Monika Zurawska-Klis

Not much is currently known about disturbances in insulin signaling and glucose transport in leukocytes of women with gestational diabetes mellitus (GDM) during and after pregnancy. In this study, the expression of insulin signaling (INSR, IRS1, IRS2 and PIK3R1)- and glucose transporter (SLC2A1, SLC2A3 and SLC2A4)-related genes in the leukocytes of 92 pregnant women was assayed using quantitative RT-PCR. The cohort consisted of 44 women without GDM (NGT group) and 48 with GDM (GDM group) at 24–28 weeks of gestation. GDM women were then tested again one year after childbirth (pGDM group: 14 women (29.2%) with abnormal glucose tolerance (AGT) and 34 women (70.8%) with normoglycemia). The GDM and NGT groups were closely matched for gestational age and parameters of obesity, such as pre-pregnancy body mass index (BMI), pregnancy weight, and gestational weight gain (GWG) (p > 0.05). Compared to the NGT group, the GDM and pGDM groups were hyperglycemic, but the GDM group featured a more highly insulin-resistant condition than the pGDM group, as reflected by higher fasting insulin (FI) levels and the values of the homeostasis model assessment for insulin resistance (HOMA-IR) (p < 0.05). In leukocytes from the GDM and pGDM groups, PIK3R1, SLC2A1, and SLC2A3 were upregulated and IRS1 was downregulated, with a larger magnitude in fold change (FC) values for PIK3R1 and IRS1 in the GDM group and for SLC2A1 and SLC2A3 in the pGDM group. The expression of SLC2A4 was unchanged in the GDM group but upregulated in the pGDM group, where it was inversely correlated with HOMA-IR (rho = −0.48; p = 0.007). Although the INSR and IRS2 levels did not significantly differ between the groups, the IRS2 transcript positively correlated with pregnancy weight, fasting plasma glucose, FI, and HOMA-IR in the GDM group. Our findings indicate that pronounced quantitative changes exist between the GDM and pGDM groups with respect to the expression of certain genes engaged in insulin signaling and glucose transport in leukocytes, with insulin resistance of a variable degree. These data also highlight the relationship of leukocyte SLC2A4 expression with insulin resistance in the postpartum period.

We aimed to evaluate glycaemic control in patients with type 1 diabetes during the first three months of use of the flash glucose monitoring (FGM) system. Methods: We conducted a study of a cohort of 81 people with type 1 diabetes mellitus who used the FreeStyle Libre 2 (FSL2) sensor continuously for 3 months. Patients had not used a CGM before. The effectiveness of using the FSL2 system was assessed using AGP reports at two time points (3–4 weeks and 11–12 weeks of system use). Results: Eight weeks after using FSL2, compared with results from 3–4 weeks of use, there were no differences in the glucose management indicator, time spent in range, above range and below range, or glucose variability. In the first month of FGM use, patients scanned the sensor significantly more often than in the following two months (p = 0.021). No significant differences were found in the change of the evaluated parameters when comparing patients by duration of diabetes and treatment method. Conclusions: Short-term use of FSL2 promotes a significant reduction in GMI in patients with more time spent in hyperglycaemia (especially > 250 mg/dL). In this short period of use, no other changes in glycaemic control parameters are observed.

Although the immune system has been implicated in the pathophysiology of gestational diabetes mellitus (GDM) and postpartum abnormal glucose tolerance (AGT), little is known about the transcriptional response of inflammation-related genes linked to metabolic phenotypes of GDM women during and after pregnancy, which may be potential diagnostic classifiers for GDM and biomarkers for predicting AGT. To address these questions, gene expression of IL6, IL8, IL10, IL13, IL18, TNFA, and the nuclear factor κB (NFκB)/RELA transcription factor were quantified in leukocytes of 28 diabetic women at GDM diagnosis (GDM group) and 1-year postpartum (pGDM group: 10 women with AGT and 18 normoglycemic women), using a nested RT-PCR method. Control pregnancies with normal glucose tolerance (NGT group; n = 31) were closely matched for maternal age, gestational age, pre-pregnancy BMI, pregnancy weight, and gestational weight gain. Compared with the NGT group, IL8 was downregulated in the GDM group, and IL13 and RELA were upregulated in the pGDM group, whereas IL6, IL10, and IL18 were upregulated in the GDM and pGDM groups. The TNFA level did not change from pregnancy to postpartum. Associations of some cytokines with glycemic measures were detected in pregnancy (IL6 and RELA) and postpartum (IL10) (p < 0.05). Receiver operating characteristic (ROC) curves showed that IL6, IL8, and IL18, if employed alone, can discriminate GDM patients from NGT individuals at GDM diagnosis, with the area under the ROC curves (AUCs) of 0.844, (95% CI 0.736–0.953), 0.771 (95% CI 0.651–0.890), and 0.714 (95% CI 0.582–0.846), respectively. By the logistic regression method, we also identified a three-gene panel (IL8, IL13, and TNFA) for postpartum AGT prediction. This study demonstrates a different transcriptional response of the studied genes in clinically well-characterized women with GDM at GDM diagnosis and 1-year postpartum, and provides novel transcriptomic biomarkers for future efforts aimed at diagnosing GDM and identifying the high risk of postpartum AGT groups.

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.

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.

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 SIRT1 expression at the time of GDM diagnosis. For this purpose, 122 GDM patients were screened for leukocyte SIRT1 expression, and two subgroups were distinguished, namely GDM/SIRT1(↑) (n = 30, p < 0.05) and GDM/SIRT1(↔) (n = 92, p > 0.05), with significant and insignificant changes in leukocyte SIRT1 expression compared to a normal glucose tolerant (NGT) group (n = 41), respectively. PCR array analysis identified 11 diabetes-related genes with at least a ± 2-fold difference in expression in GDM/SIRT1(↑) patients (n = 9) vs. NGT controls (n = 7); in addition, significant differences in the expression of four of the six investigated genes were confirmed between the entire GDM/SIRT1(↑) group and the whole NGT group (p < 0.05). Interestingly, of these four genes, only ACLY expression was found to significantly differ between GDM/SIRT1(↑) and GDM/SIRT1(↔). This study demonstrates that under hyperglycemic conditions, leukocyte SIRT1 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 ACLY under-expression in GDM/SIRT1(↑) women.