miRNAs as Predictive Factors in Early Diagnosis of Gestational Diabetes Mellitus.

Introduction: Circulating miRNAs are important mediators in epigenetic changes. These non-coding molecules regulate post-transcriptional gene expression by binding to mRNA. As a result, they influence the development of many diseases, such as gestational diabetes mellitus (GDM). Therefore, this study investigates the changes in the miRNA profile in GDM patients before hyperglycemia appears. Materials and Methods: The study group consisted of 24 patients with GDM, and the control group was 24 normoglycemic pregnant women who were matched for body mass index (BMI), age, and gestational age. GDM was diagnosed with an oral glucose tolerance test between the 24th and 26th weeks of pregnancy. The study had a prospective design, and serum for analysis was obtained in the first trimester of pregnancy. Circulating miRNAs were measured using the NanoString quantitative assay platform. Validation with real time-polymerase chain reaction (RT-PCR) was performed on the same group of patients. Mann-Whitney U-test and Spearman correlation were done to assess the significance of the results. Results: Among the 800 miRNAs, 221 miRNAs were not detected, and 439 were close to background noise. The remaining miRNAs were carefully investigated for their average counts, fold changes, p-values, and false discovery rate (FDR) scores. We selected four miRNAs for further validation: miR-16-5p, miR-142-3p, miR-144-3p, and miR-320e, which showed the most prominent changes between the studied groups. The validation showed up-regulation of miR-16-5p (p<0.0001), miR-142-3p (p=0.001), and miR-144-3p (p=0.003). Conclusion: We present changes in miRNA profile in the serum of GDM women, which may indicate significance in the pathophysiology of GDM. These findings emphasize the role of miRNAs as a predictive factor that could potentially be useful in early diagnosis.

Serum C18:1-Cer as a Potential Biomarker for Early Detection of Gestational Diabetes.

We hypothesized that sphingolipids may be early biomarkers of gestational diabetes mellitus (GDM). Here, 520 women with normal fasting plasma glucose levels were recruited in the first trimester and tested with a 75 g oral glucose tolerance test in the 24th-28th week of pregnancy. Serum sphingolipids concentrations were measured in the first and the second trimester by ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC/MS/MS) in 53 patients who were diagnosed with GDM, as well as 82 pregnant women with normal glucose tolerance (NGT) and 32 non-pregnant women. In the first trimester, pregnant women showed higher concentrations of C16:0, C18:1, C22:0, C24:1, and C24:0-Cer and lower levels of sphinganine (SPA) and sphingosine-1-phosphate (S1P) compared to non-pregnant women. During pregnancy, we observed significant changes in C16:0, C18:0, C18:1, and C24:1-Cer levels in the GDM group and C18:1 and C24:0-Cer in NGT. The GDM (pre-conversion) and NGT groups in the first trimester differed solely in the levels of C18:1-Cer (AUC = 0.702 p = 0.008), also considering glycemia. Thus, C18:1-Cer revealed its potential as a GDM biomarker. Sphingolipids are known to be a modulator of insulin resistance, and our results indicate that ceramide measurements in early pregnancy may help with GDM screening.

Assessment of Clinical Utility of Assaying FGF-23, Klotho Protein, Osteocalcin, NTX, and Sclerostin in Patients with Primary Hyperparathyroidism.

The purpose of this study was to assess the clinical usefulness of assaying the fibroblast growth factor (FGF-23), Klotho, osteocalcin, N-terminal telopeptide of type I collagen (NTX), and sclerostin levels in patients with primary hyperparathyroidism (PHPT) as markers of bone damage as well as for surgical treatment success. Seventeen patients with hypercalcemic PHPT and normal kidney function were studied. In all patients, PTH (parathormone), serum calcium, and creatinine were performed before and six months after parathyroidectomy (PTX). The studied group included patients whose PTH and calcium concentrations normalized post-operatively and with confirmed histopathological diagnosis. The control group consisted of nine age-matched healthy volunteers. The PHPT patients had elevated concentrations of FGF-23, osteocalcin, and NTX and reduced levels of sclerostin, as compared to the control group. After PTX, osteocalcin, NTX, and sclerostin levels normalized. The plasma values of FGF-23 decreased significantly, but remained higher than in healthy subjects. Serum Klotho protein levels did not differ significantly in the two groups. These results suggest that osteocalcin and NTX may potentially be considered as markers of PHPT progression. Additionally, serum normalization of osteocalcin, NTX, and sclerostin might be considered as indicators of PTX success. On the other hand, FGF-23 can represent a parameter reflecting the degree of calcium-phosphate imbalance in PHPT patients, but its usefulness in monitoring the effects of PTX requires further research. The clinical utility of assaying Klotho in PHPT remains to be confirmed.

Influence of MiRNAs in gestational diabetes mellitus development.

Gestational Diabetes Mellitus (GDM) is a metabolic disorder that is considered a prediabetes state. According to the International Diabetes Federation every year an increase in the number of women diagnosed with gestational diabetes is being noticed. It is known that GDM can cause many complications during pregnancy and labor. What is more, women with GDM history and their offspring are at risk of developing diabetes in the future. A new factor in the pathogenesis of GDM is epigenetics, which is described as changes in gene expression without directly modifying the DNA sequence. One of its regulating mechanisms is based on microRNA (miRNA). A small non-coding RNA sequence that has an influence on protein formation by suppressing gene expression. A better understanding of the miRNA's function could potentially lead to their usage as potential new biomarkers or treatment targets. In this article we review the most significant miRNA molecules in gestational diabetes.

Ceramides and Sphingosino-1-Phosphate in Obesity.

Obesity is a growing worldwide problem, especially in developed countries. This disease adversely affects the quality of life and notably contributes to the development of type 2 diabetes, metabolic syndrome, and cardiovascular disorders. It is characterised by excessive lipids accumulation in the subcutaneous and visceral adipose tissue. Considering the secretory function of adipose tissue, this leads to impaired adipokines and cytokines release. Changes in adipose tissue metabolism result in chronic inflammation, pancreatic islets dysfunction and peripheral insulin resistance. In addition to saturating various adipocytes, excess lipids are deposited into non-adipose peripheral tissues, which disturbs cell metabolism and causes a harmful effect known as lipotoxicity. Fatty acids are metabolised into bioactive lipids such as ceramides, from which sphingolipids are formed. Ceramides and sphingosine-1-phosphate (S1P) are involved in intracellular signalling, cell proliferation, migration, and apoptosis. Studies demonstrate that bioactive lipids have a crucial role in regulating insulin signalling pathways, glucose homeostasis and ß cell death. Data suggests that ceramides may have an opposite cellular effect than S1P; however, the role of S1P remains controversial. This review summarises the available data on ceramide and sphingolipid metabolism and their role in obesity.