Hypertrophic and hypoxic visceral adipose tissue (VAT) secretes proinflammatory cytokines promoting insulin resistance (IR), prediabetes and type 2 diabetes (T2DM) microRNAs (miRNAs) are markers of metabolic disorders regulating genes critical for e.g., inflammation, glucose metabolism, and antioxidant defense, with raising diagnostic value. The aim of the current study was to evaluate whether hyperglycemia is able to affect the expression of selected miRNAs in VAT of prediabetic (IFG) and diabetic (T2DM) patients vs. normoglycemic (NG) subjects using qPCR. Statistical analyses suggested that miRNAs expression could be sex-dependent. Thus, we determined 15 miRNAs as differentially expressed (DE) among NG, T2DM, IFG females (miR-10a-5p, let-7d-5p, miR-532-5p, miR-127-3p, miR-125b-5p, let-7a-5p, let-7e-5p, miR-199a-3p, miR-365a-3p, miR-99a-5p, miR-100-5p, miR-342-3p, miR-146b-5p, miR-204-5p, miR-409-3p). Majority of significantly changed miRNAs was similarly upregulated in VAT of female T2DM and IFG patients in comparison to NG subjects, positively correlated with FPG and HbA1c, yet, uncorrelated with WHR/BMI. Enrichment analyses indicated involvement of 11 top DE miRNAs in oxidative stress, inflammation and insulin signaling. Those miRNAs expression changes could be possibly associated with low-grade chronic inflammation and oxidative stress in VAT of hyperglycemic subjects.

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.

Irisin is a cytokine involved in many metabolic pathways occurring, among others, in muscles, adipose tissue and liver. Thus, fluctuations in irisin levels are suggested to be related to metabolic diseases. Therefore, the purpose of our study was to evaluate whether irisin may be associated with non-alcoholic fatty liver disease (NAFLD). A total of 138 patients (70/68 male/female, mean age 65.61 ± 10.44 years) were enrolled in the study. The patients were assigned to the NAFLD group (n = 72, including 46 patients with type 2 diabetes (T2DM]) and the group without NAFLD (n = 66, 31 patients with T2DM). NAFLD was diagnosed based on ultrasound examination, Hepatic Steatosis Index (HSI) and Fatty Liver Index. Baseline anthropometric, blood pressure and biochemical parameters were collected. The serum irisin level was determined using an ELISA test. We observed that NAFLD was associated with an increased concentration of irisin. Moreover, Spearman correlations and linear regression analysis revealed that irisin level correlates with some anthropometric and biochemical parameters such as body mass index, glycated hemoglobin, aspartic aminotransferase, creatinine and urea. Logistic regression analysis depicted that odds for NAFLD increase 1.17 times for each 1 μg/mL rise of irisin concentration. Finally, ROC analysis showed that the concentration of irisin possesses a discriminate capacity for NAFLD and optimal cut points concentration could be designed. The risk of NAFLD in the subgroup with irisin concentration above 3.235 μg/mL was 4.57 times higher than in patients with the lower concentration of irisin. To conclude, the obtained results suggest that irisin concentration is associated with some anthropometric and biochemical parameters and should be further investigated toward its usage as a diagnostic biomarker of NAFLD.

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.

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.

Abstract: The A1 adenosine receptors (A1AR), belonging to the rhodopsin-like superfamily of the G-protein-coupled receptors (GPCRs), may regulate many various cellular processes in cardiovascular, renal, and central nervous systems. In addition, since the A1AR possesses antilipolytic properties, numerous A1AR agonists and antagonists have been developed, but only some of them with the most promising selective properties in vitro have been advanced to animal studies and clinical trials. In this review, we have summarized the studies on the utility of A1AR selective agonists and antagonists in the regulation of lipid and carbohydrate metabolism and their potential therapeutic applications in diabetes.