Insight into the Molecular Mechanism of Diabetic Kidney Disease and the Role of Metformin in Its Pathogenesis.

Diabetic kidney disease (DKD) is one of the leading causes of death among patients diagnosed with diabetes mellitus. Despite the growing knowledge about the pathogenesis of DKD, we still do not have effective direct pharmacotherapy. Accurate blood sugar control is essential in slowing down DKD. It seems that metformin has a positive impact on kidneys and this effect is not only mediated by its hypoglycemic action, but also by direct molecular regulation of pathways involved in DKD. The molecular mechanism of DKD is complex and we can distinguish polyol, hexosamine, PKC, and AGE pathways which play key roles in the development and progression of this disease. Each of these pathways is overactivated in a hyperglycemic environment and it seems that most of them may be regulated by metformin. In this article, we summarize the knowledge about DKD pathogenesis and the potential mechanism of the nephroprotective effect of metformin. Additionally, we describe the impact of metformin on glomerular endothelial cells and podocytes, which are harmed in DKD.

A new algorithm for the management of diabetic foot ulcer: recommendations from Central and Eastern Europe.

There is wide regional variation in clinical practice and access to treatment for patients with diabetic foot ulcer (DFU) from countries in Central and Eastern Europe (CEE). A treatment algorithm that reflects current treatment practices while providing a common framework may facilitate best practice in DFU management and improve outcomes across the CEE region. Following a series of regional advisory board meetings with experts from Poland, the Czech Republic, Hungary and Croatia, we present consensus recommendations for the management of DFU and outline the key features of a unified algorithm for dissemination and use as a quick tool in clinical practice in CEE. The algorithm should be accessible to specialists as well as non-specialist clinicians and should incorporate: patient screening; checkpoints for assessment and referral; triggers of treatment change; and strategies for infection control, wound bed preparation and offloading. Among adjunctive treatments in DFU, there is a clear role for topical oxygen therapy, which can be used concomitantly with most existing treatment regimens in hard-to-heal wounds following standard of care. Countries from CEE face a number of challenges in the management of DFU. It is hoped that such an algorithm will help standardise the approach to DFU management and overcome some of these challenges. Ultimately, a regionwide treatment algorithm in CEE has the potential to improve clinical outcomes and save limbs.

Allogenic Adipose-Derived Stem Cells in Diabetic Foot Ulcer Treatment: Clinical Effectiveness, Safety, Survival in the Wound Site, and Proteomic Impact.

Although encouraging results of adipose-derived stem cell (ADSC) use in wound healing are available, the mechanism of action has been studied mainly in vitro and in animals. This work aimed to examine the safety and efficacy of allogenic ADSCs in human diabetic foot ulcer treatment, in combination with the analyses of the wound. Equal groups of 23 participants each received fibrin gel with ADSCs or fibrin gel alone. The clinical effects were assessed at four time points: days 7, 14, 21 and 49. Material collected during debridement from a subset of each group was analyzed for the presence of ADSC donor DNA and proteomic changes. The reduction in wound size was greater at all subsequent visits, significantly on day 21 and 49, and the time to 50% reduction in the wound size was significantly shorter in patients who received ADSCs. Complete healing was achieved at the end of the study in seven patients treated with ADSCs vs. one treated without ADSCs. One week after ADSC application, 34 proteins significantly differentiated the material from both groups, seven of which, i.e., GAPDH, CAT, ACTN1, KRT1, KRT9, SCL4A1, and TPI, positively correlated with the healing rate. We detected ADSC donor DNA up to 21 days after administration. We confirmed ADSC-related improvement in wound healing that correlated with the molecular background, which provides insights into the role of ADSCs in wound healing-a step toward the development of cell-based therapies.

[Association of antithyroid peroxidase antibodies with cardiac function in euthyroid women with type 1 diabetes mellitus - assessment with two-dimensional speckle­tracking echocardiography].

INTRODUCTION: The presence of diabetes is associated with loss of cardioprotection in premenopausal women; however, the mechanisms involved remain unknown. Autoimmune factors are suspected to play a role in cardiovascular complications, especially in type 1 diabetes (T1DM). The aim of this pilot study was to explore whether antithyroid peroxidase antibody (aTPO) as a marker of increased immune activity is related to cardiac dysfunction in young, asymptomatic women with T1DM. MATERIAL AND METHODS: Eighty-eight euthyroid women (59 with T1DM and 29 healthy controls) underwent physical examination, laboratory tests, thyroid ultrasound, and two-dimensional speckle-tracking echocardiography. According to the antiperoxidase antibodies (aTPO) titre, the T1DM women were divided into an aTPO positive (T1DM aTPO+) (n = 34) and an aTPO negative (T1DM aTPO-) (n = 25) group. The relationship between thyroid autoimmunity parameters and echocardiographic parameters was evaluated. RESULTS: Global longitudinal strain (GLS) was slightly reduced in the T1DM aTPO+ group compared to T1DM aTPO- and significantly compared to controls (p = 0.051 and p = 0.015, respectively). Although, the lower values of longitudinal strain of left ventricular were found in the majority of segments in the T1DM aTPO+ group in comparison to T1DM aTPO- and controls, significant differences were only found in the two-chamber view (specifically in the anterior segments) between the T1DM aTPO+ and T1DM aTPO- groups (p = 0.030) and in the four-chamber view (specifically in the anterolateral segments) between the T1DM aTPO+ group and controls (p = 0.021). Echocardiographic parameters of diastolic and systolic function of both ventricles were significantly correlated with parameters of thyroid autoimmunity. A logistic regression analysis showed that Hashimoto's thyroiditis (HT) duration [odds ratio (OR): 0.997, 95% confidence interval (CI): 0.995-0.999, p = 0.008), the dose of levothyroxine (OR: 0.814, 95% CI: 0.689-0.960, p = 0.013), and reduced echogenicity on thyroid ultrasound (OR: 0.309, 95% CI: 0.120-0.793, p = 0.013) had a significant influence on reduced GLS. CONCLUSIONS: Our results suggest that coexistence of aTPO with T1DM was associated with poorer myocardial function, particularly in the anterior and anterolateral segments, which may be related to an autoimmune factor. The impaired function of these segments is probably the first sign of myocardial systolic dysfunction in women with T1DM, which needs to be confirmed in further studies.

The Problem of Wound Healing in Diabetes-From Molecular Pathways to the Design of an Animal Model.

Chronic wounds are becoming an increasingly common clinical problem due to an aging population and an increased incidence of diabetes, atherosclerosis, and venous insufficiency, which are the conditions that impair and delay the healing process. Patients with diabetes constitute a group of subjects in whom the healing process is particularly prolonged regardless of its initial etiology. Circulatory dysfunction, both at the microvascular and macrovascular levels, is a leading factor in delaying or precluding wound healing in diabetes. The prolonged period of wound healing increases the risk of complications such as the development of infection, including sepsis and even amputation. Currently, many substances applied topically or systemically are supposed to accelerate the process of wound regeneration and finally wound closure. The role of clinical trials and preclinical studies, including research based on animal models, is to create safe medicinal products and ensure the fastest possible healing. To achieve this goal and minimize the wide-ranging burdens associated with conducting clinical trials, a correct animal model is needed to replicate the wound conditions in patients with diabetes as closely as possible. The aim of the paper is to summarize the most important molecular pathways which are impaired in the hyperglycemic state in the context of designing an animal model of diabetic chronic wounds. The authors focus on research optimization, including economic aspects and model reproducibility, as well as the ethical dimension of minimizing the suffering of research subjects according to the 3 Rs principle (Replacement, Reduction, Refinement).

[Is thyroid autoimmunity associated with subclinical atherosclerosis in young women with type 1 diabetes mellitus?]

INTRODUCTION: It has been hypothesized that autoimmunity may contribute to cardiovascular complications and may be an important trigger for processes leading to atherosclerosis, especially in type 1 diabetes mellitus (T1DM). This pilot study aimed to answer the question of whether markers of thyroid autoimmunity are associated with increased carotid intima-media thickness (cIMT) in young, asymptomatic T1DM women. MATERIAL AND METHODS: The study population consisted of 102 women, including 72 with T1DM and 30 healthy controls. All patients had thyroid hormones within the normal range. According to the antiperoxidase antibodies (aTPO) titre, the T1DM women were divided into an aTPO-positive (T1DM aTPO+) (n = 41) and an aTPO-negative (T1DM aTPO-) (n = 31) group. In all patients, aTPO, thyroglobulin antibody (aTG) titres, thyroid-stimulating hormone (TSH), free thyroxine (FT3), free triiodothyronine (FT4), lipid parameters, glycated haemoglobin, thyroid ultrasonography, and cIMT assessment were evaluated. The association of cIMT with different risk factors related to thyroid autoimmunity was determined. RESULTS: Carotid intima-media thickness was significantly greater in T1DM aTPO+ females (0.66 ± 0.10 mm) than in T1DM aTPO- (0.59 ± 0.11 mm) and healthy controls (0.58 ± 0.10 mm) (p = 0.007, p = 0.001, respectively). In all women cIMT was significantly, positively correlated with aTPO (p = 0.005, r = 0.273), Hashimoto's thyroiditis (HT) duration (p = 0.00015, r = 0.367), levothyroxine dose per week (p = 0.006, r = 0.269), and ultrasound features of HT (p = 0.004, r = 0.281) and inversely with fT3 concentration (p = 0.014, r = -0.243) and FT3/FT4 ratio (p = 0.042, r = -0.201). A logistic regression analysis showed that HT duration (OR: 1.102, 95% CI: 1.008-1.206, p = 0.032) and a positive history family of HT (OR: 3.909, 95%CI: 1.014-15.071, p = 0.045) were risk factors for increased cIMT. However, multivariate regression analysis showed that the studied parameters related to thyroid autoimmunity are not independent risk factors for increased cIMT. CONCLUSIONS: We expanded the data on cIMT in young women with T1DM and showed that thyroid autoimmunity, and in particular the duration of exposure to anti-thyroid antibodies, despite adequate levothyroxine substitution, is associated with subclinical atherosclerosis in young women with T1DM. However, thyroid-related parameters are not independent risk factors for increased cIMT in euthyroid women.

Breakdown of Diabetic Foot Ulcer Care during the First Year of the Pandemic in Poland: A Retrospective National Cohort Study.

The COVID-19 pandemic revealed a breakdown of the system of DFU patient care. This retrospective national cohort study analyses the epidemiological status of DFU patients in relation to urgent and elective hospitalizations, amputation rates, and deaths in Poland from 2017 to 2019, and during 2020 when the COVID-19 pandemic began. The data were obtained from national medical records gathered by the National Health Fund (NHF). Discharge diagnoses were categorized according to ICD-10 and ICD-9 codes. Analysis of the data showed a statistically significant decrease in elective hospital admissions (from 29.6% to 26.3%, p = 0.001). There was a decrease in the percentage of hospitalizations related to limb-salvage procedures (from 79.4% to 71.3%, p = 0.001). The opposite tendency was observed among urgent hospital admissions (from 67.0% to 73.2%, p = 0.01), which was related to a significant increase in the number of minor amputations (from 3146 to 4269, p = 0.017). This rise was in parallel with the increase in the percentage of patients who died during hospitalization due to DFU (from 3.9% to 4.8%, p = 0.03). The number of deaths has not changed significantly (from 590.7 to 668.0, p = 0.26). The results of the conducted analyses confirm the negative tendencies in the medical care of patients with DFU during the first year of the pandemic in Poland. Changes in therapy schemes and stronger patient support following this period are necessary to avoid further complications in patients with DFU.

Embedding Wound Hygiene into a proactive wound healing strategy.

FOREWORD. WOUND HYGIENE: THE NEXT STAGE: Since a panel published the first consensus document on Wound Hygiene in March 2020, there has been a flurry of activity in support of this newly established concept in proactive wound healing.1 The document concluded that all wounds, particularly hard-to-heal ones, will benefit from Wound Hygiene, which should be initiated at the first referral, following a full holistic assessment to identify the wound aetiology and comorbidities, and then implemented at every dressing change until full healing occurs.1 The consensus has since been bolstered by educational webinars; competency-based skills training and support; development of international Wound Hygiene ambassadors; a survey of 1478 respondents, published in July 2021;2 and a case study supplement, published in January 2022, featuring a range of wound types, anatomies and underlying conditions on the improvements in wound-healing progress that can be achieved.3 Wound Hygiene has gained its own identity and is now a term in and of itself, that encompasses a 4-step protocol of care. It is an antibiofilm approach that is increasingly being used across wound care. The results of the survey2 were particularly encouraging for seeing how far Wound Hygiene has come, and how quickly: More than half (57.4%) had heard of the concept of Wound Hygiene Of those, 75.3% have implemented Wound Hygiene Overall, following implementation of Wound Hygiene, 80.3% of respondents reported improved healing rates.2 However, the top three barriers identified by the survey-lack of confidence, competence and research data-show that there is more to be done to support Wound Hygiene in practice.2 As a result, a consensus panel of international key opinion leaders convened virtually in the summer of 2021 to discuss what has been done so far, the outputs of the survey, and ideas for addressing the unmet needs identified by the results. The result is this publication, which represents an addendum to the initial consensus document, broadening support for implementation of Wound Hygiene. This document will reflect on the reasons Wound Hygiene has been successful in its first two years of implementation, reiterating its DNA: Do not wait to treat hard-to-heal wounds Use a simple 4-step approach Enable all healthcare professionals to implement and use Wound Hygiene. The document will also discuss the evolution of the Wound Hygiene concept, focusing on how and when to implement Wound Hygiene on all tissue types of hard-to-heal wounds, and proposing what these are. The panel has expanded the framework in which Wound Hygiene is used, with the ultimate objective of introducing the concept of 'embedding Wound Hygiene intro a proactive wound healing strategy.' Key inefficiencies are often observed along the journeys of people living with hard-to-heal wounds. The limited number of specialised healthcare professionals and the resulting delays in reaching them may increase the likelihood of a hard-to-heal wound developing. In a world where so much is happening so quickly that we may, at times, feel powerless to drive change, the panel wants to provide further guidance to propel the use of Wound Hygiene. The concept of Wound Hygiene is resonating, and the panel wants you to know that in whatever region you work, in whatever area of clinical practice, you are enabled to make this change. Wielding the 4-step Wound Hygiene protocol consistently is a key action every healthcare professional in every care setting can take to tackle the global wound care crisis. Wound Hygiene has taken off-now, where do we want to land? In a place where Wound Hygiene is practised on all wounds, at every stage, until healing. The panel once again recognises that the community of global healthcare providers should consider their local standards and guidelines when applying the recommendations of this document. To this end, the panel has created a flexible 3-phase framework that situates Wound Hygiene as integral to proactive wound healing. The panel hopes you will continue to implement Wound Hygiene and see the benefits it can bring to people living with wounds, as well as those who care for them.

Implementation of Wound Hygiene in clinical practice: early use of an antibiofilm strategy promotes positive patient outcomes.

Non-healing wounds are devastating for patients, potentially causing long-term morbidity and an impaired quality of life. They also incur a huge health economic burden for health-care services. Understanding of the causes of non-healing wounds has increased significantly. While the need to address the underlying aetiology has always been acknowledged, the role of biofilm in delaying or preventing healing is now accepted. There is a consensus on the need to debride the wound to remove biofilm and then prevent its reformation, to kickstart healing. The potential benefits of incorporating an antibiofilm component within the wound bed preparation framework are clear. However, such a strategy needs to be flexible enough so that it can be implemented by all practitioners, regardless of their expertise or specialty. Wound Hygiene does this. This supplement describes the Wound Hygiene protocol, and includes a selection of case studies on different wound types, demonstrating its ease of use and effectiveness in clinical practice.

Sirtuin 1, Visfatin and IL-27 Serum Levels of Type 1 Diabetic Females in Relation to Cardiovascular Parameters and Autoimmune Thyroid Disease.

The loss of cardioprotection observed in premenopausal, diabetic women may result from the interplay between epigenetic, metabolic, and immunological factors. The aim of this study was to evaluate the concentration of sirtuin 1, visfatin, and IL-27 in relation to cardiovascular parameters and Hashimoto's disease (HD) in young, asymptomatic women with type 1 diabetes mellitus (T1DM). Thyroid ultrasound, carotid intima-media thickness (cIMT) measurement, electrocardiography, and echocardiography were performed in 50 euthyroid females with T1DM (28 with HD and 22 without concomitant diseases) and 30 controls. The concentrations of serum sirtuin 1, visfatin and IL-27 were assessed using ELISA. The T1DM and HD group had higher cIMT (p = 0.018) and lower left ventricular global longitudinal strain (p = 0.025) compared to females with T1DM exclusively. In women with a double diagnosis, the sirtuin 1 and IL-27 concentrations were non-significantly higher than in other groups and significantly positively correlated with each other (r = 0.445, p = 0.018) and thyroid volume (r = 0.511, p = 0.005; r = 0.482, p = 0.009, respectively) and negatively correlated with relative wall thickness (r = -0.451, p = 0.016; r = -0.387, p = 0.041, respectively). These relationships were not observed in the control group nor for the visfatin concentration. These results suggest that sirtuin 1 and IL-27 contribute to the pathogenesis of early cardiac dysfunction in women with T1DM and HD.

The Use of Glucocorticoids for Better Control of Diabetes Mellitus: The Paradox of Sclerosing Mesenteritis (The Rare Could Become Common).

BACKGROUND Sclerosing mesenteritis is a rare disease characterized by chronic inflammation of mesenteric adipose tissue. To our knowledge, this is the first case report that presents the effects of glucocorticoid therapy on metabolic control in diabetes mellitus, aggravated by sclerosing mesenteritis. We want to show the significance of this rare disease, which could be underestimated as a cause of decompensation of diabetes mellitus. CASE REPORT A 57-year-old man with diabetes type 2 was admitted to the hospital to obtain better metabolic control of this disease. In addition, he reported persistent pain in the left side of his abdomen. Sclerosing mesenteritis was diagnosed based on the CT and MRI images. Prednisone was administered. The treatment resulted in better glycemic control and abdominal pain reduction. On follow-up after 1 year, the patient reported a decrease in the abdominal pain and an MRI showed a significant reduction of abnormalities in the mesentery. CONCLUSIONS It is known that glucocorticoids exacerbate hyperglycemia, particularly in patients with diabetes mellitus. However, we noticed contrary effects in the case of our patient. We suggest that the inflammatory process occurring in sclerosing mesenteritis was one of the main causes of metabolic decompensation in our patient. The effect of reduction of inflammation with glucocorticoids was stronger than the hyperglycemic effect of this treatment. That is why, in the presence of this autoimmune disease, the use of glucocorticoids can paradoxically lead to better glycemic control.

Insulin, but Not Metformin, Supports Wound Healing Process in Rats with Streptozotocin-Induced Diabetes.

PURPOSE: Optimal glycemic control is crucial for proper wound healing in patients with diabetes. However, it is not clear whether other antidiabetic drugs support wound healing in mechanisms different from the normalization of blood glucose control. We assessed the effect of insulin and metformin administration on the wound healing process in rats with streptozotocin-induced diabetes. METHODS: The study was conducted on 200 male Wistar rats with streptozotocin-induced diabetes. In the last phase of the study, 45 rats, with the most stable glucose levels in the range of 350-500 mg/dL, were divided into three groups: group I received human non-protamine insulin subcutaneously (5 IU/kg body mass) once a day, group II received metformin intragastrically (500 mg/kg b.m.), and group III (control) was given saline subcutaneously. After 14 days of antidiabetic treatment, a 2 cm × 2 cm thin layer of skin was cut from each rat's dorsum and a 4 cm disk with a hole in its center was sewn in to stabilize the skin and standardize the healing process. The wound healing process was followed up for 9 days, with assessment every 3 days. Biopsy samples were subjected to hematoxylin and eosin staining and immunohistochemical assays. RESULTS: Analysis of variance revealed significant influence of treatment type (insulin, control, or metformin) on the relative change in wound surface area. The wound healing process in rats treated with insulin was more effective than in the metformin and control groups. Wound tissue samples taken from the insulin-treated animals presented significantly lower levels of inflammatory infiltration. Immunohistochemical assessment showed the greatest density of centers of proliferation Ki-67 in insulin-treated animals. CONCLUSION: These results suggest that an insulin-based treatment is more beneficial than metformin, in terms of accelerating the wound healing process in an animal model of streptozocin-induced diabetes.

The MDR1/ABCB1 gene rs 1045642 polymorphism in colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) is one of the most frequently diagnosed tumors in Western countries. CRC is a heterogeneous group of tumors with regards to its molecular pathogenesis and genetic factors. Both genetic variations and anthropometric factors may affect morbidity in CRC patients. The aim of this study was to assess the impact of multidrug resistance 1/ATP-binding cassette sub-family B member 1 gene (MDR1/ABCB1) polymorphism rs1045642 and general anthropometric factors on the CRC risk. MATERIAL AND METHODS: The study included 250 patients who underwent colonoscopy and polypectomy between 2006 and 2013 in a single endoscopy unit in Warsaw, Poland. RESULTS: The CRC was diagnosed in 50 individuals, and 200 patients were included in the control group. Cases and controls were matched for mean age and sex (p > 0.05). Factors that were found to significantly increase the risk of CRC were ulcerative colitis (8/35 in the CRC group vs. 8/181 in the control group; p = 0.001), family history of CRC (11/33 vs. 26/172; p = 0.05), and diabetes mellitus (12/34 vs. 28/170; p = 0.04). Allele T of the rs 1045642 polymorphism was more frequently present in CRC cases (in both a co-dominant and recessive model) and in males (in a co-dominant model), although these associations were not statistically significant (p > 0.05). CONCLUSIONS: The MDR1/ABCB1 gene polymorphism rs 1045642 may be involved in the pathogenesis of CRC and this relationship may be sex-specific for males. However, further population studies are necessary to assess this relationship.

Selected RANKL/RANK/OPG system genetic variants in diabetic foot patients.

PURPOSE: Diabetic foot is a complication of long-lasting diabetes mellitus affecting up to 15% of patients, both in type 1 and type 2 diabetes. Osteoprotegerin is involved in osteogenesis and calcification. The aim of the study was to assess the role of selected osteoprotegerin gene variants in diabetes patients with diabetic foot. METHODS: The study involved 300 patients with diabetes and diabetic foot and 968 healthy controls. The study group was formed by 243 patients with diabetic foot of neuropathic origin, 102 with diabetic foot of neuroischemic origin and 77 with Charcot neuroarthropathy. RESULTS: Compared to controls, rs1872426 and rs1485286 showed correlation with diabetic foot in diabetes subjects. Significant associations between rs2073618, rs1872426, rs7464496 and rs1485286 in men were reported. The aforementioned correlations were also present in type 2 diabetes patient subgroup. Variant rs1485286 was associated to diabetic foot of neuropathic origin. Sex-specificity for females was present for rs6993813 in patients with diabetic foot of neuropathic origin and type 1 diabetes. Variants rs1872426, rs2073617 and rs1485286 were correlated with CN. We found that age, body weight, body mass index, waist circumference, hip circumference and waist-hip ratio were among the basic risk factors of diabetic foot. CONCLUSIONS: The following variants TNFRSF11B (rs2073618, rs2073617, rs1872426, rs1032128, rs7464496, rs11573829 and rs1485286), COLEC10 (rs6993813, rs3134069) and TNFSF11 (rs9533156) present differences in allele frequencies in diabetic foot patients and show correlation with gender, diabetes type and diabetic foot etiology.

Genetic predictors associated with diabetic retinopathy in patients with diabetic foot.

INTRODUCTION    Early detection of diabetic retinopathy (DR) is crucial for preventing irreversible blindness. Recent studies identified some of the genetic factors involved in the pathology of DR, although their precise underlying mechanisms remain unclear. OBJECTIVES    This pilot study aimed to determine genetic predictors of DR among patients with type 2 diabetes (T2D) and diabetic foot (DF) based on pathogenetic pathways. PATIENTS AND METHODS    The study included 114 patients with T2D and DF (64 with DR, 50 without DR). Genetic analysis was performed for each patient and the following alterations were analyzed: rs759853 (AKR1B1), rs1800469 (TGFB1), rs2073618 and rs3134069 (TNFRSF11B), rs6330 and rs11466112 (NGF), rs1801133 (MTHFR), rs8192678 (PPARGC1A), rs1799983 (NOS3), rs1553005 (CALCA), and rs121917832 (CDKN1B). RESULTS    Correlations with DR were identified for the following single nucleotide variants (SNVs): rs759853, rs2073618, and rs3134069. Carriers of the G allele of the rs759853 variant had a higher risk of DR in the dominant model (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.15-7.81; P = 0.02). We analyzed 2 SNVs of the osteoprotegerin gene (rs3134069 and rs2073618), and found that the A allele of the rs3134069 variant decreased the risk of DR in both the recessive and additive models (OR, 3.33; 95% CI, 1.07-10.3; P = 0.04). Conversely, there were fewer carriers of the C allele of the rs2073618 variant in patients with DR in the dominant model (OR, 0.28; 95% CI, 0.09-0.92; P = 0.04). CONCLUSIONS    The results of our study suggest that the SNVs rs759853, rs3134069, and rs2073618 may be involved in the development of DR in patients with T2D and DF.

Role of the rs2274907 allelic variant of the ITLN1 gene in patients with diabetic foot.

INTRODUCTION Diabetic foot (DF) is a serious complication of diabetes mellitus (DM) that occurs due to neuropathy or atherosclerosis of the lower limbs. Omentin (encoded by the ITLN1 gene) has been implicated as a protective factor in vascular complications of diabetes, likely due to its endothelial vasodilator activity and its anti­inflammatory actions. However, susceptibility to DF with respect to the allelic variants of the ITLN1 gene has not been studied so far. OBJECTIVES This study aimed to evaluate the association between the rs2274907 allelic variant of the ITLN1 gene and the occurrence of DF in patients with type 2 diabetes mellitus (T2DM).  PATIENTS AND METHODS The study included 670 individuals: 204 with T2DM and DF (DF group), 299 with T2DM without DF (T2DM group), and 167 healthy controls.  RESULTS Ischemic heart disease, retinopathy, nephropathy, neuropathy, obesity, hyperlipidemia, and active smoking were more frequent in the DF group than in the T2DM group. Allele A of the rs2274907 variant was observed more frequently in the DF group compared with healthy controls in an additive model (odds ratio [OR] = 0.7, P = 0.034). This effect was also sex­specific for males in both the additive and recessive models (OR = 0.6, P = 0.015 and OR = 0.52, P = 0.0017, respectively). However, no differences in the distribution of alleles was observed between the DF and T2DM groups. CONCLUSIONS The rs2274907 variant of the ITLN1 gene is associated with increased prevalence of DF.

Health related quality of life in patients with diabetic foot ulceration - translation and Polish adaptation of Diabetic Foot Ulcer Scale short form.

OBJECTIVES: Diabetic foot ulcer (DFU) is a common complication of diabetes and not only an important factor of mortality among patients with diabetes but also decreases the quality of life. The short form of Diabetic Foot Ulcer Scale (DFS-SF) provides comprehensive measurement of the impact of diabetic foot ulcers on patients' health related quality of life (HRQoL). The purpose of this study was to translate DFS-SF into Polish and evaluate its psychometric performance in patients with diabetic foot ulcers. METHODS: The DFS-SF translation process was performed in line with Principles of Good Practice for the Translation and Cultural Adaptation Process for patient reported outcome measures (PROMs) developed by ISPOR TCA group. Assessment of the reliability and validity of Polish DFS-SF was performed in native Polish patients with current DFU. RESULTS: The DFS-SF validation study involved 212 patients diagnosed with DFU, with 4.4 years of DFU duration on average. The average ulcer size was 5.5 sq. cm, and generally only one limb was affected. Men (72%) and type 2 diabetes patients (86%) prevailed, with 17.8 years representing the mean time since diagnosis. The mean population age was 62.5 years. The internal consistency of all scales of the Polish DFS-SF was high (Cronbach's alpha ranged from 0.82 to 0.93). Item convergent and discriminant validity was satisfactory (median corrected item-scale correlation ranged from 0.61 to 0.81). The Polish DFS-SF demonstrated good construct validity when correlated with the SF-36v2 and showed better psychometric performance than SF-36v2. CONCLUSIONS: The newly translated Polish DFS-SF may be used to assess the impact of DFU on HRQoL in Polish patients.

Radionuclide imaging and therapy in a patient with coexistent diabetic foot syndrome and psoriatic arthritis.

We report a case of 67-year-old man suffering from psoriatic arthritis, type 2 diabetes and diabetic foot syndrome. The patient presented symptoms of inflammation of the right ankle joint. Scintigraphic imaging with radiolabeled white blood cells was performed to differentiate whether the inflammation was related to psoriatic arthritis or diabetic foot syndrome. After revealing that, the inflammatory process was restricted only to the articular space of subtalar joint, the patient was diagnosed with exacerbation of psoriatic arthritis and qualified for radionuclide synovectomy. In patients with coexistent diabetic foot syndrome and inflammatory arthritis of the foot it is of vital importance to accurately differentiate these two conditions. We conclude that this can be potentially achieved with radiolabeled white blood cells scintigraphic imaging.