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).

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.

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.

Obesity is strongly associated with an increased risk of heart failure. Recent studies indicate that epicardial adipose tissue plays a critical role in the development of obesity-related cardiomyopathy. This distinct visceral fat depot, located between the myocardium and the visceral pericardium, is involved in direct cross-talk with the adjacent myocardium, influencing both its structural integrity and electrophysiological function. This review aims to provide an up-to-date overview of the morphological, metabolic, immunological, and functional alterations of this adipose compartment in the context of obesity, and to explore its contribution to the pathogenesis of heart failure. Moreover, the article synthesizes current evidence on the potential cardioprotective effects of emerging anti-obesity pharmacotherapies—particularly GLP-1 and dual GLP-1/GIP receptor agonists—on metabolic pathways associated with epicardial fat that are implicated in obesity-induced cardiomyopathy. Further clinical trials are required to clarify the impact of these therapies on the course and prognosis of heart failure, as well as on the epidemiology and societal burden of the disease.

Background: Diabetic foot is a serious condition in patients with a long lasting diabetes mellitus. Diabetic foot treated improperly may lead not only to delayed ulceration healing, generalized inflammation, unnecessary surgical intervention, but also to the lower limb amputation. The aim of this study was to compare diabetic foot risk factors in population with type 2 diabetes and risk factors for diabetes in healthy subjects.Methods: The study included 900 subjects: 145 with diabetic foot, 293 with type 2 diabetes without diabetic foot and 462 healthy controls matched in terms of mean age, gender structure and cardiovascular diseases absence. Study was conducted in Gastroenterology and Metabolic Diseases Department, Medical University of Warsaw, Poland. In statistical analysis a logistic regression model,UMann-Whitney’s andt-Student test were used.Results: The binomial logit models analysis showed that the risk of diabetic foot in patients with type 2 diabetes was decreased by patient’s age (odds ratio [OR] = 0.94; 95% confidence interval [CI]: 0.92-0.96; p = 0.00001) and hyperlipidaemia (OR = 0.54; 95% CI: 0.36-0.81; p = 0.01). In contrast, male gender (OR = 2.83; 95% CI: 1.86-4.28; p = 0.00001) diabetes duration (OR = 1.04; 95% CI: 1.03-1.06; p = 0.0003), weight (OR = 1.04; 95% CI: 1.03-1.06; p = 0.00001), height (OR = 1.08; 95% CI: 1.05-1.11; p = 0.00001) and waist circumference (OR = 1.028; 95% CI: 1.007-1.050; p = 0.006) increase the risk of diabetic foot. The onset of type 2 diabetes in healthy subjects was increased by weight (OR = 1.035; 95% CI: 1.024-1.046; p = 0.00001), WC (OR = 1.075; 95% CI: 1.055-1.096; p = 00001), hip circumference (OR = 1.03; 95% CI: 1.01-1.05; p = 0.005), overweight defined with body mass index (BMI) above 24,9 kg/m²(OR = 2.49; 95% CI: 1.77-3.51; p = 0.00001) and hyperlipidaemia (OR = 3.53; 95% CI: 2.57-4.84; p = 0.00001).Conclusions: Risk factors for Type 2 diabetes and diabetic foot are only partially common. Study proved that patients who are prone to developing diabetic foot experience different risk factors than patients who are at risk of diabetes. Identification of relationship between diabetic foot and diabetes risk factors in appropriate groups may help clinicians to focus on certain factors in diabetic foot prevention.