Publications by authors named "Maciej T Małecki"

132 Publications

Continuous glucose monitoring and insulin pump therapy in pregnant women with type 1 diabetes mellitus.

Ginekol Pol 2021 Apr 29. Epub 2021 Apr 29.

Department of Metabolic Diseases, University Hospital, Cracow, Poland.

Objectives: We examined the impact of continuous subcutaneous insulin infusion (CSII) and continuous glucose moni-toring systems (CGM) during pregnancy in women with pre-gestational type 1 diabetes (T1DM) on glycemic control and subsequent adverse outcomes.

Material And Methods: In this observational, one-center study we analyzed records of consecutive 109 T1DM pregnancies (2016-2017). The final analyzed group consisted of 81 singleton pregnancies who met inclusion and exclusion criteria. We searched for the association between the use of CSII with or without CGM and pregnancy planning with glycated hemo-globin A1c (HbA1c) through pregnancy and after delivery as well as maternal and infant outcomes.

Results: Patients using CSII and CGM vs CSII without CGM and MDI (multiple daily injections) users had the lowest HbA1c levels during and after pregnancy (5.3%, 5.3%, 5.2% and 5.5% in the 1st, 2nd, 3rd trimester and postpartum visit, p = 0.003, p = 0.030, p = 0.039 and p = 0.002, respectively). Patients treated with insulin pumps with CGM and additional functions of automatic insulin delivery suspension on low glucose level (SLG) or predictive low glucose suspend (PLGS) during the third trimester and after pregnancy achieved a significantly lower HbA1c than the other CSII patients. We did not find any differences between the study groups in gestational age at delivery, preterm births, birth weight or macrosomia risk. Despite very good glycemic control, the risk of macrosomia remained high (19.7%).

Conclusions: The use of pumps equipped with CGM, especially with automatic insulin delivery suspension, may improve glycemic control in pregnant T1DM women. The proportion of macrosomia remained high.
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http://dx.doi.org/10.5603/GP.a2021.0029DOI Listing
April 2021

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox subunit polymorphisms, systemic oxidative stress, endothelial dysfunction, and atherosclerosis in type 2 diabetes mellitus.

Pol Arch Intern Med 2021 Apr 14. Epub 2021 Apr 14.

Introduction: Diabetes mellitus is an important and rapidly increasing problem in public health. It associates with endothelial dysfunction and increased endothelial permeability, which may lead to severe cardiovascular events.

Objectives: We aimed to evaluate the relationship between polymorphisms in the cytochrome b-245 alpha chain (CYBA) gene encoding p22phox, a key subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, with endothelial function, atherosclerosis and systemic oxidative stress in type 2 diabetes mellitus (T2DM).

Patients And Methods: Intima-media thickness (IMT), flow- and nitroglycerin-mediated dilatation (FMD and NMD) were measured in 182 patients with T2DM. Assessment of plasma levels of von Willebrand factor (vWF) and malondialdehyde (MDA) levels as well as genotyping of coding sequence C242T (rs4673) and promoter region A-930G (rs9932581) polymorphisms of CYBA were performed using standardized protocols.

Results: We observed a significant association of the impaired endothelial function, as measured by FMD, with the C allele of C242T, but not with the A-930G polymorphism. Functional relationship of the C242T polymorphism with endothelial dysfunction remained significant following a multivariable adjustment for major risk factors for atherosclerosis. Mean IMT, NMD, concentrations of MDA or vWF were not related to the specific genotypes of the investigated polymorphisms.

Conclusions: C242T, but not A-930G, polymorphism of CYBA significantly affects endothelial function in T2DM. Thus, it might be a useful marker of endothelial dysfunction in T2DM patients.
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http://dx.doi.org/10.20452/pamw.15937DOI Listing
April 2021

Analysis of the Gut Mycobiome in Adult Patients with Type 1 and Type 2 Diabetes Using Next-Generation Sequencing (NGS) with Increased Sensitivity-Pilot Study.

Nutrients 2021 Mar 25;13(4). Epub 2021 Mar 25.

Department of Molecular Medical Microbiology, Chair of Microbiology, Faculty of Medicine, Jagiellonian University Medical College, 18 Czysta Street, 31-121 Krakow, Poland.

The studies on microbiome in the human digestive tract indicate that fungi could also be one of the external factors affecting development of diabetes. The aim of this study was to evaluate the quantitative and qualitative mycobiome composition in the colon of the adults with type 1 (T1D), = 26 and type 2 (T2D) diabetes, = 24 compared to the control group, = 26. The gut mycobiome was characterized in the stool samples using the analysis of the whole internal transcribed spacer (ITS) region of the fungal rDNA gene cluster by next-generation sequencing (NGS) with increased sensitivity. At the L2 (phylum) level, Basidiomycota fungi were predominant in all 3 study groups. Group T1D presented significantly lower number of Ascomycota compared to the T2D group, and at the L6 (genus) level, the T1D group presented significantly lower number of genus compared to control and T2D groups. In the T1D group, a significant positive correlation between total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and fungi of the genus and in the T2D group, a negative correlation between the total cholesterol level and genus was found. The obtained results seem to be a good foundation to extend the analysis of the relationship between individual genera and species of fungi and the parameters determining the metabolism of carbohydrates and lipids in the human body.
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http://dx.doi.org/10.3390/nu13041066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064496PMC
March 2021

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.
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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.
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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.
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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.
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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.
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http://dx.doi.org/10.1155/2020/8068710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519997PMC
September 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.
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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.
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http://dx.doi.org/10.1016/j.diabres.2020.108251DOI Listing
July 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.
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http://dx.doi.org/10.1089/dia.2020.0129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698997PMC
November 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.
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http://dx.doi.org/10.1007/s12020-019-02164-9DOI Listing
April 2020

Changes in the clinical characteristics of women with gestational diabetes mellitus - a retrospective decade-long single center analysis.

Folia Med Cracov 2020 ;60(4):19-29

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

Aims: Gestational diabetes mellitus (GDM) is an emerging worldwide problem. Changes in clinical characteristics of women affected by GDM in a long-term perspective are still not properly investigated. We aimed to examine such changes over a decade in a retrospective single-center analysis.

Methods: The medical documentation from Department of Metabolic Diseases, Krakow, Poland was analyzed. We included 633 women consecutively diagnosed with GDM in one of three time intervals: 2007-2008 (N = 157), 2012-2013 (N = 272), 2016-2017 (N = 234). Statistical analyses were performed.

Results: Comparison of the three groups identified differences in the mean age of women at the GDM diagnosis (30.7 ± 5.0 years vs. 31.2 ± 4.7 vs. 32.5 ± 4.7, respectively, starting from the earliest 2007-2008 group), pregnancy week at GDM diagnosis (28.0 ± 5.3 wks. vs. 25.9 ± 4.9 vs. 23.4 ± 6.8), the proportion of women diagnosed before the 24th week of pregnancy (12.8% vs. 16.5% vs. 31.3%), and gestational weight gain (12.4 ± 5.0 kg vs. 10.4 ± 5.2 vs. 10.0 ± 5.7); (p = 0.001 or less for all comparisons). We also found differences for glucose values on fasting and at 2 hours with the highest (0 min) and lowest level (120 min) in the 2016-2017, respectively. Finally, a borderline difference for the weight, but not for BMI, was found (64.1 ± 14.1 kg vs. 66.2 ± 13.1 vs. 67.8 ± 15.6; p = 0.04). Differences were also identified in the post hoc analysis between cohorts.

Conclusion: This retrospective analysis illustrates changes in characteristics of women with GDM occurring over the period of decade in Poland. They likely result from both epidemiological trends and modifications of the WHO criteria for the GDM diagnosis.
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January 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.
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http://dx.doi.org/10.1177/1753425919891628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903534PMC
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.

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

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

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

Raman spectral signatures of urinary extracellular vesicles from diabetic patients and hyperglycemic endothelial cells as potential biomarkers in diabetes.

Nanomedicine 2019 04 28;17:137-149. Epub 2019 Jan 28.

Department of Medical Physics, Marian Smoluchowski Institute of Physics Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, Krakow, Poland.

Raman spectroscopy was applied to the measurement of urinary and in vitro endothelium-derived extracellular vesicles (EVs) isolated by hydrostatic filtration dialysis (HFD) method. Raman spectra obtained for urinary EVs (UEVs) showed distinct differences in the fingerprint region. In contrast, average Raman spectra of endothelium-derived EVs samples were almost identical. Cluster Analysis of UEVs significantly discriminated diabetic samples from control, moreover endothelium-derived EVs revealed stronger similarity between long hyperglycemia and normoglycemia samples compared to short hyperglycemia. Results obtained from Partial Least Squares analysis corresponded well with integral intensities of selected bands. Our proof-of-concept approach demonstrates the potential for Raman spectroscopy to be used both for identification of EVs molecular signatures in urine samples from patients with type 2 diabetes mellitus and good glycemic control and unsatisfactory glycemic control as well as for in vitro hyperglycemic model. This noninvasive technique may be useful in identifying new biomarkers of diabetes and renal complications.
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http://dx.doi.org/10.1016/j.nano.2019.01.011DOI Listing
April 2019

Plasma Protein Oxidation as a Determinant of Impaired Fibrinolysis in Type 2 Diabetes.

Thromb Haemost 2019 Feb 3;119(2):213-222. Epub 2019 Jan 3.

Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland.

Objective:  We investigated clinical and laboratory determinants of plasma protein oxidation and its associations with clot fibrinolysis in type 2 diabetes patients.

Materials And Methods:  Our cross-sectional study consisted of 246 type 2 diabetic patients, 143 (58%) with concomitant cardiovascular disease (CVD), including 41 (17%) with previous myocardial infarction (MI). We measured total protein carbonylation (PC), thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) along with clot lysis time (CLT) and clot permeation ( ), fibrinogen, plasminogen, α-2-antiplasmin, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI) and thrombomodulin.

Results:  Total PC correlated positively, while TAC correlated inversely with glycated haemoglobin and diabetes duration (all  < 0.05). Diabetic patients with CVD had higher total PC, TBARS and lower TAC compared with the remainder (all  < 0.001). Among correlations of total PC with , PAI-1, thrombomodulin and TAFI, the strongest was with CLT ( = 0.687, all  < 0.01). High total PC, defined as ≥ 3.45 nmol/mg, was predicted by time since diabetes diagnosis ≥ 5 years (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.36-6.63) and previous MI (OR: 11.31, 95% CI: 4.37-29.32). After adjustment for potential confounders, total PC accounted for 34.9% of the total variance in CLT. Total PC at a cut-off of 3.44 nmol/mg showed high discriminatory power for identifying patients with prolonged CLT (area under the curve: 0.845, 95% CI: 0.792-0.898,  < 0.001).

Conclusion:  Elevated plasma PC, largely driven by a long history of diabetes and concomitant CVD, is an important determinant of hypofibrinolysis in type 2 diabetes.
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http://dx.doi.org/10.1055/s-0038-1676609DOI Listing
February 2019

Negative pressure wound therapy use in diabetic foot syndrome-from mechanisms of action to clinical practice.

Eur J Clin Invest 2019 Apr 29;49(4):e13067. Epub 2019 Jan 29.

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

Background: Diabetes and its complications constitute a rising medical challenge. Special attention should be given to diabetic foot syndrome (DFS) due to its high rate of associated amputation and mortality. Negative pressure wound therapy (NPWT) is a frequently used supportive modality in a diabetic foot with ulcerations (DFUs).

Design: Here, we reviewed the current knowledge concerning the tissue and molecular mechanisms of NPWT action with an emphasis on diabetes research followed by a summary of clinical DFU studies and practice guidelines.

Results: Negative pressure wound therapy action results in two types of tissue deformations-macrodeformation, such as wound contraction, and microdeformation occurring at microscopic level. Both of them stimulate a wound healing cascade including tissue granulation promotion, vessel proliferation, neoangiogenesis, epithelialization and excess extracellular fluid removal. On the molecular level, NPWT results in an alteration towards more pro-angiogenic and anti-inflammatory conditions. It increases expression of several key growth factors, including vascular endothelial growth factor and fibroblast growth factor 2, while expression of inflammatory cytokinesis reduced. The NPWT application also alters the presence and function of matrix metalloproteinases. Clinical studies in DFU patients showed a superiority of NPWT over standard therapy in terms of efficacy outcomes, primarily wound healing and amputation rate, without a rise in adverse events. International guidelines point to NPWT as an important adjuvant therapy in DFU whose use is expected to increase.

Conclusions: This current knowledge improves our understanding of NPWT action and its tailoring for application in diabetic patients. It may inform the development of new treatments for DFU.
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http://dx.doi.org/10.1111/eci.13067DOI Listing
April 2019

Insulin pump settings and glucose patterns during a 1008-km non-stop bicycle race in a patient with type 1 diabetes mellitus.

Acta Diabetol 2019 05 15;56(5):593-595. Epub 2018 Nov 15.

Department of Metabolic Diseases, Jagiellonian University Medical College, 15 Kopernika Street, 31-501, Kraków, Poland.

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http://dx.doi.org/10.1007/s00592-018-1254-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451704PMC
May 2019

Quality of life assessment in patients with HNF1A-MODY and GCK-MODY.

Endocrine 2019 05 12;64(2):246-253. Epub 2018 Nov 12.

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

Aim: The impact of maturity onset diabetes of the young (MODY) on quality of life (QoL) has never been examined. We assessed disease impact on QoL among patients with HNF1A-MODY and GCK mutation carrier status.

Methods: The study included 80 patients with HNF1A-MODY and 89 GCK gene mutation carriers. We also examined 128 type 1 diabetes (T1DM) patients for comparison. Diabetes-specific QoL was assessed using the Audit of Diabetes Dependent Quality of Life questionnaire.

Results: HNF1A-MODY and GCK-MODY groups had similar mean age (41.7 vs. 38.0 years, respectively) and BMI (24.1 vs. 24.3 kg/m), whereas T1DM patients were on average younger (34.2 years) with similar BMI (25.0 kg/m). Less than a third of GCK mutation carriers were on pharmacotherapy (n = 20, 31%), while the majority of HNF1A mutation carriers used oral drugs or insulin (n = 66, 82.5%). While current QoL was similar across the three groups (p = 0.66), two other major indices-the impact of diabetes on QoL and the average weighted impact (AWI)-differed among them (p < 0.001 for both comparisons). The impact of diabetes on patient QoL and AWI observed in both MODY groups was smaller than in T1DM. Etiological diagnosis of diabetes and a diagnosis of retinopathy were the only independent factors influencing the impact of diabetes on QoL and AWI in regression analysis. In HNF1A-MODY, all three major indices of QoL were more heavily influenced for patients on insulin in comparison to other treatment sub-groups.

Conclusion: MODY has a smaller negative impact on QoL compared to T1DM. Mode of treatment further stratifies QoL decline for HNF1A-MODY subjects.
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http://dx.doi.org/10.1007/s12020-018-1812-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531383PMC
May 2019

Negative pressure wound therapy in the treatment of diabetic foot ulcers may be mediated through differential gene expression.

Acta Diabetol 2019 Jan 17;56(1):115-120. Epub 2018 Sep 17.

Department of Metabolic Diseases, Jagiellonian University Medical College, 15 Kopernika Street, 31-501, Kraków, Poland.

Aims: Negative pressure wound therapy (NPWT) has been successfully used as a treatment for diabetic foot ulceration (DFU). Its mechanism of action on the molecular level, however, is not fully understood. We assessed the effect of NPWT on gene expression in patients with type 2 diabetes (T2DM) and DFU.

Methods: We included two cohorts of patients-individuals treated with either NPWT or standard therapy. The assignment to NWPT was non-randomized and based on wound characteristics. Differential gene expression profiling was performed using Illumina gene expression arrays and R Bioconductor pipelines based on the 'limma' package.

Results: The final cohort encompassed 21 patients treated with NPWT and 8 with standard therapy. The groups were similar in terms of age (69.0 versus 67.5 years) and duration of T2DM (14.5 versus 14.4 years). We identified four genes differentially expressed between the two study arms post-treatment, but not pre-treatment: GFRA2 (GDNF family receptor alpha-2), C1QBP (complement C1q binding protein), RAB35 (member of RAS oncogene family) and SYNJ1 (synaptic inositol 1,4,5-trisphosphate 5-phosphatase 1). Interestingly, all four genes seemed to be functionally involved in wound healing by influencing re-epithelialization and angiogenesis. Subsequently, we utilized co-expression analysis in publicly available RNA-seq data to reveal the molecular functions of GFRA2 and C1QBP, which appeared to be through direct protein-protein interactions.

Conclusions: We found initial evidence that the NPWT effect on DFUs may be mediated through differential gene expression. A discovery of the specific molecular mechanisms of NPWT is potentially valuable for its clinical application and development of new therapies.
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http://dx.doi.org/10.1007/s00592-018-1223-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346079PMC
January 2019