Selected microRNA Expression and Protein Regulator Secretion by Adipose Tissue-Derived Mesenchymal Stem Cells and Metabolic Syndrome.

The role of adipose mesenchymal stem cells (Ad-MSCs) in metabolic syndrome remains unclear. We aimed to assess the expression of selected microRNAs in Ad-MSCs of non-diabetic adults in relation to Ad-MSC secretion of protein regulators and basic metabolic parameters. Ten obese, eight overweight, and five normal weight subjects were enrolled: 19 females and 4 males; aged 43.0 ± 8.9 years. Ad-MSCs were harvested from abdominal subcutaneous fat. Ad-MSC cellular expressions of four microRNAs (2-ΔCt values) and concentrations of IL-6, IL-10, VEGF, and IGF-1 in the Ad-MSC-conditioned medium were assessed. The expressions of miR-21, miR-122, or miR-192 did not correlate with clinical parameters (age, sex, BMI, visceral fat, HOMA-IR, fasting glycemia, HbA1c, serum lipids, CRP, and eGFR). Conversely, the expression of miR-155 was lowest in obese subjects (3.69 ± 2.67 × 10-3 vs. 7.07 ± 4.42 × 10-3 in overweight and 10.25 ± 7.05 × 10-3 in normal weight ones, p = 0.04). The expression of miR-155 correlated inversely with BMI (sex-adjusted r = -0.64; p < 0.01), visceral adiposity (r = -0.49; p = 0.03), and serum CRP (r = -0.63; p < 0.01), whereas it correlated positively with serum HDL cholesterol (r = 0.51; p = 0.02). Moreover, miR-155 synthesis was associated marginally negatively with Ad-MSC secretion of IGF-1 (r = -0.42; p = 0.05), and positively with that of IL-10 (r = 0.40; p = 0.06). Ad-MSC expression of miR-155 appears blunted in visceral obesity, which correlates with Ad-MSC IGF-1 hypersecretion and IL-10 hyposecretion, systemic microinflammation, and HDL dyslipidemia. Ad-MSC studies in metabolic syndrome should focus on miR-155.

The prognostic impact of insulin resistance surrogates in patients with acute myocardial infarction with and without type 2 diabetes.

BACKGROUND: Cardiovascular disease is the major cause of morbidity and mortality, particularly in type 2 diabetes mellitus (T2DM). Novel markers of insulin resistance and progression of atherosclerosis include the triglycerides and glucose index (TyG index), the triglycerides and body mass index (Tyg-BMI) and the metabolic score for insulin resistance (METS-IR). Establishing independent risk factors for in-hospital death and major adverse cardiac and cerebrovascular events (MACCE) in patients with myocardial infarction (MI) remains critical. The aim of the study was to assess the risk of in-hospital death and MACCE within 12 months after ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) in patients with and without T2DM based on TyG index, Tyg-BMI and METS-IR. METHODS: Retrospective analysis included 1706 patients with STEMI and NSTEMI hospitalized between 2013 and 2021. We analyzed prognostic value of TyG index, Tyg-BMI and METS-IR for in-hospital death and MACCE as its components (death from any cause, MI, stroke, revascularization) within 12 months after STEMI or NSTEMI in patients with and without T2DM. RESULTS: Of 1706 patients, 58 in-hospital deaths were reported (29 patients [4.3%] in the group with T2DM and 29 patients [2.8%] in the group without T2DM; p = 0.1). MACCE occurred in 18.9% of the total study population (25.8% in the group with T2DM and 14.4% in the group without T2DM; p < 0.001). TyG index, Tyg-BMI and METS-IR were significantly higher in the group of patients with T2DM compared to those without T2DM (p < 0.001). Long-term MACCE were more prevalent in patients with T2DM (p < 0.001). The area under the ROC curve (AUC-ROC) for the prediction of in-hospital death and the TyG index was 0.69 (p < 0.001). The ROC curve for predicting in-hospital death based on METS-IR was 0.682 (p < 0.001). The AUC-ROC values for MACCE prediction based on the TyG index and METS-IR were 0.582 (p < 0.001) and 0.57 (p < 0.001), respectively. CONCLUSIONS: TyG index was an independent risk factor for in-hospital death in patients with STEMI or NSTEMI. TyG index, TyG-BMI and METS-IR were not independent risk factors for MACCE at 12 month follow-up. TyG index and METS-IR have low predictive value in predicting MACCE within 12 months after STEMI and NSTEMI.

Use of metformin in patients who require intravascular administration of a contrast agent.

Metformin is a drug that has been widely used around the world for many years. Due to its properties, metformin is used in the treatment of carbohydrate disorders (in type 2 diabetes, prediabetes) and in insulin resistance syndromes (including polycystic ovary syndrome). Many patients using metformin, due to complications of carbohydrate metabolism disorders, including cardiovascular complications or other accompanying diseases, require cardiological or radiological diagnostics related to the administration of a contrast agent. The aim of this study is to summarize the recommendations regarding the use of metformin before procedures involving the use of contrast agents and to share our own experience in this area, based on observations of a large group of patients with cardiological diseases hospitalized at the Silesian Centre for Heart Diseases in Zabrze.

Cementless femoral neck endoprosthesis SPIRON in men in aspects of clinical status and quality of life in an average 7-year follow-up.

BACKGROUND: We report the clinical evaluation, quality of life and pain assessment in patients who had a femoral neck SPIRON endoprosthesis. METHODS: The study group consisted of 27 men in whom 35 femoral neck endoprosthesis were implanted (8 on the left side, 12 on the right side and 7 bilateral) due to idiopathic osteoarthritis of the hip (20 patients) or avascular femoral osteonecrosis (7 patients) in a mean 7-year follow-up. RESULTS: The median pre-operative Harris Hip score (HHS) was 35.5 and post-operative 98.5 (p < 0.001). The median WOMAC HIP score was pre-operatively 57 and post-operatively 0 (p < 0.001). The median SF-12 score was pre-operatively 4 and post-operatively 33 (p < 0.001). The median pain assessment in VAS scale was 7 pre-operatively and 0 post-operatively (p < 0.001). CONCLUSIONS: The results of all examined patients have changed significantly in every category showing that SPIRON endoprosthesis improved their quality of life and statistically reduced pain ailments. Moreover we have proved that higher BMI (> 30) is associated with worse operation outcomes.

Antioxidant System and Ions Concentrations After Femoral Neck and Resurfacing Hip Arthroplasty.

BACKGROUND Oxidative stress is a disruption of the pro-oxidative-antioxidant balance, caused by excessive production or ineffective removal of reactive oxygen species. MATERIAL AND METHODS The study included 42 male patients aged 38 to 69 years. The first group consisted of 21 men with osteoarthritis after primary hip arthroplasty using the Smith & Nephew Birmingham Hip Resurfacing implant. The second group included 21 men after hip arthroplasty using the femoral neck SPIRON K-implant. In both groups, concentrations of ions, the antioxidant system in the blood, and parameters of oxidative stress were evaluated twice. Clinical assessment using the Western Ontario and McMaster Universities Osteoarthritis Index, Harris Hip Score, and Short Form (12) Health Survey (SF-12) scales was performed. RESULTS Concentrations of metal ions in the blood and the level of oxidative stress were significantly higher in the resurfacing group than in the femoral neck arthroplasty group. The response of the antioxidant system was significantly greater in the femoral neck arthroplasty group. During clinical evaluation, groups did not show significant differences, with the exception of greater shortening of the operated limb and a lower score in the mental-sphere of the SF-12 scale in the resurfacing arthroplasty group. CONCLUSIONS Resurfacing hip arthroplasty increased oxidative stress, increased the concentration of metal ions, and did not affect alignment of the abbreviation of the operated limb. A significant improvement in the quality of life of patients in the mental sphere according to the SF-12 occurred after the application of resurfacing arthroplasty, in the first month after the procedure.

Are there really specific risk factors for heterotopic ossifications? A case report of 'non-risk factor' after total hip replacement.

Femoral neck fractures are one of the most common fractures in the elderly population. Due to frequent complications of the fixation of these fractures, patients are more and more often eligible for hip replacement surgery. One of the most frequently mentioned postoperative complication is the formation of heterotopic ossification. This case report describes as a 70-year-old male patient that presented with an old hip fracture accompanied by a mild craniocerebral trauma. The patient underwent total cementless hip arthroplasty followed by rehabilitation. At 8 months after surgery, the patient was diagnosed with Brooker IV° heterotopic ossification in the area of the operated hip joint. Due to the persistent pain and complete loss of mobility in the operated joint, computed tomography imaging was performed and the patient was recommended for a revision surgery. The procedure was performed 14 months after the original surgical treatment, resulting in a significant improvement in the range of motion and reduction of pain.

ESCRT-I fuels lysosomal degradation to restrict TFEB/TFE3 signaling via the Rag-mTORC1 pathway.

Within the endolysosomal pathway in mammalian cells, ESCRT complexes facilitate degradation of proteins residing in endosomal membranes. Here, we show that mammalian ESCRT-I restricts the size of lysosomes and promotes degradation of proteins from lysosomal membranes, including MCOLN1, a Ca2+ channel protein. The altered lysosome morphology upon ESCRT-I depletion coincided with elevated expression of genes annotated to biogenesis of lysosomes due to prolonged activation of TFEB/TFE3 transcription factors. Lack of ESCRT-I also induced transcription of cholesterol biosynthesis genes, in response to inefficient delivery of cholesterol from endolysosomal compartments. Among factors that could possibly activate TFEB/TFE3 signaling upon ESCRT-I deficiency, we excluded lysosomal cholesterol accumulation and Ca2+-mediated dephosphorylation of TFEB/TFE3. However, we discovered that this activation occurs due to the inhibition of Rag GTPase-dependent mTORC1 pathway that specifically reduced phosphorylation of TFEB at S112. Constitutive activation of the Rag GTPase complex in cells lacking ESCRT-I restored S112 phosphorylation and prevented TFEB/TFE3 activation. Our results indicate that ESCRT-I deficiency evokes a homeostatic response to counteract lysosomal nutrient starvation, that is, improper supply of nutrients derived from lysosomal degradation.

The influence of resistance training on muscle strength, irisin concentration, and metabolic parameters in type 1 diabetic patients.

INTRODUCTION: Resistance effort has a beneficial effect on muscle mass, body composition, bone density, and cardiac parameters. It is also a modulator of the inflammatory reaction. The aim of the study was to assess the impact of 3 months of resistance training on muscle strength, irisin levels, and metabolic parameters in patients with long-term type 1 diabetes. MATERIAL AND METHODS: Eleven type 1 male diabetic patients with low levels of physical activity were recruited, with mean age 38 ± 6 years, body mass index (BMI) 28.4 ± 2.6 kg/m², and diabetes duration 23 ± 7 years. All subjects participated in 60-minute resistance training sessions twice a week, for three months. At baseline and after 3 months in all patients, maximal muscle strength level, serum irisin concentration, metabolic control parameters, and anthropometric measures were assessed. RESULTS: After 3 months there was a statistically significant increase of maximal muscle strength in comparison to baseline. There was no significant change in serum irisin concentration, HbA1c, or other assessed parameters. CONCLUSION: A 3-month resistance training programme in patients with long-term type 1 diabetes and low level of physical activity significantly affects their maximum strength level. This indicates that people with diabetes are more adaptive to additional loads, which allows them to increase their load faster.

Carbohydrate Metabolism Disorders in Relation to Cardiac Allograft Vasculopathy (CAV) Intensification in Heart Transplant Patients According to the Grading Scheme Developed by the International Society for Heart and Lung Transplantation (ISHLT).

BACKGROUND Cardiac allograft vasculopathy (CAV) is the leading complication limiting the long-term survival of heart transplant (HTx) patients. The goal of this study was to assess carbohydrate metabolism disorders in relation to CAV intensification in heart transplant patients according to the ISHLT grading scheme. MATERIAL AND METHODS This retrospective study involved 477 HTx recipients undergoing angiographic observation for up to 20 years after transplantation. The patients were assigned to 4 groups on the basis of their carbohydrate metabolism status: without diabetes, with type 2 diabetes prior to HTx, with new-onset diabetes after transplantation, and with transient hyperglycemia. RESULTS In the study, 62.7% (n=299) of the patients manifested no diabetes after HTx, while 14.3% (n=68) of patients had type II diabetes prior to HTx and 18.4% (n=88) developed new-onset diabetes after transplantation. In total, 1442 coronary angiograms were taken in the specified control periods. CAV incidence increased over time after transplantation, reaching 11% after 1 year, 57% after 10 years, and 50% after 20 years. The longest survival time was observed for patients who had developed type II diabetes prior to HTx, but the difference was not statistically significant. The multivariate analysis failed to identify an independent risk factor for developing cardiac allograft vasculopathy. CONCLUSIONS Despite the relatively high rates of CAV and carbohydrate metabolism disorders in heart transplant patients, our retrospective analysis revealed no statistically significant link between these 2 diseases.

Identification of Silent Myocardial Ischemia in Patients with Long-Term Type 1 and Type 2 Diabetes.

(1) Background: This study aimed to analyze epidemiological data to identify risk factors for silent myocardial ischemia in patients with long-term type 1 and type 2 diabetes. (2) Methods: An analysis was performed on 104 patients with long-term type 1 and type 2 diabetes who had not previously been diagnosed with cardiovascular disease. During hospitalization, patients were subjected to a standard ECG exercise test on a treadmill. If the test could not be performed or the result was uncertain, a pharmacological exercise test with dobutamine was performed. In the case of a positive exercise ECG test or a positive dobutamine test, the patient underwent coronary angiography. (3) Results: Atherosclerotic lesions were found in 24 patients. Patients with silent ischemia were significantly older and had a lower mean left ventricular ejection fraction and a higher incidence of carotid atherosclerosis. The presence of microvascular complications did not increase the risk of silent ischemia. (4) Conclusions: Silent heart ischemia is more common in type 2 than type 1 diabetes. Predisposing factors include older age, coexistence of carotid atherosclerosis, lower left ventricular ejection fraction, and smoking in patients with type 1 diabetes. Concomitant microvascular complications are not a risk factor.

Revision arthroplasty using a custom-made implant in the course of acetabular loosening of the J&J DePuy ASR replacement system - case report.

RATIONALE: Resurfacing arthroplasty using the J&J DePuy ASR system was withdrawn from surgical treatment due to the necessity of frequent revision procedures after its application. There have been many studies concerning treatment of acetabular bone loss using different operating techniques. However, we felt that data of custom - made implant usage in such cases is highly insufficient, and there is lack of evidence on its application in treatment of loosening of the previous implant. The aim of the study was to evaluate the effectiveness of surgical treatment with a custom-made implant in a patient with extensive acetabular bone loss after aseptic loosening of the acetabular component of the J&J DePuy ASR surface prosthesis in the early period of observation. PATIENT CONCERNS: A 74-year-old patient was taken to the Orthopaedic Trauma Emergency Room due to increasing pain in the right hip for about 3 months. Nine years earlier he underwent resurfacing arthroplasty of the right hip using the J&J DePuy ASR method. DIAGNOSES: The imaging diagnostics (X-ray, computed tomography, ultrasound) revealed the presence of a pseudotumor and lysis around the acetabular implant, which caused a fracture in the acetabulum. INTERVENTIONS: Revision arthroplasty of the right hip joint was performed with the removal of the ASR implant. During the procedure extensive bone defects were visualized, preventing the insertion of the revision acetabulum. After extensive plasticization of the defects with the use of allogeneic cancellous chips the "hanging hip" was left with the intention of making another attempt to insert the implant after the reconstitution of the acetabular bone. A computed tomography examination 2.5 years after the ASR removal revealed the lack of an adequate degree of bone remodeling for the planned implant. Arthroplasty using custom - made aMace Acetabular Revision System by Materialize was performed 3 years after the removal of ASR. OUTCOMES: Optimal implant adherence to the bone base and full osseointegration with the pelvic bone bearing has been achieved. Significant improvement in clinical parameters has been noted, with no complications in the postoperative period. LESSONS: The use of an individual custom-made implant in extensive acetabular bone loss after aseptic loosening of the acetabular component of the J&J DePuy ASR surface prosthesis in patients is an effective method of surgical treatment.

Combined Aerobic and Resistance Training Performed under Conditions of Normobaric Hypoxia and Normoxia Has the Same Impact on Metabolic Control in Men with Type 1 Diabetes.

(1) Background: The aim was to assess whether combined aerobic and resistance training performed under hypoxic and normoxic conditions had an impact on diabetes control, VO2max (maximum oxygen consumption), and echocardiological and anthropometric parameters in men with long-term type 1 diabetes. (2) Methods: Sixteen male participants (mean age: 37 years, mean HbA1c (glycated hemoglobin): 7.0%) were randomly assigned to two groups: training in normoxic conditions or training in conditions of altitude hypoxia. All subjects participated in 60 min combined aerobic and resistance training sessions twice a week for 6 weeks. At baseline and in the 6th week, echocardiography, incremental exercise test, and anthropometric and diabetes control parameters were assessed. (3) Results: After 6 weeks, there was no significant change in HbA1c value in any group. We noted a more stable glycemia profile during training in the hypoxia group (p > 0.05). Patients in the hypoxia group required less carbohydrates during training than in the normoxia group. A comparable increase in VO2max was observed in both groups (p > 0.05). There were no significant differences in cardiological and anthropometric parameters. (4) Conclusions: Combined aerobic and resistance training improved VO2max after 6 weeks regardless of the conditions of the experiments. This exercise is safe in terms of glycemic control in patients with well-controlled diabetes.

Metformin in patients with type 2 diabetes mellitus and heart failure: a review.

Diabetes mellitus is a major, global problem. Among the numerous complications of diabetes, there is increasing concern over the coexisting heart failure. Metformin is the most frequently used oral antidiabetic drug that is considered to be safe and effective in the management of type 2 diabetes mellitus. Since the publication of the UK Prospective Diabetes Study, it has been suggested that metformin might improve cardiovascular prognoses. Results from available studies have shown that metformin therapy in patients with type 2 diabetes mellitus and heart failure was associated with improved clinical outcomes when compared with other oral antidiabetic agents, insulin, or lifestyle management. However, there have been no randomized controlled trials evaluating the influence of metformin use on clinical outcomes in patients with type 2 diabetes mellitus and heart failure. New evidence from large cardiovascular outcome trials that showed a reduction in heart failure hospitalization for SGLT2 inhibitors caused changes in recommendations on the management of hyperglycaemia. Currently, the European Society of Cardiology recommends sodium-glucose co-transporter 2 inhibitors in patients with type 2 diabetes mellitus and heart failure or at high risk for heart failure, as a first choice in drug naïve patients, or as a second drug if the patient is already on metformin. The aim of our study is to review the current state of knowledge about the position of metformin in the treatment of patients with type 2 diabetes mellitus and heart failure.

Physiological Characteristics of Type 1 Diabetes Patients during High Mountain Trekking.

In this study, the aim was to provide observational data from an ascent to the summit of Mount Damavand (5670 meters above sea level (m.a.s.l), Iran) by a group of people with type 1 diabetes (T1DM), with a focus on their physiological characteristics. After a 3-day expedition, 18 T1DM patients, all treated with personal insulin pumps, successfully climbed Mount Damavand. Information was collected on their physiological and dietary behaviors, as well as medical parameters, such as carbohydrate consumption, glucose patterns, insulin dosing, and the number of hypo- and hyperglycemic episodes during this time frame. The participants consumed significantly less carbohydrates on day 3 compared to day 1 (16.4 vs. 23.1 carbohydrate units; p = 0.037). Despite this, a gradual rise in the mean daily glucose concentration as measured with a glucometer was observed. Interestingly, the patients did not fully respond to higher insulin delivery as there was no significant difference in mean daily insulin dose during the expedition. There were more hyperglycemic episodes (≥180 mg/dL) per patient on day 3 vs. day 1 (p < 0.05) and more severe hyperglycemic episodes (>250 mg/dL) per patient on days 2 (p < 0.05) and 3 (p < 0.05) vs. day 1. In summary, high mountain trekking is feasible for T1DM patients with good glycemic control and no chronic complications. However, some changes in dietary preferences and an observable rise in glucose levels may occur. This requires an adequate therapeutic response.

Prevalence and Risk Factors of New-Onset Diabetes After Transplantation (NODAT).

BACKGROUND New-onset diabetes after transplantation (NODAT) is a serious complication after a solid organ transplant. NODAT occurs in 2% to 53% of all solid organ transplant recipients. The identification of high-risk patients and the implementation of measures to limit the development of NODAT can improve the long-term patient prognosis. MATERIAL AND METHODS Our study group consisted of 336 patients undergoing heart transplant. Patients with prior diabetes (60 patients) were excluded from analysis. The remaining 276 patients were divided in 2 groups: with NODAT (n=109) and without NODAT (n=167). Logistic regression analysis was used for NODAT risk factor assessment. RESULTS NODAT occurred in 109 (32%) out of 336 patients without diagnosed diabetes before heart transplantation. Risk factors for post-transplant diabetes mellitus, which was shown by the analysis of the collected data, were BMI at discharge (OR=1.082, CI 1.011-1.158, p=0.0233), history of diagnosed CMV infection (OR=1.464, CI 1.068-2.007, p=0.0179), and age over 51 years (OR=1.634, CI 1.274-2.095, p=0.0001). CONCLUSIONS 1. New-onset diabetes after transplantation (NODAT) or long-lasting hypoglycemia (over 2 years after transplantation) was diagnosed in 32% patients after heart transplantation developed. 2. The risk factors of NODAT were BMI at discharge and history of diagnosed CMV infection, and age over 51 years was an independent risk factor.

Hypoglycaemia in endocrine, diabetic, and internal diseases [Hipoglikemia w schorzeniach endokrynologicznych, diabetologicznych i internistycznych].

Hypoglycemia is a decrease in blood glucose concentration below the physiological level. It occurs in healthy people and in people with various diseases with inadequate secretion of insulin by ß cells, or deficiency of counterregulatory hormones secreted at the moment of hypoglycemia. Hypoglycemia is also associated with diabetes therapy, regardless of whether behavioral therapy, oral hypoglycemic agents, or insulin are used. Distinguishing the causes of hypoglycemia is the basis for taking appropriate therapeutic actions that protect patients against subsequent episodes of lowering blood glucose and complications caused by hypoglycemia.

Aerobic as well as resistance exercises are good for patients with type 1 diabetes.

AIMS: To assess whether aerobic or resistance training has greater benefits in non-physically active men with a long lasting type 1 diabetes. The effects of exercise were evaluated in terms of diabetes control and risk factors for cardiovascular complications. METHODS: 21 male participants (mean age: 37 yrs, diabetes duration: 23 yrs, mean HbA1c: 7.4%) randomly assigned to 2 groups: 1-aerobic training (n = 10) and 2-resistance training (n = 11). All subjects participated in 60-min training sessions, either aerobic or resistance, twice a week for three months. At baseline and after 3 months: echocardiography, ECG and incremental exercise test, ECG and blood pressure monitoring, lipid profile, lactate and diabetes control parameters were assessed in all patients. RESULTS: Baseline HbA1c was 7.44% in aerobic group and 7.36% in resistance group (p = 0.84). After 3 months there was no significant change in HbA1c value in any exercise group but a non-statistically significant downward trend was seen particularly in aerobic exercise group (p = 0.07) vs the resistance group (p = 0.15). There was no significant difference in body mass, risk of hypoglycemia and cardiovascular risk factors. CONCLUSIONS: Both forms of exercise are safe in terms of glycemic control and cardiovascular risk factors in patients with quite well-controlled type 1 diabetes without advanced late complications.