Publications by authors named "Katarzyna Cypryk"

50 Publications

Metformin administration during pregnancy - current insight.

Ginekol Pol 2021 ;92(1):46-50

Department of Internal Diseases and Diabetology, Central Clinical Hospital of The Medical University, Lodz, Poland, Poland.

The main mechanism of gestational diabetes mellitus (GDM) is insulin resistance, therefore using metformin as a medicine reducing insulin resistance appears to be promising. Currently, the majority of medical associations do not recommend using metformin during pregnancy as the first-line of therapy when the diet regimen is insufficient for glycaemic control. However, they do allow its administration if there is no possibility of insulin treatment. There is some evidence which suggests that using metformin during pregnancy is not related to an increased risk of obstetric complications during delivery and that its influence on the foetus can be beneficial. Since metformin crosses the placenta, the major argument for cautious use of this drug are the potential long-term effects of the treatment for the child and its development in later life. In this article, the authors attempt to discuss the use of metformin during pregnancy and the safety of the treatment in the light of current studies and recommendations.
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http://dx.doi.org/10.5603/GP.a2020.0149DOI Listing
January 2021

Identification of a novel association for the WWOX/HIF1A axis with gestational diabetes mellitus (GDM).

PeerJ 2021 14;9:e10604. Epub 2021 Jan 14.

Department of Molecular Carcinogenesis, Medical University of Lodz, Lodz, Poland.

Background: Although the WW-domain-containing oxidoreductase (WWOX)/Hypoxia-inducible factor 1 (HIF1) pathway is a well-known regulator of cellular glucose and energy metabolism in pathophysiological processes, its role in gestational diabetes mellitus (GDM), remains elusive. We undertook this study to determine the effect of WWOX/HIF1A signaling on the expression of glucose metabolism genes in GDM patients.

Methods: Leukocytes were obtained from 135 pregnant women with ( = 98) or without ( = 37) GDM and, in turn, 3 months ( = 8) and 1 year ( = 12) postpartum. Quantitative RT-PCR was performed to determine gene expression profiles of the WWOX/HIF1A-related genes, including those involved in glucose transport (), glycolytic pathway (), Wnt pathway (), and inflammatory response ().

Results: GDM patients displayed a significant downregulation of with simultaneous upregulation of which resulted in approximately six times reduction in ratio. As a consequence, induced genes () were found to be overexpressed in GDM compared to normal pregnancy and negative correlate with ratio. The postpartum expression was higher than during GDM, but its level was comparable to that observed in normal pregnancy.

Conclusions: The obtained results suggest a significant contribution of the gene to glucose metabolism in patients with gestational diabetes. Decreased expression in GDM compared to normal pregnancy, and in particular reduction of ratio, indicate that WWOX modulates HIF1α activity in normal tissues as described in the tumor. The effect of HIF1α excessive activation is to increase the expression of genes encoding proteins directly involved in the glycolysis which may lead to pathological changes in glucose metabolism observed in gestational diabetes.
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http://dx.doi.org/10.7717/peerj.10604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811782PMC
January 2021

Continuous subcutaneous insulin infusion does not correspond with pregnancy outcomes despite better glycemic control as compared to multiple daily injections in type 1 diabetes - Significance of pregnancy planning and prepregnancy HbA1c.

Diabetes Res Clin Pract 2021 Feb 22;172:108628. Epub 2020 Dec 22.

Department of Internal Diseases and Diabetology, Medical University of Lodz, Poland.

Objective: The aim of the study was to compare pregnancy outcomes with glycemic control, total increase in insulin requirement, and body weight gain in the women with Type 1 Diabetes Mellitus (T1DM) using continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI).

Material And Methods: This was a single center retrospective observational study involving 209 pregnant Caucasian women. Among the study participants, 95 subjects were treated with MDI and 114 patients were using CSII therapy. The primary outcomes were pregnancy results, while secondary ones were HbA1c, increase in daily dose of insulin (DDI), and body weight gain.

Results: At baseline, the CSII users were older (P = 0.0373), they were diagnosed with T1DM at a younger age (P = 0.047), and more often planned pregnancy (P = 0.032). A majority of the women were classified as class D, according to the White classification. Among the CSII users, a significantly higher proportion of the subjects in class B was noted than in the MDI users, with no differences in the proportion of the remaining White classes. Prepregnancy HbA1c was insignificantly lower in the CSII group, however, a significantly higher proportion of the CSII users reached the target value of HbA1c (P = 0.008). A prepregnancy daily dose of insulin (both total and per kg of body weight), body weight, and body mass index (BMI) did not differ between the groups. The 1st and 2nd trimester HbA1c was lower among the CSII users (6.83 ± 1.38 vs 7.52 ± 2.11%, P = 0.01 and 6.17 ± 0.9 vs 6.57 ± 1.12%, P = 0.009, respectively), while the 3rd trimester HbA1c as well as the total change in HbA1c were comparable. Neither DDI and body weight in concecutive trimesters, nor their total gestational increase, differed between the groups. The rate of pregnancy loss, such as abortions, fetal and neonatal death did not differ between the groups. As regards composite pregnancy loss, prepregnancy HbA1c was 8.41%±2.81% among the MDI cohort vs 7.22%±1.31% in the CSII users (P = 0.517). No differences were found in the gestational age at delivery, the mode of delivery, neonatal birth weight, the rate of macrosomy, LGA or SGA. A higher Apgar score was noted among the CSII users (8.63 ± 1.63 vs 8.03 ± 2.49%, P = 0.047), however, the proportion of neonates with an Apgar score lower than 7 points was similar. In the women planning pregnancy, as compared to the subjects who did not, HbA1c was significantly lower in the 1st trimester, together with a significantly higher rate of the women achieving the target HbA1c value during planning as well as in the 1st trimester. In the group of women planning pregnancy, significantly lower 1st trimester HbA1c and composite outcome of pregnancy loss were observed in the CSII users vs the MDI treated women. Lack of pregnancy planning and a high HbA1c level in the 1st trimester were independent predictors of both LGA (OR = 4.99 [95%CI 1.12-21.0], P = 0.033 and OR = 3.02 [95%CI 1.19-7.65], P = 0.019, respectively) and macrosomia (OR = 8.43 [95%CI 1.36-51.93], P = 0.021 and OR = 5.47 [95%CI 1.77-16.87], P = 0.003, respectively).

Conclusions: The course of pregnancy and obstetric outcomes were not dependent on the mode of insulin delivery, but only on pregnancy planning and HbA1c in early pregnancy. Further studies are needed to explore more precise parameters describing both glycemic control in pregnant women as well as perinatal infant well-being.
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http://dx.doi.org/10.1016/j.diabres.2020.108628DOI Listing
February 2021

Procoagulant Disorders in Patients with Newly Diagnosed Pancreatic Adenocarcinoma.

Medicina (Kaunas) 2020 Dec 9;56(12). Epub 2020 Dec 9.

Department of Digestive Tract Diseases, Medical University of Lodz, Kopcinskiego 22, 90-153 Lodz, Poland.

: Cancer coagulopathy is thought to be partially due to the up-regulation of tissue factor (TF), thrombin-antithrombin complex (TAT) and soluble P-selectin (sP-selectin). The purpose of this study was to evaluate the clinical significance of TF, TAT and sP-selectin in patients with pancreatic cancer. The study included 93 subjects: 73 newly diagnosed patients with pancreatic adenocarcinoma (42 with stage I-III and 31 with metastatic cancer (stage IV)) and a control group of 20 healthy subjects. Analyzed patients were hospitalized in the Department of Digestive Tract Diseases, Medical University of Lodz or in the Department of Digestive Tract Surgery, Silesian University, Katowice, Poland. All laboratory parameters were measured using ELISA procedures. TF plasma levels were detectable in all patients and were significantly higher in metastatic cancer compared to stage I-III patients and the control group ( < 0.05). In patients with pancreatic adenocarcinoma, the median levels of TAT were also elevated compared to the control group. Moreover, patients with metastases had significantly higher TAT concentration compared to the I-III cancer group. On the other hand, only the metastatic patients group showed significantly higher plasma sP-selectin levels compared to the controls ( = 0.009), whereas there was no difference between localized and metastatic cancer patients. The coagulation disorders are present in the majority of patients with pancreatic adenocarcinoma already at the diagnosis stage and reflect cancer progression and spread.
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http://dx.doi.org/10.3390/medicina56120677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763230PMC
December 2020

Associations of Arginine with Gestational Diabetes Mellitus in a Follow-Up Study.

Int J Mol Sci 2020 Oct 22;21(21). Epub 2020 Oct 22.

Chair of Medical Biology, Laboratory of Metabolomic Studies, Department of Structural Biology, Faculty of Medicine Department of Biomedical Sciences, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, Poland.

In the reported study we applied the targeted metabolomic profiling employing high pressure liquid chromatography coupled with triple quadrupole tandem mass spectrometry (HPLC-MS/MS) to understand the pathophysiology of gestational diabetes mellitus (GDM), early identification of women who are at risk of developing GDM, and the differences in recovery postpartum between these women and normoglycemic women. We profiled the peripheral blood from patients during the second trimester of pregnancy and three months, and one year postpartum. In the GDM group Arg, Gln, His, Met, Phe and Ser were downregulated with statistical significance in comparison to normoglycemic (NGT) women. From the analysis of the association of all amino acid profiles of GDM and NGT women, several statistical models predicting diabetic status were formulated and compared with the literature, with the arginine-based model as the most promising of the screened ones (area under the curve (AUC) = 0.749). Our research results have shed light on the critical role of arginine in the development of GDM and may help in precisely distinguishing between GDM and NGT and earlier detection of GDM but also in predicting women with the increased type 2 diabetes mellitus (T2DM) risk.
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http://dx.doi.org/10.3390/ijms21217811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659483PMC
October 2020

The Influence of Dietary Fatty Acids on Immune Responses.

Nutrients 2019 Dec 6;11(12). Epub 2019 Dec 6.

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, 7265 Davos Wolfgang, Switzerland.

Diet-derived fatty acids (FAs) are essential sources of energy and fundamental structural components of cells. They also play important roles in the modulation of immune responses in health and disease. Saturated and unsaturated FAs influence the effector and regulatory functions of innate and adaptive immune cells by changing membrane composition and fluidity and by acting through specific receptors. Impaired balance of saturated/unsaturated FAs, as well as -6/-3 polyunsaturated FAs has significant consequences on immune system homeostasis, contributing to the development of many allergic, autoimmune, and metabolic diseases. In this paper, we discuss up-to-date knowledge and the clinical relevance of the influence of dietary FAs on the biology, homeostasis, and functions of epithelial cells, macrophages, dendritic cells, neutrophils, innate lymphoid cells, T cells and B cells. Additionally, we review the effects of dietary FAs on the pathogenesis of many diseases, including asthma, allergic rhinitis, food allergy, atopic dermatitis, rheumatoid arthritis, multiple sclerosis as well as type 1 and 2 diabetes.
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http://dx.doi.org/10.3390/nu11122990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950146PMC
December 2019

Flow Mediated Skin Fluorescence technique reveals remarkable effect of age on microcirculation and metabolic regulation in type 1 diabetes.

Microvasc Res 2019 07 23;124:19-24. Epub 2019 Feb 23.

Angionica Ltd., Lodz, Poland; Institute of Applied Radiation Chemistry, Lodz University of Technology, Lodz, Poland. Electronic address:

Study Description: Flow Mediated Skin Fluorescence (FMSF) is a novel technique for non-invasive evaluation of the microcirculation and metabolic regulation. This study describes the diagnostic potential of FMSF for type 1 diabetes (DM1).

Study Population: All study participants, in both the control (n = 31) and DM1 (n = 40) groups, were between the ages of 30-49 y. The patients in the DM1 group had all been suffering from diabetes for at least 10 y.

Results: The parameters HR, HR and MR inversely correlate with age and BMI. An unidentified compensatory effect was observed among the younger members of the DM1 group. The majority of DM1 patients with HR < 8% showed signs of dysfunctional metabolic regulation.

Conclusion: FMSF appears to be an extremely useful technique for monitoring diabetic patients over time, enabling early diagnosis of potentially dysfunctional microcirculation and metabolic regulation.
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http://dx.doi.org/10.1016/j.mvr.2019.02.005DOI Listing
July 2019

The Impact of Pregnancy and Parity on Type 1 Diabetes Complications.

Curr Diabetes Rev 2019 ;15(6):429-434

Department of Internal Diseases and Diabetology, Medical University of Lodz, Pomorska Str. 251, 92-213 Lodz, Poland.

Background: The potential influence of pregnancy and parity on the risk of chronic diabetic complications is a matter of great concern and constant discussion. This aspect seems relevant and should be the subject of thorough discussion with the woman planning childbirth.

Introduction: Current data concerning the impact of pregnancy and parity covers primarily retinopathy and nephropathy, while the aspects of neuropathy and macrovascular complications are unsatisfactorily documented. Majority of studies focus on single complication only, while the number of papers assessing this problem in a complex setting is limited. The available body of evidence concerns mainly the short-term impact of pregnancy on diabetic chronic complications while the data concerning the longer perspective are scarce. Moreover, the results found in the available literature are conflicting. The aim of the study was to summarize all available data concerning the longer impact of parity on the chronic complications in the women with type 1 diabetes.

Methods: PubMed database has been searched between October 2013 and September 2018 and all relevant papers were selected. This review summarizes data on the impact of pregnancy and parity on chronic complications in type 1 diabetic women.

Results: Current data assessing this matter in a complex way are limited, and the available results are controversial. It seems however that pregnancy itself may rather influence pre-existing diabetic complication than affect risk of its development. Additionally, evidence suggests that any deleterious changes appearing during pregnancy are transient and tend to remit after delivery.

Conclusion: It seems that neither pregnancy nor parity affects the risk of diabetic chronic complications in the longer perspective.
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http://dx.doi.org/10.2174/1573399815666190115143538DOI Listing
February 2020

Expression Profile of Diabetes-Related Genes Associated with Leukocyte Sirtuin 1 Overexpression in Gestational Diabetes.

Int J Mol Sci 2018 Nov 30;19(12). Epub 2018 Nov 30.

Department of Structural Biology, Faculty of Biomedical Sciences and Postgraduate Education, Medical University of Lodz, 90-752 Lodz, Poland.

Although compelling evidence indicates that Sirtuin 1 (SIRT1) plays a prominent role in type 2 diabetes, its relationship with gestational diabetes (GDM) remains elusive. This study was aimed at identifying diabetes-related genes and cellular pathways linked to changes of leukocyte expression at the time of GDM diagnosis. For this purpose, 122 GDM patients were screened for leukocyte expression, and two subgroups were distinguished, namely GDM/(↑) ( = 30, < 0.05) and GDM/(↔) ( = 92, > 0.05), with significant and insignificant changes in leukocyte expression compared to a normal glucose tolerant (NGT) group ( = 41), respectively. PCR array analysis identified 11 diabetes-related genes with at least a ± 2-fold difference in expression in GDM/(↑) patients ( = 9) vs. NGT controls ( = 7); in addition, significant differences in the expression of four of the six investigated genes were confirmed between the entire GDM/(↑) group and the whole NGT group ( < 0.05). Interestingly, of these four genes, only expression was found to significantly differ between GDM/(↑) and GDM/(↔). This study demonstrates that under hyperglycemic conditions, leukocyte overexpression is accompanied by an over-abundance of three transcripts and an under-abundance of another; these four govern related metabolism, inflammation, and transport functions, suggesting that such alterations might represent systemic biological adaptations with a unique under-expression in GDM/(↑) women.
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http://dx.doi.org/10.3390/ijms19123826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321739PMC
November 2018

Artificial Pancreas Systems for People With Type 2 Diabetes: Conception and Design of the European CLOSE Project.

J Diabetes Sci Technol 2019 03 21;13(2):261-267. Epub 2018 Sep 21.

1 Profil, Neuss, Germany.

In the last 10 years tremendous progress has been made in the development of artificial pancreas (AP) systems for people with type 1 diabetes (T1D). The pan-European consortium CLOSE (Automated Glu cose Contro l at H ome for People with Chronic Disea se) is aiming to develop integrated AP solutions (APplus) tailored to the needs of people with type 2 diabetes (T2D). APplus comprises a product and service package complementing the AP system by obligatory training as well as home visits and telemedical consultations on demand. Outcome predictors and performance indicators shall help to identify people who could benefit most from AP usage and facilitate the measurement of AP impact in diabetes care. In a first step CLOSE will establish a scalable APplus model case working at the interface between patients, homecare service providers, and payers in France. CLOSE will then scale up APplus by pursuing geographic distribution, targeting additional audiences, and enhancing AP functionalities and interconnectedness. By being part of the European Institute of Innovation and Technology (EIT) Health public-private partnership, CLOSE is committed to the EIT "knowledge triangle" pursuing the integrated advancement of technology, education, and business creation. Putting stakeholders, education, and impact into the center of APplus advancement is considered key for achieving wide AP use in T2D care.
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http://dx.doi.org/10.1177/1932296818803588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399797PMC
March 2019

Lipid profile changes in erythrocyte membranes of women with diagnosed GDM.

PLoS One 2018 14;13(9):e0203799. Epub 2018 Sep 14.

Medical University of Lodz, Department of Structural Biology, Lodz, Poland.

Gestational diabetes mellitus (GDM) is a glucose intolerance that begins or is first recognized during pregnancy. It is currently a growing health problem worldwide affecting from 1% to 14% of all pregnant women depending on racial and ethnic group as well as the diagnostic and screening criteria. Our preliminary study aimed at investigating the erythrocyte membrane fatty acid profiles of pregnant women, in particular with diagnosed with gestational diabetes mellitus (GDM), and with normal glucose tolerant (NGT) pregnant women as a control group. The study group comprised 43 pregnant women, 32 of whom were diagnosed with GDM according to the WHO criteria, and 11 with normal glucose tolerance. The erythrocyte membrane phospholipids were obtained according to the Folch extraction procedure. Fatty acids (FA) were analyzed by gas chromatography (GC) as the corresponding fatty acid methyl esters (FAME). A cluster of 14 fatty acids identified contained >98% of the recognized peaks in the GC analysis. The analysis of fatty acids from erythrocytes revealed important differences between GDM and NGT women in the third trimester, and the results were correlated with biochemical data. Among the 14 measured FA representing the membrane lipidomic profile, the levels of three saturated FA (myristic, palmitic, stearic acids) tended to decrease in GDM patients, with the percentage content of stearic acid significantly changed. The relative content of monounsaturated fatty acids (MUFA) tended to increase, in particular the oleic acid and vaccenic acid contents were significantly increased in erythrocyte membranes of the GDM group in comparison with the NGT group. The GDM group demonstrated higher sapienic acid levels (+29%) but this change was not statistically significant. This study revealed association between an impaired cis-vaccenic acid concentration in erythrocytes membrane and GDM development. No significant changes of polyunsaturated fatty acids (PUFA) were observed in GDM and NGT erythrocytes. We postulate, basing on the differences between the GDM and NGT lipidomic profiles, that stearic and cis-vaccenic acids can be considered as dual biomarkers of specific SFA-MUFA conversion pathway, involving the coupling of delta-9 desaturase and elongase enzymes. Our results indicate that the SFA-MUFA families may be involved in the pathophysiology of metabolic diseases such as GDM, but the further studies are needed to confirm our hypothesis. In conclusion, the erythrocyte membranes of GDM women undergo remodeling resulting in abnormal fatty acid profiles, which are reflection of the long-term status of organism and can have great impact on both the mother and her offspring.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203799PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138398PMC
February 2019

A review of cardiovascular outcome trials in type 2 diabetes.

Endokrynol Pol 2018 ;69(4)

Type 2 diabetes is a complex metabolic disorder associated with a high risk of cardiovascular complications. In December 2008, due to concerns about the cardiac safety of antihyperglycaemic therapies, the Food and Drug Administration (FDA) published a new guidance on special requirements for the demonstration of cardiovascular safety for these medications. In 2012, similar recommendations were made for antidiabetic drug manufacturers by the European Medicines Agency (EMA). Since then, both FDA and EMA recommendations have been applied in cardiovascular outcome trials (CVOTs) for several new antihyperglycaemic drugs. Unlike conventional trials, CVOTs are usually placebo controlled, non-inferiority trials that examine the cardiovascular safety of a drug compared to standard of care in large cohorts of patients with high cardiovascular risk or established cardiovascular disease. Patients in CVOTs are also monitored for a longer observation period than in typical randomised controlled trials to provide data on long-term cardiovascular risk. To date, nine CVOTs involving patients with type 2 diabetes have been completed, and at least 13 are still ongoing. These studies focus on a variety of antihyper-glycaemic drugs, including incretin-based agents, sodium-glucose cotransporter 2 inhibitor (SGLT-2) inhibitors, and insulin formulations. This article takes a critical look at these CVOTs and summarises the results of the completed trials.
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http://dx.doi.org/10.5603/EP.2018.0053DOI Listing
December 2018

Efficacy and safety of dapagliflozin or dapagliflozin plus saxagliptin versus glimepiride as add-on to metformin in patients with type 2 diabetes.

Diabetes Obes Metab 2018 11 16;20(11):2598-2607. Epub 2018 Jul 16.

CRU Hungary Kft, Miskolc, Hungary.

Objective: To compare the efficacy and safety of dapagliflozin and dapagliflozin plus saxagliptin vs glimepiride as add-on to metformin in patients with type 2 diabetes.

Research Design And Methods: This 52-week, multicentre, double-blind, active-controlled study (NCT02471404) randomized (1:1:1) patients (n = 939; HbA1c 7.5%-10.5%) on metformin monotherapy (≥1500 mg/day) to add-on dapagliflozin 10 mg, dapagliflozin 10 mg plus saxagliptin 5 mg, or glimepiride 1 to 6 mg (titrated). The primary efficacy end point was change in HbA1c from baseline to Week 52.

Results: Baseline mean age, diabetes duration and HbA1c were 58.4 years, 7.0 years and 8.3%, respectively. Adjusted mean HbA1c change from baseline was -1.20% with dapagliflozin plus saxagliptin and -0.82% with dapagliflozin, vs -0.99% with glimepiride (mean dose at Week 52, 4.6 mg). Changes in body weight (-3.2 kg and -3.5 kg vs +1.8 kg) and systolic blood pressure (SBP; -6.4 mm Hg and -5.6 mm Hg vs -1.6 mm Hg) were significantly greater with dapagliflozin plus saxagliptin and dapagliflozin than with glimepiride. FPG decreased significantly with dapagliflozin plus saxagliptin compared with glimepiride (-2.1 mmol/L vs -1.5 mmol/L) and was similar with dapagliflozin (-1.6 mmol/L) compared with glimepiride. Confirmed incidence of hypoglycaemia was lower with dapagliflozin regimens than with glimepiride (0 and 1 vs 13 patients) and fewer patients required rescue. Genital infections were more frequent with dapagliflozin; other AE profiles were similar.

Conclusions: Dapagliflozin, saxagliptin and metformin improved glycaemic control compared with glimepiride plus metformin; add-on of dapagliflozin alone showed efficacy similar to that of glimepiride. Both dapagliflozin regimens decreased body weight and SBP, with a lower incidence of hypoglycaemia compared with glimepiride.
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http://dx.doi.org/10.1111/dom.13437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220756PMC
November 2018

Molecular Mechanisms Underlying Curcumin-Mediated Therapeutic Effects in Type 2 Diabetes and Cancer.

Oxid Med Cell Longev 2018 20;2018:9698258. Epub 2018 Mar 20.

Department of Structural Biology, Faculty of Biomedical Sciences and Postgraduate Education, Medical University of Lodz, ul. Zeligowskiego 7/9, 90-752 Lodz, Poland.

The growing prevalence of age-related diseases, especially type 2 diabetes mellitus (T2DM) and cancer, has become global health and economic problems. Due to multifactorial nature of both diseases, their pathophysiology is not completely understood so far. Compelling evidence indicates that increased oxidative stress, resulting from an imbalance between production of reactive oxygen species (ROS) and their clearance by antioxidant defense mechanisms, as well as the proinflammatory state contributes to the development and progression of the diseases. Curcumin (CUR; diferuloylmethane), a well-known polyphenol derived from the rhizomes of turmeric , has attracted a great deal of attention as a natural compound with beneficial antidiabetic and anticancer properties, partly due to its antioxidative and anti-inflammatory actions. Although this polyphenolic compound is increasingly being recognized for its growing number of protective health effects, the precise molecular mechanisms through which it reduces diabetes- and cancer-related pathological events have not been fully unraveled. Hence, CUR is the subject of intensive research in the fields Diabetology and Oncology as a potential candidate in the treatment of both T2DM and cancer, particularly since current therapeutic options for their treatment are not satisfactory in clinics. In this review, we summarize the recent progress made on the molecular targets and pathways involved in antidiabetic and anticancer activities of CUR that are responsible for its beneficial health effects.
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http://dx.doi.org/10.1155/2018/9698258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884026PMC
October 2018

Parity does not affect diabetes complications in women with type 1 diabetes.

Ann Agric Environ Med 2018 Mar 11;25(1):114-119. Epub 2017 Jan 11.

Department of Diabetology and Metabolic Diseases, Medical University of Lodz, Poland.

Introduction: The problem concerning the impact of pregnancy on diabetic complications is a matter for discussion as there is some evidence suggesting that pregnancy may trigger development or progression of diabetic chronic complications. However, currently available data concerning this issue is still controversial.

Objective: The aim of the study was to evaluate the impact of obstetric history on the development of chronic microangiopatic and macroangiopatic complications in type 1 diabetic women.

Material And Methods: The retrospective study comprised 226 white Caucasian type 1 diabetic women, including 190 parous and 36 nulliparous women. Anthropometric data, information concerning the course of the disease, including metabolic control and chronic complications, together with obstetric history, were registered.

Results: Parous women were older (p<0.001), but did not differ significantly regarding metabolic control in the course of the disease (p>0.05) and diabetes duration (p>0.05) from nulliparous subjects. There were no significant differences in the incidence (p>0.05) nor onset (p>0.05) of chronic diabetes complications between the groups. The number of deliveries did not correlate with either the incidence nor the onset of chronic complications. Longer DM duration at the moment of first delivery was related to the higher incidence of retinopathy (p<0.01), nephropathy (p<0.05) and neuropathy (p<0.001).

Conclusions: The incidence of chronic diabetic complications does not differ between parous women and the subjects that were never pregnant, and is not related to the number of pregnancies.
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http://dx.doi.org/10.5604/12321966.1230738DOI Listing
March 2018

Melatonin as a Pleiotropic Molecule with Therapeutic Potential for Type 2 Diabetes and Cancer.

Curr Med Chem 2017 Nov;24(35):3829-3850

Department of Structural Biology, Faculty of Biomedical Sciences and Postgraduate Education, Medical University of Lodz, Lodz, Poland.

Background: The incidence of both type 2 diabetes (T2DM) and cancer is increasing worldwide, making these diseases a global health problem along with increasing healthcare expenditures. The current therapeutic approaches for treating these multifactorial diseases are far from satisfactory. As increasing evidence shows beneficial effects of melatonin (MLT) on typical pathological changes occurring during the development of T2DM and cancer, the present review focuses on molecular aspects of antidiabetic and anticancer activities of MLT and, moreover, discusses several future directions of research regarding MLT application as potential therapeutic agent.

Methods: Critical literature analysis in PubMed central combined with personal expertise.

Results: Numerous in vitro and in vivo studies have revealed that MLT possesses a number of antidiabetic health benefits by diminishing hyperglycemia, insulin resistance, oxidative stress, and inflammation through modulating various intracellular signaling pathways or other targets involved in the pathophysiology of this disease. Mounting evidence also indicates that MLT exhibits multi-targeted anticancer effects in numerous human malignancies, mainly resulting from its ability to modulate several signal transduction pathways associated with cell survival, proliferation, and apoptosis. Furthermore, beneficial synergistic action of MLT with chemotherapy and radiotherapy has also been observed. Importantly, no adverse outcomes have been found from the clinical use of MLT, which highlights its therapeutic usefulness, either alone or in combination with other conventional therapies, in cancer treatment.

Conclusion: The findings described in this review suggest that MLT may confer potential benefits to human health, particularly in respect to T2DM and cancer.
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http://dx.doi.org/10.2174/0929867324666170718110606DOI Listing
November 2017

Comparison of leukocyte IL6 expression in patients with gestational diabetes mellitus (GDM) diagnosed by the Polish Diabetes Association (PDA) 2011 and 2014 criteria.

Endokrynol Pol 2017 29;68(3):317-325. Epub 2017 Mar 29.

Department of Structural Biology, Faculty of Biomedical Sciences and Postgraduate Education, Medical University, Lodz, Poland.

Introduction: Controversial data exist in the literature regarding relationship of IL-6 with gestational diabetes mellitus (GDM), partially resulting from different criteria for GDM classification. In the present study, we revised this linkage by investigating leukocyte IL6 expression and its associations with clinical characteristics of patients diagnosed by the Polish Diabetes Association (PDA) 2011 and 2014 criteria.

Material And Methods: A total of 145 pregnant women underwent 75 g two-hour OGTT, and GDM was diagnosed according to PDA 2011 criteria (GDM/PDA 2011 group; n = 113) and PDA 2014 criteria (GDM/PDA 2014 group; n = 104). IL6 gene expression was investigated in leukocytes of all participants by using real-time PCR method.

Results: Compared to respective NGT control groups, the GDM/PDA 2011 group exhibited higher FPG, two-hour OGTT, HbA1C and IL6 expression and lower HDL-C, whereas the GDM/PDA 2014 group had higher FPG, one-hour and two-hour OGTT, HbA1C and HOMA-IR, lower QUICKI-IS, and unchanged IL6 expression. No differences in metabolic parameters and IL6 expression were found between the two GDM groups. Compared to the NGT/PDA 2011 group, the NGT/PDA 2014 group had lower one-hour and higher two-hour OGTT and increased IL6 expression. With PDA 2014 criteria, IL6 expression correlated positively with two-hour OGTT in both NGT and GDM groups as well as with LDL-C in NGT group, and negatively with HDL-C in NGT group. With PDA 2011 criteria, no associations were evident in NGT and GDM groups. Nevertheless, significant positive correlation of IL6 mRNA with two-hour OGTT was observed in the entire study group.

Conclusions: Differences in metabolic phenotypes as well as gene expression and correlation data between GDM and NGT groups, categorised based on PDA 2011 and 2014 criteria, are related to changes in gestational glucose tolerance status resulting from using PDA 2014 criteria. Moreover, our findings support the hypothesis that IL-6 is associated with glucose metabolism during pregnancy.
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http://dx.doi.org/10.5603/EP.a2017.0014DOI Listing
December 2017

Obstetric results of the multicenter, nationwide, scientific-educational program for pregnant women with gestational diabetes mellitus (GDM).

Ginekol Pol 2016 ;87(9):651-658

Department of Diabetology and Metabolic Diseases, Lodz, Poland.

Objectives: The aim of the present study was to compare the obstetric results in women with GDM in a Polish population based on the criterion for the diagnosis of GDM.

Material And Methods: The study was a questionnaire study covering the data of 2853 patients with GDM treated in centers nationwide in the years 2011-2013. The principles of self-control, glycemic targets and treatment were based on the then-current PDA guidelines. Analysis of the collected data included an assessment of obstetric results based on the diagnostic criteria for GDM. Depending on the result of the glucose tolerance test, the patients were divided into subgroups.

Results: 6.28% of births were preterm, and 47% were caesarean. A significant difference was observed in the number of preterm births between a subgroups: PDA(+) meeting only criterion 0' and a PDA(+)meeting only criterion 120' (16.67% vs. 5.83%); and between WHO(+) subgroup meeting only criterion 0' with respect to the subgroup PDA(+) meeting only criterion 0' (4.69% vs. 16.67%). Significant difference was found in the frequency of LGA between the WHO(-)PDA(+) and WHO(+)PDA(-) subgroups (6,57% vs. 14.93%), and between the WHO(-)PDA(+) group and a group of isolated hyperglycemia in 60'(6.57% vs. 12.5%). Also a significant positive correlation was observed between birth weight, the occurrence of LGA and macrosomia, and maternal weight and BMI before pregnancy.

Conclusions: The results of the analysis indicate the new criteria have greater sensitivity in the prediction of prematurity and birth weight. However, it cannot be ruled out that the final results were affected by the therapeutic intervention employed.
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http://dx.doi.org/10.5603/GP.2016.0061DOI Listing
July 2018

The possible impact of advanced glycation end products on pregnancy outcome in women with diabetes mellitus type 1.

Minerva Endocrinol 2017 Sep 15;42(3):271-279. Epub 2016 Jun 15.

Diabetology and Metabolic Diseases Department, Medical University of Lodz, Lodz, Poland.

Diabetes mellitus (DM) is a group of metabolic disorders of carbohydrate metabolism in which glucose is underutilized, resulting in hyperglycemia. Reproductive impairment in poorly controlled diabetes mellitus type 1 (T1DM) results from a combined effect of insulin deficiency and hyperglycemia that disrupt the functioning of metabolic signals participating in the regulation of the reproductive system. Good metabolic control as a result of intensive insulin therapy has a great impact on the fertility and childbearing possibilities in the T1DM females. Advanced glycation end products (AGEs) are formed by nonenzymatic modification of proteins, lipids, and nucleic acids by glucose. The formation and accumulation of AGEs are known to progress at an accelerated rate in diabetes. AGEs either act on the pro-inflammatory cell surface receptors called RAGE or bind to the circulating anti-inflammatory sRAGE that prevents activation of cell-surface RAGE by AGEs and other proinflammatory ligands. Pregnancy has been found to induce a significant increase in RAGE protein levels in both myometrium and omental vasculature. This review will focus on the role of AGEs and RAGE in pregnancy complicated by DM type 1 as well as ways to reduce the rate of congenital malformations in the offspring of diabetic type 1 women.
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http://dx.doi.org/10.23736/S0391-1977.16.02477-9DOI Listing
September 2017

The impact of having siblings - analysis of "hygiene theory" of chronic diseases in patients with type 1 diabetes in population of the Łódz region Hygiene theory and type 1 diabetes.

Pediatr Endocrinol Diabetes Metab 2015 ;20(3):95-100

Klinika Diabetologii i Chorób Przemiany Materii, Uniwersytet Medyczny w Łodzi.

Introduction: In the recent years there has been a significant increase in the incidence of the type 1 diabetes mellitus. Therefore, numerous studies are underway to evaluate the possible factors underlying this trend. Some studies suggest that better sanitary conditions and lack of contact with microorganisms might be important, thus increasing the risk of disease in firstborns. Moreover, siblings could play an important role in the transmission of pathogens, which, by stimulating the immune system, may prevent the development of atopic and autoimmune diseases including such as type 1 diabetes. Current data, however, are still inconclusive.

Purpose: The aim of the study was to evaluate the effect of having siblings on the incidence of type 1 diabetes among children and adults.

Materials And Methods: A group of 469 patients with type 1 diabetes was selected. The study population was composed of 245 adults and 224 youth patients. Information from Outpatient Diabetologic Departments database was gathered. Data such as age at the diagnosis of diabetes, sex of siblings, number and birth order were analyzed.

Results: In the studied population, 4.5% were only children, and 30.3% patients came from large families. In the group of type 1 diabetic patients 39.7% were firstborns and this proportion was comparable to the group of healthy subject. The highest proportion of firstborns was noted in the group that was diagnosed after 18 years of age (45,1%) compared to the group that was diagnosed between 10 and 14 (29,1%) (p<0.05). Type 1 diabetic patients that were not firstborns much more often had older siblings of the opposite sex than the same sex.

Conclusions: he firstborns in the population of type 1 diabetes from the Łódz region did not outnumber the healthy subjects. Significantly higher proportion of firstborns in the group that was diagnosed after 18 years of age compared to the group that was diagnosed between 10 an 14 years was noted.
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http://dx.doi.org/10.18544/PEDM-20.03.0008DOI Listing
September 2017

Increased expression of immune-related genes in leukocytes of patients with diagnosed gestational diabetes mellitus (GDM).

Exp Biol Med (Maywood) 2016 Mar 13;241(5):457-65. Epub 2015 Nov 13.

Department of Structural Biology, Faculty of Biomedical Sciences and Postgraduate Education, Medical University of Lodz, 90-752 Lodz, Poland.

Compelling evidence indicates that the immune system is linked to metabolism in gestational diabetes mellitus (GDM), but factors participating in these processes still are awaiting identification. Inducible nitric oxide synthase, encoded by the NOS2 gene, and surfactant protein D, encoded by the SFTPD gene, have been implicated in diabetes. We investigated NOS2 and SFTPD mRNA levels in leukocytes obtained from 125 pregnant women with (n = 87) or without (control group; n = 38) GDM, and, in turn, correlated their expression with clinical parameters of subjects. Leukocytes were isolated from the blood of pregnant women and NOS2 and SFTPD expression in these cells was determined by quantitative real time PCR (qRT-PCR). Univariate correlation analyses were performed to assess an association between leukocyte NOS2 and SFTPD expression and clinical characteristics of patients. qRT-PCR experiments disclosed significantly increased leukocyte NOS2 and SFTPD mRNA levels in hyperglycemic GDM patients (P < 0.05). In the entire study group, there were significant positive associations of leukocyte NOS2 and SFTPD mRNAs with C-reactive protein. Additionally, transcript level of SFTPD also correlated positively with fasting glycemia and insulin resistance. This study demonstrates that an impaired glucose metabolism in GDM may be predominant predictor of leukocyte NOS2 and SFTPD overexpression in diabetic patients. Furthermore, alterations in the expression of these genes are associated with glucose metabolism dysfunction and/or inflammation during pregnancy. In addition, these findings support the utilization of leukocytes as good experimental model to study a relationship between immune-related genes and metabolic changes in women with GDM, as well as to assess the potential mechanisms underlying these alterations.
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http://dx.doi.org/10.1177/1535370215615699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950477PMC
March 2016

Family, anthropometric and biochemical factors affecting birth weight of infants born to GDM women.

Ginekol Pol 2015 Jul;86(7):499-503

Objectives: Gestational diabetes mellitus (GDM) affects up to 25% of all pregnancies worldwide. If untreated, GDM leads to increased complication rates both, in the mother and the fetus. Early diagnosis and adequate management of GDM are essential to avoid macrosomia. Nonetheless, neonates born to GDM mothers often have high birth weight. The aim of the study was to evaluate selected factors which can affect neonatal birth weight.

Material And Methods: The study included 152 women with GDM and 58 healthy pregnant controls. Anthropometric data of both parents, maternal biochemical parameters, and neonatal birth weight were collected.

Results: The independent factors influencing neonatal birth weight were pregnancy duration, maternal smoking, as well as birth weight and current weight of the father. The risk of delivering a large for gestational age (LGA) infant increases with the diagnosis of GDM, higher maternal pre-pregnancy weight, and higher fasting glycaemia. No correlation between maternal fasting glycaemia, HbA1c, 1,5-AG, lipids and neonatal birth weight was found.

Conclusions: Risk factors for LGA include gestational diabetes, high maternal pre-pregnancy weight, and current body weight of the father. Neither HbA1c nor 1,5-AG were reliable predictors of neonatal birth weight and occurrence of LGA in the studied population.
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http://dx.doi.org/10.17772/gp/652DOI Listing
July 2015

Gestational diabetes mellitus is associated with increased leukocyte peroxisome proliferator-activated receptor γ expression.

Arch Med Sci 2015 Aug 14;11(4):779-87. Epub 2015 Jan 14.

Polish Mother's Memorial Hospital, Research Institute, Lodz, Poland ; Diabetology and Metabolic Diseases Department, Medical University of Lodz, Lodz, Poland.

Introduction: Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor of the nuclear receptor superfamily that is involved in lipid and carbohydrate metabolism as well as inflammation; thereby it participates in metabolic diseases including diabetes. Although PPARγ expression has been observed in different tissues of diabetic patients, its level in leukocytes from subjects affected by gestational diabetes mellitus (GDM) has not yet been reported. This study aimed to investigate leukocyte PPARG expression in GDM patients at 24-33 weeks of gestation and, in turn, to correlate these alterations with anthropometric and metabolic parameters of patients.

Material And Methods: Leukocytes were isolated from the blood of normal glucose tolerant (NGT; n = 34) and GDM (n = 77) pregnant women between 24 and 33 weeks of gestation. Leukocyte PPARG mRNA expression was determined by semi-quantitative polymerase chain reaction. Univariate correlation analysis was performed to investigate associations between PPARG expression and clinical characteristics of patients.

Results: Leukocyte PPARG mRNA level was significantly higher in GDM than NGT women (p < 0.05). In the whole study group, PPARG expression positively correlated with plasma glucose concentrations at 1 h (r = 0.222, p = 0.049) and 2 h (r = 0.315, p = 0.020) of 75 g oral glucose tolerance test (OGTT), and negatively correlated with plasma HDL cholesterol concentration (r = -0.351, p = 0.010).

Conclusions: The correlation between leukocyte PPARG overexpression and hyperglycaemia suggests that PPARG mRNA expression in these cells might be up-regulated in high-glucose conditions in GDM patients at 24-33 weeks of gestation.
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http://dx.doi.org/10.5114/aoms.2015.47692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548020PMC
August 2015

Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Shows that Fetal Heart Rate Correlates with Maternal Glycemia.

Diabetes Technol Ther 2015 Sep 30;17(9):619-24. Epub 2015 Apr 30.

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

Background: Much evidence has shown that pregnancies in women with preexisting diabetes are affected by an increased risk of maternal and fetal adverse outcomes, probably linked to poor glycemic control. Despite great progress in medical care, the rate of stillbirths remains much higher in diabetes patients than in the general population. Recent technological advances in the field of glucose monitoring and noninvasive fetal heart rate monitoring made it possible to observe the fetal-maternal dependencies in a continuous manner.

Subjects And Methods: Fourteen type 1 diabetes patients were involved into the study and fitted with a blinded continuous glucose monitoring (CGM) recorder. Fetal electrocardiogram data were recorded using the Monica AN24™ device (Monica Healthcare Ltd., Nottingham, United Kingdom), the recordings of which were matched with CGM data. Statistical analysis was performed using a generalized mixed-effect logistic regression to account for individual factors.

Results: The mean number of paired data points per patient was 254±106, representing an observation period of 21.2±8.8 h. Mean glycemia equaled 5.64±0.68 mmol/L, and mean fetal heart rate was 135±6 beats/min. Higher glycemia correlated with fetal heart rate (R=0.32; P<0.0001) and was associated with higher odds of the fetus developing small accelerations (odds ratio=1.05; 95% confidence interval, 1.00-1.10; P=0.04).

Conclusions: Elevated maternal glycemia of mothers with diabetes is associated with accelerations of fetal heart rate.
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http://dx.doi.org/10.1089/dia.2014.0255DOI Listing
September 2015

The relationship between adipose tissue-derived hormones and gestational diabetes mellitus (GDM).

Endokrynol Pol 2014 ;65(2):134-42

Gestational diabetes mellitus (GDM) is defined as a glucose intolerance of varying severity with onset or first recognition during pregnancy. The prevalence of GDM is growing rapidly worldwide, resulting in numerous and serious complications for both mother and foetus. Two major metabolic disorders, insulin resistance and β cells dysfunction, are currently linked to the pathogenesis of GDM, although the cellular mechanisms involved in the development of GDM are not yet completely understood. Increasing evidence from clinical and experimental studies indicates that adipose tissue dysfunction, characterised by abnormal production of adipokines, is an essential factor linked to insulin resistance and GDM. To date, several adipose tissue-derived hormones have been identified, including leptin, adiponectin, resistin, visfatin, apelin, retinol-binding protein 4 (RBP-4), vaspin, and omentin. The relationship of leptin and adiponectin to insulin resistance in GDM is relatively well documented, but the molecular mechanisms by which these hormones affect insulin resistance are not yet fully known. The other aforementioned adipokines appear to be also important players in the pathophysiology of GDM, although their precise function in this complex process remains to be established. The aim of this article is to review the literature concerning the relationship between the above-mentioned adipokines and GDM, and to clarify their role in the pathophysiology of GDM.
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http://dx.doi.org/10.5603/EP.2014.0019DOI Listing
December 2015

Self-monitoring of blood glucose in diabetes: from evidence to clinical reality in Central and Eastern Europe--recommendations from the international Central-Eastern European expert group.

Diabetes Technol Ther 2014 Jul 9;16(7):460-75. Epub 2014 Apr 9.

1 Internal Medicine and Diabetology Department, Medical University of Lodz , Lodz, Poland .

Self-monitoring of blood glucose (SMBG) is universally considered to be an integral part of type 1 diabetes management and crucial for optimizing the safety and efficacy of complex insulin regimens. This extends to type 2 diabetes patients on intensive insulin therapy, and there is also a growing body of evidence suggesting that structured SMBG is beneficial for all type 2 diabetes patients, regardless of therapy. However, access to SMBG can be limited in many countries in Central and Eastern Europe. A consensus group of diabetes experts from 10 countries in this region (with overlapping historical, political, and social environments)--Bulgaria, Croatia, Czech Republic, Hungary, Poland, Romania, Serbia, Slovakia, Slovenia, and Ukraine--was formed to discuss the role of SMBG across the spectrum of patients with diabetes. The group considered SMBG to be an essential tool that should be accessible to all patients with diabetes, including those with non-insulin-treated type 2 diabetes. The current article summarizes the evidence put forward by the consensus group and provides their recommendations for the appropriate use of SMBG as part of individualized patient management. The ultimate goal of these evidence-based recommendations is to help patients and providers in Central and Eastern Europe to make optimal use of SMBG in order to maximize the efficacy and safety of glucose-lowering therapies, to prevent complications, and to empower the patient to play a more active role in the management of their diabetes.
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http://dx.doi.org/10.1089/dia.2013.0302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074758PMC
July 2014

The association of leukocyte phosphatidylinositol 3-kinase delta overexpression with gestational diabetes mellitus (GDM).

Endokrynol Pol 2014 ;65(1):17-24

Introduction: An increasing body of evidence has linked diabetes to inflammation. The phosphatidylinositol 3-kinase delta (PI3-K delta), a member of the PI3K class IA family, has been implicated in the regulation of inflammation since it is predominantly expressed in leukocytes. To date, no information has been available on the relationship of leukocyte PI3-K delta with gestational diabetes mellitus (GDM). Therefore, the aim of this study was to investigate changes in leukocyte PIK3CD mRNA expression in GDM women and, in turn, to correlate them with anthropometric and metabolic parameters of patients. Additionally, an association between leukocyte mRNA expression of PIK3CD and Sirtuin 1 (SIRT1) was determined.

Material And Methods: Blood samples from women with normal glucose tolerance (NGT; n = 43) and GDM (n = 132) at 24-33 weeks of gestation were collected. After isolating leukocytes from the blood, quantitative real time PCR (qRT-PCR) was performed to determine PIK3CD gene expression in these cells. Univariate regression analyses were used to assess an association of leukocyte PIK3CD mRNA level with clinical characteristics of patients as well as with leukocyte SIRT1 mRNA expression.

Results: Leukocyte PIK3CD mRNA was increased by 1.98-fold in the GDM v. NGT subjects and inversely correlated with low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) in diabetic pregnancy. There were also significant positive correlations of leukocyte PIK3CD mRNA with plasma glucose concentration at 2h of 75 g oral glucose tolerance test (OGTT) and SIRT1 mRNA in the whole study population (both P < 0.05).

Conclusions: GDM is accompanied by leukocyte PIK3CD overexpression associated with reduced plasma LDL-C and TC levels, as well as with hyperglycaemia and elevated leukocyte SIRT1 mRNA.
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http://dx.doi.org/10.5603/EP.2014.0003DOI Listing
October 2015

The elevated gene expression level of the A(2B) adenosine receptor is associated with hyperglycemia in women with gestational diabetes mellitus.

Diabetes Metab Res Rev 2014 Jan;30(1):42-53

Department of Structural Biology, Faculty of Biomedical Sciences and Postgraduate Education, Medical University of Lodz, Zeligowskiego 7/9 St., 90-752, Lodz, Poland.

Background: Adenosine receptors denoted by A1 , A2A , A2B , and A3 and encoded by ADORA1, ADORA2A, ADORA2B, and ADORA3 genes, respectively, are adenosine-activated G-protein-coupled receptors that play an important role in obesity and type 2 diabetes mellitus. However, little is known about their significance in gestational diabetes mellitus (GDM). The purpose of this study was to investigate whether there are changes in leukocyte AR expression in GDM patients and whether these alterations are linked to well-known diabetic genes.

Methods: Leukocytes were isolated from the blood of normal glucose tolerant (NGT; n = 35) and GDM (n = 82) pregnant women, and expression of ARs was determined by a semi-quantitative polymerase chain reaction (PCR). Univariate correlation analysis was performed to investigate associations between expression of ARs and anthropometric and metabolic parameters of patients. Furthermore, the identification of diabetic genes linked to significantly differentiated leukocyte adenosine receptors expression in GDM women was also carried out with the use of the human diabetes RT(2) profiler PCR arrays.

Results: ADORA2B mRNA expression was significantly higher in GDM versus NGT pregnant women (p < 0.05), and positively correlated with the glucose level at 1-h 75-g oral glucose tolerance test (OGTT; r = 0.21, p = 0.044). Nineteen diabetic genes linked to leukocyte ADORA2B overexpression associated with hyperglycemia in GDM women were also identified.

Conclusions: Maternal leukocyte ADORA2B overexpression is associated with hyperglycemia in GDM subjects, and it is accompanied by complex alterations in the expression of diabetes-related genes involved in insulin action, carbohydrate and lipid metabolism, oxidative stress, and inflammation.
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http://dx.doi.org/10.1002/dmrr.2446DOI Listing
January 2014