A Mediterranean Diet May Be Protective in the Development of Diabetic Retinopathy.

The Mediterranean diet is recognized as one of the healthiest available dietary patterns. This perception results from its beneficial effects on the cardiovascular system and, also, on hypertension, diabetes, and cancer compared with other diets. Its impact on the course of diabetes is assessed in the available scientific literature; however, little information is available about its impact on diabetic retinopathy. The MD is characterized mainly by the consumption of fish, seafood, foods of plant origin, and fresh fruit and vegetables. It is also recommended to consume legumes, which are a source of folic acid, magnesium, iron, and dietary fiber. High consumption of nuts and unrefined grains is also recommended in the MD. Marine fish provide polyunsaturated acids from the omega-3 group. Olive oil plays a very important role, especially olive oil obtained from mechanical pressing. Additionally, olive oil contains vitamins E, K, and polyphenols. Polyphenols, which are present in a diverse range of vegetables, fruits, and seeds, have the ability to decrease oxidative stress, inflammation, and insulin resistance. Resveratrol is naturally found in grape skins and seeds, as well as in peanuts and berries, and is a constituent of red wine. Resveratrol can inhibit increased vascular leakage and loss of pericytes and regulate the level of VEGF protein in the retina, thus inhibiting the development of DR. Consumption of fruits, vegetables, fish, and olive oil may be correlated with a lower risk of diabetic retinopathy. This paper presents the definition of the Mediterranean diet and its influence on the course of diabetes and diabetic retinopathy.

Prevention and Treatment of Retinal Vein Occlusion: The Role of Diet-A Review.

Retinal vein occlusion (RVO) is the second most common retinal disorder. In comparison to diabetic retinopathy or age-related macular degeneration, RVO is usually an unexpected event that carries a greater psychological impact. There is strong evidence to suggest that cardiovascular diseases are the most common risk factors in this pathology and it has long been known that a higher consumption of fish, nuts, fruits, and vegetables has a protective effect against these types of conditions. In the last several years, interest in plant-based diets has grown in both the general population and in the scientific community, to the point to which it has become one of the main dietary patterns adopted in Western countries. The aim of this review is to investigate the potential impact of macro- and micronutrients on retinal vein occlusion.

Impact of hydration with beverages containing free sugars or xylitol on metabolic and acute kidney injury markers after physical exercise.

The proper fluid and carbohydrates intake is essential before and during physical exercise, and for this reason most athletes drink beverages containing a high amount of free sugars. Sweetened soft drinks are also commonly consumed by those not doing any sport, and this habit seems to be both unhealthy and also the cause of metabolic problems. Recently, several sweeteners have been proposed to replace sugars in popular beverages. To examine the impact of free sugars and the popular sweetener xylitol on metabolic profile and the markers of kidney function and injury after exercise the present study was conducted with semi-professional football players. All participants were healthy, with a mean age of 21.91 years. Their sports skills were on the level of the 4th-5th division of the league. The subjects took part in four football training sessions. During each session they drank a 7% solution of sugar (sucrose, fructose, glucose) or xylitol. The tolerability of these beverages and well-being during exercise was monitored. Before and after each training session, blood and urine were collected. The markers of kidney function and injury, uric acid, electrolytes, complete blood count, CRP, serum albumin, serum glucose and the lipid profile were analyzed. The main finding of this study was that the xylitol beverage is the least tolerated during exercise and 38.89% of participants experienced diarrhea after training and xylitol intake. Xylitol also led to unfavorable metabolic changes and a large increase in uric acid and creatinine levels. A mean increase of 1.8 mg/dl in the uric acid level was observed after xylitol intake. Increases in acute kidney injury markers were observed after all experiments, but changes in urine albumin and cystatin C were highest after xylitol. The other three beverages (containing "free sugars" - glucose, fructose and sucrose) had a similar impact on the variables studied, although the glucose solution seems to have some advantages over other beverages. The conclusion is that sweeteners are not a good alternative to sugars, especially during exercise. Pure water without sweeteners should be drunk by those who need to limit their calorie consumption. Clinical Trial Registration: ClinicalTrials.gov, (NCT04310514).

The Role of Resveratrol in Eye Diseases-A Review of the Literature.

Resveratrol (3,5,4'-trans-trihydroxystilbene) is a polyphenolic phytoalexin belonging to the stilbene family. It is commonly found in grape skins and seeds, as well as other plant-based foods. Oxidative stress and inflammation play a key role in the initiation and progression of age-related eye disorders (glaucoma, cataracts, diabetic retinopathy, and macular degeneration) that lead to a progressive loss of vision and blindness. Even though the way resveratrol affects the human body and the course of many diseases is still the subject of ongoing scientific research, it has been shown that the broad spectrum of anti-inflammatory and neuroprotective properties of resveratrol has a beneficial effect on eye tissues. In our research, we decided to analyze the current scientific literature on resveratrol, its possible mechanisms of action, and its therapeutic application in order to assess its effectiveness in eye diseases.

Adipose Tissue and Biological Factors. Possible Link between Lymphatic System Dysfunction and Obesity.

The World Health Organization (WHO) has recognised obesity as one of the top ten threats to human health. Obesity is not only a state of abnormally increased adipose tissue in the body, but also of an increased release of biologically active metabolites. Moreover, obesity predisposes the development of metabolic syndrome and increases the incidence of type 2 diabetes (T2DM), increases the risk of developing insulin resistance, atherosclerosis, ischemic heart disease, polycystic ovary syndrome, hypertension and cancer. The lymphatic system is a one-directional network of thin-walled capillaries and larger vessels covered by a continuous layer of endothelial cells that provides a unidirectional conduit to return filtered arterial and tissue metabolites towards the venous circulation. Recent studies have shown that obesity can markedly impair lymphatic function. Conversely, dysfunction in the lymphatic system may also be involved in the pathogenesis of obesity. This review highlights the important findings regarding obesity related to lymphatic system dysfunction, including clinical implications and experimental studies. Moreover, we present the role of biological factors in the pathophysiology of the lymphatic system and we propose the possibility of a therapy supporting the function of the lymphatic system in the course of obesity.

Common carotid pulsatility is deteriorated by autoimmune thyroiditis in children with type 1 diabetes mellitus - A pilot study.

Autoimmune thyroiditis (AIT) frequently coexists with type 1 diabetes (DM1) and additionally increases the extent of microcirculatory complications due to DM1. We hypothesized that in pediatric patients with DM1, impairment of macrocirculation could be further augmented by a coexisting autoimmune process. Therefore, we investigated the influence of AIT on large arteries in DM1 pediatric patients. Our group consisted of 19 DM1, 19 DM1 + AIT patients and 29 control subjects. The groups were comparable regarding age and gender. The DM1 and DM1 + AIT patients were matched for age at onset of DM1 and diabetes duration. Macrocirculation was described using pulsatility indices (PIs) determined for common carotid (CCA) and peripheral arteries of upper and lower limbs. CCA resistance index (RI) and ABI were also assessed. Children with DM1 + AIT had only significantly lower CCA_PI and CCA_RI in comparison with controls whereas in the absence of AIT such difference was not found. The diabetes duration and age of onset did not correlate with carotid indices. Total cholesterol level was higher both in DM1 + AIT and DM1 groups than in the control group. For low density lipoproteins cholesterol, a significant difference was found between DM1 + AIT and control groups. Age-independent impact of AIT on CCA_PI was confirmed by multivariate analysis. Common carotid pulsatility is deteriorated by autoimmune thyroiditis independently of age in children with type 1 diabetes mellitus.

Dysmenorrhea and Associated Factors among Polish Women: A Cross-Sectional Study.

Purpose: The aim of the research was to conduct an assessment of the prevalence of dysmenorrhea and associated factors among Polish women. Patients and Methods. A cross-sectional study was conducted among Polish women using an online questionnaire. The mean age of the participants was 23 ± 4 years. Out of the total of 1,317 women who took part in the study, 1,127 were included in the analysis, and 190 were excluded due to incomplete answers. The questionnaire consisted of 19 questions that were grouped into three parts. The first concerned sociodemographic data such as age, weight, education, and residence (urban or rural). The second part of the questionnaire pertained to the factors of dysmenorrhea (premenstrual syndrome, age of menarche, and family history of dysmenorrhea.). In the third part, the women were asked about their diet, alcohol intake, cigarette smoking, and physical activity. Results: Dysmenorrhea affected 94% of the interviewed women. Dysmenorrhea was most likely to occur among respondents whose mothers had a history of dysmenorrhea (p < 0.005). Significant relationship between the occurrence of dysmenorrhea among respondents and their sisters was also observed (p < 0.005). The prevalence of premenstrual syndrome (PMS) was significantly higher in women reporting dysmenorrhea (p < 0.005). Other significant factors associated with dysmenorrhea were age of menarche (p < 0.005), stress frequency (p=0.005), lack of physical activity (p=0.037), and self-esteem (p=0.042). However, in the respondents, no significant relationship was observed between dysmenorrhea and diet, smoking, body mass index, and alcohol intake. Conclusion: The study points to the fact that the problem of dysmenorrhea affects many Polish women. Women with dysmenorrhea were characterized with a family history of dysmenorrhea, occurrence of PMS, early age of menarche, stressful lifestyle, lack of physical activity, and low self-esteem. We suggest that further assessment of factors contributing for dysmenorrhea among women is necessary.

Tumor Suppressors-HTRA Proteases and Interleukin-12-in Pediatric Asthma and Allergic Rhinitis Patients.

Background and objective: Allergy belongs to a group of mast cell-related disorders and is one of the most common diseases of childhood. It was shown that asthma and allergic rhinitis diminish the risk of various cancers, including colon cancer and acute lymphoblastic leukemia. On the other hand, asthma augments the risk of lung cancer and an increased risk of breast cancer in patients with allergy has been observed. Thus, the relation between allergy and cancer is not straightforward and furthermore, its biological mechanism is unknown. The HTRA (high temperature requirement A) proteases promote apoptosis, may function as tumor suppressors and HTRA1 is known to be released by mast cells. Interleukin-12 (Il-12) is an important cytokine that induces antitumor immune responses and is produced mainly by dendritic cells that co-localize with mast cells in superficial organs. Material and methods: In the present study we have assessed with ELISA plasma levels of the HTRA proteins, Il-12, and of the anti-HTRA autoantibodies in children with allergy (40) and in age matched controls (39). Children are a special population, since they usually do not have comorbidities and take not many drugs the processes we want to observe are not influenced by many other factors. Results: We have found a significant increase of HTRA1, 2 and 3, and of the Il-12 levels in the children with atopy (asthma and allergic rhinitis) compared to controls. Conclusion: Our results suggest that the HTRA1-3 and Il-12 levels might be useful in analyzing the pro- and antioncogenic potential in young atopic patients.

Changes in Water Soluble Uremic Toxins and Urinary Acute Kidney Injury Biomarkers After 10- and 100-km Runs.

Acute kidney injury (AKI) is described as a relatively common complication of exercise. In clinical practice the diagnosis of AKI is based on serum creatinine, the level of which is dependent not only on glomerular filtration rate but also on muscle mass and injury. Therefore, the diagnosis of AKI is overestimated after physical exercise. The aim of this study was to determine changes in uremic toxins: creatinine, urea, uric acid, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), trimethylamine N-oxide (TMAO) and urinary makers of AKI: albumin, neutrophil gelatinase-associated lipocalin (uNGAL), kidney injury molecule-1 and cystatin-C (uCyst-C) after long runs. Sixteen runners, mean age 36.7 ± 8.2 years, (2 women, 14 men) participating in 10- and 100-km races were studied. Blood and urine were taken before and after the races to assess markers of AKI. A statistically significant increase in creatinine, urea, uric acid, SDMA and all studied urinary AKI markers was observed. TMAO and ADMA levels did not change. The changes in studied markers seem to be a physiological reaction, because they were observed almost in every runner. The diagnosis of kidney failure after exercise is challenging. The most valuable novel markers which can help in post-exercise AKI diagnosis are uCyst-C and uNGAL.

Urinary Kidney Injury Molecule-1 but Not Urinary Neutrophil Gelatinase Associated Lipocalin Is Increased after Short Maximal Exercise.

BACKGROUND AND AIMS: Urinary neutrophil gelatinase associated lipocalin (uNGAL) and urinary kidney injury molecule-1 (uKIM-1) are markers of acute kidney injury. The albuminuria is a well-known abnormality after physical exercise. The aim of this study was to investigate changes in uNGAL and uKIM-1 after intensive exercise causing albuminuria. METHODS: The study population consisted of 19 participants (10 males and 9 females). The mean age of participants was 35.74 years. All were fit amateur runners; the mean body mass index was 21.99 in females and 24.71 in males. The subjects underwent a graded treadmill exercise test (GXT) according to the Bruce protocol. Maximal oxygen consumption (VO2max) was measured. Immediately before and after the test urine was collected. Urinary creatinine, albumin, NGAL, and KIM-1 were measured. Albumin to creatinine (ACR), KIM-1 to creatinine (KCR), and NGAL to creatinine (NCR) ratios were calculated. RESULTS: The mean VO2max was 53.68 in females and 59.54 mL/min/kg in males. Albuminuria and ACR were significantly higher after exercise. An increase in the ACR from 8.82 to 114.35 mg/g (p < 0.01) was observed. uKIM-1 increased significantly after exercise from 849.02 to 1,243.26 pg/mL (p < 0.05). KCR increased from 1,239.1 to 1,725.9 ng/g but without statistical significance (p = 0.07). There were no statistical changes in pre- and post-run uNGAL levels. There was no correlation between post-GXT albuminuria and uKIM-1. CONCLUSIONS: uKIM-1 is a very sensitive marker of kidney dysfunction. In our study, uKIM-1 increased significantly after a very short period of exercise. It is not clear if the increase in KIM-1 is caused by post-exercise albuminuria.

No effect of yeast-like fungi on lipid metabolism and vascular endothelial growth factor level in children and adolescents with type 1 diabetes mellitus.

BACKGROUND: The objective of the research was to investigate vascular endothelial growth factor (VEGF) levels in the context of lipid metabolism and amount of yeast-like fungi colonizing the digestive tract in children and adolescents with type 1 diabetes mellitus (T1DM). METHODS: The study included 45 children with T1DM and 27 age- and sex-matched healthy control subjects. In the study sample 33 T1DM patients were administered insulin pump therapy and 12 T1DM patients were administered multiple daily injections with insulin pen devices. All T1DM patients were free of micro- and macrovascular complications. In T1DM patients and healthy controls biochemical tests were performed and measurements of yeast-like fungi colonizing the alimentary tract were conducted. Moreover all study subjects had their serum VEGF levels measured with ELISA test. RESULTS: The subgroup of children and adolescents with T1DM and yeast-like fungus colony number 10^3 CFU/g was shown statistically significantly lower HbA1c levels, and lower but not statistically significantly total cholesterol, LDL cholesterol and VEGF levels versus T1DM patients with the amount of yeast-like fungi 10^6 CFU/g. Moreover higher HDL levels were observed in this subgroup versus T1DM patients with the amount of yeast-like fungi 10^6 CFU/g although the difference was not statistically significant. CONCLUSIONS: Our study has shown no influence of yeast-like fungi on lipid metabolism and VEGF level in children and adolescents with T1DM. Comprehensive treatment of T1DM patients and intensive insulin therapy with help of personal insulin pumps can reduce or prevent the development of long-term diabetic complications. Further studies in this field are needed.

Chitinases and immunity: Ancestral molecules with new functions.

Chitinases belonging to 18 glycosyl hydrolase family is an ancient gene family that is widely expressed from prokaryotes to eukaryotes. In humans, despite the absence of endogenous chitin, a number of Chitinases and Chitinase-like Proteins (C/CLPs) have been identified. Chitinases with enzymatic activity have a chitin binding domain containing six cysteine residues responsible for their binding to chitin. In contrast, CLPs do not contain such typical chitin-binding domains, but still can bind to chitin with high affinity. Molecular phylogenetic analyses suggest that active Chitinases result from an early gene duplication event. Further duplication events, followed by mutations leading to loss of chitinase activity, allowed evolution of the chi-lectins. For the majority of the mammalian chitinases the last decades have witnessed the appearance of a substantial number of studies describing their expression differentially regulated during more specific immunologic activities. It is becoming increasingly clear that their function is not exclusive to catalyse the hydrolysis of chitin producing pathogens, but include crucial role in bacterial infections and inflammatory diseases. Here we provide an overview of all family members to shed light on the mechanisms and molecular interactions of Chitinases and CLPs in relation to immune response regulation, in order to delineate their future utilization as diagnostic and prognostic markers for numerous diseases.

Current trends in the monitoring and treatment of diabetic retinopathy in young adults.

The diagnosis and treatment of diabetic retinopathy (DR) in young adults have significantly improved in recent years. Research methods have widened significantly, for example, by introducing spectral optical tomography of the eye. Invasive diagnostics, for example, fluorescein angiography, are done less frequently. The early introduction of an insulin pump to improve the administration of insulin is likely to delay the development of diabetic retinopathy, which is particularly important for young patients with type 1 diabetes mellitus (T1DM). The first years of diabetes occurring during childhood and youth are the most appropriate to introduce proper therapeutic intervention before any irreversible changes in the eyes appear. The treatment of DR includes increased metabolic control, laserotherapy, pharmacological treatment (antiangiogenic and anti-inflammatory treatment, enzymatic vitreolysis, and intravitreal injections), and surgery. This paper summarizes the up-to-date developments in the diagnostics and treatment of DR. In the literature search, authors used online databases, PubMed, and clinitrials.gov and browsed through individual ophthalmology journals, books, and leading pharmaceutical company websites.

Biomarkers in diabetic retinopathy and the therapeutic implications.

The main problem both in type 1 (T1DM) and type 2 (T2DM) diabetes is the development of chronic vascular complications encompassing micro- as well as macrocirculation. Chronic complications lower the quality of life, lead to disability, and are the cause of premature death in DM patients. One of the chronic vascular complications is a diabetic retinopathy (DR) which leads to a complete loss of sight in DM patients. Recent trials show that the primary cause of diabetic retinopathy is retinal neovascularization caused by disequilibrium between pro- and antiangiogenic factors. Gaining knowledge of the mechanisms of action of factors influencing retinal neovascularization as well as the search for new, effective treatment methods, especially in advanced stages of DR, puts special importance on research concentrating on the implementation of biological drugs in DR therapy. At present, it is antivascular endothelial growth factor and antitumor necrosis factor that gain particular significance.

Threshold serum concentrations of tumour necrosis factor alpha (TNFα) as a potential marker of the presence of microangiopathy in children and adolescents with type 1 diabetes mellitus (T1DM).

The aim of this study was to estimate the threshold serum concentrations of advanced glycation end products (AGEs) and their soluble receptors (sRAGE) as well as tumour necrosis factor alpha (TNFα), vascular endothelial growth factor(165) (VEGF(165)) and interleukin-12 (IL-12) in predicting the occurrence of microangiopathy in children and adolescents with type 1 diabetes mellitus (T1DM). We studied 88 children and adolescents (age range: 6-20 yrs) with T1DM and 32 control subjects (age range: 7-20 yrs). All study participants had their daily urinary albumin excretion, HbA1c and serum creatinine levels measured, and underwent an eye examination and 24-h blood pressure monitoring. Moreover, serum concentrations of AGEs, sRAGE, TNFα, VEGF(165) and IL-12 were measured. In order to calculate the threshold values of the studied parameters, the Receiver Operating Characteristic (ROC) curve analysis was used. The results of our study have shown that among all the studied parameters a discriminative ability was found for TNFα, VEGF(165), duration of the disease, serum AGEs concentrations and daily urinary albumin excretion. However, the highest value of the area under the ROC curve (AUC(ROC)) in predicting the occurrence of diabetic microangiopathy was found for serum TNFα concentrations with its threshold value of 1.7 pg/ml [AUC(ROC) = 0.88 (95% CI: 0.79-0.97)]. The sensitivity and specificity for this variable was at the level of 85.7% and 94.3%, respectively. In conclusion, according to our results serum TNFα concentrations over 1.7 pg/ml may point to the presence of diabetic microangiopathy in children and adolescents T1DM.

Lower frequency of CD62L(high) and higher frequency of TNFR2(+) Tregs are associated with inflammatory conditions in type 1 diabetic patients.

Diabetes type 1 is a chronic autoimmune disease in which insulin-producing cells are gradually destroyed by autoreactive T cells. Human regulatory cells play important role in controlling autoimmunity, and their qualitative or quantitative dysfunctions may result in ineffective suppression of autoreactive T cells. CD62L is a surface molecule that plays role in homing capabilities of Tregs, and only cells with high expression of CD62L have high suppressive potential. Tregs are also characterized by the constant expression of TNFR2. The frequency of Tregs carrying TNFR2 is higher in inflammatory conditions. We investigated blood regulatory T cells with CD62L expression and regulatory T cells expressing TNFR2 in type 1 diabetic patients. We found differences in these populations when comparing to healthy individuals. We propose that these may be associated with inflammatory conditions that are present in patients with type 1 diabetes. The lower percentage of Tregs and Treg CD62L(high) may contribute to ineffective suppression of proinflammatory cytokines production during type 1 diabetes.

Decreased angiogenin concentration in vitreous and serum in proliferative diabetic retinopathy.

Diabetic retinopathy is the most common cause of vision loss in young adults in developed countries. The disease therapy with anti-vascular endothelial growth factor (VEGF) agents gives some positive results, but is associated with retinal ischemia and vasoconstriction. Therefore, determination of factors involved in the physiological and pathological angiogenesis in the diabetic eye is of great importance for understanding of the pathogenesis of diabetic retinopathy and its effective treatment. Previously, we found that diabetic patients were characterized by increased serum concentration of VEGF, but decreased levels of other proangiogenic factor-angiogenin. The involvement of VEGF in pathogenesis of diabetic retinopathy is well established, but there is lack of data regarding angiogenin in retinopathy. Therefore, in the present study we measured angiogenin concentration in vitreous and serum samples of the patients with type 1 diabetes to determine its role in diabetic retinopathy. In addition, in each time, we compared the level of angiogenin with level of VEGF as a known factor involved in the pathogenesis of the disease. Angiogenin was found to be significantly more abundant in serum than in vitreous in both diabetic groups. In addition, patients with retinopathy had twofold lower vitreous angiogenin levels than diabetic individuals without complications. On the contrary, vitreous concentration of VEGF was dramatically increased only in participants with retinopathy. Patients without diabetic complications had significantly lower VEGF levels in vitreous than in serum and were characterized by high local and systemic concentration of angiogenin. These data suggest a local imbalance between two proangiogenic factors-VEGF and angiogenin in retinopathy. Low vitreous concentration of angiogenin in diabetic patients suggests that this factor is not responsible for pathological neovascularization in diabetic eye. Further studies will elucidate if angiogenin can be used to improve the insufficient angiogenesis in diabetes and prevent retinal ischemia after retinopathy treatment with anti-VEGF agents.

Increased spontaneous production of VEGF by CD4+ T cells in type 1 diabetes.

In the present study we report that CD4(+) T cells from patients with type 1 diabetes produce significantly higher amounts of VEGF than respective cells from the healthy individuals. Among CD4(+) T cells memory subsets were the main source of VEGF. In addition, memory CD4(+) T subsets were the most numerous in patients with diabetic retinopathy (DR). DR was also characterized by significant increase of VEGF concentration in serum and culture supernatants. Hence, these data indicate that there is a sustained spontaneous production of VEGF by CD4(+) T cells in type 1 diabetes, which is additionally exacerbated in DR. In our opinion alterations in the proportions of CD4(+) T cell subsets and their VEGF production may be a useful tool for early assessment of the risk of DR onset and progression.

[Regulatory T lymphocytes expressing L-selectin in children and adolescents with type 1 diabetes mellitus]. / Limfocyty T regulatorowe z ekspresja L-selektyny u dzieci i mlodziezy z przewlekla cukrzyca typu 1.

INTRODUCTION: Quantitative and/or qualitative dysfunctions in a subset of naturally arising regulatory T lymphocytes may have impact on autoimmune disease development, including diabetes type 1. CD62L is a homing receptor that directs T lymphocytes to lymph nodes. Studies conducted on NOD mice showed that depletion of Tregs expressing CD62L results in diabetes and only CD62Lhigh Tregs are able to protect against the disease. AIM OF THE STUDY: The purpose of the paper was to analyze the regulatory T lymphocyte subset with CD62L expression in children with diabetes type 1 in peripheral blood and after in vitro stimulation with anti-TNF antibody. MATERIAL AND METHODS: 55 patients with diabetes type 1 were examined. Mean duration of the disease in the diabetic group was 6.45 (+/-3.7) years. The percentage of Tregs and Tregs carrying CD62L was evaluated using flow cytometry in peripheral blood of diabetic patients as well as after in vitro stimulation with the anti-CD3 (control), the anti-CD3 with the anti-TNF and anti-CD3 with TNF. RESULTS: Diabetic type 1 patients were characterized by a lower percentage of Tregs and Tregs expressing CD62L subset compared to their healthy counterparts. In addition, these cells reacted differently to anti-CD3 antibody stimulation than the cells from the healthy individuals. Anti-TNF induced a significant increase in the percentage of CD4+Foxp3+ and CD4+Foxp3+CD62Lhigh regulatory T cells. After treatment with TNF-alpha the frequency of these cells significantly decreased. In the diabetic group we showed a negative correlation between CD4+CD25highCD62Lhigh T lymphocytes and HbA1c [r=(-0.25)] as well as CRP level [r=(-0.38)]. CONCLUSIONS: The lower percentage of Tregs and CD62Lhigh Tregs may contribute to ineffective suppression of proinflammatory cytokine production during type 1 diabetes. We suggest the protective role of anti-TNF on Treg subset in diabetic type 1 patients and we highlight the importance of proinflammatory cytokine - TNF-alpha, which may be responsible for quantitative abnormalities in Treg subset in these patients.

The -174GG interleukin-6 genotype is protective from retinopathy and nephropathy in juvenile onset type 1 diabetes mellitus.

The aim of our study was to determine an association between the -174G>C IL-6 polymorphism (rs1800795) and occurrence of retinopathy and nephropathy in type 1 diabetes mellitus (T1DM) patients. Two hundred ten children/adolescents with long-standing T1DM (16.5 +/- 3.8 y; with diabetes duration of 8.4 +/- 3.0 y) were enrolled into the study. A group of 170 healthy young (16.9 +/- 5.2 y) sex-matched volunteers was qualified as the control. The IL-6 polymorphism was genotyped with the PCR-RFLP method. Serum and urine IL-6 concentrations were measured by the ultra-sensitive ELISA tests. The -174GG genotype was under represented in the diabetic patients compared with the controls. Patients with this genotype were free from nephropathy and retinopathy. The group of -174GG carriers was characterized by the highest urine IL-6 concentrations in relation to other genotypes. In the multivariate logistic regression analysis adjusted for age, duration of the disease, age of disease onset, HbA1c, and albumin excretion rate, the -174GG genotype was the only independent variable that significantly decreased the risk of jointly analyzed retinopathy and nephropathy [OR = 0.65; 95% CI = 0.52-0.82; p = 0.0003]. We propose that the -174GG patients are protected from late diabetic complications by different IL-6 dependent mechanisms.