Publications by authors named "Katarzyna Cyganek"

26 Publications

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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

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

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

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

Genetic Parameters and QTLs for Total Phenolic Content and Yield of Wheat Mapping Population of CSDH Lines under Drought Stress.

Int J Mol Sci 2019 Dec 1;20(23). Epub 2019 Dec 1.

Department of Mathematical and Statistical Methods, Poznań University of Life Sciences, Wojska Polskiego 28, 60-637 Poznań, Poland.

A doubled haploid population of 94 lines from the Chinese Spring × SQ1 wheat cross (CSDH) was used to evaluate additive and epistatic gene action effects on total phenolic content, grain yield of the main stem, grain number per plant, thousand grain weight, and dry weight per plant at harvest based on phenotypic and genotypic observations of CSDH lines. These traits were evaluated under moderate and severe drought stress and compared with well-watered plants. Plants were grown in pots in an open-sided greenhouse. Genetic parameters, such as additive and epistatic effects, affecting total phenolic content, were estimated for eight year-by-drought combinations. Twenty-one markers showed a significant additive effect on total phenolic content in all eight year-by-drought combinations. These markers were located on chromosomes: 1A, 1B, 2A, 2B, 2D, 3A, 3B, 3D, 4A, and 4D. A region on 4AL with a stable QTL controlling the phenolic content, confirmed by various statistical methods is particularly noteworthy. In all years and treatments, three markers significantly linked to QTLs have been identified for both phenols and yield. Thirteen markers were coincident with candidate genes. Our results indicated the importance of both additive and epistatic gene effects on total phenolic content in eight year-by-drought combinations.
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http://dx.doi.org/10.3390/ijms20236064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929150PMC
December 2019

Continuous subcutaneous insulin infusion vs multiple daily injections in pregnant women with type 1 diabetes mellitus: a systematic review and meta-analysis of randomised controlled trials and observational studies.

Eur J Endocrinol 2018 May 15;178(5):545-563. Epub 2018 Mar 15.

University HospitalKrakow, Poland

Background: Randomised controlled trials (RCTs) have shown an advantage of continuous subcutaneous insulin infusion (CSII) over multiple daily injections (MDI) in the general type 1 diabetes mellitus (T1DM) population. RCT data on T1DM management in pregnancy remain limited.

Objective: We performed a systematic review of both RCTs and non-RCTs evaluating CSII vs MDI in T1DM-complicated pregnancy.

Study Design: Electronic databases were searched for studies comparing CSII with MDI in T1DM-complicated pregnancy.

Methods: A meta-analysis provided point estimates with 95% confidence intervals (CI). Continuous outcomes were reported as weighted mean differences (WMD) or standardised mean differences (SMD), and dichotomous data as relative risk (RR).

Results: The search identified 47 studies, including 43 non-RCTs, reporting on 7824 pregnancies. The meta-analysis showed a lower HbA1c level with CSII vs MDI in the first trimester (WMD: -0.45%; 95%CI: -0.62, -0.27). This difference decreased in subsequent trimesters. Compared to MDI, therapy with CSII resulted in higher gestational weight gain (GWG) (WMD: 1.02 kg; 95%CI: 0.41, 1.62), and lower daily insulin dose requirements in the first (SMD: -0.46; 95%CI: -0.68, -0.24) and subsequent trimesters. Moreover, infants from the CSII group were more likely to be large for gestational age (LGA) (RR: 1.16; 95%CI: 1.07, 1.24) and less likely to be small for gestational age (SGA) (RR: 0.66; 95%CI: 0.45; 0.97).

Conclusions: In T1DM-complicated pregnancy, CSII compared to MDI therapy resulted in better first trimester glycaemic control; this difference decreased in subsequent trimesters. CSII therapy was associated with lower insulin requirements, higher GWG and altered risk for infants being LGA and SGA.
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http://dx.doi.org/10.1530/EJE-17-0804DOI Listing
May 2018

Risk of macrosomia remains glucose-dependent in a cohort of women with pregestational type 1 diabetes and good glycemic control.

Endocrine 2017 Feb 11;55(2):447-455. Epub 2016 Oct 11.

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

Macrosomia risk remains high in type 1 diabetes (T1DM) complicated pregnancies. A linear relationship between macrosomia risk and glycated hemoglobin A (HbA) was described; however, low range of HbA has not been studied. We aimed to identify risk factors and examine the impact of HbA on the occurrence of macrosomia in newborns of T1DM women from a cohort with good glycemic control. In this observational retrospective one-center study we analyzed records of 510 consecutive T1DM pregnancies (1998-2012). The analyzed group consisted of 375 term singleton pregnancies. We used multiple regression models to examine the impact of HbA and self-monitored glucose in each trimester on the risk of macrosomia and birth weight. The median age of T1DM women was 28 years, median T1DM duration-11 years, median pregestational BMI-23.3 kg/m. Median birth weight reached 3520 g (1st and 3rd quartiles 3150 and 3960, respectively) at median 39 weeks of gestation. There were 85 (22.7 %) macrosomic (>4000 g) newborns. Median HbA levels in the 1st, 2nd, and 3rd trimester were 6.4, 5.7, and 5.6 %. Third trimester HbA, mean fasting self-monitored glucose and maternal age were independent predictors of birth weight and macrosomia. There was a linear relationship between 3rd trimester HbA and macrosomia risk in HbA range from 4.5 to 7.0 %. Macrosomia in children of T1DM mothers was common despite excellent metabolic control. Glycemia during the 3rd trimester was predominantly responsible for this condition.
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http://dx.doi.org/10.1007/s12020-016-1134-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5272887PMC
February 2017

Changes in preconception treatment and glycemic control in women with type 1 diabetes mellitus: a 15‑year single‑center follow‑up.

Pol Arch Med Wewn 2016 Aug 29;126(10):739-745. Epub 2016 Aug 29.

INTRODUCTION    Pregnancy in women with type 1 diabetes mellitus (T1DM) is associated with higher risk of complications. Strict glycemic control before conception reduces the risk of unfavorable outcomes. OBJECTIVES    The aim of the study was to assess changes in clinical characteristics, preconception treatment, and glycemic control of women with T1DM at the first antinatal visit. PATIENTS AND METHODS    We analyzed the records from the first antenatal visit of 524 women with T1DM in the years 1998-2012. The follow‑up period was divided into 3 5‑year periods. RESULTS    Differences in the age of patients between the 3 follow‑up periods were observed (28.2 ±5.7 years for 1998-2002; 27.3 ±4.5 years for 2003-2007; and 29.4 ±4.8 years for 2008-2012; P <0.0001). The number of women planning pregnancy did not change and reached 32.1% in the first, 44.4% in the second, and 40.4% in the third period (P = 0.2). The use of rapid‑acting insulin analogues increased from 2.6% to 46.5% and then to 95.6% (P <0.001). The rate of therapy with personal insulin pumps before pregnancy increased from 4.6% in the first, through 23.5% in the second, to 33.3% in the third period (P <0.001). Over the subsequent periods, we observed a decrease in hemoglobin A1c (HbA1c) levels at the first antenatal visit (from 7.4% ±1.6%, through 6.9% ±1.4%, to 7.0% ±1.4%; P = 0.06), as well as a decrease in HbA1c levels between the subgroups of women planning pregnancy (6.8% ±1.4%, 6.6% ±1.2%, and 6.1% ±0.8%, P = 0.015). CONCLUSIONS    In the years 1998-2012, an increase in the use of insulin analogues and personal insulin pumps by women with T1DM before conception was observed, and these changes were accompanied by a slight improvement in glycemic control, particularly among women planning pregnancy. The percentage of women planning pregnancy did not change during the follow‑up.
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http://dx.doi.org/10.20452/pamw.3543DOI Listing
August 2016

Diabetic pregnancy: an overview of current guidelines and clinical practice.

Curr Opin Obstet Gynecol 2014 Dec;26(6):431-7

aDepartment of Metabolic Diseases, Jagiellonian University, Medical College bUniversity Hospital, Krakow, Poland.

Purpose Of Review: We review the recent changes in diagnostic criteria of gestational diabetes mellitus (GDM), describe problems with maintaining and monitoring adequate blood glucose, especially in type 1 diabetes, and provide a brief overview of the currently approved glucose-lowering therapies in pregnancy.

Recent Findings: After the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study, the definition of GDM was revised under the auspices of the International Association of Diabetes and Pregnancy Study Groups. The guidelines, with minor modifications, were endorsed by WHO in 2013. Intensive debate continues, focused on the expected large increase in prevalence of GDM and shortage of experimental evidence of clinical benefits from the new diagnostic criteria. Despite a very good glycaemic control, the prevalence of macrosomia remains high. This indicates a serious deficiency in current monitoring tools and the available therapies. So far, the only glucose-lowering medications approved for use during pregnancy are insulins.

Summary: The HAPO study provides a very suggestive evidence for a strong, continuous association of maternal glucose levels with an increased risk of excessive foetal weight gain. The new definition of GDM results in higher healthcare expenditure, but remains cost-effective. The current therapeutic goals require careful revision to further reduce the risk of adverse outcomes. New glucose-monitoring strategies and markers, and approval of new pharmacotherapies are needed.
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http://dx.doi.org/10.1097/GCO.0000000000000111DOI Listing
December 2014

Factors associated with glycemic control in adult type 1 diabetes patients treated with insulin pump therapy.

Endocrine 2015 Feb 6;48(1):164-9. Epub 2014 May 6.

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

Continuous subcutaneous insulin infusion (CSII) by insulin pump seems to improve glycemia and quality of life as compared to conventional insulin therapy in type 1 diabetes (T1DM). However, while many T1DM subjects achieve excellent glycemic control, some others cannot reach recommended goals. In a retrospective analysis, we searched for factors associated with glycemic control in T1DM patients treated with insulin pump therapy. Data from 192 patients (133 women and 59 men) treated with personal insulin pumps at the Department of Metabolic Diseases, University Hospital, Krakow, Poland were analyzed. Sources of information included medical records, memory read-outs from insulin pumps and data from glucose meters. Univariate, multivariate linear and logistic regression analysis for the association with hemoglobin A1c (HbA1c) level were performed. The mean age of the subjects was 28.9 (±11.2) years, the mean duration of T1DM-14.6 (±7.6) years, mean body mass index-23.5 (±3.1) kg/m2. The mean HbA1c level in the entire study group was 7.4% (57 mmol/mol). In the multivariate linear regression analysis, HbA1c correlated with the mean number of daily blood glucose measurements, number of hypoglycemic episodes per 100 blood glucose measurements, age at the examination, and continuous glucose monitoring system use. Multivariate logistic regression analysis for reaching the therapeutic target of HbA1c<7.0% (53 mmol/mol) showed that the independent predictors of achieving this goal included the same four variables. In a large clinical observation, we identified that patient-related and technological factors associated with glycemic control in adult pump-treated T1DM subjects.
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http://dx.doi.org/10.1007/s12020-014-0274-2DOI Listing
February 2015

Alleviation of osmotic stress effects by exogenous application of salicylic or abscisic acid on wheat seedlings.

Int J Mol Sci 2013 Jun 26;14(7):13171-93. Epub 2013 Jun 26.

The F. Górski Institute of Plant Physiology, Polish Academy of Sciences, Kraków 30-239, Poland.

The aim of the study was to assess the role of salicylic acid (SA) and abscisic acid (ABA) in osmotic stress tolerance of wheat seedlings. This was accomplished by determining the impact of the acids applied exogenously on seedlings grown under osmotic stress in hydroponics. The investigation was unique in its comprehensiveness, examining changes under osmotic stress and other conditions, and testing a number of parameters simultaneously. In both drought susceptible (SQ1) and drought resistant (CS) wheat cultivars, significant physiological and biochemical changes were observed upon the addition of SA (0.05 mM) or ABA (0.1 μM) to solutions containing half-strength Hoagland medium and PEG 6000 (-0.75 MPa). The most noticeable result of supplementing SA or ABA to the medium (PEG + SA and PEG + ABA) was a decrease in the length of leaves and roots in both cultivars. While PEG treatment reduced gas exchange parameters, chlorophyll content in CS, and osmotic potential, and conversely, increased lipid peroxidation, soluble carbohydrates in SQ1, proline content in both cultivars and total antioxidants activity in SQ1, PEG + SA or PEG + ABA did not change the values of these parameters. Furthermore, PEG caused a two-fold increase of endogenous ABA content in SQ1 and a four-fold increase in CS. PEG + ABA increased endogenous ABA only in SQ1, whereas PEG + SA caused a greater increase of ABA content in both cultivars compared to PEG. In PEG-treated plants growing until the harvest, a greater decrease of yield components was observed in SQ1 than in CS. PEG + SA, and particularly PEG + ABA, caused a greater increase of these yield parameters in CS compared to SQ1. In conclusion, SA and ABA ameliorate, particularly in the tolerant wheat cultivar, the harmful effects and after effects of osmotic stress induced by PEG in hydroponics through better osmotic adjustment achieved by an increase in proline and carbohydrate content as well as by an increase in antioxidant activity.
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http://dx.doi.org/10.3390/ijms140713171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742181PMC
June 2013

Medical care of pregnant women with type 1 diabetes: current guidelines and clinical practice.

Pol Arch Med Wewn 2013 23;123(1-2):59-65. Epub 2013 Jan 23.

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

The prevalence of all types of diabetes mellitus is increasing worldwide. Diabetes is a common metabolic complication of pregnancy. For many years, pregnancy complicated by type 1 diabetes was associated with a particularly poor prognosis, and while this has changed dramatically over the last 2 decades, a lot has yet to be done. The continuous relationship between the maternal glucose level and the prevalence of pregnancy complications is well‑documented. The list of outcomes includes congenital malformations, stillbirths, neonatal mortality, macrosomia, hypoglycemia, and many others. Several new therapeutic and monitoring tools have become available over the recent years, for example, short- and long‑acting insulin analogs, personal pumps, and continuous glucose monitoring systems. Interestingly, pregnancy planning and preconception education proved to be particularly effective in improving glycemic control in type 1 diabetic women and achieving therapeutic goals recommended by clinical guidelines. This resulted in the reduction of some maternal and neonatal pregnancy outcomes reported from various populations, but despite this remarkable progress the prevalence of the most common complication, neonatal macrosomia, is still substantially higher than in the newborns of mothers without diabetes. The likely causes of this phenomenon are short episodes of hyperglycemia, particularly postprandial ones, liberal diet, maternal obesity, and substantial weight gain during pregnancy - these potential reasons should be addressed in clinical practice. In the future, new therapeutic devices, such as close‑loop insulin pumps, may help further improve the prognosis in pregnant women with type 1 diabetes.
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http://dx.doi.org/10.20452/pamw.1595DOI Listing
January 2014

Postpregnancy glycemic control and weight changes in type 1 diabetic women.

Diabetes Care 2013 May 18;36(5):1083-7. Epub 2012 Dec 18.

University Hospital, Krakow, Poland.

Objective: Pregnancy in type 1 diabetes requires excellent glycemic control. Most pregnant type 1 diabetic women achieve normoglycemia; however, there is scarce data on their postdelivery characteristics. We aimed to examine postpregnancy glycemic control and weight changes in type 1 diabetes.

Research Design And Methods: We identified and followed (median 20 months) 254 women with singleton pregnancies receiving postdelivery medical care at a single institution.

Results: Study subjects were 28.3 ± 4.7 years of age (mean ± SD), with a diabetes duration of 12.0 ± 7.7 years. Mean A1C before conception was 6.9 ± 1.4%, and preconception weight and BMI were 64.4 ± 10.0 kg and 23.9 ± 3.3 kg/m(2), respectively. Mean A1C decreased during pregnancy, reaching 5.7 ± 0.8% in the third trimester. We observed a mean weight gain of 14.4 ± 6.5 kg during pregnancy. Within 6 months after delivery, A1C increased by 0.8% (P < 0.0001) compared with the last trimester, and body weight and BMI were 4.4 kg and 2.5 kg/m(2) higher (P < 0.0001) compared with the preconception baseline. A1C further deteriorated by 0.8% until the end of follow-up. For women in the "pregnancy planning" program (n = 117), A1C >12 months after delivery was worse compared with before conception (7.1 vs. 6.5%, P = 0.0018), whereas in women with unplanned pregnancies, it was similar to the pregestational levels (7.3 vs.7.4%, P = 0.59). Weight and BMI in the entire study group did not return to prepregnancy levels and were 2.5 kg (P = 0.0079) and 0.9 kg/m(2) higher (P = 0.0058).

Conclusions: In this clinical observation, type 1 diabetic women showed postpregnancy deterioration in glycemic control and were unable to return to prepregnancy weight. Type 1 diabetic women seem to require special attention after delivery to meet therapeutic targets.
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http://dx.doi.org/10.2337/dc12-1340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3631857PMC
May 2013

Efficacy and safety of insulin pump treatment in adult T1DM patients--influence of age and social environment.

Ann Agric Environ Med 2012 ;19(3):573-5

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

Introduction And Objective: Continuous subcutaneous insulin infusion (CSII) via personal insulin pump is a valuable therapeutic tool in T1DM patients. However, adherence to recommended CSII-related behaviours may be of concern to young adults with intensive, variable daily activities (students, young professionals). The aim of this observational study was to estimate treatment outcomes in young adult patients with T1DM, and compare them with older individuals.

Materials And Methods: Overall, 140 adults with T1DM on CSII were examined, divided into 2 subgroups: 77 patients younger than 26 years of age (mean 20.6 years) and 63 older subjects (mean 39.0). We compared the glycaemic control in both groups of T1DM subjects and analyzed treatment attitudes to identify potentially modifiable behaviours influencing the efficacy of the treatment.

Results: The younger individuals were characterized by significantly worse treatment outcomes, compared to the older ones: the mean HbA1c levels were 7.6 ± 1.3% and 6.9±1.3% (p=0.00001), while the mean glucose levels based on glucometer downloads were 161±33.6 mg/dL and 136±21.8 mg/dL (p=0.00001), respectively. The frequency of self-monitoring of blood glucose (SMBG) was lower in younger individuals (5.3±2.1 vs. 7.0±2.8 daily, p=0.0005, respectively); they were also less frequently used advanced pump functions, e.g. the bolus calculator (48% vs. 67% users, p=0.0014, respectively).

Conclusions: The efficacy of CSII treatment observed in young T1DM adults was worse than in older patients. The reason for this phenomenon remains unclear, it may be due simply to age-dependend behaviours, to social environment, or both.
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March 2013

Insulin pump therapy is equally effective and safe in elderly and young type 1 diabetes patients.

Rev Diabet Stud 2011 10;8(2):254-8. Epub 2011 Aug 10.

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

Objectives: It is generally accepted that in adult type 1 diabetes patients (T1D) continuous subcutaneous insulin infusion (CSII) via a personal pump is more effective than the multiple daily injections (MDI) model. However, it is not clear whether all age groups of adult T1D patients may equally benefit from CSII therapy. We aimed to compare the glycemic control and use of selected pump tools in T1D subjects using CSII over the age of 50 (50+ T1D) with patients younger than 50 years of age.

Methods: The last available insulin pump/blood glucose meter downloads and last available HbA1c levels of 124 adult T1D subjects using CSII were reviewed. We divided our cohort into two subgroups: 50+ T1D patients (n = 13) and younger patients (n = 111).

Results: There were no differences in glycemic control achieved with CSII treatment in 50+ T1D patients vs. younger subjects. HbA1c levels were 7.01 ± 0.67% and 7.34 ± 1.24% (p = 0.46), and the mean glycemia based on glucometer downloads was 141.8 ± 17.7 mg/dl and 150.8 ± 35.7 mg/dl (p = 0.69), respectively. Also, there were no differences with respect to the use of important personal pump options and tools.

Conclusion: In conclusion, insulin pump therapy appears to be effective and safe in T1D patients regardless of age.
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http://dx.doi.org/10.1900/RDS.2011.8.254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280010PMC
April 2012

Glycemic control and pregnancy outcomes in women with type 2 diabetes from Poland. The impact of pregnancy planning and a comparison with type 1 diabetes subjects.

Endocrine 2011 Oct 29;40(2):243-9. Epub 2011 Apr 29.

Department of Metabolic Diseases, Jagiellonian University, Medical College, 15 Kopernika Street, 31-511, Krakow, Poland.

The number of pregnancies complicated by type 2 diabetes mellitus (T2DM) is growing; however, their clinical characteristics remain incomplete. We aimed to assess clinical characteristics, glycemic control, and selected pregnancy outcomes in pregestational T2DM from Poland and to compare them with those of T1DM. We analyzed 415 consecutive singleton pregnancies; among them, there were 70 women with T2DM and 345 with T1DM. As compared to T1DM patients, women with T2DM were older (mean age 33.1 years vs. 27.8, respectively), heavier before pregnancy (mean BMI 30.8 kg/m² vs. 23.9), and had a shorter duration of diabetes (mean 3.3 years vs. 11.4); ( P<0.0001 for all comparisons). The gestational age at the first visit was higher in T2DM (mean 11.4 weeks vs. 8.6; P=0.0004). Nevertheless, they had better glycemic control in the first trimester (mean HbA1c 6.2% vs. 7.0; P=0.003); in subsequent months, the differences in HbA1c were no longer significant. T2DM women gained less weight during pregnancy (mean 9.9 kgs vs. 14.1; P<0.0001). The proportion of miscarriages (10.0 vs. 7.3%; P=0.32), preterm deliveries (12.7 vs. 17.8%; P=0.32), combined infant deaths, and congenital malformations were similar in both groups (9.5 vs. 8.8%; P=0.4) as was the frequency of caesarean sections (58.7 vs. 64.1%; P=0.30). Macrosomic babies were more than twice less frequent in T2DM and the difference reached borderline significance (7.9 vs. 17.5%, P=0.07). Pregnancy planning in T2DM had a significant impact on HbA1c in the first trimester (5.7 vs. 6.4% in the planning vs. the not planning group, P=0.02); the difference was not significant in the second and third trimester. T2DM women had better glycemic control in the first trimester than T1DM subjects and gained less weight during pregnancy. This could have been the reason for the slightly lower number of macrosomic babies but did not affect other outcomes. In T2DM, pregnancy planning had a beneficial glycemic effect in the first trimester.
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http://dx.doi.org/10.1007/s12020-011-9475-0DOI Listing
October 2011

The first case report of sulfonylurea use in a woman with permanent neonatal diabetes mellitus due to KCNJ11 mutation during a high-risk pregnancy.

J Clin Endocrinol Metab 2010 Aug 13;95(8):3599-604. Epub 2010 May 13.

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

Sulfonylureas (SUs) were proven to be more effective than insulin in most Kir6.2 permanent neonatal diabetes mellitus (PNDM) patients. We report SU use during pregnancy in PNDM. A woman with the R201H Kir6.2 mutation became pregnant at the age of 37. The patient had been on glipizide 30 mg for 3 yr; her glycosylated hemoglobin level was 5.8%. She was diagnosed with chronic diabetes complications and a congenital defect of the urogenitary tract-a bicornuate uterus with septum. Because the effect of SU on fetal development is uncertain, she was switched to insulin after the pregnancy diagnosis; however, the subsequent glycemic control was unsatisfactory, with episodes of hyper- and hypoglycemia. Thus, in the second trimester, the patient was transferred to SU (glibenclamide, 40 mg), which resulted in stabilization of glycemic control; glycosylated hemoglobin in the third trimester was 5.8%. Prenatal genetic testing excluded the Kir6.2 R201H mutation in the fetus. A preterm cesarean delivery was carried out in the 35th week. The Apgar score of the newborn boy (weight, 3010 g; 75th percentile) was 8 at 1 min. He presented with hypoglycemia, transient tachypnea of the newborn, and hyperbilirubinemia. The recovery was uneventful. No birth defects were recorded. His development at the ninth month of life was normal. In summary, we show a high-risk pregnancy in long-term PNDM that despite perinatal complications ended with the birth of a healthy child. SUs, which seem to constitute an alternative to insulin during pregnancy in Kir6.2-related PNDM, were used during the conception period and most of the second and third trimesters.
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http://dx.doi.org/10.1210/jc.2010-0096DOI Listing
August 2010

Glycemic control and selected pregnancy outcomes in type 1 diabetes women on continuous subcutaneous insulin infusion and multiple daily injections: the significance of pregnancy planning.

Diabetes Technol Ther 2010 Jan;12(1):41-7

Department of Metabolic Diseases, Jagiellonian University Medical College, 31-511 Krakow, Poland.

Background: Two regimens are used to achieve excellent glycemic control during pregnancy in type 1 diabetes mellitus (T1DM): continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI). We assessed their efficacy and safety and the effect of pregnancy planning.

Methods: We examined 269 pregnant T1DM women: 157 treated with MDI (MDI group), 42 with CSII (CSII group), and 70 who switched from MDI to CSII in the first trimester (MDI/CSII group). There were 116 women who planned pregnancy: 58 in the MDI group, 38 in the CSII group, and 20 in the MDI/CSII group. The estimated differences in glycemic control and maternal and fetal outcomes were adjusted for baseline characteristics.

Results: Mean glycated A1c (HbA1c) in the first trimester in the whole group was 6.9%, and the women differed depending on whether they planned pregnancy or not (P < 0.0001). A multiple regression model showed an average difference of about 0.9% in favor of pregnancy planning, with no interaction between the planning and treatments. In the second trimester, HbA1c decreased to a mean value of 5.8%, with improvement of HbA1c across all treatments: by 1.5% in not-planning and 0.9% in planning women. Despite greater improvement, not-planning women still had a higher HbA1c (by 0.3%, P = 0.05). In the third trimester, there was no further significant changes; nevertheless, women who planned pregnancy still had a lower HbA1c (by 0.5%, P = 0.02). There were 14 malformations, stillbirths, and perinatal infant deaths in the not-planning versus five in the planning group (P = 0.07). Patients in the CSII group had a 2 kg greater weight gain compared to the MDI group (15.0 kg vs. 13.0 kg; P = 0.005).

Conclusions: In pregnancy with T1DM, both MDI and CSII can provide excellent glycemic control. Pregnancy planning has a beneficial effect on glycemic control, independent from the therapy model. CSII seems to predispose to a larger weight gain in mothers.
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http://dx.doi.org/10.1089/dia.2009.0081DOI Listing
January 2010

The dual-wave bolus feature in type 1 diabetes adult users of insulin pumps.

Acta Diabetol 2011 Mar 9;48(1):11-4. Epub 2010 Jan 9.

Department of Metabolic Diseases, Jagiellonian University, Medical College, 15 Kopernika Street, Krakow, Poland.

One of the attributes of CSII (continuous subcutaneous insulin infusion) is its ability to tailor prandial insulin delivery to the composition of a meal and anticipated glycemic effects. The dual-wave bolus (DWB) is a tool implemented in contemporary insulin pumps that delivers a combination of an instant insulin bolus followed by a square bolus (SB) infused over several hours. We assessed the effectiveness of DWB in 56 adult patients with type 1 diabetes (T1DM) who were on continuous subcutaneous insulin infusion via insulin pump for at least 2 years. We divided patients into frequent (DWB+, n = 32) and infrequent (DWB-, n = 24) DWB users (>20% vs. <20% of daily bolus dose delivered as SB). CSII implementation resulted in a decrease of adjusted HbA1c level by 0.80% (95% CI 0.67-0.93, P < 0.0001) and adjusted mean glycemia by 18.4 mg/dl (95% CI 15.3-21.4, P < 0.0001) in the whole cohort within the first year of observation. It was sustained in the second year, but without further improvement. Frequent DWB use was associated with male sex (59% vs. 17%, p = 0.001) and shorter duration of T1DM (3.4 vs. 11.3 yrs, p < 0.0001), but not with patients' age (25.7 vs. 27.0 years, P = 0.6). DWB+ patients improved their HbA1c by 0.45% more (95% CI 0.20-0.71, P = 0.0009) than DWB- individuals. In conclusion, DWB might be a tool potentially helping to improve glycemic control in T1DM adult users of insulin pumps. Male patients and those with a shorter duration of diabetes seem to use it more willingly.
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http://dx.doi.org/10.1007/s00592-009-0173-9DOI Listing
March 2011

LMNA gene mutation search in Polish patients: new features of the heterozygous Arg482Gln mutation phenotype.

Endocrine 2009 Dec 27;36(3):518-23. Epub 2009 Oct 27.

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

Mutations of the LMNA gene have been shown to cause an autosomal dominant form of insulin resistance with familial partial lipodystrophy (PLD), frequently accompanied by diabetes. LMNA mutations are considered to be a rare cause of monogenic diabetes; however, they are probably sometimes misdiagnosed as type 2 diabetes (T2DM). We examined whether skin fold thickness measurements may be an effective screening procedure to select individuals with T2DM for molecular testing of the LMNA gene. We also aimed to search for mutations in diabetic patients with evident clinical features of lipodystrophy. Skin fold measurements were performed in 249 not pre-selected T2DM patients. The sum of two trunk skin fold measurements divided by the sum of two peripheral was obtained. Men with a skin fold ratio above 2.5 and women above 1.5 were selected for further molecular analysis of the LMNA gene by direct sequencing. We also examined eight patients presenting typical clinical features of lipodystrophy. We selected 16 patients with T2DM on the basis of skin fold measurements. LMNA gene sequencing in this group revealed no mutation that could be attributable to diabetic phenotype. However, in the group of subjects with apparent lipodystrophic phenotype, we identified one Arg482Gln mutation. This female, diagnosed with diabetes at the age of 51 years, was characterized by insulin resistance but, unlike previously reported LMNA Arg48Gln mutation carriers, she was not overweight. The patient also presented with chronic kidney disease and pulmonary fibrosis that could potentially be a part of the phenotype related to the identified LMNA mutation. We did not find the evidence that screening based on skin fold measurements alone could be an efficient approach to select T2DM patients for molecular testing of the LMNA gene; the presence of features typical for laminopathy seems to be required for such testing. A clinical picture related to the LMNA Arg482Gln mutation may be more diversified than it was previously considered and include low BMI and pulmonary fibrosis.
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http://dx.doi.org/10.1007/s12020-009-9265-0DOI Listing
December 2009

Use of sensor-augmented insulin pump in patient with diabetes and cystic fibrosis: evidence for improvement in metabolic control.

Diabetes Technol Ther 2008 Feb;10(1):46-9

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

Cystic fibrosis-related diabetes (CFRD) is a frequent complication of cystic fibrosis. We report the significant improvement of diabetes control and quality of life in a CFRD patient using the sensor-augmented insulin pump. The system gives the patient the highest degree of flexibility, which is required in CFRD since food intake and activity levels vary widely from day to day, depending on the rapid changes of health status.
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http://dx.doi.org/10.1089/dia.2007.0238DOI Listing
February 2008

Alanine variant of the Pro12Ala polymorphism of the PPARgamma gene might be associated with decreased risk of diabetic retinopathy in type 2 diabetes.

Diabetes Res Clin Pract 2008 Apr 20;80(1):139-45. Epub 2008 Feb 20.

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

Objective: Molecular background of diabetic retinopathy (DR) remains unknown. An interesting group of candidate genes encode proteins involved in insulin resistance.

Aim: To search for association between the PPARgamma, calpain 10, PTPN1 genes and DR in type 2 diabetes mellitus (T2DM).

Methods: We examined 238 T2DM subjects without DR (NDR) and 121 with DR (mean diabetes duration: 9.1+/-6.8 and 15.1+/-7.7, respectively). The subjects were genotyped for four markers: Pro12Ala of PPARgamma, SNP43 of calpain 10, rs3787345 and rs754118 of PTPN1. The distributions of the genotypes were compared using the chi(2)-test and Fisher exact test.

Results: The alleles and genotypes were not associated with DR in non-stratified analysis. To investigate the impact of T2DM duration, we performed analysis that excluded short duration NDR subjects and long-duration DR subjects. It allowed obtaining groups with similar T2DM duration but different DR status (DR: 88 individuals, 11.4+/-5.3 years; NDR: 136 individuals, 13.2 years+/-6.2, respectively). This analysis suggested that the alanine variant of Pro12Ala might be associated with decreased risk of DR (p=0.026 for alleles, p=0.038 and p=0.014 for genotypes in additive and dominant models, respectively). In multivariable logistic regression that included non-genetic parameters, Pro12Ala was not an independent risk factor (p=0.28). Further analysis showed, however, that Pro12Ala remained significant when urea level was excluded from the model.

Conclusion: The alanine variant of the Pro12Ala polymorphism of PPARgamma might be associated with decreased risk of DR in T2DM. This effect may be indirect, at least in part, due to diabetic kidney disease.
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http://dx.doi.org/10.1016/j.diabres.2007.11.001DOI Listing
April 2008

Plasma asymmetric dimethylarginine (ADMA) is associated with retinopathy in type 2 diabetes.

Diabetes Care 2007 Nov 17;30(11):2899-901. Epub 2007 Aug 17.

Department of Metabolic Diseases, Jagiellonian University, 15 Kopernika St., 31-501 Krakow, Poland.

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http://dx.doi.org/10.2337/dc07-1138DOI Listing
November 2007

Vitamin D binding protein gene and genetic susceptibility to type 2 diabetes mellitus in a Polish population.

Diabetes Res Clin Pract 2002 Aug;57(2):99-104

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

Polymorphisms of the genes involved in the metabolism of vitamin D may predispose to type 2 diabetes mellitus (T2DM). For example, there is evidence suggesting that vitamin D binding protein (DBP) amino acid variants at codons 416 (aspartic acid-->glutamic acid) and 420 (threonine-->lysine) may affect genetic susceptibility to T2DM. The aims of this study are: (1) to determine the allele, genotype, haplotype and haplotype combination frequencies of those DBP amino acid variants in a Polish population and (2) to examine their role in the genetic susceptibility to T2DM in a Polish population. Overall 393 individuals were included in this study: 231 T2DM patients and 162 controls. The sequence of DBP exon 11, which contains both examined variants, was amplified by polymerase chain reaction (PCR). Alleles and genotypes were determined based on electrophoresis of the DNA digestion products by specific restriction enzymes HaeIII and StyI. Since variants of DBP were in very strong linkage disequilibrium, haplotypes could be assigned to phase-unknown individuals. Differences in distributions between the groups were examined by chi(2) test. At codon 416 the frequency of Asp/Glu alleles was 44.6/55.4% in T2DM patients and 40.7/59.3% in controls (chi(2)=2.1, d.f.=1, P=0.28). At codon 420 the frequency of Thr/Lys alleles were 69.4/30.6% and 71.6/28.4%, (chi(2)=0.41, d.f.=1, P=0.52), respectively. Distribution of genotypes, haplotypes and haplotype combinations were similar in both groups. In conclusion, the frequency of amino acid variants at codons 416 and 420 of vitamin D binding protein gene in a Polish population is similar to other Caucasian populations, but differs significantly from other races. No evidence was found for an association between DBP frequent polymorphisms and T2DM in this population.
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http://dx.doi.org/10.1016/s0168-8227(02)00020-7DOI Listing
August 2002

Homozygous combination of calpain 10 gene haplotypes is associated with type 2 diabetes mellitus in a Polish population.

Eur J Endocrinol 2002 May;146(5):695-9

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

Objective: The polymorphisms of two genes have recently been associated with complex forms of type 2 diabetes mellitus (T2DM): calpain 10 and peroxisome proliferator-activated receptor-gamma (PPARgamma). Calpain 10 is a member of a large family of intracellular proteases. It was shown in Mexican-Americans and other populations that variants of three single nucleotide polymorphisms (SNPs), -43, -19, and -63, of this ubiquitously expressed protein influence susceptibility to T2DM. However, substantial differences were shown between ethnic groups in at risk alleles and haplotypes as well as in their attributable risk. Thus, it is important to determine the role of calpain 10 in various populations.

Aim: To examine the role of calpain 10 SNPs -43, -19, and -63 in genetic susceptibility to T2DM in a Polish population.

Methods: Overall, 377 individuals were examined: 229 T2DM patients and 148 control individuals. The groups were genotyped for calpain 10 SNP-43, SNP-19, and SNP-63. SNP-19 was examined by electrophoresis of the PCR product on agarose gel by size, while the restriction fragment length polymorphism (RFLP) method was used for the two other markers. Differences in allele, genotype, haplotype, and haplotype combination distribution between the groups were examined by chi(2) test.

Results: Distributions of alleles, genotypes, and haplotypes at three loci defined by examined SNPs were not significantly different between the groups. However, the homozygote combination of 121 haplotype was more prevalent in the T2DM group than in the controls (17.9% vs 10.1%, P=0.039). No difference was observed in the 112/121 haplotype distribution. This heterozygous haplotype combination was associated with increased risk of T2DM in several populations.

Conclusion: The results of our study suggest the association of calpain 10 121/121 haplotype combination created by SNPs -43, -19, and -63 with T2DM in a Polish population. However, we were not able to confirm the previously described role of the heterozygous 112/121 haplotype combination in susceptibility to T2DM.
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http://dx.doi.org/10.1530/eje.0.1460695DOI Listing
May 2002