Arnon Blum

Allogeneic Mesenchymal Stem Cells Restore Endothelial Function in Heart Failure by Stimulating Endothelial Progenitor Cells

Background Endothelial dysfunction, characterized by diminished endothelial progenitor cell (EPC) function and flow-mediated vasodilation (FMD), is a clinically significant feature of heart failure (HF). Mesenchymal stem cells (MSCs), which have pro-angiogenic properties, have the potential to restore endothelial function. Accordingly, we tested the hypothesis that MSCs increase EPC function and restore flow-mediated vasodilation (FMD). Methods Idiopathic dilated and ischemic cardiomyopathy patients were randomly assigned to receive autologous (n = 7) or allogeneic (n = 15) MSCs. We assessed EPC-colony forming units (EPC-CFUs), FMD, and circulating levels of vascular endothelial growth factor (VEGF) in patients before and three months after MSC transendocardial injection (n = 22) and in healthy controls (n = 10). Findings EPC-colony forming units (CFUs) were markedly reduced in HF compared to healthy controls (4 ± 3 vs. 25 ± 16 CFUs, P < 0.0001). Similarly, FMD% was impaired in HF (5.6 ± 3.2% vs. 9.0 ± 3.3%, P = 0.01). Allogeneic, but not autologous, MSCs improved endothelial function three months after treatment (Δ10 ± 5 vs. Δ1 ± 3 CFUs, P = 0.0067; Δ3.7 ± 3% vs. Δ-0.46 ± 3% FMD, P = 0.005). Patients who received allogeneic MSCs had a reduction in serum VEGF levels three months after treatment, while patients who received autologous MSCs had an increase (P = 0.0012), and these changes correlated with the change in EPC-CFUs (P < 0.0001). Lastly, human umbilical vein endothelial cells (HUVECs) with impaired vasculogenesis due to pharmacologic nitric oxide synthase inhibition, were rescued by allogeneic MSC conditioned medium (P = 0.006). Interpretation These findings reveal a novel mechanism whereby allogeneic, but not autologous, MSC administration results in the proliferation of functional EPCs and improvement in vascular reactivity, which in turn restores endothelial function towards normal in patients with HF. These findings have significant clinical and biological implications for the use of MSCs in HF and other disorders associated with endothelial dysfunction.

What is the oncologic risk of stem cell treatment for heart disease

See related article, pages 1340–1347 Every therapy has toxic and therapeutic windows, and defining the side effects of any new therapeutic modality is the first order of business in the development of a treatment. With transformative therapies such as cell-based approaches, treatment side effects can be unpredictable and unanticipated. In some cases, experimental data raise serious concerns that must be appropriately managed. In the face of the promise and enthusiasm for cell-based therapy for heart disease, results from rodent experiments have consistently raised the specter of a dreaded side effect—can the use of stem cells lead to cancer, either directly or through promotion of existing early-stage neoplasms? Mesenchymal stem cells (MSCs) are a multipotent immunotolerant cell source that can be readily expanded into therapeutic quantities from a variety of tissues such as the bone marrow, cord blood, and fat, and as such their use in cell-based therapeutic strategies holds great promise.1 With regard to heart disease, accumulating preclinical2–11 and clinical studies12–15 demonstrate that MSC transplantation may be salutary for both acute myocardial infarction and cardiomyopathy with an acceptable risk profile. The translational development of cell-based therapy has required rigorous large-animal experimentation, recognizing inherent limitations with rodent experimentation. In this context, more than 500 large animals (swine, canine, and sheep) have been tested to assess the safety and efficacy of MSC therapeutics for treating heart disease with the results demonstrating that MSC transplantation is a safe and durable approach that may be more effective than bone marrow mononuclear cells.16 Importantly, large-animal work provides a phenotyping opportunity not available in rodents, and rigorous cardiac MRI (CMR) and histological analysis in porcine hearts supported the regenerative effects subsequently demonstrated in the adult human heart.12,15 The mechanism of action appears multifaceted, involving direct …

Vascular responsiveness in patients with chronic obstructive pulmonary disease (COPD)

BACKGROUND Ischemic heart disease and peripheral vascular diseases are prevalent in COPD and it is estimated that any 10% decrease in forced expiratory volume in 1 second (FEV1) is associated with 30% increased cardiovascular risk of death. Endothelial dysfunction may be one of the mechanistic pathways that link between COPD and cardiovascular mortality. Our aim was to study the vascular reactivity of patients with stable COPD and to try to correlate endothelial dysfunction, vascular reactivity and functional capacity of these patients that eventually may lead to cardiovascular mortality. METHODS This was a prospective study. Twenty-three consecutive ambulatory COPD patients were enrolled. All were smoking men, aged 64.4 ± 8.4 years. Twenty-two healthy volunteers aged 44.7 ± 11.7 years, BMI of 25.2 ± 4.2, height of 172 ± 8 cm served as the control group. Vascular studies included endothelial function and ankle brachial index. RESULTS Baseline diameter of the brachial artery was larger in COPD patients compared with controls. The absolute change in diameter post hyperemia was significantly less in patients (0.004 ± 0.02 cm vs. 0.05 ± 0.02 cm, p<0.001) and COPD patients responded to hyperemia by constriction instead of dilatation (FMD% was -0.6 ± 6.3% in patients vs. 15.6 ± 7.6% in controls, p<0.001). There was no difference in ABI in patients and controls (0.95 ± 0.26 vs. 1.06 ± 0.16, p=0.07). DISCUSSION We found that patients with COPD have dilated arteries, have impaired ability to respond to high shear stress that triggers nitric oxide dependent flow mediated dilatation, and have also impaired ability to function - represented by the poor 6 minute walk test.

Colony Forming Unites - Endothelial Progenitor Cells (CFU-EPCs) A surrogate marker for diabetic retinopathy and high cardiovascular mortality rate

Purpose: Diabetic retinopathy is a risk factor for increased cardiovascular death. Our purpose was to find a significant difference in levels of endothelial progenitor cells (EPCs) in the peripheral blood of patients at different stages of diabetic retinopathy. Design: A prospective study. Colony forming units of endothelial progenitor cells (CFU-EPCs) in peripheral blood were counted. 40 subjects were enrolled (10 healthy [41±8 y], 10 type 2 diabetes mellitus (T2DM) [64±12 y] without retinopathy, 10 T2DM patients [62±26 y] with non-proliferative retinopathy (NPDR), 10 T2DM patients [66±9 y] with proliferative retinopathy (PDR)). The study was approevd by the ethics committee of the hospital and every subject signed a soncent form before enrollment. Methods: Growing CFU-EPCs was by the Hills EPCs protocol. Blood was drawn early in the morning and was processed within 1 hour. Mononuclear cells were separated and cultured on fibronectin-coated plates with EndoCult medium (StemCell technologies, Vancouver BC Canada) for 5 days. CFU-EPCs were counted on day 5 (an average of 8 wells). Results: Healthy subjects had 36±8 CFU-EPCs, patients without retinopathy had 13±12 CFU-EPCs (p<0.01), patients with NPDR 22±26 CFU-EPCs (p=NS), and 2±2 CFU-EPCs in patients with PDR (p<0.01). A significant difference was found between patients with PDR and with NPDR (p<0.05). Conclusions: CFU-EPCs are inhibited in T2DM patients with DPR. Levels of CFU-EPCs may be used as a surrogate biologic marker for severity of diabetic retinopathy and for cumulative vascular risk.Purpose: Representing the algorithm of periorbital area rejuvenation Materials: As part of the research, 1216 eyes of 608 patients were included. According to patients’ complaints and evaluating their situation, treatments were carried out as medical and surgical. Treatment was not applied to 75 patients that their request and the cure were not compromise. Patients were followed approximately 11,3 months (1-32 months). The study is evaluated according to patients’ reason of request, their general characteristics and the treatments that are applied. Findings: Age average of 608 patients who are applied to my clinic with the intent of periorbital area rejuvenation and enhancing eyelid deformity between the dates of March 2014-January 2017 is 38. 81,25% patients were female and 18,75% was male. 538 patients (88,5%) were applied medical treatment. 260 patients (42,8%) got surgical treatment and to 31,3% patients, combined treatment was applied. The treatment that I applied and the complaints of 89% patients harmonized with each other. 11% of patients were not treated since their complaints and their treatment request were not corresponded to each other. Result: The most important phase is pre-treatment to become successful in the treatment. First thing to do is listening and understanding the patient carefully, because the problem we observe and patient’s complaint may not be the same. In this case, no matter how successful the treatment is, we can not satisfy the patient. Sometimes, patient has unrealistic expectations. When such a patient like this is encountered, it must be kept away from him or her and the treatment should not be applied. Volume 2 | Issue 2 | 1 of 4 Keyword: Periorbital Area, Rejuvenation, Surgical, Medical Aesthetics, Eyelid Blepharoplasty. Introduction Periorbital area is the most frequently-consulted and watched out area in bilateral relations so it has gained much more importance in recent years. It is possible to be looked healthier and younger with lots of practice applied around eye. With this reason, more and more patients apply to clinics to look better everyday. As an ophthalmologist, I would like to mention about the treatments that I provide to make my patients look better, younger and healthier. Most people want to look better with the improvement of technology, increasement of using social media and importance of visual quality. With this aim in their minds, patients consult health institutions. In my clinic, consultation request is generally for periorbital area. The mistreatments in the periorbital area which has an important function as seeing cause vision loss. This situation could arise from unrealistic expectations of the patient or insufficiency in the health experience of health center. Also, the misunderstanding between the patient and the doctor may cause this problem [1]. I think that ophthalmologists should actively participate in the treatments of periorbital area. After examining the patient in detail, the treatment should be explained loud and clear. It can be repeated until he or she understands the approach clearly. While the treatment is thought as surgical and medical, it can be also combined. It should be decided according to the request of patient and its satisfying outcome. In the patient who complains about upper droopy eyelid, contexts of the eyelid and whether they include additional pathology or not should be examined. Eyelid, eyebrow and eyelash ptosis should be evaluated. Whether excised area includes fat package or not without skin and orbicularis should be reviewed. In the patient with the request of low eyelid blepharoplasty, the trace of entropion and ectropion should be looked. With the snap back test, the laxity of low eyelid should be examined. In this part, the existence of scleral show helps us. Additionally, cheek looseness and laxity in the malar pad should be evaluated [2]. In the patient, medical treatment can be thought not surgical or in addition to that surgery, medical treatment can be planned. In this part, the treatments that help us are botox in eyebrow lid andL Eye” syndrome or amblyopia is a common phenomenon scattered throughout the human population. It is estimated that around 5% of the human population suffers from this syndrome along with diplopia, and refractive squint present in many or rather most of the cases. It is quite possible that other animal species that depend on stereoscopic vision for their survival are also prone to this condition in the same frequency as the human population. During prehistoric and ancient times, this condition did not interfere with human survival and this is the reason of its prevalence among the human population even in the present times. As it is present among 5% of the human population, it is no doubt a genetic condition. It has presented itself in individuals that have a genetic history of this condition in the maternal or paternal lineages. This condition is a major liability for the sufferer in the modern world. During ancient times, when man started as a hunter-gatherer and until the human world did not depend on the written word, this condition was a benign syndrome, possibly without any competitive disadvantage. That is the reason this condition has survived into the modern world. In the modern world, the major disadvantage is in field of academics. Children suffering from this condition are at a disadvantage due to their inability to study like other normal children. In the amblyopic patients, having diplopia and refractive squint near stereoscopic vision is disrupted during reading and other near vision activities. Two different images that are created in the visual cortices do not overlap. The glasses force the visual cortices to fuse the two different images into one which otherwise is impossible and makes amblyopia comorbid with refractive squint a difficult malady to correct with present treatment options. These glasses are based on the neurobiology of vision. How stereoscopic vision is processed by the brain and the understanding of underlying cause that produces this deficit in the brain of individuals afflicted with this disorder is also conceptualized in this treatment option. Why 3D optics is helpful in correcting this disorder in the brain is also hypothesized in this paper. These glasses should only be used for near vision activities like reading through a book but not for reading through a computer screen or watching television, as no diplopia is present when words or visuals are seen on an illuminated background, although amblyopic patients who suffer headache while using a computer shall benefit immensely from this procedure. This method will correct the visual deficit and convergence insufficiency with 100% positive results and shall improve the academic capabilities of children suffering from amblyopia and refractive squint who complain of diplopia and headache while reading. These glasses will also correct the binocular acuity of individuals suffering from amblyopia. This can be done by breaking the suppression of visual signals sent by the amblyopic eye to the brain. Prolonged use of these glasses will train the brain to make use of signals and images created in both the visual cortices into one. Hence, the brain will be forced to utilize visual signals from both the eyes due to its neurophysiology.Purpose: To evaluate the results of patients with complaint of under eye hollowness and dark circles and application of under eye hyaluronic acid filler, comparison of the cannula and injection techniques. Method: Under eye hyaluronic acid filler was applied to the patients who consult to the clinic with complaint of hollows and dark circles under eye between March 2014 and December 2016. Application method was evaluated according to the success of results, satisfaction and complications. Findings: 356 eyes of 178 patients were included to the research. There were 148 (83%) female and 30 (17%) male patients. Average age was 33 (age range 19 60). It was defined that the most frequently complaint was under eye hollowness with 84% and followed by dark circles with 74%. It is seen that in over 40 year old patients, the most common complaint was dark circles with 80%. The filler was applied to 140 patients with cannula and to 38 patients with injection. The hyaluronic acid filler was implemented 0,83ml (0,4 1,25ml) total for each eye approximately. Patients were followed averagely 14 month (1 32 month). While the most frequent complication was ecchymosis in 14 patients (8%), the second one was edema which lasts over two weeks in 8 patients. Emboli was not seen in any patient. When the cannula and injection techniques were compared, a distinct difference was seen in terms of ecchymosis risk. The risk of ecchymosis was 3% with usage of cannula, whereas with needle, it was 26%. Besides, while ecchymosis caused by injection was seen in more extensive area, the area caused by cannula was more limited. As satisfaction evaluation, 93% patients graded the filler application as good. 5% patients thought that it was average and 2% of them scored it as bad. 4 patients who evaluated the application bad were the ones that their filler was applied with injection and occurred ecchymosis in their under eye. Result: The procedure of hyaluronic acid filler is an alternative treatment in the patients who have dark circles and hollows under eye. The procedure with cannula technique is safer for the patience satisfaction and risks of application, but this technique should be used with experienced doctor.

Inhibition of endothelial progenitor cells may explain the high cardiovascular event rate in patients with rheumatoid arthritis

Background Rheumatoid arthritis (RA) patients may suffer cardiovascular (CV) events much more than the general population, and CV disease is the leading cause of death in patients with RA. Our hypothesis was that impaired function of endothelial progenitor cells may contribute to endothelial dysfunction and the clinical CV events of patients with RA. Methods 27 RA patients (9 males and 18 females) with an active disease and 13 healthy subjects who served as the control group (9 males and 4 females) were enrolled to this prospective study. The ability to grow in culture colony-forming units of endothelial progenitor cells (CFU-EPCs) was measured, as well as their endothelial function using high-resolution ultrasonography of the brachial artery, and levels of C reactive protein (CRP) in the serum. For statistical analysis we used the students T-test test. Results As a group, patients with RA were older (p < 0.0001), had severe endothelial dysfunction (<0.0001), with impaired ability to grow CFU-EPCs (<0.0001), and a higher inflammatory state (p = 0001). No difference was observed in BMI. All RA patients had an active disease (DAS28 3.9±0.9) for 9.2±6.5 years. The same differences were observed in both genders. Conclusions Patients with RA had an impaired ability to grow endothelial progenitor cells and severe endothelial dysfunction. Inability to grow colonies of endothelial progenitor cells reflects the impaired regenerative capacity of patients with RA, and may explain the endothelial dysfunction and the high CV event rate among patients with RA.

Endothelial function in rheumatoid arthritis

Background Rheumatoid arthritis (RA) patients are at higher risk of accelerated atherosclerosis. Aims To assess endothelial dysfunction in RA to find a possible mechanistic pathway that will explain the clinical phenomenon. Methods A prospective study recruited 44 RA patients with an active long standing (>12 months) disease. All underwent a detailed assessment of disease activity. To estimate the endothelial function the brachial artery method was performed, measuring flow mediated diameter percent (FMD%) change. Clustering analyses (hierarchical and k-means) were performed. Patients were compared to healthy subjects. Results Forty four RA patients (54.42 ± 11.14 years, females (72.7%)) with co-morbidities (70.5%), not taking tumor necrosis factor-blockers or disease modifying anti rheumatic drugs (63.6%). Only 6 (13.6%) had a normal endothelial function. Hierarchical and k-means clustering techniques showed statistically significant differences among the three clusters concerning disease activity score-28 (DAS-28)- erythrocyte sedimentation rate (ESR) (P = 0.000), DAS-28- C-reactive protein (CRP; P = 0.001), clinical disease activity index (P = 0.002), simplified disease activity index (P = 0.001), ESR (P = 0.000), (CRP) (P = 0.003) and FMD% (P = 0.009). The group with the highest FMD% values exhibited the lowest clinical scores and laboratory parameters. Patients with the lowest FMD% values co-clustered with subjects with positive but low FMD% changes and elevated clinical and laboratory parameters. Conclusions Our study confirmed the feasibility of exploiting endothelial function in clinical practice as an early predictor of atherosclerosis in RA patients.

Levels of adhesion molecules in peripheral blood correlat with stages of diabetic retinopathy and may serve as bio markers for microvascular complications

Background Proliferative diabetic retinopathy is a devastating complication of diabetes mellitus, developing within 15 years in 50% of patients with type 1 diabetes mellitus (DM) and in 10% of patients with type 2 DM. The correlation between levels of inflammatory markers in the peripheral blood and retinopathy staging has not been studied yet, and the purpose of this prospective study was to find a possible association between inflammation and staging of diabetic retinopathy. Methods A prospective (pilot) study that measured level of adhesion molecules in the peripheral blood of 10 healthy subjects and 30 patients with type 2 diabetes mellitus. Patients were grouped by the degree of retinopathy: 10 without retinopathy, 10 with non‐proliferative retinopathy [NPDR] and 10 with proliferative retinopathy [PDR]. After signing the consent form, an ophthalmologic examination was performed, and 10 mL of blood was drawn. In order to assess adhesion molecules’ level serum samples were collected, frozen, and stored at a temperature of −80 °C until analysis was performed as one batch. Results 10 healthy volunteers and 30 patients were enrolled. Healthy volunteers were younger (36.6 ± 7.9 years) compared to patients (no retinopathy 64.5 ± 10.8 years, NPDR 71.4 ± 8.9 years, and PDR 63.3 ± 11.6 years) (p = .0003 for all groups of patients in comparison with the healthy subjects). VCAM‐1 levels were increased by retinopathy staging – starting from 81.86 ± 3.80 ng/ml (healthy), 105.55 ± 1.37 ng/ml (no retinopathy), 111.78 ± 4.14 ng/ml (NPDR), and 123.45 ± 3.99 ng/ml (PDR), with a significant difference between healthy and patients without retinopathy (p = .03), between no retinopathy and NPDR (p = .001), and between NPDR and PDR (p < .0001). E selectin was increased in correlation with severity of the retinopathy, with a significant difference between groups of patients (p = .03 between healthy subjects and T2DM patients without retinopathy, p = .001 between patients with T2DM no retinopathy and NPDR, p < .0001 between NPDR and PDR). Conclusions We found a significant increase in levels of adhesion molecules (VCAM‐1) and selectins (E‐selectin) in parallel with increased severity of diabetic retinopathy, with a significant difference of inflammatory markers between stages of retinopathy. HighlightsDiabetics have increased adhesion molecules.Diabetic patients have an impaired ability to grow colonies of endothelial stem cells.Inflammation affects vascular complications in diabetics.

Vascular responsiveness in type 2 diabetes mellitus (T2DM)

BACKGROUND Diabetic retinopathy is used for staging of progression of micro and macro-vascular complications of patients with DM. Our hypothesis was that diabetic patients at different stages of retinopathy would have different vascular responsiveness that will be used as a surrogate marker of macro-vascular disease for risk assessment of cardiovascular complications. METHODS A prospective study enrolled 96 patients. Twenty-three healthy volunteers (44 ± 11 years), 25 diabetic patients without retinopathy (63 ± 11 years), 25 patients with non-proliferative retinopathy [NPDR] (62 ± 9 years) and 23 patients with proliferative diabetic retinopathy [PDR] (59 ± 10 years). All patients underwent an ophthalmologic examination to diagnose retinopathy staging, and vascular responsiveness evaluation that included endothelial function evaluation (using the brachial artery method to measure flow mediated diameter change (FMD%)) and measuring the ankle-brachial blood pressure ratio, a measure of arterial stiffness. RESULTS Endothelial function was severely impaired in all diabetic patients. Patients with PDR had an FMD% of -3.1 ± 6.6%, patients with NPDR had -3.3 ± 9.2%, patients without retinopathy -1.9 ± 7.4% (P = NS between all groups of patients). Healthy controls had an FMD% of 16.5 ± 7.5% with a significant difference (P < 0.001) compared with each group of patients. No difference in FMD% was observed among patients (P = 0.93 between PDR and NPDR groups, P = 0.54 between NPDR and no retinopathy groups and P = 0.71 between patients without retinopathy and those with PDR).The ankle brachial (ABI) ratio was 1.03 ± 0.28 in the PDR group, 1.14 ± 0.24 in the NPDR group and 0.97 ± 0.18 in the no-retinopathy group. Healthy volunteers had an ABI of 1.07 ± 0.18. No difference was observed between ABI of PDR and NPDR patients (P = 0.17) and between patients without retinopathy and PDR patients (P = 0.91). However, a significant difference was observed between the NPDR and no-retinopathy groups (P = 0.008). No significant difference was found between ABI ratios when compared with the control group (P = 0.62 for PDR, P = 0.26 for NPDR and P = 0.07 for the no-retinopathy group). No difference was observed in age and BMI among all groups of patients (P = NS for all). Patients were older (P < 0.001) and had a higher BMI (P < 0.001). Interestingly there was no difference in height among groups of patients, but controls were significantly taller compared with each group of patients (P < 0.02). CONCLUSIONS All patients with T2DM had severe endothelial dysfunction with no difference among the different retinopathy groups. In our patients, all patients had a normal arterial stiffness but patients without retinopathy who had the highest arterial stiffness. We could not distinguish vascular traits that would define diabetic patients at the highest risk to develop cardiovascular complications.

Clinical Characteristics of Diabetic Patients with Diabetic Retinopathy

Abstarct: Background : Proliferative diabetic retinopathy is a consequence of retinal ischemia due to capillary occlusion resulting from damage to the retinal endothelium, and is associated with increased risk of cardiovascular morbidity and mortality. Methods : We randomly assigned seventy three patients with DM type II and grouped them according to their retinal proliferative disease (Group A - 25 patients [12 males], mean age 62.8±10.8 years, no diabetic retinopathy; Group B - 25 patients [19 males], mean age 61.9±9.4 years, non-proliferative retinopathy; and Group C - 23 patients [13 males], mean age 59.2±10.3 years, proliferative retinopathy). Twenty three healthy subjects (14 males; mean age 44.3±11.6 years) served as the control group. We studied their retinal vasculopathy status, height, weight, body mass index (BMI), waist circumference, age, endothelial function (flow mediated diameter [FMD%] percent change) and their peripheral artery disease (ankle brachial index [ABI]). Results : A significant difference was found between the duration of length of DM type II between patients without retinopathy [group A] (9±6 years) and patients with non-proliferative retinopathy [group B] (17±9 years) (p=0.001). No difference in length of diabetes was observed between patients with non-proliferative retinopathy [group B] and patients with proliferative retinopathy [group C] (19±6 years) (p=0.30). A significant difference was observed in HgA1C% between group A (7.1±2.7%) and group B (8.5±1.5%) (p=0.02). No such difference was noted between group B and group C (8.5±1.6%) (p=0.98). Only 6 patients (out of 23) used insulin treatment in group A compared with 16 group B (out of 25) and 17 in group C (out of 25) (p=0.004). All three groups of diabetic patients were older (62.8±10.8, 61.9±9.4, 59.2±10.3 years, respectively) than volunteers (44.3±11.6 years) (p≤0.001), had a lower stature (1.65±0.09, 1.68±0.07, 1.65±0.09 meters, respectively) compared with controls (1.73±0.08 meters) (p≤0.05), had a larger waist circumference (110.04±14.17, 108.88±13.00, 109.30±13.49 cm, respectively) than controls (93.43±11.66 cm) (p≤0.001), and larger BMIs (30±6, 29±4, 30±5) compared with controls (25±4) (p≤0.001). All diabetic patients had severe endothelial dysfunction measured by FMD% (-1.9±7.4, -3.3±9.2, -3.1±6.6 %, respectively) compared with the control group (16.5±7.5%) (p≤0.001). ABI was within normal range in all patient (0.97±0.18, 1.14±0.24, 1.03±0.28, respectively), and in volunteers (1.06±0.18) (p≥0.05). There was no significant change within the 3 subgroups of diabetic retinopathy patients in age, height, weight, BMI, or FMD%. Conclusions : All patients with DM type II had severe endothelial dysfunction, higher BMIs, lower statures, larger waist circumferences; however they all had normal ABIs.