The Republic of Srpska (RS), as a part of the Western Balkans (WB) region, has a higher diabetes prevalence than the EU. This study aims to assess the cost-effectiveness of early treatment of high-risk patients with pre-diabetes and undiagnosed diabetes in our setting. We designed a Markov chain Monte Carlo (MCMC) model which reflects the current International Diabetes Federation (IDF) three-step plan for the prevention of T2DM in those at increased risk. The model captures the evolution of the disease in FINDRISC high-risk patients from normal glucose tolerance (NGT) to impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) and then to T2DM and its complications. We developed two MCMC models, in order to follow the progression of the disease in high-risk cases, ie, when early treatment is undertaken or when it is not undertaken. The health costs and quality adjusted life years (QALY) were discounted at an annual rate of 3%. The key model parameters were varied in one-way and probabilistic sensitivity analysis. Early treatment resulted in increased life expectancy, postponement of the onset of diabetes and increased QALY for all patients. The discounted incremental cost-effectiveness-ratios (ICER) in NGT, IFG, IGT, and T2DM patients were -289.9, 9724.03, -1478.59 and 4084.67 €. In high-risk IGT patients, ICER was the most favorable, being both a cost saving and QALY gaining, with the consistent results confirmed by the sensitivity analysis. The results recommend the acceptance of a new health policy of identifying IGT patients with the use of FINDRISC questionnaire and plasma glucose measurements; providing them with a lifestyle change program; and implementing intensive diabetes treatment, as their disease progresses. Our results are especially significant for the Western Balkan countries, since this was the first cost-effectiveness study of T2DM prevention in this region.

ObjectivesTotal contact casting (TCC) is used to promote wound closure in diabetic foot ulcers (DFUs); however, this technique is underused today. This study aims to further evaluate the efficacy of TCC in a large cohort, including patients with peripheral artery disease (PAD).MethodsThis was a retrospective analysis of patients with DFUs who underwent TCC from 2017 to 2021. PAD was defined as absence of pedal pulse or ABI <0.9. Demographic data, DFU characteristics, and peripheral arterial intervention were evaluated. Outcomes included complete healing, healing time, and rate of major amputation. Subgroup analysis was performed on patients undergoing peripheral intervention.Results152 patients underwent TCC. Mean age was 58.8 ± 12.1 years, 79.6% were male, and 26.3% had PAD. Mean DFU size was 8.27 ± 9.9 cm2, with mean depth 0.61 ± 0.49 cm. 112 patients had palpable pedal pulses on the affected extremity (73.7%). Average ABI was 1.12 ± 0.22 (n = 90). Complete healing was observed in 122 (80.3%) patients, with average healing time of 81.5 ± 57.1 days. Thirteen (8.6%) patients eventually required amputation (3 major). When compared to patients with healed DFUs, those without healing had higher rates of amputation (39.1% vs 3.1%, P < .001), intervention (43.4% vs 17.8%, P = .006), and noncompliance (39.1% vs 20.2%, P = .046). Thirty-three patients underwent revascularization, undergoing angioplasty (81.8%), atherectomy (63.6%), stent (15.2%), and/or bypass (9.1%). Interventions were performed in aortoiliac (3.0%), femoropopliteal (45.5%), and tibial (72.7%) segments. Twenty-two (66.7%) patients who underwent revascularization completely healed. Patients requiring revascularization were more likely to have previous intervention (57.6% vs 13.4%, P < .0001) and incompressible vessels (36.4% vs 7.6%, P < .00001), with lower ABIs (0.94 ± 0.25 vs 1.17 ± 0.18, P = .0008) compared to patients without intervention.ConclusionsTCC remains an effective option for treatment of DFUs, as most were completely healed. Patients with PAD may benefit from TCC and revascularization, however, healing rates are lower in this cohort, necessitating the need for close observation.

Diabetic macroangiopathy, a prevalent and severe complication of diabetes mellitus, significantly contributes to the increased morbidity and mortality rates among affected individuals. This complex disorder involves multifaceted molecular mechanisms that lead to the dysfunction and damage of large blood vessels, including atherosclerosis (AS) and peripheral arterial disease. Understanding the intricate pathways underlying the development and progression of diabetic macroangiopathy is crucial for the development of effective therapeutic interventions. This review aims to shed light on the molecular mechanism implicated in the pathogenesis of diabetic macroangiopathy. We delve into the intricate interplay of chronic inflammation, oxidative stress, endothelial dysfunction, and dysregulated angiogenesis, all of which contribute to the vascular complications observed in this disorder. By exploring the molecular mechanism involved in the disease we provide insight into potential therapeutic targets and strategies. Moreover, we discuss the current therapeutic approaches used for treating diabetic macroangiopathy, including glycemic control, lipid-lowering agents, and vascular interventions.

Diabetic patients in Saudi Arabia are often underinformed about proper diabetic foot care. This study aims to determine the knowledge, attitude, and practice of the risk factors of diabetic foot ulcers among diabetic patients in the Jeddah region of Saudi Arabia.

A cross-sectional study was done on 210 diabetic patients attending the international diabetic center in Jeddah, Saudi Arabia, during the study period. A validated questionnaire was used to collect data about participants' demographics and knowledge, attitudes, and practices of diabetic foot care.

Of the participants, 77 (36.7%) were aged 51-60 years; 161 (76.7%) were male; 153 (72.9%) had a university education; and approximately 138 (65%) had type 2 DM. A majority, 190 (90.5%), acknowledged that DM patients might have reduced foot sensation; 204 (97.1%) agreed that diabetics could develop gangrene; 188 (89.5%) concurred that poor foot sensation increases the risk of foot ulcers; and 193 (91.9%) agreed that poor blood flow to the feet heightens this risk. Among them, 152 (72.4%) demonstrated good knowledge about foot care and the risk of foot ulcers; eight (3.8%) exhibited a positive attitude; and 95 (45.2%) showed a good level of practice. Good knowledge was significantly higher among married patients, and good practice was notably higher among older patients (>50 years). A significant positive correlation was found between knowledge scores and both attitude and practice scores.

The study revealed adequate knowledge and practice of foot care and the risk of foot ulcers among diabetic patients. However, a high percentage of negative attitudes toward these issues were observed.

Peripheral artery disease (PAD) serves as a risk factor for diabetic foot ulcers (DFUs). PAD pathology involves atherosclerosis and impaired immunity. Non-classical monocytes are believed to have an anti-inflammatory role. 1,25-Dihydroxy vitamin D (vitamin D3 ) is claimed to have immune-modulating and lipid-regulating roles. Vitamin D receptor is expressed on monocytes. We aimed to investigate if circulating non-classical monocytes and vitamin D3 were implicated in DFUs associated with PAD.

There were two groups of DFU patients: group 1 (n = 40) included patients with first-degree DFUs not associated with PAD, and group 2 (n = 50) included patients with DFU with PAD. The monocyte phenotypes were detected using flow cytometry. Vitamin D3 was assessed by enzyme-linked immunosorbent assay.

DFU patients with PAD showed a significant reduction in the frequency of non-classical monocytes and vitamin D3 levels, when compared with DFU patients without PAD. The percentage of non-classical monocytes positively correlated with vitamin D3 level (r = 0.4, P < 0.01) and high-density lipoprotein (r = 0.5, P < 0.001), whereas it was negatively correlated with cholesterol (r = -0.5, P < 0.001). Vitamin D3 was negatively correlated with triglyceride/high-density lipoprotein (r = -0.4, P < 0.01). Regression analysis showed that a high vitamin D3 serum level was a protective factor against PAD occurrence.

Non-classical monocytes frequency and vitamin D3 levels were significantly reduced in DFU patients with PAD. Non-classical monocytes frequency was associated with vitamin D3 in DFUs patients, and both parameters were linked to lipid profile. Vitamin D3 upregulation was a risk-reducing factor for PAD occurrence.

Peripheral artery disease (PAD) and diabetic peripheral neuropathy (DPN) are two of the leading causes of non-traumatic amputation worldwide with tremendous negative effects on the quality of life, psychosocial well-being of persons with diabetes mellitus; and a great burden on health care expenditure. It is therefore imperative, to identify the common and contrast determinants of PAD and DPN in order to ease adoption of common and specific strategies for their early prevention.

This was a multi-center cross-sectional study which involved the consecutive enrolment of one thousand and forty (1040) participants following consent and waiver of ethical approval. Relevant medical history, anthropometric measurements, other clinical examinations including measurement of ankle-brachial index (ABI) and neurological examinations were undertaken. IBM SPSS version 23 was used for statistical analysis and logistic regression was used to assess for the common and contrast determinants of PAD and DPN. Significance level used was p < 0.05.

Multiple stepwise logistic regression showed that common predictors of PAD vs DPN respectively include age, odds ratio (OR) 1.51 vs 1.99, 95 % confidence interval (CI) 1.18-2.34 vs 1.35-2.54, p = 0.033 vs 0.003; duration of DM (OR 1.51 vs 2.01, CI 1.23-1.85 vs 1.00-3.02, p = <.001 vs 0.032); central obesity (OR 9.77 vs 1.12, CI 5.07-18.82 vs 1.08-3.25, p = <.001 vs 0.047); poor SBP control (OR 2.47 vs 1.78, CI 1.26-4.87 vs 1.18-3.31, p = .016 vs 0.001); poor DBP control (OR 2.45 vs 1.45, CI 1.24-4.84 vs 1.13-2.59, p = .010 vs 0.006); poor 2HrPP control (OR 3.43 vs 2.83, CI 1.79-6.56 vs 1.31-4.17, p = <.001 vs 0.001); poor HbA1c control (OR 2.59 vs 2.31, CI 1.50-5.71 vs 1.47-3.69, p = <.001 vs 0.004). Common negative predictors or probable protective factors of PAD and DPN respectively include statins (OR 3.01 vs 2.21, CI 1.99-9.19 vs 1.45-3.26, p = .023 vs 0.004); and antiplatelets (OR 7.14 vs 2.46, CI 3.03-15.61 vs 1.09-5.53, p = .008 vs 0.030). However, only DPN was significantly predicted by female gender (OR 1.94, CI 1.39-2.25, p = 0.023), height (OR 2.02, CI 1.85-2.20, p = 0.001), generalized obesity (OR 2.02, CI 1.58-2.79, p = 0.002), and poor FPG control (OR 2.43, CI 1.50-4.10, p = 0.004) CONCLUSION: Common determinants of PAD and DPN included age, duration of DM, central obesity, and poor control of SBP, DBP, and 2HrPP control. Additionally, the use of antiplatelets and statins use were common inverse determinants of PAD and DPN which means they may help protect against PAD and DPN. However, only DPN was significantly predicted by female gender, height, generalized obesity, and poor control of FPG.

Diabetes foot ulcers (DFUs) are a type of foot infection, ulcer, and/or deep tissue destruction caused by neuropathy and vascular disease in the distal extremities of diabetic patients. Its pathogenesis and its microenvironment are not entirely understood.

Initially, the GSE165816 data set from the GEO database was utilized for single cell analysis to reveal the microenvironment and functional status of DFUs. The GSE199939 RNA-seq data set was utilized for external validation. On the basis of the logistic regression machine learning algorithm (OCLR), pseudo time series analysis, dryness index analysis, and drug target gene analysis were then performed. By constructing drug-gene and gene-gene networks, we can locate the most recent DFUs treatments. Finally, immunofluorescence technology was used to detect the cell-related markers of the DFUs microenvironment, and qPCR was used to detect the expression of drug targets in DFUs.

Firstly, we used the Cell Maker database to obtain information about human cells and related gene markers, and manually reviewed a total of 45 kinds of cells and maker information that may appear in the DFUs microenvironment, which were divided into 17 cell clusters after annotation. Subsequently, we counted the proportions of DM and DFUs in different types of cells, and the results showed that the proportions of macrophages, white blood cells, and monocytes were higher in patients with DFUs, while the proportions of pluripotent stem cells and stromal cells were higher in patients with DM. The Pseudo-time series analysis of cells in DFUs showed that the differentiation pathways of immune cells, mesenchymal cells and stem cells were similar in the three states, while the other cells were distributed in different stages. At the level of a single cell, the scores of both multipotential stem cells and hematopoietic stem cells were significantly lower in DFU healing and non-healing than in DM. Additionally, the highly expressed genes in DFU were chosen as drug targets. We identified seven potential target genes and discovered twenty drugs with high significance. Finally, the colocalization relationship between CD19, ITGAM, and HLA-DR expression in monocytes and macrophages of DFU skin tissue and healthy subjects was analyzed by laser confocal microscopy with the immunofluorescence triple labeling method. The results showed that the expressions of CD19, ITGAM, and HLA-DR in the skin of DFUs were significantly higher than those in the skin of healthy subjects, and the co-localization relationship was significant in DFUs.

This study can serve as a resource for the treatment of DFUs.

Background and Objectives: Diabetic foot (DF) disease is one of the myriad complications of diabetes. Positive outcomes are expected through a multidisciplinary approach as provided by primary care providers (PCPs). This study aimed to assess the knowledge of DF and attitude of physicians in primary healthcare settings toward DF diagnosis and prevention in Saudi Arabia. Materials and Methods: This observational cross-sectional study used a self-administered questionnaire that was completed by family medicine consultants, residents, and general practitioners working in primary care settings in Riyadh. Results: Of the 152 physicians who completed the survey, (43.4%) completed more than 10 h of diabetes continuing medical education (CME) over the past three years. Most (96.1%) PCPs educate patients about foot self-inspection, and only (64.5%) perform foot inspection at every visit in high-risk diabetic foot patients. PCP knowledge about diagnosing and managing diabetic foot infection was suboptimal. Only 53.9% of participants reported performing a probe-to-bone in DF patients with open wounds. Conclusions: We identified knowledge and action gaps among PCPs. Physicians had acceptable knowledge about preventive measures. However, deficits were found regarding diagnosing and management of DF infections. We recommend addressing these knowledge gaps by incorporating DF lectures and workshops within family medicine conferences and residency programs.