Publications by authors named "Maciej Małecki"

211 Publications

The transcriptome-wide association search for genes and genetic variants which associate with BMI and gestational weight gain in women with type 1 diabetes.

Mol Med 2021 01 20;27(1). Epub 2021 Jan 20.

Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Kraków, Poland.

Background: Clinical data suggest that BMI and gestational weight gain (GWG) are strongly interconnected phenotypes; however, the genetic basis of the latter is rather unclear. Here we aim to find genes and genetic variants which influence BMI and/or GWG.

Methods: We have genotyped 316 type 1 diabetics using Illumina Infinium Omni Express Exome-8 v1.4 arrays. The GIANT, ARIC and T2D-GENES summary statistics were used for TWAS (performed with PrediXcan) in adipose tissue. Next, the analysis of association of imputed expression with BMI in the general and diabetic cohorts (Analysis 1 and 2) or GWG (Analysis 3 and 4) was performed, followed by variant association analysis (1 Mb around identified loci) with the mentioned phenotypes.

Results: In Analysis 1 we have found 175 BMI associated genes and 19 variants (p < 10) which influenced GWG, with the strongest association for rs11465293 in CCL24 (p = 3.18E-06). Analysis 2, with diabetes included in the model, led to discovery of 1812 BMI associated loci and 207 variants (p < 10) influencing GWG, with the strongest association for rs9690213 in PODXL (p = 9.86E-07). In Analysis 3, among 648 GWG associated loci, 2091 variants were associated with BMI (FDR < 0.05). In Analysis 4, 7 variants in GWG associated loci influenced BMI in the ARIC cohort.

Conclusions: Here, we have shown that loci influencing BMI might have an impact on GWG and GWG associated loci might influence BMI, both in the general and T1DM cohorts. The results suggest that both phenotypes are related to insulin signaling, glucose homeostasis, mitochondrial metabolism, ubiquitinoylation and inflammatory responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s10020-020-00266-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818927PMC
January 2021

"Fighting spirit": specific personality traits as one of the key factors for sport championship in type 1 diabetes mellitus.

Diabetol Int 2021 Jan 13:1-7. Epub 2021 Jan 13.

Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland.

There is ample evidence that sport is a protective factor against a number of health risks, across all ages, in the general population. An in-depth understanding of energy metabolism has reasonably entailed exercise as a cornerstone in the lifestyle of almost all subjects with type 1 diabetes mellitus (T1DM). Nevertheless, individuals with T1DM often fail in accomplishing exercise guidelines and they are often less active than their peer without diabetes. Two major obstacles are feared: management of blood glucose control and hypoglycemia. Nowadays, strategies, including glucose monitoring technology and insulin pump therapy, have significantly contributed to the participation in regular physical activity, and even in competitive sports, for T1DM people. The case report presents an analysis of specific personality traits and psychological parameters of 20 years old female Polish multiple champion in weightlifting with excellent T1DM control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13340-020-00488-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804577PMC
January 2021

The Gut Microbiota Profile According to Glycemic Control in Type 1 Diabetes Patients Treated with Personal Insulin Pumps.

Microorganisms 2021 Jan 12;9(1). Epub 2021 Jan 12.

Department of Metabolic Diseases, Jagiellonian University Medical College, 2 Jakubowskiego Street, 30-688 Krakow, Poland.

Recently, several studies explored associations between type 1 diabetes (T1DM) and microbiota. The aim of our study was to assess the colonic microbiota structure according to the metabolic control in T1DM patients treated with insulin pumps. We studied 89 T1DM patients (50.6% women) at the median age of 25 (IQR, 22-29) years. Pielou's evenness ( = 0.02), and Shannon's ( = 0.04) and Simpson's diversity indexes ( = 0.01), were higher in patients with glycosylated hemoglobin (HbA1c) ≥ 53 mmol/mol (7%). There were no differences in beta diversity between groups. A linear discriminant analysis effect size (LEfSe) algorithm showed that one family () was enriched in patients with HbA1c < 53 mmol/mol, whereas one family () and four species (, unclassified species of , , and ) were enriched in patients with HbA1c ≥ 53 mmol/mol. We found that at class level, the following pathways according to Kyoto Encyclopedia of Genes and Genomes were enriched in patients with HbA1c < 53 mmol/mol: bacterial motility proteins, secretion system, bacterial secretion system, ribosome biogenesis, translation proteins, and lipid biosynthesis, whereas in patients with HbA1c ≥ 53 mmol/mol, the galactose metabolism, oxidative phosphorylation, phosphotransferase system, fructose, and mannose metabolism were enriched. Observed differences in alpha diversity, metabolic pathways, and associations between bacteria and HbA1c in colonic flora need further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/microorganisms9010155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826603PMC
January 2021

Predictors of the maximal oxygen consumption in adult patients with type 1 diabetes treated with personal insulin pumps.

J Diabetes Investig 2020 Dec 30. Epub 2020 Dec 30.

Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland.

Aims/introduction: Regular physical activity for adults with type 1 diabetes mellitus improves cardiorespiratory fitness (CF) and quality of life. The aim of our study was to evaluate clinical and biochemical features that might be associated with CF in a homogenous group of adults with type 1 diabetes mellitus who are all treated with a personal insulin pump (continuous subcutaneous insulin infusion).

Materials And Methods: We assessed CF in 62 patients (74.2% of whom were men) who fulfilled the eligibility criteria. To determine maximal oxygen consumption, the march-running test on the treadmill was carried out. Two hours before the test, the patients consumed a defined meal covered by a dose of rapid acting insulin analog that was reduced by 25% from their regular dose. Basal insulin infusion was reduced by 50% for an hour. Additionally, the Perceived Stress Scale-10 questionnaire was used to measure the perception of stress.

Results: There was no episode of severe hypoglycemia during or after the test. In the final model, independent predictors of maximal oxygen consumption were sex, body fat percentage, lactate at 20 min after CF test and Perceived Stress Scale-10 score. Of interest, neither short-term (continuous glucose monitoring) nor long-term (glycosylated hemoglobin) metabolic control parameters were predictors of CF.

Conclusions: In our selected homogenous group of patients with type 1 diabetes mellitus treated with personal insulin pumps, higher CF was associated with a lower percentage of body fat, male sex, higher lactate level after the CF test and the Perceived Stress Scale-10 score. The proposed protocol in our cohort proved to be safe with regard to glycemic control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jdi.13490DOI Listing
December 2020

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

J Diabetes Res 2020 15;2020:8068710. Epub 2020 Sep 15.

Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland.

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; = 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 ( < 0.05) and more severe hyperglycemic episodes (>250 mg/dL) per patient on days 2 ( < 0.05) and 3 ( < 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/8068710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519997PMC
September 2020

Downregulated expression of microRNAs associated with cardiac hypertrophy and fibrosis in physiological pregnancy and the association with echocardiographically-evaluated myocardial function.

Biomed Rep 2020 Nov 27;13(5):41. Epub 2020 Aug 27.

Department of Cardiology, Institute of Mother and Child, 01-211 Warsaw, Poland.

The aim of the present study was to analyze the profiles of cardiac microRNAs (miRNAs/miRs) in healthy pregnant women and non-pregnant controls. A total of 61 healthy women >18 years of age with singleton pregnancies in the third trimester were compared with 19 non-pregnant controls. Specifically, expression of miRNAs associated with cardiac hypertrophy (miR-1, miR-17-5, miR-22, miR-34a, miR-124, miR-133a, miR-195, miR-199a-3p, miR-199b, miR-210, miR-222 and miR-1249) and miRNAs associated with cardiac hypertrophy and fibrosis (miR-15b, miR-21, miR-26a, miR-29-a, miR-29c, miR-30c, miR-101, miR-146a, miR-191, miR-208a-5p and miR-328) were analyzed and compared with echocardiographic examination results. Both groups had similar cardiac miRNA expression profiles, but differed in quantitative evaluation. Women in the third trimester of physiological pregnancy exhibited downregulation of certain profibrotic miRNAs (miR-21, miR-30c and miR-328), decreased expression of a hypertrophic and antimetabolic miRNAs (miR-146a), downregulation of an antifibrotic miRNA (miR-222), and downregulation of a hypertrophic miRNA (miR-195). In pregnant women, the indices of systolic function were associated with miR-195 expression, and an interplay between miR-17-5p and diastolic function was observed. While the profiles of cardiac miRNAs expressed in healthy pregnant women and healthy non-pregnant controls were similar, these two groups differed in terms of expression of specific miRNAs. In the third trimester of physiological pregnancy, a downregulation of miR-17-5p, miR-21, miR-30c, miR-146a, miR-195, miR-222 and miR-328 was observed. The differences in the association between echocardiographic indices with miRNAs in pregnant and non-pregnant women suggest that miRNAs regulate both the structure and function of the pregnant heart, influencing cardiac muscle thickness as well as systolic and diastolic function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/br.2020.1348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469559PMC
November 2020

Anticancer activity of topical ointments with histone deacetylase inhibitor, trichostatin A.

Adv Clin Exp Med 2020 Sep;29(9):1039-1049

Department of Applied Pharmacy, Faculty of Pharmacy, Medical University of Warsaw, Poland.

Background: Trichostatin A (TSA), being a strong specific histone deacetylase (HDAC) inhibitor, may lead to the inhibition of growth, differentiation and/or apoptosis of cells in a number of tumors. Semisolid drug formulations for topical release of anticancer agents may be an alternative strategy or a supplement of the systemic therapy.

Objectives: To prepare semisolid formulations with TSA to be used directly on the skin and to assess the anticancer effect in vivo on a mouse model with L1 neoplastic tumors.

Material And Methods: Twenty-four formulations were prepared in the form of semisolid systems containing TSA as the active ingredient. Then, an in vitro study was performed concerning the release of the active substance from the prepared formulations. Four formulations were selected for in vivo studies: oil-in-water cream, hydrogel, w/o emulsion ointment on the absorptive hydrophobic medium, and o/w emulsion gel. The tumor size and mouse body weight were measured during the experiment. The tumors and healthy skin of the mice were assessed regarding the skin barrier function with the Corneometer and Tewameter probes.

Results: The semisolid formulation with TSA applied on the skin reduced the growth of neoplastic tumors as compared with the control group. This is especially pronounced in the case of w/o emulsion ointment and o/w emulsion gel. The Corneometer shows that neoplastic tumor growth and formulations on the skin have no effect on the skin condition in comparison with the mouse skin without tumor. The measurement performed with the Tewameter has revealed impaired skin barrier function of neoplastic tumors.

Conclusions: Semisolid formulations with TSA fit well in the mainstream of research into topical medicines applied directly on neoplastic tumors, which may support and supplement current oncological treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17219/acem/124439DOI Listing
September 2020

Mosaic Recombinant Adeno-associated Virus Vector rAAV/DJ/CAG for Targeted Gene Delivery to Melanoma Cells Metastasized to the Lung.

Anticancer Res 2020 Aug;40(8):4425-4444

Department of Applied Pharmacy, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland.

Background/aim: Patients with metastasized melanoma have limited treatment options and poor diagnosis. Therefore, the development of treatments requires a new therapeutic approach, of which gene therapy using rAAV vectors can be proposed. The aim of the study was to examine the efficiency of the rAAV vector to transduce mouse melanoma cells both in vitro and in vivo.

Materials And Methods: Different rAAV serotypes encoding GFP under the control of both chicken beta-actin and cytomegalovirus promoters were used in the experiments. Intranasal, intraperitoneal, intravenous and intratumoral pathways of administration of rAAV vectors were tested using quantitative-PCR and immunohistochemical staining.

Results: The highest transduction efficiency in metastatic cells in vivo was observed 7 days after intranasal administration of a 10 gc/0.03 ml dose of rAAV/DJ-CAG.

Conclusion: Melanoma gene therapy based on rAAV vectors is a possible treatment option.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.14448DOI Listing
August 2020

Mitochondrial GWAS and association of nuclear - mitochondrial epistasis with BMI in T1DM patients.

BMC Med Genomics 2020 07 7;13(1):97. Epub 2020 Jul 7.

Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Kraków, Poland.

Background: BMI is a strong indicator of complications from type I diabetes, especially under intensive treatment.

Methods: We have genotyped 435 type 1 diabetics using Illumina Infinium Omni Express Exome-8 v1.4 arrays and performed mitoGWAS on BMI. We identified additive interactions between mitochondrial and nuclear variants in genes associated with mitochondrial functioning MitoCarta2.0 and confirmed and refined the results on external cohorts: the Framingham Heart Study (FHS) and GTEx data. Linear mixed model analysis was performed using the GENESIS package in R/Bioconductor.

Results: We find a borderline significant association between the mitochondrial variant rs28357980, localized to MT-ND2, and BMI (β = - 0.69, p = 0.056). This BMI association was confirmed on 1889 patients from FHS cohort (β = - 0.312, p = 0.047). Next, we searched for additive interactions between mitochondrial and nuclear variants. MT-ND2 variants interacted with variants in the genes SIRT3, ATP5B, CYCS, TFB2M and POLRMT. TFB2M is a mitochondrial transcription factor and together with TFAM creates a transcription promoter complex for the mitochondrial polymerase POLRMT. We have found an interaction between rs3021088 in MT-ND2 and rs6701836 in TFB2M leading to BMI decrease (inter_pval = 0.0241), while interaction of rs3021088 in MT-ND2 and rs41542013 in POLRMT led to BMI increase (inter_pval = 0.0004). The influence of these interactions on BMI was confirmed in external cohorts.

Conclusions: Here, we have shown that variants in the mitochondrial genome as well as additive interactions between mitochondrial and nuclear SNPs influence BMI in T1DM and general cohorts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12920-020-00752-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341625PMC
July 2020

Negative pressure wound therapy affects circulating plasma microRNAs in patients with diabetic foot ulceration.

Diabetes Res Clin Pract 2020 Jul 10;165:108251. Epub 2020 Jun 10.

Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland; University Hospital, Krakow, Poland. Electronic address:

Aims: Negative pressure wound therapy (NPWT) is commonly used in diabetic foot ulceration (DFU). The molecular mechanisms of NPWT action, particularly outside of the wound site, have not been described. We assessed NPWT's effect on circulating miRNA expression levels in type 2 diabetes (T2DM) patients with DFU.

Methods: We examined 34 T2DM patients treated with either NPWT (n = 24) or standard therapy (ST, n = 10). The group assignment was based on clinical criteria and local practice. Next-generation sequencing-based microRNA expression was determined on the patient's plasma collected before therapy and after 8 days.

Results: NPWT patients were similar to the ST group in terms of age, BMI, and HbA1c level; however, they differed by mean wound area (12.6 cm vs. 1.1 cm p = 0.0005). First, we analyzed the change of miRNA after NPWT or ST and observed an upregulation of let-7f-2 only in the NPWT group. Then, we analyzed the differential expression between NPWT and ST groups, looking at possible wound size effects. We found 12 differentially expressed miRNAs in pre-treatment comparison, including let-7f-2, while in post-treatment analysis we identified 28 miRNAs. The pathway enrichment analysis suggests that identified miRNAs may be involved in wound healing, particularly through angiogenesis.

Conclusion: We found initial evidence that NPWT in T2DM patients with DFU affects miRNA expression in plasma. Additionally, some differences in plasma miRNA expression may be related to wound size.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.diabres.2020.108251DOI Listing
July 2020

Resistance of melanoma cells to anticancer treatment: a role of vascular endothelial growth factor.

Postepy Dermatol Alergol 2020 Feb 9;37(1):11-18. Epub 2020 Mar 9.

Department of Applied Pharmacy, Medical University of Warsaw, Warsaw, Poland.

Melanoma is one of the most aggressive and resistant to treatment neoplasms. There are still many challenges despite many promising advances in anticancer treatment. Currently, the main problem for all types of treatment is associated with heterogeneity. Due to heterogeneity of cancer cells, "precise" targeting of a medicine against a single phenotype limits the efficacy of treatment and affects resistance to applied therapy. Therefore it is important to understand aetiology and reasons for heterogeneity in order to develop effective and long-lasting treatment. This review summarises roles of vascular endothelial growth factor (VEGF) that may stimulate growth of a melanoma tumour irrespective of its proangiogenic effects, contributing to cancer heterogeneity. VEGF triggers processes associated with extracellular matrix remodelling, cell migration, invasion, angiogenesis, inhibition of immune responses and favours phenotypic plasticity and epithelial-mesenchymal transition. Consequently, it participates in mechanisms of interactions between melanoma cancer cells and microenvironment and it can modify sensitivity to therapeutic factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5114/ada.2020.93378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247075PMC
February 2020

Ultra-Rapid Lispro Improves Postprandial Glucose Control and Time in Range in Type 1 Diabetes Compared to Lispro: PRONTO-T1D Continuous Glucose Monitoring Substudy.

Diabetes Technol Ther 2020 11 10;22(11):853-860. Epub 2020 Jun 10.

DC and RL Clinical Design, Delivery, and Analytics, TH and JB-V Connected Care and Insulins-Medical Development, Eli Lilly and Company, Indianapolis, Indiana, USA.

This study evaluated glucose control by continuous glucose monitoring (CGM) during treatment with ultra-rapid lispro (URLi) or lispro used in combination with insulin glargine or degludec in adults with type 1 diabetes in a substudy of the PRONTO-T1D study. Ambulatory glucose profiles were evaluated in 269 patients from PRONTO-T1D assigned to double-blind URLi ( = 97) or lispro ( = 99) given 0-2 min before the start of the meal (mealtime), or open-label URLi ( = 73) given 20 min after the meal (postmeal URLi). Blinded CGM was used for up to 14 days before baseline and the 26-week primary endpoint. The primary objective was to compare mealtime URLi and lispro with respect to incremental area under the serum glucose concentration versus time curve from 0 to 2 h (iAUC) after breakfast. Mealtime URLi was superior in reducing the iAUC when compared to lispro for breakfast (least squares mean [LSM] difference -28.1 mg·h/L,  = 0.048) and for all meals combined. iAUC and iAUC were also reduced. Postmeal URLi resulted in similar postprandial glucose (PPG) control to mealtime lispro, but less optimal PPG control compared to mealtime URLi. Mealtime URLi increased daytime time in range (71-180 mg/dL [3.9-10.0 mmo/L]) (LSM difference = +43.6 min,  = 0.020) and decreased nighttime time in hypoglycemia (LSM difference ≤70 mg/dL [3.9 mmol/L] = -11.5 min,  = 0.009) compared to mealtime lispro. Results of this CGM substudy support the improved PPG control seen with mealtime URLi in the PRONTO-T1D study and show that mealtime URLi resulted in improved daytime time in target range.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/dia.2020.0129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698997PMC
November 2020

Simple -Platinum Complex Bearing 3-Aminoflavone Ligand Could Be a Useful Drug: Structure-Activity Relationship of Platinum Complex in Comparison with Cisplatin.

Int J Mol Sci 2020 Mar 19;21(6). Epub 2020 Mar 19.

Department of Bioinorganic Chemistry, Medical University of Lodz, 1 Muszynskiego St., 90-151 Łódź, Poland.

Following previous studies devoted to -Pt(3-af)Cl, in this paper, the molecular structure and intermolecular interactions of the title complex are compared with other cisplatin analogues of which the crystal structures are presented in the Cambridge Structural Database (CSD). Molecular Hirshfeld surface analysis and computational methods were used to examine a possible relationship between the structure and anticancer activity of -Pt(3-af)Cl. The purpose of the article was also to investigate the effect of hyperthermia on the anticancer activity of cisplatin, cytostatics used in the treatment of patients with ovarian cancer and a new analogue of cisplatin--Pt(3-af)Cl. The study was conducted on two cell lines of ovarian cancer sensitive to Caov-3 cytostatics and the OVCAR-3 resistant cisplatin line. The study used the MTT (3-(4,5-dimethylthiazol-2,5-diphenyltetrazolium bromide) cell viability assay, LDH (lactate dehydrogenase), and the quantitative evaluation method for measuring gene expression, i.e., qPCR with TagMan probes. Reduced survivability of OVCAR-3 and Caov-3 cells exposed to cytostatics at elevated temperatures (37 °C, 40 °C, 43 °C) was observed. Hyperthermia may increase the sensitivity of cells to platinum-based antineoplastic drugs and paclitaxel, which may be associated with the reduction of gene expression related to apoptotic processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21062116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139614PMC
March 2020

Increased Temperature Facilitates Adeno-Associated Virus Vector Transduction of Colorectal Cancer Cell Lines in a Manner Dependent on Heat Shock Protein Signature.

Biomed Res Int 2020 8;2020:9107140. Epub 2020 Feb 8.

Department of Applied Pharmacy, Faculty of Pharmacy with Laboratory Medicine, Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland.

Colorectal cancer (CRC) is one of the most common cancers in human population. A great achievement in the treatment of CRC was the introduction of targeted biological drugs and solutions of chemotherapy, combined with hyperthermia. Cytoreductive surgery and HIPEC (hyperthermic intraperitoneal chemotherapy) extends the patients' survival with CRC. Recently, gene therapy approaches are also postulated. The studies indicate the possibility of enhancing the gene transfer to cells by recombinant adeno-associated vectors (rAAV) at hyperthermia. The rAAV vectors arouse a lot of attention in the field of cancer treatment due to many advantages. In this study, the effect of elevated temperature on the transduction efficiency of rAAV vectors on CRC cells with different origin and gene profile was examined. The effect of heat shock on the penetration of rAAV vectors into CRC cells in relation with the expression of HSP and AAV receptor genes was tested. It was found that the examined cells under hyperthermia (43°C, 1 h) are transduced at a higher level than in normal conditions (37°C). The results also indicate that studied RKO, HT-29, and LS411N cell lines express HSP genes at different levels under both 37°C and 43°C. Moreover, the results showed that the expression of AAV receptors increases in response to elevated temperature. The study suggests that increased rAAV transfer to CRC can be achieved under elevated temperature conditions. The obtained results provide information relevant to the design of new solutions in CRC therapy based on the combination of hyperthermia, chemotherapy, and gene therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/9107140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031720PMC
November 2020

Efficacy and safety of long-term insulin pump treatment in patients with type 1 diabetes aged over 50 years.

Endocr J 2020 Mar 4;67(3):367-371. Epub 2020 Mar 4.

Department of Metabolic Diseases, Jagiellonian University Medical College, Kraków, Poland.

Continuous subcutaneous insulin infusion (CSII) therapy using insulin pumps has become widely used in the treatment of type 1 diabetes mellitus (T1DM). This retrospective study aimed to assess the efficacy and safety of long-term insulin pump treatment in patients with T1DM aged ≥50 years. The study included patients aged ≥50 years, who had a diagnosis of T1DM based on clinical criteria and/or presence of autoantibodies characteristic of autoimmune diabetes, and had received ≥5 years of recent and uninterrupted treatment with a personal insulin pump. We analyzed records on HbA1c levels across the entire observation period. The cohort comprised 17 patients, of whom 6 (35%) were men and 11 (65%) were women. The mean duration of observation was 6.6 years, during which patients had a mean of 8.4 HbA1c measurements. Mean HbA1c level over the entire observation period was 6.7% (range, 5.3-7.4%). Overall, 11 patients (65%) had mean HbA1c levels at the ADA-recommended target of <7% and 5 patients (29%) had mean HbA1c <6.5%. Mean HbA1c level was significantly lower at the end of the observation period than at the start (6.52% versus 6.91%; difference, -0.39%; p < 0.01), indicating an improvement in glycaemic control over time. On average, patients experienced one level 1 hypoglycaemia episode every 2.4 days. This retrospective analysis of at least 5 years of follow-up of selected patients with T1DM aged ≥50 years at the start of observation, showed that CSII is a safe and effective treatment option in this age group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1507/endocrj.EJ19-0188DOI Listing
March 2020

NPWT in diabetic foot wounds-a systematic review and meta-analysis of observational studies.

Endocrine 2020 04 9;68(1):44-55. Epub 2020 Jan 9.

Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland.

Purpose: Negative-pressure wound therapy (NPWT) is an adjunct modality in diabetic foot ulcerations (DFUs). Randomized controlled trials (RCTs) have shown its advantage over standard approaches; however, data from observational studies remain scarce.We performed a systematic review of observational non-RCTs evaluating NPWT efficacy and safety in patients with DFU.

Methods: Electronic databases were searched for observational studies involving NPWT. The results of single-arm studies were presented as percentages of patients with the outcome of interest. A meta-analysis of comparative studies provided point estimates of outcomes. Continuous outcomes were reported as either weighted or standardized mean differences and dichotomous data as relative risks (RR).

Results: The search identified 16 relevant observational studies, 12 single-arm, and 4 comparative, reporting on a total of 18,449 patients with DFU, of whom 1882 were managed with NPWT. In the NPWT-treated patients, ulcers were larger (average size range 6.6-27.9 cm), as compared with controls (≤3 cm). The pooled results showed healing and major amputation in 51% and 5% of NPWT patients, respectively. The meta-analysis of comparative studies revealed lower risk of major amputation [RR = 0.23 (0.07; 0.80)] in NPWT-treated patients. The pooled results for healing rate and risk of any amputation were inconclusive due to large between-study heterogeneity. Overall, 6 deaths out of 158 patients were reported, none of them related to NPWT. Serious adverse events occurred in 6% of patients on NPWT.

Conclusions: This systematic review of observational studies provided supportive evidence that NWPT is an efficient and safe adjunct treatment in the management of DFUs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-019-02164-9DOI Listing
April 2020

Correlates of pentraxin 3 serum concentration in men and women with type 2 diabetes.

Innate Immun 2020 07 25;26(5):351-357. Epub 2019 Dec 25.

Department of Metabolic Diseases, Jagiellonian University Medical College, Poland.

Elevated levels of plasma pentraxin 3 (PTX3), a marker of inflammation, are associated with the risk of developing cardiovascular diseases in the general population, as well as in patients with type 2 diabetes (DM2). In this study, we aimed to determine factors associated with PTX3 serum concentrations in men and women with DM2. The study included 116 consecutive patients (67 men and 49 women) with DM2 from an outpatient diabetic clinic. Men were characterised by lower age and higher uric acid, creatinine and bilirubin concentrations and waist/hip ratio than women. In women, low-density lipoprotein cholesterol (LDL-C) levels were higher than in men. In men, median (interquartile range) values of PTX3 concentration were 4.02 (1.99), and in women they were 4.53 (3.31) ng/ml (NS). In men, PTX3 concentrations correlated with total cholesterol (TC), triglycerides, apolipoprotein (Apo) C3, Apo B48, Glc and creatinine levels. In women, PTX3 correlated significantly with TC and LDL-C and Apo B100. Partial regression analysis revealed that after adjusting for age, PTX3 concentrations in men were significantly associated with TC, LDL-C, triglycerides, creatinine, Apo C3 and Apo B48, while in women they were associated with TC, LDL-C and Apo B100. The results could be of importance in sex-specific prevention of vascular complications in DM2 patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1753425919891628DOI Listing
July 2020

Meta-analysis of association of FTO genetic variation with PCOS must account for obesity.

Genomics 2020 05 16;112(3):2164-2165. Epub 2019 Dec 16.

Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygeno.2019.12.010DOI Listing
May 2020

Effects of Negative Pressure Wound Therapy on Levels of Angiopoetin-2 and Other Selected Circulating Signaling Molecules in Patients with Diabetic Foot Ulcer.

J Diabetes Res 2019 28;2019:1756798. Epub 2019 Oct 28.

Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland.

Background And Aims: Diabetic foot ulcers (DFUs) are linked to amputations and premature deaths. Negative pressure wound therapy (NPWT) has been used for DFUs. The mechanism of NPWT's action may be associated with its influence on circulating molecules. We assessed NPWT's effect on the plasma levels of angiopoietin-2 (Ang2), a key regulator of angiogenesis, and its microvesicular receptors (Tie2) as well as the microvesicles (MVs) themselves in DFU patients.

Materials And Methods: We included 69 patients with type 2 diabetes mellitus (T2DM) and neuropathic, noninfected DFUs-49 were treated with NPWT and 20 were treated with standard therapy (ST). Assigning patients to the NPWT group was not random but based on DFU characteristics, especially wound area. Ang2 was measured by ELISA in the entire group, while in a subgroup of 19 individuals on NPWT and 10 on ST, flow cytometry was used to measure Tie2+ and the corresponding isotype control (Iso+) and annexin V (AnnV+) as well as total MVs. Measurements were performed at the beginning and after 8 ± 1 days of therapy.

Results: Treatment groups were similar for basic characteristics but differed by their median DFU areas (10.3 (4.2-18.9) vs. 1.3 (0.9-3.4) cm, = 0.0001). At day 0, no difference was observed in Ang2 levels, total MVs, MV Tie+, and MV AnnV+ between the groups. Ang2 decreased after 8 days in the NPWT group, unlike in the ST group (3.54 (2.40-5.40) vs. 3.32 (2.33-4.61), = 0.02, and 3.19 ± 1.11 vs. 3.19 ± 1.29 ng/mL, = 0.98, respectively). No other parameters were identified that may have been influenced by the NPWT treatment.

Conclusion: NPWT in T2DM patients with neuropathic, noninfected DFU seems to lead to reduction of the Ang2 level. Influencing the level of Ang2 may constitute one of NPWT-related mechanisms to accelerate wound healing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/1756798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855047PMC
April 2020

Increased temperature-related adeno-associated virus vectors transduction of ovarian cancer cells - essential signatures of AAV receptor and heat shock proteins.

Exp Ther Med 2019 Dec 21;18(6):4718-4732. Epub 2019 Oct 21.

Department of Applied Pharmacy, Faculty of Pharmacy with Laboratory Medicine, Medical University of Warsaw, Warsaw 02-097, Poland.

Recombinant adeno-associated viruses (rAAVs) are becoming more commonly used in clinical trials involving gene therapy. Additionally AAV-based drugs have already been registered. Gene therapy aims to increase transduction efficiency, increase selectivity and reduce side effects. One approach to achieve this is the use of physical factors, such as temperature or more specifically, hyperthermia, which is already utilized in oncology. The aim of the present study was to investigate the effect of hyperthermic conditions (40°C and 43°C) on the rAAV transduction efficiency of ovarian cancer cells (Caov-3 and NIH:OVCAR-3) and non-cancerous cells (AAV-293). The present study was designed to identify functional associations between the level of gene transfer and the expression of representative genes for rAAV transmission (AAVR (AAV receptor), heparan sulfate proteoglycan (HSPG) 1 and HSPG2) and heat shock proteins (HSPs). The expressions of selected genes were measured via reverse transcription-quantitative PCR and cell adhesion/invasion chamber tests were also performed. The results revealed that ovarian cancer cell lines were more efficiently transduced with rAAV vectors at an elevated temperature. Additionally, the expression patterns of AAVR, HSPG1 and HSPG2 genes were different between the tested lines. The expression of certain receptors in ascites-derived NIH:OVCAR-3 ovarian cancer cells was higher compared with tumor-derived Caov-3 cells at 37, 40 and 43°C, which indicates a higher transduction efficiency in the formerly mentioned cells. Ascites-derived ovarian cancer cells were characterized by high expressions of HSP40, HSP90 and HSP70 families. Lower levels of HSP expression were demonstrated in less-effectively transduced Caov-3 cells. Furthermore, expressions of the examined genes changed with increasing temperature. The results indicated that temperature-dependent transduction is associated with the expression of the rAAV receptor and HSP genes. The results of the current study may aid the design of effective protocols for ovarian cancer gene therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2019.8112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861878PMC
December 2019

The utility of MODY Probability Calculator in probands of families with early-onset autosomal dominant diabetes from Poland.

Minerva Med 2019 Dec 14;110(6):499-506. Epub 2019 Oct 14.

Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland -

Background: Maturity-onset diabetes of the young (MODY) accounts for 1-2% of all diabetes cases. Unfortunately, circa 90% of MODY cases are misdiagnosed as type 1 or type 2 diabetes. A proper genetic diagnosis based on automatic sequencing is crucial for the use of a tailored treatment. However, this method is still expensive and, thus, patients' selection for testing should be performed precisely. In 2012, an easy-to-use tool was developed in Exeter, UK, to support genetic testing for MODY in the British population. The aim of the study was to assess the utility of MODY Probability Calculator in probands from Polish families with early-onset autosomal dominant diabetes.

Methods: We have performed a retrospective analysis of 155 probands who were qualified for genetic testing between 2006 and 2018. Probands were recruited for MODY testing based on the following criteria: 1) early age of diagnosis (≤35 years); 2) a positive, multigenerational family history of diabetes. Automatic sequencing, Sanger and, in case of initial negative results, new generation sequencing (NGS) of a set of 28 genes, were performed. MODY Probability was calculated on the website www.diabetesgenes.org.

Results: The group of probands consisted of 64 GCK-, 37 HNF1A-, and three HNF4A-MODY patients and 51 NGS-negative subjects. The median positive predictive value (PPV) was 75.5% (95% CI: 75.5-75.5%), 49.4% (95% CI: 24.4-75.5%), 45.5% (95% CI: 21.0-75.5%) and 49.4% (95% CI: 32.9-75.5%) for GCK-, HNF1A-, HNF4A-MODY and NGS-negative, respectively. The discriminative accuracy, as expressed by AUC, of PPV between MODY and NGS negative groups was 0.62 (95% CI: 0.52-0.71) with the corresponding sensitivity of 71.2% and specificity of 51.0%.

Conclusions: In this highly pre-selected group of probands that were qualified for genetic testing based on clinical features, the use of MODY Probability Calculator would not substantially improve the patients' selection process for genetic testing. Further efforts to improve this tool are desirable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.23736/S0026-4806.19.06053-1DOI Listing
December 2019

Assessment of selected food intake frequency in patients with type 1 diabetes treated with personal insulin pumps

Rocz Panstw Zakl Hig 2019 ;70(3):259-265

Department of Metabolic Diseases, University Hospital, Krakow, Poland

Background: It has been established that in Type 1 Diabetes Mellitus (T1DM), regardless of the insulin therapy model used, diet and proper eating habits are still important in the treatment of the disease. The dietary intervention in these patients is aimed at maintaining proper body weight, obtaining target fasting and post meal blood glucose levels, optimizing lipid profiles.

Objective: The aim of the study was to assess dietary habits in a homogeneous group of adults with T1DM treated with personal insulin pumps.

Material And Methods: The study included 141 adult patients (57% women) with type 1 diabetes treated with personal insulin pumps. The surveyed population was characterized by an average age of 25.8 ± 6.2 years, an average duration of diabetes 13.9 ± 6.9 years, and treatment with a personal pump for 8.2 ± 4.1 years and mean BMI 23.0 ± 2.8 g/m2. All were dwellers of south-eastern Poland. The validated KomPAN questionnaire was used to assess the frequency of consumption of individual food products.

Results: The mean percentage of HbA1c in the study group was 7.3% [56 mmol/mol]. The mean total cholesterol level was 4.4 mmol/l, HDL - 1.7 mmol/l, LDL - 2.3 mmol/l and triglycerides - 0.8 mmol/l. In the multivariate regression model, no correlation was found between dietary quality parameters and metabolic compensation measured with HbA1c or lipidogram and the place of residence (village, small town, big city). However, there were differences in the quality of the diet depending on the sex. Women were characterized by higher index of a healthy diet (pHDI-10) (26.3 vs 21.4, p=0.005) and lower index of unhealthy diet (nHDI-14) (13.3 vs 18.6, p <0.001) than men.

Conclusions: The results of this study clearly suggest, that despite good metabolic control, patients require more education on the choice of healthy product groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.32394/rpzh.2019.0076DOI Listing
February 2020

Serum pentraxin 3 concentration in patients with type 2 diabetes and nonalcoholic fatty liver disease.

Pol Arch Intern Med 2019 08 30;129(7-8):499-505. Epub 2019 Jul 30.

Department of Metabolic Diseases, Jagiellonian University Medical College, Kraków, Poland

Introduction: Nonalcoholic fatty liver disease (NAFLD) is common in patients with type 2 diabetes (T2D). Pentraxin 3 (PTX3), a marker of inflammation, is a cardiovascular risk factor.

Objectives: We examined clinical and biochemical factors associated with serum PTX3 concentrations in patients with T2D with and without NAFLD.

Patients And Methods: Serum material was obtained from 116 patients with T2D (mean age, 59.1 years), including 79 patients with NAFLD.

Results: Median (interquartile range) PTX3 level was 4.264 (2.293) ng/ml in patients with and 3.773 (3.223) ng/ml in patients without NAFLD (P = 0.93). In the whole group, PTX3 level was associated with total cholesterol, low‑density lipoprotein cholesterol (LDL‑C), apolipoprotein (apo) B100, apo C3, triglyceride (TG) concentrations, and waist circumference after adjustment for age and gender. As indicated by partial regression coefficient b, increase of independent variable LDL‑C by 1 mmol/l was associated with the rise of PTX3 by 1.2017 ng/ml, increase of apo B100 by 1 mg/dl with the rise of PTX3 by 1.0051 ng/ml, and increase of apo C3 by 1 μg/dl with the rise of PTX3 by 1.0012 ng/ml. In patients with T2D with NAFLD, total cholesterol, LDL‑C, TG, apo C3, and apo B100 were associated with PTX3. Associations of PTX3 with apolipoproteins were observed only in the NAFLD group.

Conclusions: Reported associations of PTX3 level add new insight into possible mechanisms of its atherogenic actions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.20452/pamw.14913DOI Listing
August 2019

Risk factors of hypoglycaemia in type 1 diabetes individuals during intensive sport exercise-Data from the SPORTGIVECHANCE event.

Int J Clin Pract 2019 Nov 4;73(11):e13411. Epub 2019 Sep 4.

Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland.

Aims: Fear of hypoglycaemia seems to be one of the strongest barrier to physical activity for individuals with type 1 diabetes mellitus (T1DM).The aim of the study was to describe clinical characteristics of participants with T1DM in the intense sporting event of runs and bike rides"SPORTGIVECHANCE-Diabetic runners and cyclists for more sport for all in Europe", and investigate factors associated with self-reported hypoglycaemia episodes during the competition, in particular the use of continuous and flash glucose monitoring systems (CGM/FGM).

Methods: The sporting event took place in Spoleto, Italy from 30 August 2018 to 2 September 2018. An online survey was distributed among 150 participants with diabetes. Only T1DM patients were invited to complete the survey that included questions on baseline clinical characteristics as well as glucose control and meal related issues during the competition. Logistic regression was used to determine factors associated with reported hypoglycaemia.

Results: There were 35 T1DM individuals who completed the questionnaire: eight subjects were continuous glucose monitoring system (CGM) users, 10 used flash glucose monitoring systems (FGM), while the others performed self-measured blood glucose measurements (SMBG) on glucose meters. Mild hypoglycaemia episodes during the competition were reported by four CGM/FGM users and six non-users (OR: 0.73, CI: 0.34-1.53). No severe hypoglycaemic episode was reported. Body mass index (BMI) (OR: 1.47, CI: 1.01-2.13) and subjectively very hard or maximal intensity of the competition (OR: 4.90, CI: 1.51-15.89) were associated with a higher risk of hypoglycaemia.

Conclusions: Data obtained from the self-selected sample of T1DM patients suggests that T1DM individuals can participate in intense sport competitions with moderate risk of mild hypoglycaemia regardless of CGM/FGM or SMBG use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijcp.13411DOI Listing
November 2019

Predictors of neutrophil extracellular traps markers in type 2 diabetes mellitus: associations with a prothrombotic state and hypofibrinolysis.

Cardiovasc Diabetol 2019 04 16;18(1):49. Epub 2019 Apr 16.

Institute of Cardiology, Jagiellonian University Medical College, 80 Pradnicka St., 31-202, Krakow, Poland.

Background: Type 2 diabetes mellitus (T2DM) is associated with a hypercoagulable state and increased neutrophil extracellular traps formation (NETosis). We investigated predictors of NETosis and cell death markers in circulating blood and their association with a prothrombotic state in T2DM.

Methods: In a cross-sectional study involving 113 T2DM patients aged 63.7 ± 8.2 years, we investigated citrullinated histone H3 (H3Cit), cell-free deoxyribonucleic acid (cfDNA), myeloperoxidase, neutrophil elastase, and inflammation markers, along with thrombin generation (TG), plasma clot lysis time (CLT), clot permeability (K) and fibrinolysis inhibitors.

Results: On multivariate logistic regression analysis adjusted for age and gender, predictors of high H3Cit (≥ 7.36 ng/mL, upper quartile) were: glycated hemoglobin (HbA1c) ≥ 7.0% and interleukin-6. Interleukin-6 was also found to be a predictor of high cfDNA (≥ 2.84 µg/mL, upper quartile) along with glucose. Citrullinated histone H3 and cfDNA correlated positively with CLT and inversely with K, while TG associated solely with cfDNA. These associations were not seen with myeloperoxidase and neutrophil elastase. Patients with previous myocardial infarction (n = 21, 18.6%) had higher H3Cit (+108%, p < 0.001) and cfDNA (+45%, p = 0.022). On multivariable analysis adjusted for potential confounders, H3Cit and cfDNA, along with plasminogen activator inhibitor-1 and concomitant cardiovascular disease, were predictors of CLT. Citrullinated histone H3 alone was a predictor of K and only cfDNA was a predictor of peak thrombin generated.

Conclusions: In T2DM, NETosis detectable in circulating blood is associated with inflammatory state and a prothrombotic state, especially hypofibrinolysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12933-019-0850-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469138PMC
April 2019

A decision algorithm to identify patients with high probability of monogenic diabetes due to HNF1A mutations.

Endocrine 2019 04 18;64(1):75-81. Epub 2019 Feb 18.

Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland.

Purpose: To investigate the utility of biomarkers of maturity-onset diabetes of the young (MODY), high-sensitivity C-reactive protein (hsCRP), and 1,5-anhydroglucitol (1,5-AG) in conjunction with other clinical and laboratory features to improve diagnostic accuracy and provide a diagnostic algorithm for HNF1A MODY.

Methods: We examined 77 patients with HNF1A MODY, 88 with GCK MODY mutations, 99 with type 1 diabetes, and 92 with type 2 diabetes. In addition to 1,5-AG and hsCRP, we considered body mass index (BMI), fasting glucose, and fasting serum C-peptide as potential biomarkers. Logistic regression and receiver operating characteristic curves were used in marker evaluation.

Results: Concentration of hsCRP was lowest in HNF1A MODY (0.51 mg/l) and highest in type 2 diabetes (1.33 mg/l). The level of 1,5-AG was lowest in type 1 diabetes and HNF1A MODY, 3.8 and 4.7 μg/ml, respectively, and highest (11.2 μg/ml) in GCK MODY. In the diagnostic algorithm, we first excluded patients with type 1 diabetes based on low C-peptide (C-statistic 0.98) before using high BMI and C-peptide to identify type 2 diabetes patients (C-statistic 0.92). Finally, 1,5-AG and hsCRP in conjunction yielded a C-statistic of 0.86 in discriminating HNF1A from GCK MODY. We correctly classified 92.9% of patients with type 1 diabetes, 84.8% with type 2 diabetes, 64.9% HNF1A MODY, and 52.3% GCK MODY patients.

Conclusions: Plasma 1,5-AG and serum hsCRP do not discriminate sufficiently HNF1A MODY from common diabetes types, but could be potentially useful in prioritizing Sanger sequencing of HNF1A gene.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-019-01863-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453873PMC
April 2019

Obstructive and nonobstructive coronary artery disease in long-lasting type 1 diabetes: a 7-year prospective cohort study.

Pol Arch Intern Med 2019 02 13;129(2):97-105. Epub 2019 Feb 13.

Department of Coronary Disease and Heart Failure, Jagiellonian University Medical College, John Paul II Hospital, Kraków, Poland

INTRODUCTION It is widely believed that patients with diabetes are at increased risk of severe and premature coronary artery disease (CAD) when compared with nondiabetic individuals. OBJECTIVES The aim of the study was to evaluate the prevalence, 7‑year incidence, predictors, and outcomes of obstructive and nonobstructive CAD in patients with long‑lasting type 1 diabetes. PATIENTS AND METHODS We enrolled 2330 patients at a median age of 50 years and a median diabetes duration of 32 years. All participants underwent diagnostic workup for CAD with an exercise treadmill test (ETT), single‑photon emission computed tomography (SPECT), or both. Coronary angiography was performed in patients with abnormal ETT/SPECT results and repeated during the study if clinically indicated. RESULTS The prevalence of obstructive and nonobstructive CAD was 6.9% and 42%, respectively, while the 7‑year incidence, 1.9% and 7.4%, respectively. Of the 160 revascularized patients, 38% underwent complete revascularization. Acute coronary syndromes were reported in 3.6% of patients (54% with nonobstructive CAD). Cardiac deaths were reported in 1.07% of the population, and only in patients with obstructive CAD. Age, diabetes duration, hypertension, and renal failure were predictors of obstructive CAD, while type 1 diabetes duration, glycated hemoglobin A1c levels, frequent severe hypoglycemia, hypertension, triglyceride levels, renal failure, and cardiac autonomic neuropathy predicted nonobstructive CAD. CONCLUSIONS Nonobstructive CAD was the most frequent coronary complication in patients with type 1 diabetes. Both obstructive and nonobstructive CAD showed a similar incidence of nonfatal outcomes and selected predictors. Positive ETT/SPECT results were related to glycemic control only in patients with nonobstructive CAD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.20452/pamw.4440DOI Listing
February 2019

Bifurcation in the angular velocity of a circular disk propelled by symmetrically distributed camphor pills.

Chaos 2019 Jan;29(1):013125

Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw 01-224, Poland.

We studied rotation of a disk propelled by a number of camphor pills symmetrically distributed at its edge. The disk was put on a water surface so that it could rotate around a vertical axis located at the disk center. In such a system, the driving torque originates from surface tension difference resulting from inhomogeneous surface concentration of camphor molecules released from the pills. Here, we investigated the dependence of the stationary angular velocity on the disk radius and on the number of pills. The work extends our previous study on a linear rotor propelled by two camphor pills [Y. Koyano et al., Phys. Rev. E 96, 012609 (2017)]. It was observed that the angular velocity dropped to zero after a critical number of pills was exceeded. Such behavior was confirmed by a numerical model of time evolution of the rotor. The model predicts that, for a fixed friction coefficient, the speed of pills can be accurately represented by a function of the linear number density of pills. We also present bifurcation analysis of the conditions at which the transition between a standing and a rotating disk appears.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1063/1.5061027DOI Listing
January 2019