Publications by authors named "Arkadiusz Michalak"

20 Publications

  • Page 1 of 1

Clinical heterogeneity among pediatric patients with autoimmune type 1 diabetes stratified by immunoglobulin deficiency.

Pediatr Diabetes 2021 Apr 10. Epub 2021 Apr 10.

Department of Pediatrics, Oncology, and Hematology, Medical University of Łódź, Łódź, Poland.

Background: Type 1 diabetes (T1D) may coexist with primary immunodeficiencies, indicating a shared genetic background.

Objective: To evaluate the prevalence and clinical characteristics of immunoglobulin deficiency (IgD) among children with T1D.

Methods: Serum samples and medical history questionnaires were obtained during routine visits from T1D patients aged 4-18 years. IgG, IgA, IgM, and IgE were measured by nephelometry and enzyme-linked immunosorbent assay (ELISA). IgG and IgM deficiency (IgGD, IgMD) were defined as IgG/IgM >2 standard deviations (SD) below age-adjusted mean. IgE deficiency was defined as IgE <2 kIU/L. IgA deficiency (IgAD) was defined as IgA >2 SD below age-adjusted mean irrespective of other immunoglobulin classes (absolute if <0.07 g/L, partial otherwise) and as selective IgAD when IgA >2 SD below age-adjusted mean with normal IgG and IgM (absolute if <0.07 g/L, partial otherwise).

Results: Among 395 patients (53.4% boys) with the median age of 11.2 (8.4-13.7) and diabetes duration 3.6 (1.1-6.0) years, 90 (22.8%) were found to have hypogammaglobulinemia. The IgGD and IgAD were the most common each in 40/395 (10.1%). Complex IgD was found in seven patients. Increased odds of infection-related hospitalization (compared to children without any IgD) was related to having any kind of IgD and IgAD; OR (95%CI) = 2.1 (1.2-3.7) and 3.7 (1.8-7.5), respectively. Furthermore, IgAD was associated with having a first-degree relative with T1D OR (95%CI) = 3.3 (1.4-7.6) and suffering from non-autoimmune comorbidities 3.3 (1.4-7.6), especially neurological disorders 3.5 (1.2-10.5).

Conclusions: IgDs frequently coexist with T1D and may be associated with several autoimmune and nonimmune related disorders suggesting their common genetic background.
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http://dx.doi.org/10.1111/pedi.13208DOI Listing
April 2021

Remus: A Web Application for Prioritization of Regulatory Regions and Variants in Monogenic Diseases.

Front Genet 2021 5;12:638960. Epub 2021 Mar 5.

Department of Biostatistics and Translational Medicine, Medical University of Lodz, Łódź, Poland.

Background: Analysis of variants in distant regulatory elements could improve the current 25-50% yield of genetic testing for monogenic diseases. However, the vast size of the regulome, great number of variants, and the difficulty in predicting their phenotypic impact make searching for pathogenic variants in the regulatory genome challenging. New tools for the identification of regulatory variants based on their relevance to the phenotype are needed.

Methods: We used tissue-specific regulatory mapped by ENCODE and FANTOM, together with miRNA-gene interactions from miRTarBase and miRWalk, to develop Remus, a web application for the identification of tissue-specific regulatory regions. Remus searches for regulatory features linked to the known disease-associated genes and filters them using activity status in the target tissues relevant for the studied disorder. For user convenience, Remus provides a web interface and facilitates in-browser filtering of variant files suitable for sensitive patient data.

Results: To evaluate our approach, we used a set of 146 regulatory mutations reported causative for 68 distinct monogenic disorders and a manually curated a list of tissues affected by these disorders. In 89.7% of cases, Remus identified the regulator containing the pathogenic mutation. The tissue-specific search limited the number of considered variants by 82.5% as compared to a tissue-agnostic search.

Conclusion: Remus facilitates the identification of regulatory regions potentially associated with a monogenic disease and can supplement classical analysis of coding variations with the aim of improving the diagnostic yield in whole-genome sequencing experiments.
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http://dx.doi.org/10.3389/fgene.2021.638960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978111PMC
March 2021

Responses to Low- and High-Intensity Exercise in Adolescents with Type 1 Diabetes in Relation to Their Level of VO Max.

Int J Environ Res Public Health 2021 01 15;18(2). Epub 2021 Jan 15.

Department of Physiology, Gdansk University of Physical Education and Sport, 80-336 Gdansk, Poland.

The purpose of this study was to investigate the influence of maximal oxygen uptake (VO max) on the glycemic changes during low and high intensity exercises in young type 1 diabetic patients. Twenty boys (age: 14.3 ± 1.6 years; height: 171.0 ± 11.3 cm; weight; 59.5 ± 12.8 kg) were divided into low-fit group (LFG, = 10) and high-fit group (HFG, = 10). According to the experimental design, participants performed three physical efforts (VO max test, mixed aerobic-anaerobic effort and aerobic effort) on the cycloergometer, during which real-time glycemia was measured. Mixed aerobic-anaerobic exercise demanded significantly smaller carbohydrate supplementation (0.2 ± 0.2 g/kg during exercise) than the aerobic test session (0.4 ± 0.3 g/kg during exercise). Moreover, patients with higher VO max had lower tendency for glycemic changes during the aerobic effort. The results of the current study suggest that young type 1 diabetic patients should perform different intensity activities using continuous glycemic monitoring system to avoid acute and chronic complications of the disease.
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http://dx.doi.org/10.3390/ijerph18020692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830455PMC
January 2021

Biological Activity of c-Peptide in Microvascular Complications of Type 1 Diabetes-Time for Translational Studies or Back to the Basics?

Int J Mol Sci 2020 Dec 20;21(24). Epub 2020 Dec 20.

Department of Biostatistics and Translational Medicine, Medical University of Lodz, 92-215 Lodz, Poland.

People with type 1 diabetes have an increased risk of developing microvascular complications, which have a negative impact on the quality of life and reduce life expectancy. Numerous studies in animals with experimental diabetes show that c-peptide supplementation exerts beneficial effects on diabetes-induced damage in peripheral nerves and kidneys. There is substantial evidence that c-peptide counteracts the detrimental changes caused by hyperglycemia at the cellular level, such as decreased activation of endothelial nitric oxide synthase and sodium potassium ATPase, and increase in formation of pro-inflammatory molecules mediated by nuclear factor kappa-light-chain-enhancer of activated B cells: cytokines, chemokines, cell adhesion molecules, vascular endothelial growth factor, and transforming growth factor beta. However, despite positive results from cell and animal studies, no successful c-peptide replacement therapies have been developed so far. Therefore, it is important to improve our understanding of the impact of c-peptide on the pathophysiology of microvascular complications to develop novel c-peptide-based treatments. This article aims to review current knowledge on the impact of c-peptide on diabetic neuro- and nephropathy and to evaluate its potential therapeutic role.
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http://dx.doi.org/10.3390/ijms21249723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766542PMC
December 2020

Improved Estimation of Glycated Hemoglobin from Continuous Glucose Monitoring and Past Glycated Hemoglobin Data.

Diabetes Technol Ther 2021 Apr 9;23(4):293-305. Epub 2021 Mar 9.

Department of Biostatistics and Translational Medicine, Diabetology, Endocrinology and Nephrology, Medical University of Lodz, Lodz, Poland.

Accurate estimation of glycated hemoglobin (HbA1c) from continuous glucose monitoring (CGM) remains challenging in clinic. We propose two statistical models and validate them in real-life conditions against the current standard, glucose management indicator (GMI). Modeling utilized routinely collected data from patients with type 1 diabetes from central Poland (eligibility criteria: age >1 year, diabetes duration >3 months, and CGM use between 01/01/2015 and 12/31/2019). CGM records were extracted from dedicated Medtronic/Abbott databases and cross-referenced with HbA1c values; 28-day periods preceding HbA1c measurement with >75% of the sensor-active time were analyzed. We developed a mixed linear regression, including glycemic variability indices and patient's ID (glucose variability-based patient specific model, GV-PS) intended for closed-group use and linear regression using patient-specific error of GMI (proportional error-based patient agnostic model, PE-PA) for general use. Models were validated with either new HbA1cs from closed-group patients or separate patient-HbA1c pool. External validation was performed with data from clinical trials. Performance metrics included bias, its 95% confidence interval (95% CI), coefficient of determination (), and root mean square error (RMSE). We included 723 HbA1c-CGM pairs from 174 patients (mean age 9.9 ± 4.4 years and diabetes duration 3.7 ± 3.6 years). GMI yielded  = 0.58, with different bias between Medtronic and Abbott devices [0.120% vs. -0.152%,  < 0.0001], and overall 95% CI = -0.9% to +1%, RMSE = 0.47%. GV-PS successfully captured patient-specific variance (closed-group validation:  = 0.83, bias = 0.026%, 95% CI = -0.562% to 0.591%, RMSE = 0.31%). PE-PA performed similarly on new patients ( = 0.76, bias = -0.069%, 95% CI = -0.790% to 0.653%, RMSE = 0.37%). In external validation GMI, GV-PS, and PE-PA produced 73.8%, 87.5%, and 91.0% predictions within 0.5% (5.5 mmol/mol) from the true value. Constructed models performed better than GMI. PE-PA provided an accurate estimate of HbA1c with fast and straightforward implementation.
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http://dx.doi.org/10.1089/dia.2020.0433DOI Listing
April 2021

Impact of factory-calibrated Freestyle Libre System with new glucose algorithm measurement accuracy and clinical performance in children with type 1 diabetes during summer camp.

Pediatr Diabetes 2021 Mar 20;22(2):261-270. Epub 2020 Oct 20.

Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland.

Background: Factory-calibrated intermittently-scanned Continuous Glucose Monitoring (isCGM) device FreeStyle Libre (FSL) has recently received improvements in its glucose tracking algorithm and calibration procedures, which are claimed to have improved its accuracy.

Objective: To compare the accuracy of two generations of 14-days FSL devices (A in 2016, B in 2019) to self-monitored blood glucose measurements (SMBG) in children with type 1 diabetes in real-life conditions during a summer camp.

Materials And Methods: Two largely independent groups of youth with type 1 diabetes took part in summer camps. In 2016 they used FSL-A, in 2019 FSL-B. On scheduled days, participants performed supervised 8-point glucose profiles with FSL and SMBG. The accuracy vs SMBG was assessed with mean absolute relative difference (MARD) and clinical surveillance error grid (SEG).

Results: We collected 1655 FSL-SMBG measurement pairs from 78 FSL-A patients (age 13 ± 2.3 years old; HbA1c: 7.6 ± 0.8%) and 1796 from 58 in FSL-B group (age 13.8 ± 2.3 years old, HbA1c: 7.5 ± 1.1%)-in total 3451 measurements. FSL-B displayed lower MARD than FSL-A (11.3 ± 3.1% vs 13.7 ± 4.6%, P = .0003), lower SD of errors (20.2 ± 6.7 mg/dL vs 24.1 ± 9.6 mg/dL, P = .0090) but similar bias (-7.6 ± 11.8 mg/dL vs -6.5 ± 8 mg/dL, P = .5240). Both FSL-A and FSL-B showed significantly higher MARD when glycaemia was decreasing >2 mg/dL/min (FSL-A:22.3 ± 18.5%; FSL-B:17.9 ± 15.8%, P < .0001) compared with stable conditions (FSL-A: 11.4 ± 10.4%, FSL-B:10.1 ± 9.1%) and when the system could not define the glycaemic trend (FSL-A:16.5 ± 16.3%; FSL-B:15.2 ± 14.9%, P < .0001). Both generations demonstrated high percentage of A-class and B-class results in SEG (FSL-A: 96.4%, FSL-B: 97.6%) with a significant shift from B (decrease by 3.7%) to A category (increase by 3.9%) between generations (FSL-A: 16/80.4%; FSL-B:12.3/85.3%, P = .0012).

Conclusion: FSL-B demonstrated higher accuracy when compared to FSL-A However, when glycemia is decreasing or its trend is uncertain, the verification with a glucose meter is still advisable.
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http://dx.doi.org/10.1111/pedi.13135DOI Listing
March 2021

Nighttime Hypoglycemia in Children with Type 1 Diabetes after one Day of Football Tournament.

Int J Sports Med 2020 Oct 7;41(13):972-980. Epub 2020 Jul 7.

Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznan, Poland.

The aim of the study was to investigate factors related to the occurrence of nighttime hypoglycemia after a football tournament in children with type 1 diabetes mellitus. The multicenter study (GoalDiab study) included 189 children and adolescents with type 1 diabetes mellitus, from 11 diabetes care centers in Poland. Hypoglycemia was defined according to the International Hypoglycemia Study Group Statement. We analyzed the data of 95 participants with completed protocols with regards to nighttime hypoglycemia (82% male), aged 11.6 (9.8-14.2) years, diabetes duration 5.0 (2.0-8.0) years. There were 47 episodes of nighttime Level 1 hypoglycemia (≤3.9 mmol/L). Occurrence of clinically important Level 2 hypoglycemia (<3.0 mmol/L) during a game period was positively associated with nighttime hypoglycemia (≤3.9 mmol/L) incident (Odds Ratio=10.7; 95% Confidence Interval: 1.1-100.2; p=0.04). Using Continuous Glucose Monitoring was negatively associated with the occurrence of nighttime hypoglycemia (≤3.9 mmol/L) compared with using glucose meters or Flash Glucose Monitoring (Odds Ratio=0.31; 95% Confidence Interval: 0.12-0.83; p=0.02). The occurrence of clinically important hypoglycemia related to physical activity is associated with the occurrence of hypoglycemia during the night. Continuous Glucose Monitoring is negatively associated with nighttime hypoglycemia after a day of competition.
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http://dx.doi.org/10.1055/a-1192-5992DOI Listing
October 2020

Klotho and fibroblast growth factors 19 and 21 serum concentrations in children and adolescents with normal body weight and obesity and their associations with metabolic parameters.

BMC Pediatr 2020 06 16;20(1):294. Epub 2020 Jun 16.

Department of Gastroenterology, Allergology and Pediatrics, Polish Mother's Memorial Hospital-Research Institute, 281/289 Rzgowska St, 93-338, Lodz, Poland.

Background: Fibroblast growth factor 19 (FGF19), fibroblast growth factor 21 (FGF21) and Klotho are regulators of energy homeostasis. However, in the pediatric population, the relationships between obesity, metabolic disorders and the aforementioned factors have not been clearly investigated. We analyzed the role of FGF19, FGF21 and Klotho protein in children with normal body weight as well as in overweight and obese subjects and explored their associations with insulin resistance (IR) and metabolic syndrome (MS) and its components.

Methods: This was a cross-sectional study conducted in a group of hospitalized children and adolescents. Laboratory investigations included serum analysis of FGF19, FGF21, and Klotho with ELISA kits as well as the analysis of the lipid profile and ALT serum concentrations. Moreover, each subject underwent an oral glucose tolerance test (OGTT) with fasting insulinemia measurement to detect glucose tolerance abnormalities and calculate the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index. Furthermore, the clinical analysis included blood pressure measurement, body fat percentage estimation and assessment of the prevalence of MS and its components.

Results: The study was conducted with 174 children/adolescents aged 6-17 years with normal body weight (N = 48), obesity (N = 92) and overweight (N = 34). Klotho concentration was significantly higher in the obese children [median 168.6 pg/ml (90.2 to 375.9)]) than in the overweight [131.3 pg/ml (78.0 to 313.0)] and normal-body-weight subjects [116.6 pg/ml (38.5 to 163.9)] (p = 0.0334) and was also significantly higher in insulin-resistant children than in insulin-sensitive children [185.3 pg/ml (102.1 to 398.2) vs 132.6 pg/ml (63.9 to 275.6), p = 0.0283]. FGF21 was elevated in patients with MS compared to the FGF21 levels in other subjects [136.2 pg/ml (86.5 to 239.9) vs 82.6 pg/ml (41.8 to 152.4), p = 0.0286]. The multivariable model showed that FGF19 was an independent predictor of IR after adjusting for pubertal stage and BMI Z-score.

Conclusions: Klotho levels were associated with body weight status in children and adolescents. Moreover, Klotho, FGF19 and FGF21 concentrations correlated with IR status and/or components of MS.
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http://dx.doi.org/10.1186/s12887-020-02199-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296965PMC
June 2020

Evaluation of skin autofluorescence as a surrogate of advanced glycation end products accumulation in children and adolescents with normal haemoglobin A1c values.

Pediatr Endocrinol Diabetes Metab 2020 ;26(1):1-9

Department of Paediatrics, Diabetology, Endocrinology, and Nephrology, Medical University of Lodz, Poland.

Introduction: Skin autofluorescence (sAF) represents tissue accumulation of advanced glycation end products (AGEs) and correlates with cardiovas-cular morbidity and diabetes risk.

The Aim: To assess sAF in Polish children without diabetes and to investigate whether sAF values in children with chronic diseases (but without glucose metabolism disorders) differ from sAF in healthy children.

Material And Methods: Children without diseases known to influence sAF results (diabetes, renal failure) and with HbA1c < 5.7% (39 mmol/mol) were includ-ed, and the total study group was divided into two subgroups: with and without chronic conditions. Skin autofluorescence was meas-ured with an AGE Reader (Diagnoptics BV, Groningen, Netherlands). Data were presented as medians; Mann-Whitney U-test, Kruskall Wallis test, and Spearman's correlation coefficients were used in statistical analyses.

Results: The study group included 86 children (41 girls; mean age 10.1 ±4.2 years). Median sAF was 1.20 AU (25th-75th centile: 1.06-1.30). There was a positive correlation between sAF and age (R = 0.37, p = 0.0005). Skin autofluorescence values were higher in children with chronic diseases than in healthy children (1.23 AU [25th-75th centile: 1.10-1.40], n = 51 vs. 1.16 AU [1.06-1.26], n = 36, p = 0.0272).

Conclusions: To our knowledge we present the first data on sAF values in Polish children without glucose metabolism disorders. We suggest that larger, homogenous populations of different ages should be studied to determine if and which diseases affect sAF measurements, and to develop pediatric reference values for sAF. This will allow a wider use of sAF measurement in the assessment of cardiovascular risk in the paediatric population.
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http://dx.doi.org/10.5114/pedm.2020.93251DOI Listing
March 2021

A cross-sectional study of patients referred for HNF1B-MODY genetic testing due to cystic kidneys and diabetes.

Pediatr Diabetes 2020 05 29;21(3):422-430. Epub 2020 Jan 29.

Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland.

Background/objectives: Patients referred for HNF1B testing present very heterogeneous phenotypes. Despite suggestive characteristics, many do not harbor mutations in HNF1B. Our objective was to evaluate the clinical characteristics of probands referred for HNF1B genetic testing through a nationwide monogenic diabetes screening program.

Methods: Probands tested for HNF1B mutations in the 2005-2018 period (N = 50) were identified in the Polish Monogenic Diabetes Registry, which prospectively recruits primarily pediatric patients and their families on a nationwide scale. Variants that had been reported pathogenic were reassessed using criteria of the American College of Medical Genetics and Genomics (ACMG). A structured medical interview was performed with all available individuals, their parents, and/or their physicians. For each patient, HNF1B score was calculated based on available clinical information.

Results: The study group numbered 36 unrelated probands (28% lost to follow-up): 14 with pathogenic or likely-pathogenic variants in HNF1B, one with a variant of uncertain significance, and 21 negative for HNF1B mutations. Presence of cystic kidneys (OR = 9.17, 95% CI:1.87-44.92), pancreatic abnormalities (OR = 15, 95% CI:1.55-145.23), elevated liver enzymes (OR = 15, 95% CI:1.55-145.23) best discriminated HNF1B-positive cases from the negative ones. Presence of impaired glucose tolerance coupled with kidney disease in the proband and one parent was also highly predictive for HNF1B mutations (OR = 11.11, 95% CI:1.13-109.36). HNF1B-score with recommended cutoff distinguished patients with and without HNF1B findings with 100% sensitivity and 47.6% specificity. Addition of four clinical variables to select patients based on HNF1B score improved specificity to 71.4% (95% CI:47.8%-88.7%) while retaining 100% sensitivity.

Conclusions: Detailed medical interview may enable more accurate patient selection for targeted genetic testing.
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http://dx.doi.org/10.1111/pedi.12959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217165PMC
May 2020

Physical workload and glycemia changes during football matches in adolescents with type 1 diabetes can be comparable.

Acta Diabetol 2019 Nov 4;56(11):1191-1198. Epub 2019 Jun 4.

Department of Pediatrics, Diabetology, Endocrinology and Nephrology, Medical University of Lodz, ul. Sporna 36/50, 91-738, Lodz, Poland.

Aims: To analyze physical performance and diabetes-related outcomes in adolescents with type 1 diabetes (T1DM) during two semi-competitive football matches utilising precise physical activity monitoring.

Methods: The study was conducted during an annual summer camp for adolescents with T1DM. After physical examination and glycated hemoglobin measurement, 16 adolescent players completed Cooper's 12-min running test and, in the following days, took part in two football matches while wearing heart rate (HR) monitors coupled with global positioning system (GPS) tracking.

Results: Both matches were comparable in terms of covered distances, number of sprints, achieved velocities and heart rate responses. During both games, capillary blood lactate increased significantly (Match 1: 1.75 ± 0.16-6.13 ± 1.73 mmol/l; Match 2: 1.77 ± 0.18-3.91 ± 0.63 mmol/l, p = 0.004). No significant differences in blood glucose were observed between the matches (p = 0.83) or over each match (p = 0.78). Clinically significant hypoglycemia (< 54 mg/dl) occurred in two children during the first match. None of the players experienced severe hypoglycemia. Despite similar workloads, players consumed significantly less carbohydrates during Match 2 [median difference: - 20 g (25-75%: - 40 to 0), p = 0.006].

Conclusions: HR monitoring and GPS-based tracking can effectively parameterize physical activity during a football match. In T1DM patients, exercise workload and glycemic changes during similar matches are comparable, which provides an opportunity to develop individual recommendations for players with T1DM.
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http://dx.doi.org/10.1007/s00592-019-01371-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768890PMC
November 2019

Assessment of Safety and Glycemic Control During Football Tournament in Children and Adolescents With Type 1 Diabetes-Results of GoalDiab Study.

Pediatr Exerc Sci 2019 11 27;31(4):401-407. Epub 2019 Jun 27.

Poznan University of Medical Sciences.

Purpose: To assess glycemic control and safety of children and adolescents with type 1 diabetes participating in a 2-day football tournament.

Methods: In total, 189 children with type 1 diabetes from 11 diabetes care centers, in Poland, participated in a football tournament in 3 age categories: 7-9 (21.2%), 10-13 (42.9%), and 14-17 (36%) years. Participants were qualified and organized in 23 football teams, played 4 to 6 matches of 30 minutes, and were supervised by a medical team. Data on insulin dose and glycemia were downloaded from personal pumps, glucose meters, continuous glucose monitoring, and flash glucose monitoring systems.

Results: The median level of blood glucose before the matches was 6.78 (4.89-9.39) mmol/L, and after the matches, it was 7.39 (5.5-9.87) mmol/L (P = .001). There were no episodes of severe hypoglycemia or ketoacidosis. The number of episodes of low glucose value (blood glucose ≤3.9 mmol/L) was higher during the tournament versus 30 days before: 1.2 (0-1.5) versus 0.7 (0.3-1.1) event/person/day, P < .001. Lactate levels increased during the matches (2.2 [1.6-4.0] mmol/L to 4.4 [2.6-8.5] mmol/L after the matches, P < .001).

Conclusions: Large football tournaments can be organized safely for children with type 1 diabetes. For the majority of children, moderate mixed aerobic-anaerobic effort did not adversely affect glycemic results and metabolic safety.
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http://dx.doi.org/10.1123/pes.2018-0264DOI Listing
November 2019

Discrepancies between methods of continuous glucose monitoring in key metrics of glucose control in children with type 1 diabetes.

Pediatr Diabetes 2019 08 17;20(5):604-612. Epub 2019 Apr 17.

Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland.

Objective: We aimed to compare glycemic control and variability parameters obtained from paired records of real-time continuous glucose monitoring (RT-CGM) and flash glucose monitoring (FGM).

Methods: Ten Polish boys and 11 girls aged 15.3 ± 2.1 years with type 1 diabetes for 7.7 ± 4.5 years and glycated hemoglobin 7.35 ± 0.7% (57 ± 5 mmol/mol) were recruited between August 2017 and June 2018 and equipped with devices for RT-CGM (iPro2 system with Enlite electrodes) and FGM (FreeStyle Libre) for 1 week. Afterwards, Glyculator 2.0 software was used to calculate and compare key metrics of glycemic control listed in the International Consensus on Use of Continuous Glucose Monitoring, with distinction into all record/night-time/day-time blocks when appropriate.

Results: Agreement between the two systems' measurements across patients ranged from poor (R  = .39) to nearly perfect (R  = .97). Significant differences between RT-CGM and FGM were observed in five important metrics: coefficient of variation (median difference: -4.12% [25%-75%: -7.50% to -2.96%], P = .0001), low blood glucose index (-0.88 [-1.88 to -0.18], P = .0004), % of time below 70 mg/dL (3.9 mmol/L) (-4.77 [-8.39 to -1.19], P = .0015) and 54 mg/dL (3 mmol/L) (-1.33 [-4.07 to 0.00], P = .0033) and primary time in range (TIR) 70-180 mg/dL (8.58 [1.31 to 12.66], P = .0006).

Conclusions: RT-CGM and FGM differ in their estimates of clinically important indices of glycemic control. Therefore, such metrics cannot be directly compared between people using different systems. Our result necessitates system-specific guidelines and targets if TIR and glycemic variability are to be used as an endpoint in clinical trials.
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http://dx.doi.org/10.1111/pedi.12854DOI Listing
August 2019

Assessment of Exercise Capacity in Children with Type 1 Diabetes in the Cooper Running Test.

Int J Sports Med 2019 Feb 17;40(2):110-115. Epub 2018 Dec 17.

Department of Pediatrics, Diabetology, Endocrinology and Nephrology, Medical University of Lodz, Lodz, Poland.

Regular physical activity increases lifespan for those with type 1 diabetes. However, disease-related barriers may deter children from exercise and affect their fitness. This study examined the safety of the Cooper test concerning diabetes-related acute complications in children with type 1 diabetes and their fitness. Blood glucose was recorded before and 0, 30, 60 min after the test. The covered distances were transformed to z-scores based on the national charts. Body mass index, body fat percentage and glycated hemoglobin were measured. The run was completed by 80 individuals (45% boys, age 13.6±2.1 years; diabetes duration 6.3±3.5 years). During the follow-up 11 children reached glucose alert values (3-3.9 mmol/L), 3 presented clinically significant hypoglycemia (<3 mmol/L), none experienced severe hypoglycemia. The covered distance was 1914±298 m, not significantly different from the reference population (z-score -0.12±0.71 vs 0, p=0.12). The study participants were more overweight than general pediatric population in terms of body mass index (z-score 0.48±0.94 vs 0, p<0.001) and body fat percentage (z-score: 0.37±0.85 vs 0, p<0.001). In conclusion, the Cooper test can be safely used in children with diabetes to assess their physical capacity. Youth with type 1 diabetes present fitness similar to healthy children but exhibit increased body mass index and adiposity.
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http://dx.doi.org/10.1055/a-0805-1326DOI Listing
February 2019

Achieving target levels for vascular risk parameters in Polish school-age children with type 1 diabetes - a single center study.

J Pediatr Endocrinol Metab 2018 Oct;31(10):1073-1079

Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland.

Background Therapeutic goals have been established to decrease the risk of long-term complications of type 1 diabetes (T1DM). The effects of these guidelines should be constantly evaluated. Hence, the present study examines the frequency at which children with T1DM treated by one of the Polish reference centers complied with the therapeutic targets issued in 2014 by the International Society for Pediatric and Adolescent Diabetes (ISPAD) and by the Diabetes Poland (PTD). Methods A retrospective analysis (years 2011-2014) was performed in patients with T1DM aged 6.5-18 years, with diabetes duration >12 months and no change of insulin regimen within 6 months. Collected data included insulin therapy regimen, weight, height, blood pressure, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and glycated hemoglobin (HbA1c) level from the last hospitalization. Results The records of 447 patients (260 boys, 299 treated with insulin pump) were analyzed. All ISPAD goals were achieved by 123 (27.5%) patients, but only 43 (9.6%) met all PTD targets. Optimal HbA1c was achieved by 224 (50.1%) according to ISPAD criteria (HbA1c<7.5%) and by 87 (19.6%) patients according to PTD (HbA1c≤6.5%). Obesity was diagnosed in 11.6% of the patients; 19.7% of the patients were overweight. In logistic regression, patient age was the only independent predictor of failing to achieve complete T1DM control (p=0.001, OR=1.12 [1.05-1.23]) and optimal HbA1c (p=0.01, OR=1.1 [1.0-1.2]) according to ISPAD guidelines. Moreover, girls had a greater risk of failing body mass index (BMI) targets (PTD: p=0.002, OR=2.16; ISPAD: p=0.0001, OR=3.37) and LDL-C targets (p=0.005, OR=1.8) than boys. Conclusions Overall, control of vascular risk factors in Polish children with T1DM is unsatisfactory. While too few children are achieving the HbA1c target set by PTD, it is possible that such strict national target helps half of the Polish school-age patients achieve ISPAD-issued aim which is more liberal. High prevalence of overweight among children with T1DM warrants initiatives focused not only on glycemic control but also on motivation of patients to lead a healthy lifestyle.
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http://dx.doi.org/10.1515/jpem-2018-0098DOI Listing
October 2018

Coexisting psoriasis affects the clinical course of type 1 diabetes in children.

Pediatr Endocrinol Diabetes Metab 2017 ;23(3):139-145

Department of Biostatistics and Translational Medicine, Medical University of Lodz, Department of Paediatrics, Oncology, Haematology and Diabetology, Medical University of Lodz.

Introduction: Literature reports link psoriasis with insulin resistance characteristic for type 2 diabetes. However, this condition may also affect the clinical course of type 1 diabetes (T1D).

Aim: To investigate whether children with type 1 diabetes mellitus (T1D) and psoriasis have a different course of diabetes.

Methods: We evaluated patients diagnosed with T1D in the years 2002-2011 for the presence of psoriasis and matched them 1:10 with T1D-only patients by sex and duration of diabetes using propensity score. We collected T1D-onset parameters and metabolic control surrogates from six months after T1D diagnosis.

Results: We identified 14 patients with psoriasis and matched 140 controls, of whom 129 (68 boys) were eligible for the analysis. At onset T1D+psoriasis patients showed higher concentration of C-peptide than controls (median: 0.38ng/ml vs 0.15ng/ml, p=0.02). Six months later, they had non-significantly lower HbA1c (6.0 vs 6.6%, p=0.11), TC (143mg/dl vs 159mg/dl, p=0.14) HDL (54.5mg/dl vs 59mg/dl, p=0.11).

Conclusions: Patients with T1D and psoriasis present higher endogenous insulin secretion at T1D onset and a tendency for better glycemic control during the first 6 months.
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http://dx.doi.org/10.18544/PEDM-23.03.0085DOI Listing
July 2018

Flash Glucose Measurements in Children with Type 1 Diabetes in Real-Life Settings: To Trust or Not to Trust?

Diabetes Technol Ther 2018 01 13;20(1):17-24. Epub 2017 Dec 13.

1 Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz , Lodz, Poland .

Background And Aims: To evaluate the clinical accuracy of a flash glucose monitoring device FreeStyle Libre (FSL) among children with type 1 diabetes in real-world settings during a summer camp.

Materials And Methods: During a summer camp, children with type 1 diabetes (n = 79, aged 8-18 years) were provided with FSLs for 12 days. On days 3, 7, and 11 of the study, they underwent supervised glucose testing at 8 timepoints. Glycemia was estimated by using FSL and measured with a personal glucometer within a period of 2 min. The glucose trend arrows were recorded.

Results: The study was completed by 78 children (median: age 12.8 years, diabetes duration 5.8 years, HbA1c 58.5 mmol/mol). Mean absolute relative difference (MARD) between the FSL and the glucometer was 13.5% ± 12.9%. FSL was the most accurate in stable glycemic conditions: MARD 11.4% ± 10.4%, less accurate when glycemia was falling >2 mg/(dL·min) [0.111 mmol/(L·min)-MARD 22.6% ± 18.6%; P < 0.001 vs. stable conditions] and when the device could not determine the glucose trends (16.5% ± 16.3%, P = 0.01 vs. stable conditions). The FSL demonstrated lower accuracy during the day than the night [MARD 14.9% ± 14% vs. 11.2% ± 10.6%, P < 0.0001]. Out of 1655 data pairs of glucometer and FSL, using the Surveillance Error Grid methodology we determined that 80.36% of FSL readings were associated with no clinical risk, 18.73% with slight risk and only one high-risk measurement was detected.

Conclusion: FSL is accurate in children, but its accuracy depends on the glucose trend. Results flagged by the rapid fall flag and "trend undetermined" should be verified by blood glucose measurements.
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http://dx.doi.org/10.1089/dia.2017.0287DOI Listing
January 2018

Monogenic diabetes prevalence among Polish children-Summary of 11 years-long nationwide genetic screening program.

Pediatr Diabetes 2018 02 24;19(1):53-58. Epub 2017 Apr 24.

Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland.

Background: Estimated monogenic diabetes (MD) prevalence increases as screening programs proceeds.

Objective: To estimate prevalence of MD among Polish children.

Subjects: Patients and their family members suspected of suffering from MD (defined as causative mutation in one of the Maturity Onset Diabetes of the Young or permanent neonatal diabetes mellitus genes) were recruited between January 2005 and December 2015.

Methods: Nationwide prevalence was estimated based on data from 6 administrative provinces (out of 16 in Poland) with high referral rates of patients (>10 per 100 000 children).

Results: During the analysis, probands from 322 of 788 screened families tested positive yielding a total of 409 children and 299 family members with MD. An average of 70 probands/year were referred. Screening success rate reached 40% over the study period. We estimated the prevalence of MD in 2015 to 7.52/100 000 children (1 in 13 000). The most frequent MODY in this group was GCK- MODY (6.88/100 000). The prevalence estimates increased nearly 2-fold since our report in 2011 (4.4/100 000). However, the figure reached a plateau because of screening saturation in 2014 what was also proven by lowering of the median age of diagnosis lowered in time (R = -0.73, P = .0172) along with shortening of the delay between clinical and genetic diagnosis (R = -0.65, P = .0417).

Conclusions: The screening for childhood MD in Poland reached a plateau phase after 10 years showing a stable prevalence estimate. The true frequency of MD in the overall population may be higher given later onset of reportedly more frequent types of MD than GCK -MODY.
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http://dx.doi.org/10.1111/pedi.12532DOI Listing
February 2018

Polyunsaturated Fatty Acids and Their Derivatives: Therapeutic Value for Inflammatory, Functional Gastrointestinal Disorders, and Colorectal Cancer.

Front Pharmacol 2016 1;7:459. Epub 2016 Dec 1.

Department of Biochemistry, Faculty of Medicine, Medical University of Lodz Lodz, Poland.

Polyunsaturated fatty acids (PUFAs) are bioactive lipids which modulate inflammation and immunity. They gained recognition in nutritional therapy and are recommended dietary supplements. There is a growing body of evidence suggesting the usefulness of PUFAs in active therapy of various gastrointestinal (GI) diseases. In this review we briefly cover the systematics of PUFAs and their metabolites, and elaborate on their possible use in inflammatory bowel disease (IBD), functional gastrointestinal disorders (FGIDs) with focus on irritable bowel syndrome (IBS), and colorectal cancer (CRC). Each section describes the latest findings from and studies, with reports of clinical interventions when available.
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http://dx.doi.org/10.3389/fphar.2016.00459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131004PMC
December 2016

Common links between metabolic syndrome and inflammatory bowel disease: Current overview and future perspectives.

Pharmacol Rep 2016 Aug 9;68(4):837-46. Epub 2016 May 9.

Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Łódź, Poland. Electronic address:

Metabolic syndrome (MS) features a constellation of central obesity, dyslipidemia, impaired glucose metabolism and often hypertension joined by insulin resistance and chronic inflammation. All these elements greatly raise patient's risk of cardiovascular disease and type 2 diabetes, resulting in an increased mortality. Metabolic syndrome affects approximately 20-25% of the world's adult population and thus it is essential to study its pathophysiology and seek new pharmacological targets. There is a thoroughly studied link between MS and inflammatory diseases of the gastrointestinal (GI) system, i.e. steatohepatitis. However, recent findings also indicate similarities in pathophysiological features between MS and inflammatory bowel disease (IBD), including adipose tissue dysregulation, inadequate immune response, and inflammation. In this review we aim to outline the pathophysiology of MS and emphasize the aspects revealed recently, such as mineralocorticoid activity, involvement of sex hormones and an accompanying increase in prolactin secretion. More importantly, we focus on the common links between MS and IBD. Finally, we describe new strategies and drug targets that may be utilized in MS therapy, namely adiponectin mimetics, GLP-1-based multi agonists, ABCA1 agonists and possible role of miRNA. We also discuss the possible utility of selected agents as adjuvants in IBD therapy.
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http://dx.doi.org/10.1016/j.pharep.2016.04.016DOI Listing
August 2016