The aim of this study was to compare the serum levels of the anti-angiogenic factor endostatin (S-endostatin) as a potential marker of vasculogenesis after autologous cell therapy (ACT) versus ...percutaneous transluminal angioplasty (PTA) in diabetic patients with critical limb ischemia (CLI). A total of 25 diabetic patients with CLI treated in our foot clinic during the period 2008–2014 with ACT generating potential vasculogenesis were consecutively included in the study; 14 diabetic patients with CLI who underwent PTA during the same period were included in a control group in which no vasculogenesis had occurred. S-endostatin was measured before revascularization and at 1, 3, and 6 months after the procedure. The effect of ACT and PTA on tissue ischemia was confirmed by transcutaneous oxygen pressure (TcPO2) measurement at the same intervals. While S-endostatin levels increased significantly at 1 and 3 months after ACT (both P < 0.001), no significant change of S-endostatin after PTA was observed. Elevation of S-endostatin levels significantly correlated with an increase in TcPO2 at 1 month after ACT (r = 0.557; P < 0.001). Our study showed that endostatin might be a potential marker of vasculogenesis because of its significant increase after ACT in diabetic patients with CLI in contrast to those undergoing PTA. This increase may be a sign of a protective feedback mechanism of this anti-angiogenic factor.
Infections caused by Pseudomonas sp are difficult to resolve by antibiotics (ATBs) and local therapy. The aim of our pilot study was to assess the effect of different local agents—particularly ...acidifying solutions—on the healing of diabetic foot ulcers (DFUs), eradication of pathogens, and economic costs related to DFU therapy. In this case study, we monitored 32 DFU patients infected by Pseudomonas species. Patients were divided into 2 groups according to the local therapy provided: group 1 (n = 15)—modern local treatment; group 2 (n = 17)—acidifying antiseptic solutions. The study groups differed only with regard to ATB usage prior to enrolment in the study (P = .004), but did not differ with regard to age, diabetes control, peripheral arterial disease, or microcirculation status. During the follow-up period, DFUs healed in 20% of cases in group 1, but there were no cases of healing in group 2 (NS). The length of ATB therapy, the number of new osteomyelitis, lower limb amputations, and the changes of DFUs status/proportions did not differ significantly between study groups. Pseudomonas was eradicated in 67% of cases in group 1 and in 65% of cases in group 2. The local treatment given to group 2 patients was associated with lower costs (P < .0001). Conclusion. Acidifying agents had the same effect as modern healing agents on wound healing, the number of amputations, and the eradication of Pseudomonas. Moreover, therapy performed using acidifying solutions proved in our pilot study markedly cheaper.
Objective. Off-loading is one of the crucial components of diabetic foot (DF) therapy. However, there remains a paucity of studies on the most suitable off-loading for DF patients under postoperative ...care. The aim of our study was to evaluate the effect of different protective off-loading devices on healing and postoperative complications in DF patients following limb preservation surgery. Methods. This observational study comprised 127 DF patients. All enrolled patients had undergone foot surgery and were off-loaded empirically as follows: wheelchair+removable contact splint (RCS) (group R: 29.2%), wheelchair only (group W: 48%), and wheelchair+removable prefabricated device (group WP: 22.8%). We compared the primary (e.g., the number of healed patients, healing time, and duration of antibiotic (ATB) therapy) and secondary outcomes (e.g., number of reamputations and number and duration of rehospitalizations) with regard to the operation regions across all study groups. Results. The lowest number of postoperative complications (number of reamputations: p=0.028; rehospitalizations: p=0.0085; and major amputations: p=0.02) was in group R compared to groups W and WP. There was a strong trend toward a higher percentage of healed patients (78.4% vs. 55.7% and 65.5%; p=0.068) over a shorter duration (13.7 vs. 16.5 and 20.3 weeks; p=0.055) in the R group, as well. Furthermore, our subanalysis revealed better primary outcomes in patients operated in the midfoot and better secondary outcomes in patients after forefoot surgery—odds ratios favouring the R group included healing at 2.5 (95% CI, 1.04-6.15; p=0.037), reamputations at 0.32 (95% CI, 0.12-0.84; p=0.018), and rehospitalizations at 0.22 (95% CI, 0.08-0.58; p=0.0013). Conclusions. This observational study suggests that removable contact splint combined with a wheelchair is better than a wheelchair with or without removable off-loading device for accelerating wound healing after surgical procedures; it also minimises overall postoperative complications, reducing the number of reamputations by up to 77% and the number of rehospitalizations by up to 66%.
The new NICE guidelines recommend that all adults with type 1 diabetes (T1D) should have access to either Continuous Glucose Monitoring (CGM) orIntermittently Scanned CGM (isCGM). The latest ...treatment modality for T1D is represented by the hybrid closed-loop systems (HCL), which consist of an insulin pump (CSII), a CGM and a smart algorithm. The aim of the study was to evaluate the effect of methods used for glucose monitoring and insulin delivery on diabetes control in patients with T1D treated during 2019-2022. We analyzed 2132 patients with T1D (48.9% males, mean age 43, 6 years) registered in our Diabetes Centre, 1165 (54.6 %) with multiple daily injections and 967 (45.4 %) using CSII, including 354 (36.6%) using HCL in 2022. A significant increase in the proportion of patients using CGM or isCGM in comparison to Blood Glucose Monitoring (BGM) during the years 2019-2022 was noted (14%/21%/65% in 2019 vs 43%/30%/27% in 2022; p<0.001). There was a significant improvement in diabetes control in CGM and isCGM users between 2019-2022, but not in the BGM group (CGM: 2019 7.9±1.2 % vs. 2022 7.5±1.1 %; p<0.0001; isCGM: 8.1±1.4 % vs. 7.8±1.3 %; p<0.001; BGM: 7.7±1.5 % vs. 7.6±1.5 %; NS). Patients using CGM had better diabetes control than patients with isCGM in 2022 (p<0.001). HbA1c significantly decreased during the past 2 years in all patients using CSII (2020: 8±1.2 % vs. 2022 7.7±1.1 %, p<0.001). In 2022, patients using HCL reached better glycemic control than only CSII users (HCL 7.5±1.2 % vs. CSII 7.8±1.1 %; p˂0.05). Patients using HCL had a significantly more pronounced decrease of glycated hemoglobin between 2020 to 2022 as compared to CSII users (2022: 7.5±1.2 % vs. 2020: 8±1.3 %; p<0.001). Our study demonstrated that more than 2/3 of patients meet the NICE guidelines for glucose monitoring in 2022, and this ratio is improving every year. CGM, isCGM and CSII treatment, especially with HCL are associated with better diabetes control.
Disclosure
R.Bem: None. D.Vávra: None. K.Sochorova: Advisory Panel; Ypsomed AG, Consultant; Medtronic. M.Müllerová: None. M.Haluzik: Advisory Panel; Novo Nordisk, Lilly Diabetes, Boehringer-Ingelheim, Research Support; Sanofi, Speaker's Bureau; Abbott, AstraZeneca.
Funding
National Institute for Research of Metabolic and Cardiovascular Diseases (EXCELES LX22NPO5104)
The release of proangiogenic cytokines into the circulation after stem cell (SC) therapy and compensatory increase of angiogenesis inhibitors may reflect local vasculogenesis but also can increase ...the risk of side effects. The aim of our study was to evaluate serum levels of angiogenic cytokines with regard to the assessment of local and systemic vasculogenesis in diabetic patients with no-option critical limb ischemia (NO-CLI). Twenty-five diabetic patients with NO-CLI treated with SCs isolated from bone marrow or stimulated peripheral blood were included in the study. Serum levels of proangiogenic cytokines (VEGF, bFGF, Ang-1, PDGF-AA, and PDGF-BB) and an antiangiogenic cytokine (endostatin) were assessed 6 months after cell treatment, compared to baseline values, and correlated with the number of injected CD34+ cells. The clinical effect of SC therapy (assessed by changes in TcPO2) and potential systemic vasculogenesis (assessed by eye fundus examination) were evaluated after 6 months. Serum levels of angiogenic inhibitor endostatin increased significantly after 1 and 3 months (p = 0.0003), but no significant increase in serum levels of proangiogenic cytokines was observed. A significant correlation between number of injected CD34+ cells and serum levels of endostatin was observed (r = 0.41, p < 0.05); however, proangiogenic cytokines did not correlate with CD34+ cells. No correlation between increase in TcPO2 after treatment and serum levels of any of the angiogenic cytokines were seen, and no signs of systemic vasculogenesis in the retina were observed after 6 months. Despite the significant increase in the levels of the angiogenic inhibitor endostatin following SC treatment, there was no risk of systemic vasculogenesis after SC therapy as documented by serum levels of proangiogenic cytokines or changes in the retina.
Introduction & Objective: Obesity is becoming a frequent comorbidity not only in patients with type 2 but also with type 1 diabetes mellitus (T1D). The aim of this study was to compare glucose ...control and prevalence of diabetes-associated complications in patients with T1D according to the presence of overweight or obesity. Methods: Using data from the diabetes registry of a tertiary center, patients with T1D were stratified according to BMI into normal weight (BMI<25 kg/m2: n=831, age 40 (29-52) years (yr), T1D duration 20 (11-29) yr), overweight (BMI 25-30 kg/m2, n=741, age 46 (35-60) yr, T1D duration 23 (15-33) yr) and obese (BMI ≥30 kg/m2, n=366, age 48 (39-59) yr, T1D duration 24 (16-34) yr) and compared based on glucose control parameters (HbA1c, continuous glucose sensor metrics) and prevalence of diabetic complications and metabolic comorbidities. Results: Compared with overweight and obese, patients with normal weight had a significantly lower HbA1c (56 (49-64) vs. 57 (51-65) vs. 60 (52-67), mmol/l, p<0.001), time above target range of 3.9-10 mmol/l(25 (16-39) vs. 28 (18-41) vs 31 (17-43)%, p=0.004) and average sensor glycemia (8.2 (7.4-9.3) vs. 8.4 (7.6-9.6) vs 8.7 (7.7-9.7) mmol/l, p<0.001). No significant difference was found in time in range or glycemic variability, while time below range was slightly lower in patients with obesity (3 (1-7) vs. 3 (1-7) vs. 3 (1-6), %, p=0.024). Higher BMI was associated with increased prevalence of arterial hypertension (32.7 vs. 46.4 vs. 65.6%, p=<0.001), dyslipidemia (38.4 vs. 54.1 vs. 70.7%, p=<0.001) and cardiovascular complications (6.7 vs. 10.1 vs. 12.4%, p= 0.004), as well as diabetic retinopathy (35.8 vs. 45.2 vs. 53.0%, p <0.001) and diabetic foot disease (4.6 vs. 5.5 vs. 9.7%, p= 0.003). Conclusion: Our data indicate that an increase in BMI in patients with T1D is associated with worse glucose control and higher rate of diabetes complications and metabolic comorbidities. Disclosure L. Horváth: None. M. Mraz: None. D. Vávra: None. K. Sochorova: Consultant; Medtronic, Ypsomed AG. R. Bem: Speaker's Bureau; Abbott, A.import (Dexcom, Tandem), Medtronic. Research Support; Ministry of Health - Czech republic. Speaker's Bureau; Novo Nordisk. J. Klouckova: None. M. Haluzik: Advisory Panel; Sanofi, Novo Nordisk, Eli Lilly and Company, AstraZeneca, Bayer Inc., Johnson & Johnson Medical Devices Companies. Consultant; Merck & Co., Inc., Sanofi, Novo Nordisk, Eli Lilly and Company, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Johnson & Johnson Medical Devices Companies, Novatin. Research Support; Sanofi. Speaker's Bureau; Sanofi, Novo Nordisk. Funding Supported by the project CarDia (Programme EXCELES, Project No. LX22NPO5104); Funded by the European Union; Next Generation EU and Funded by Ministry of Health, Czech Republic; Conceptual Development of Research Organization ("Institute for Clinical and Experimental Medicine – IKEM, IN 00023001").
OBJECTIVE: To assess the new quantitative bone scan parameters as markers of Charcot neuroosteoarthropathy (CNO) activity. RESEARCH DESIGN AND METHODS: Forty-two patients with acute (n = 21) and ...nonacute (n = 21) CNO underwent quantitative bone scanning. Patients with acute CNO were followed for 3-12 months and bone scans were repeated after treatment. New quantitative parameters were assessed and compared with markers of bone turnover and with skin temperature difference (STD). RESULTS: Significant correlations between quantitative bone scan parameters and bone turnover markers were observed (all P < 0.05). These parameters decreased after treatment of CNO, and its reduction to the baseline value correlated with differences of bone turnover markers and STD (all P < 0.05). CONCLUSIONS: Our study suggests that bone scanning can be used not only for diagnosis of CNO but also for monitoring disease activity by quantitative bone scan parameters.
The aim of our study was to analyse immune abnormalities in patients with chronic infected diabetic foot ulcers (DFUs) especially those infected by resistant microorganisms. Methods. 68 patients ...treated in our foot clinic for infected chronic DFUs with 34 matched diabetic controls were studied. Patients with infected DFUs were subdivided into two subgroups according to the antibiotic sensitivity of causal pathogen: subgroup S infected by sensitive (n=50) and subgroup R by resistant pathogens (n=18). Selected immunological markers were compared between the study groups and subgroups. Results. Patients with infected chronic DFUs had, in comparison with diabetic controls, significantly reduced percentages (p<0.01) and total numbers of lymphocytes (p<0.001) involving B lymphocytes (p<0.01), CD4+ (p<0.01), and CD8+ T cells (p<0.01) and their naive and memory effector cells. Higher levels of IgG (p<0.05) including IgG1 (p<0.001) and IgG3 (p<0.05) were found in patients with DFUs compared to diabetic controls. Serum levels of immunoglobulin subclasses IgG2 and IgG3 correlated negatively with metabolic control (p<0.05). A trend towards an increased frequency of IgG2 deficiency was found in patients with DFUs compared to diabetic controls (22% versus 15%; NS). Subgroup R revealed lower levels of immunoglobulins, especially of IgG4 (p<0.01) in contrast to patients infected by sensitive bacteria. The innate immunity did not differ significantly between the study groups. Conclusion. Our study showed changes mainly in the adaptive immune system represented by low levels of lymphocyte subpopulations and their memory effector cells, and also changes in humoral immunity in patients with DFUs, even those infected by resistant pathogens, in comparison with diabetic controls.
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