three T2DM patients and 60 healthy participants and 15 of T2DM group took dapagliflozin for 3 months. Retinal capillary density (RCD) was examined before and after meditation. Moreover, vasculogenic capacity of EPCs cocultured with or without dapagliflozin in vitro and in vivo (hind limb ischemia model) were assessed. Mechanically, genes related to inflammation/oxidative stress, and the AMPK signaling of EPCs were determined. Our results found T2DM demonstrated a declined RCD and a decreased number of circulating EPCs compared with healthy controls. Compared with the EPCs from healthy individuals, vasculogenic capacity of T2DM EPCs was significantly impaired, which could be restored by dapagliflozin meditation or dapagliflozin coculture. Increased expression of inflammation correlative genes and decreased anti-oxidative stress related genes expression were found in EPCs form T2DM, which were accompanied with reduced phosphorylation level of AMPK. Dapagliflozin treatment activated AMPK signaling, decreased the level of inflammation and oxidative stress, and rescued vasculogenic capacity of EPCs from T2DM. Furthermore, AMPK inhibitor pretreatment diminished the enhancement vasculogenic capacity of diabetic EPCs from dapagliflozin treatment. This study demonstrates for the first time that dapagliflozin restores vasculogenic capacity of EPCs via activating AMPK-mediated inhibition of inflammation and oxidative stress in T2DM.

The evaluation of red cell distribution width in type 2 diabetic patients with acute ST- segment elevation myocardial infarction in Erbil city: a cross sectional study

Background: The relationship of high red cell distribution width (RDW) with many hematological and angiographic characteristics in type 2 diabetic patients with acute ST-segment elevation myocardial infarction (STEMI) is still a matter of debate.
 Objective: To evaluate the relationship of high RDW with multiple hematological and angiographic characteristics in type 2 diabetic patients with acute STEMI.
 Patients and Methods: In this cross-sectional study, one hundred patients with acute STEMI who underwent coronary angiography were enrolled. The patients were divided into two groups according to the presence of type 2 diabetes mellitus (T2DM); group I, diabetic patients and group II, non-diabetic patients. Further division was made to group I patients based on how high or low RDW level was; subgroup A patients with high RDW level, and subgroup B patients with low RDW level. The groups were evaluated and compared regarding baseline demographic, laboratory and angiographic characteristics.
 Results: The mean RDW was higher (P=0.04) in group I compared to group II. The mean values of white blood cell (WBC) , RDW, CK-MB, Troponin T high sensitive (hs) , and HbA1C levels were significantly higher in subgroup A compared to subgroup B (P=0.007, 0.003, 0.03 and < 0.001, respectively). Subgroup A patients have significantly more extension of coronary diseases than subgroup B (P=0.001). A positive correlation was detected between RDW and WBC, CK-MB, Troponin T hs, HbA1C as well as number of diseased vessels in diabetic patients (0.76, 0.4, 0.98 and 0.79, respectively).
 Conclusion: Diabetic patients with acute STEMI had higher levels of RDW than non-diabetics and higher levels were positively correlated with inflammatory and poor outcome cardiovascular markers as well as multiple vessel diseases involvement. It was also correlated with poor glycemic control represented by high HbA1C.

The evaluation of red cell distribution width in type 2 diabetic patients with acute ST- segment elevation myocardial infarction in Erbil city: a cross sectional study

Background: The relationship of high red cell distribution width (RDW) with many hematological and angiographic characteristics in type 2 diabetic patients with acute ST-segment elevation myocardial infarction (STEMI) is still a matter of debate. Objective: To evaluate the relationship of high RDW with multiple hematological and angiographic characteristics in type 2 diabetic patients with acute STEMI. Patients and Methods: In this cross-sectional study, one hundred patients with acute STEMI who underwent coronary angiography were enrolled. The patients were divided into two groups according to the presence of type 2 diabetes mellitus (T2DM); group I, diabetic patients and group II, non-diabetic patients. Further division was made to group I patients based on how high or low RDW level was; subgroup A patients with high RDW level, and subgroup B patients with low RDW level. The groups were evaluated and compared regarding baseline demographic, laboratory and angiographic characteristics. Results: The mean RDW was higher (P=0.04) in group I compared to group II. The mean values of white blood cell (WBC) , RDW, CK-MB, Troponin T high sensitive (hs) , and HbA1C levels were significantly higher in subgroup A compared to subgroup B (P=0.007, 0.003, 0.03 and < 0.001, respectively). Subgroup A patients have significantly more extension of coronary diseases than subgroup B (P=0.001). A positive correlation was detected between RDW and WBC, CK-MB, Troponin T hs, HbA1C as well as number of diseased vessels in diabetic patients (0.76, 0.4, 0.98 and 0.79, respectively). Conclusion: Diabetic patients with acute STEMI had higher levels of RDW than non-diabetics and higher levels were positively correlated with inflammatory and poor outcome cardiovascular markers as well as multiple vessel diseases involvement. It was also correlated with poor glycemic control represented by high HbA1C.

Coronary Angiographic Characteristics of Type 2 DM Compared with Nondiabetic Patients in Benghazi-Libya. A Cross-Sectional Study

Background/Aim: The absolute risk of death due to coronary artery disease (CAD) is two to five times higher in patients with diabetes than in those without diabetes regardless of the cholesterol concentration, and females with diabetes have the worst prognosis. The aim of the current study was to investigate the angiographic severity and extent of CAD in patients with Type 2 diabetes mellitus, compared with nondiabetic patients. Patients and Methods: A hospital-based retrospective cross-sectional study was performed on 340 patients who were diagnosed with CAD. The two groups were matched for age, gender, and other major risk factors. Data collected include demographic data, distribution, and extent of coronary artery involvement. Results: Three hundred and forty patients were included in the study, 175 of them (51.4%) were diabetics, and 165 (48.5%) were nondiabetics, comparing coronary angiographic results of both groups: One hundred and twenty-six patients (73%) of the diabetic patients have multivessel diseased (P = 0.003), 49 patients (27%) have a single-vessel diseased and none of them have a normal coronaries (0%). While for the nondiabetic patients 82 (50%) of them have a multivessel diseased, 63 patients (38%) have a single-vessel diseased, and 20 patients (12%) have normal coronaries. Conclusion: Multivessel disease with diffuse lesion is more prevalent among diabetic Libyan patients compared with nondiabetics. The affected vessels in diabetic patients are diffusely diseased more than nondiabetic.

Retinal oxygen saturation changes progressively over time in diabetic retinopathy

According to cross-sectional studies, oxygen saturation is elevated in retinal vessels in diabetic patients. We evaluated how retinal oxygenation (metabolic marker), vessel diameters and retinopathy grade (structural markers) change over time in diabetic patients. Prospective cohort study following screening in a hospital setting. Retinal oximetry images were acquired in 214 patients with the Oxymap T1 oximeter. Imaging was repeated after a median of 3.0 years (range 0.76-6.8 years). Oxygen saturation and vessel diameters were measured in the right eye. Semiquantitative grading of retinopathy according to international guidelines and red lesion count were performed on fundus photographs. Retinopathy grade according to the international semiquantitative grading system was unchanged. Arteriolar saturation increased by 0.75±0.15 percentage points per year of follow-up (p<0.0001). Venular saturation increased by 1.74±0.26 percentage points per year (p<0.0001) and arteriovenous difference decreased by 0.99±0.20 percentage points per year (p<0.0001). Arteriolar diameters decreased by 2.7±8.5μm (p<0.0001) between visits and venular diameters decreased by 2.4±9.1μm (p = 0.0002). Median increase in red lesion count between visits was 2 lesions (range -128 to 212 lesions, p<0.0001). The change in red lesion count and change in diameters did not correlate with the length of follow-up (p>0.44). Oxygen saturation in larger retinal vessels can increase and arteriovenous difference can decrease over time in diabetic patients without any observable changes in retinopathy grade. The results suggest that changes in retinal oxygen saturation may precede progression of diabetic retinopathy or that oxygen saturation is more sensitive to disease progression than retinopathy grade.

Detecting hemodynamic changes in the foot vessels of diabetic patients by photoacoustic tomography.

Limb perfusion monitoring is critical for diabetes mellitus (DM) patients as they are vulnerable to vascular complications due to prolonged hyperglycemia. However, current clinical approaches are ineffective in vascular imaging and in assessing vascular function in lower limbs. In this work, a concave ultrasound transducer array-based photoacoustic tomography (PAT) system was used to image the foot dorsal section of a subject, and a total of seven DM patients and seven healthy volunteers were enrolled in this study. Hemodynamic changes in foot vessels during vascular occlusion as well as oxygen saturation (SO2 ) in rest were analyzed for both groups. The results obtained showed that DM patients have a unique peripheral hemodynamic response to occlusion and a lower level SO2 , compared to that for healthy subjects. This suggests that PAT has the potential to detect vascular dysfunction in DM patients and to measure the effect of treatment.

Atherosclerosis in intracranial or extracranial vessels in diabetic patients and the association with stroke subtype.

Diabetes mellitus (DM) is associated with increased prevalence and severity of atherosclerosis. This study aimed to assess the prevalence and location of atherosclerosis in intracranial and extracranial vessels in diabetic patients and to investigate their association with ischemic stroke subtype. Diabetes patients (n=128) and nondiabetic patients (n=195) were enrolled. Brain MRI, MR angiography, and digital subtraction angiography (DSA) imaging findings in the two groups were retrospectively compared. The characteristics of atherosclerosis (prevalence, location, severity) and collateral flow in diabetic and nondiabetic patients and their association with stroke subtype were analyzed. Atherosclerosis in extracranial vessels was more common in diabetes patients than in nondiabetic patients (43.8% vs. 23.1%; P<0.001). Symptomatic stenoses were commonly in the proximal internal carotid artery (ICA) and proximal vertebral artery (pVA). Diabetes patients were more likely to have lacunar infarction (49.2% vs. 32.3%; P=0.002) and less likely to have large artery infarct (36.7% vs. 48.2%; P=0.042). DM (OR, 2.03; 95% CI, 1.96-4.30; P=0.006) and age >65 years (OR, 2.55; 95% CI, 1.24-5.22; P=0.011) were independent risk factors for lacunar infarct. Diabetes patients with symptomatic extracranial stenosis or occlusion, combined with good collateral circulation, had significantly higher risk of lacunar infarction than nondiabetic patients (47.8% vs. 30.5%; P=0.045). DM aggravates the severity of extracranial atherosclerosis. Lacunar stroke is relatively common in diabetic patients and could even be due to large artery disease (LAD).

Dynamic functionality and static changes of retinal vessels in diabetic patients treated with intravitreal ranibizumab.

To investigate the short-term effects of intravitreal ranibizumab on retinal vessel functionality in patients with diabetic macular edema (DME) by Dynamic Vessel Analyzer (DVA). Patients presenting with DME were enrolled in the study. All patients underwent a complete ophthalmic evaluation, including optical coherence tomography and dynamic and static vessel analysis, using the DVA before (baseline), 1week and 1month after administration of intravitreal ranibizumab. DME subject were compared with diabetic retinopathy (DR) without DME subjects, and with normal non diabetic subjects (controls) matched for age and sex. A total of 45 eyes of 45 subjects (15 eyes for each group) were included in the analysis. In DME patients, dynamic analysis showed a significant decrease in mean arterial dilation from baseline to 1week. Mean central retinal artery equivalent (CRAE) of DR patients without DME was significantly different from baseline and week 1 of DME eyes. In healthy control subjects, CRAE was significantly different from CRAE at baseline and 1week on DME patients, but not significantly different from DR patients without DME. Using DVA in patients with DME, dynamic analysis showed a significant decrease in mean arterial dilation from baseline to 1week in DME eyes. A significant reduction in arterial vessels could be demonstrated in DME patients compared to DR patients without DME and controls.

Lipidomic approach provides new clues toward solving the mystery of accelerated atherosclerosis in diabetes

Despite considerable progress in the management of major risk factors over recent decades, cardiovascular diseases (CVD) attributable to atherosclerosis are still a predominant cause of death worldwide. This is due, in large part, to the expansion of risk factors related to obesity such as insulin resistance and diabetes [1]. In fact, the risk of developing CVD in adults with diabetes is two to four times higher than in those without diabetes. Moreover, it is well established that insulin resistance and hyperglycemia promote atherosclerosis, leading to coronary artery disease. Yet the underlying mechanisms linking diabetes and atherosclerosis are still not completely understood. To overcome this lack of understanding, numerous studies have been conducted, using mouse models with targeted deletion in intimal cells, to evaluate the impact of impaired insulin signaling at the level of the arterial wall on atherosclerosis development and progression [2]. Taken together, this work highlights the critical consequences of altered insulin signaling, in both macrophages and endothelial cells, in atherogenesis and the formation of advanced plaques. In humans, comparative analyses of atherosclerotic plaques from diabetic and non-diabetic individuals have revealed some important differences in the quality and composition of plaques between these groups. Lesions from diabetic patients are characterized by a larger necrotic core, increased inflammation, neovascularization, intra-plaque hemorrhage, and calcification [3], [4], [5], [6] and [7]. Higher macrophage and T-cell content, along with increased proportions of apoptotic macrophages and smooth muscle cells, may contribute to this larger necrotic area [4] and [8]. When combined with the increased prevalence of thin-cap fibroatheroma and fibrocalcific atheroma, observed using Virtual Histology intravascular ultrasound in vessels of diabetic patients [5], these alterations of plaque morphology may explain the higher risk of acute coronary syndrome in diabetic patients. Indeed, coronary lesions of patients with diabetes mellitus are more vulnerable to rupture and subsequent thrombosis [3] and [6].

β3 Adrenergic Stimulation Restores Nitric Oxide/Redox Balance and Enhances Endothelial Function in Hyperglycemia.

BackgroundPerturbed balance between NO and O2 •−. (ie, NO/redox imbalance) is central in the pathobiology of diabetes‐induced vascular dysfunction. We examined whether stimulation of β3 adrenergic receptors (β3 ARs), coupled to endothelial nitric oxide synthase (eNOS) activation, would re‐establish NO/redox balance, relieve oxidative inhibition of the membrane proteins eNOS and Na+‐K+ (NK) pump, and improve vascular function in a new animal model of hyperglycemia.Methods and ResultsWe established hyperglycemia in male White New Zealand rabbits by infusion of S961, a competitive high‐affinity peptide inhibitor of the insulin receptor. Hyperglycemia impaired endothelium‐dependent vasorelaxation by “uncoupling” of eNOS via glutathionylation (eNOS‐GSS) that was dependent on NADPH oxidase activity. Accordingly, NO levels were lower while O2 •− levels were higher in hyperglycemic rabbits. Infusion of the β3 AR agonist CL316243 (CL) decreased eNOS‐GSS, reduced O2 •−, restored NO levels, and improved endothelium‐dependent relaxation. CL decreased hyperglycemia‐induced NADPH oxidase activation as suggested by co‐immunoprecipitation experiments, and it increased eNOS co‐immunoprecipitation with glutaredoxin‐1, which may reflect promotion of eNOS de‐glutathionylation by CL. Moreover, CL reversed hyperglycemia‐induced glutathionylation of the β1 NK pump subunit that causes NK pump inhibition, and improved K+‐induced vasorelaxation that reflects enhancement in NK pump activity. Lastly, eNOS‐GSS was higher in vessels of diabetic patients and was reduced by CL, suggesting potential significance of the experimental findings in human diabetes.Conclusionsβ3 AR activation restored NO/redox balance and improved endothelial function in hyperglycemia. β3 AR agonists may confer protection against diabetes‐induced vascular dysfunction.

Diabetic dermangiopathy - A micrometric study

Aim Diabetes mellitus (DM) is the most common endocrine disorder and cutaneous disorders associated with DM are thought to occur in about one-third of patients. The present study was undertaken to assess the alterations in the small blood vessels. Methods Skin biopsies from 100 type 2 diabetic patients and 15 non-diabetic controls were studied to observe the dermangiopathic changes. The lumen diameter and basement membrane width were measured. Depending on deposition of PAS-positive material in the vessel wall, the dermangiopathic changes were graded as 1 +, 2 + and 3 +. Results 80% of the cases showed 2 + (69%) or 3 + (11%) changes. The other 20% cases showed 1 + change and were not taken as positive evidence of microangiopathy. Mean BMT was measured as 6.06 microns and mean LD was 53.9 microns. The mean BMT:LD ratio was 0.11. No correlation was observed between age, duration of diabetes, severity of disease, diabetic complications and microangiopathy. A positive correlation was observed between the grades of microangiopathy and the basement membrane thickness. Discussion Characteristic angiopathy is demonstrable in vessels of diabetic patients and the vessel basement membrane thickness is an important criterion to grade diabetic dermangiopathy.

One year clinical and angiographic outcomes after everolimus- and paclitaxel-eluting stent implantation for small coronary vessels in diabetic patients: sub-analysis from PLUM and SACRA registries

One year clinical and angiographic outcomes after everolimus- and paclitaxel-eluting stent implantation for small coronary vessels in diabetic patients: sub-analysis from PLUM and SACRA registries

Repeated intravitreal bevacizumab (Avastin®) treatment of persistent new vessels in proliferative diabetic retinopathy after complete panretinal photocoagulation

To evaluate the effect of repeated intravitreal injections of bevacizumab (Avastin(®)) in patients with proliferative diabetic retinopathy and persistent new vessels after panretinal photocoagulation. In this prospective study we investigated 11 eyes of 10 diabetic patients with persistent new vessels after previous complete panretinal photocoagulation. Complete ophthalmological examinations were performed at baseline and during monthly follow-up visits until the final follow-up at 6 months. Colour fundus photography, fluorescein angiography (FA) and macular optical coherence tomography (OCT) were performed. The area of leakage (mm²) found in the FA was used to demonstrate the effect of bevacizumab on retinal new vessels. Patients received 1.0 mg of intravitreal bevacizumab at baseline and at each of the monthly follow-up visits when reappearance of retinal new vessels was documented. At the 1-week follow-up visit, 73% of the treated eyes showed complete regression of retinal new vessels. Eight eyes were assigned to retreatments at the 3-month follow-up because of the reappearance of retinal new vessels. After 6 months, 36% of the eyes were found to have reappearance of retinal new vessels. The retreatment rate was 1.9 ± 0.7 and the mean interval to retreatment was 2.9 ± 1.0 months. The mean leakage area decreased from 7.2 ± 2.6 mm² at baseline to 1.2 ± 0.9 mm² at the final follow-up visit. BCVA increased from 59.2 ± 14.6 Early Treatment Diabetic Retinopathy Study (ETDRS) score (range 40-80) to 70.7 ± 8.5 at the final visit (p = 0.017). Intravitreal bevacizumab led to a significant reduction of retinal new vessels for a mean period of 2.9 months. A 3-monthly retreatment regime might be a valid method to control retinal new vessels in diabetic patients with persistent new vessels.

Influence of Flickering Light on the Retinal Vessels in Diabetic Patients

We thank Wong et al. (1) for their interest in our study (2) in which we showed that retinal vessels in diabetic patients with increasing stages of diabetic retinopathy experience a continuously decreasing response to flickering light. We believe that the issue raised by Wong et al. is very important. The study by Nguyen et al. (3) showed that arteriolar and venular calibers are structurally …

Influence of Flickering Light on the Retinal Vessels in Diabetic Patients

We read with interest the article by Mandecka et al. (1) describing reduced retinal vessel reactivity, as measured by the response to flicker light, in people with diabetes and diabetic retinopathy. Findings from this study provide further insights into the early retinal vessel diameter changes involved in the pathogenesis of diabetic microvascular complications. Previous population-based studies have …

Decreasing Intracellular Superoxide Corrects Defective Ischemia-induced New Vessel Formation in Diabetic Mice

Tissue ischemia promotes vasculogenesis through chemokine-induced recruitment of bone marrow-derived endothelial progenitor cells (EPCs). Diabetes significantly impairs this process. Because hyperglycemia increases reactive oxygen species in a number of cell types, and because many of the defects responsible for impaired vasculogenesis involve HIF1-regulated genes, we hypothesized that HIF1 function is impaired in diabetes because of reactive oxygen species-induced modification of HIF1alpha by the glyoxalase 1 (GLO1) substrate methylglyoxal. Decreasing superoxide in diabetic mice by either transgenic expression of manganese superoxide dismutase or by administration of an superoxide dismutase mimetic corrected post-ischemic defects in neovascularization, oxygen delivery, and chemokine expression, and normalized tissue survival. In hypoxic fibroblasts cultured in high glucose, overexpression of GLO1 prevented reduced expression of both the EPC mobilizing chemokine stromal cell-derived factor-1 (SDF-1) and of vascular epidermal growth factor, which modulates growth and differentiation of recruited EPCs. In hypoxic EPCs cultured in high glucose, overexpression of GLO1 prevented reduced expression of both the SDF-1 receptor CXCR4, and endothelial nitric-oxide synthase, an enzyme essential for EPC mobilization. HIF1alpha modification by methylglyoxal reduced heterodimer formation and HIF1alpha binding to all relevant promoters. These results provide a basis for the rational design of new therapeutics to normalize impaired ischemia-induced vasculogenesis in patients with diabetes.