Erratum: Periphere Regionalanästhesie ohne Komplikationen – Ein Traum wird wahr?!

Anästhesiol Intensivmed Notfallmed Schmerzther
DOI: 10.1055/a-0629-0254

Georg Thieme Verlag KG Stuttgart · New York

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The Impact of Alcohol on Breathing Parameters during Sleep: A Systematic Review and Meta-analysis

Alcohol, a muscle relaxant, can potentially worsen obstructive sleep apnea (OSA) but the literature on the effects of alcohol on OSA is conflicting. This systematic review and meta-analysis of randomized controlled trials examined the impact of alcohol on breathing parameters during sleep. Ovid Medline, Embase and PsycINFO databases were queried through November 1, 2017 for studies that reported objective measures of breathing during sleep, prior to and after alcohol administration. Weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated for apnea-hypopnea index (AHI) and mean oxyhemoglobin saturation (SpO2).

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Screening effects of metsulfuron-methyl to collembolans and earthworms: the role of adjuvant addition on ecotoxicity

Abstract

Metsulfuron-methyl is a common active ingredient recommended for use in pre- and post-emergence control of annual grasses and broadleaf weeds in crops, usually applied with mineral oil as adjuvant to enhance its efficiency. Despite the increasing use of this herbicide, there are no information on its ecotoxicity effects to soil fauna. Avoidance and lethality tests were performed with earthworms and collembolans using tropical artificial soil contaminated with formulated products Ally® (600 g L⁻¹ metsulfuron-methyl) and Assist® (756 g L⁻¹ mineral oil) as adjuvant. Lethality test with earthworms showed no difference when tested with or without adjuvant. When Ally® was tested alone, it caused avoidance behavior only at high concentrations (5000 and 10,000 times field predicted dose). However, Assist® addition changed the response of soil invertebrates increasing the avoidance even at field predicted doses. The toxicity of the adjuvant was confirmed in tests exposing collembolans and earthworms to Assist® alone resulting in avoidance behavior. The results clearly show that the addition of mineral oil enhanced the ecotoxicity of metsulfuron-methyl. This study provides an important contribution to the knowledge on the toxicity of metsulfuron-methyl and indicates that adjuvants should be considered in risk assessment of pesticides, considering that under field conditions, these products are applied together.

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Chemical composition of rainwater in the Sinos River Basin, Southern Brazil: a source apportionment study

Abstract

This study aimed to assess the chemical composition of the rainwater in three areas of different environmental impact gradients in Southern Brazil using the receptor model EPA Positive Matrix Factorization (EPA PMF 5.0). The samples were collected in a bulk sampler, from October 2012 to August 2014, in three sampling sites along with the Sinos River Basin: Caraá, Taquara, and Campo Bom. The major ions NH₄⁺, Na⁺, K⁺, Ca²⁺, Mg²⁺, F⁻, Cl⁻, NO₃⁻, SO₄²⁻, and pH were analyzed, as well as identify the main emission sources. The most abundant cations and anions were Ca²⁺, Na⁺, Cl⁻, and SO₄²⁻, respectively. The mean pH value in the Sinos River Basin during the study period was 6.07 ± 0.49 (5.13–7.05), which suggests inputs of alkaline species into the atmosphere. The most important neutralizing agents of sulfuric and nitric acids in the Sinos River Basin are Ca²⁺ (NF = 1.36) and NH₄⁺ (NF = 0.57). The source apportionment provided by the EPA PMF 5.0 resulted in four factors, which demonstrate the influence of anthropogenic and natural sources, in the form of (a) industry/combustion of fossil fuels (F⁻ and SO₄²⁻), (b) marine contribution (Na⁺ and Cl⁻), (c) crustal contribution (K⁺, Ca²⁺, and NO₃⁻), and (d) agriculture/livestock (NH₄⁺). Therefore, this study allows a more appropriate understanding of factors that contribute to rainwater chemical composition and also to possible changes in air quality.

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Low-thermal remediation of mercury-contaminated soil and cultivation of treated soil

Abstract

In this study, low-thermal technology was used to treat the mercury contaminated farmland soil from a chemical plant in Guizhou Province, China. A series of field planting experiments were also aimed at determining the content of total and methyl-Hg in crop plants after thermal treatment. The results showed that the mercury concentration in soils was reduced about 70% from 255.74 mg/kg to 80.63 mg/kg when treated at 350 °C for 30 min in engineering-scale experiments, and the treated soil retained most of its original soil. Organic-bound and residual mercury in treated soil were reduced by 64.1 and 56.4% by means of a sequential extraction procedure, respectively. The total and methyl-mercury concentrations in crops decreased significantly, and the degree of soil mercury accumulation to crop roots has been reduced significantly. The total Hg concentrations in potato and corn were lower than the mercury tolerance limits for food in China, and the Hg concentration of radish was close to the limit. The technology provides a more sustainable remediation method for treating mercury-contaminated farmland soil in future engineering applications.

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Reduced arsenic availability and plant uptake and improved soil microbial diversity through combined addition of ferrihydrite and Trichoderma asperellum SM-12F1

Abstract

Arsenic (As) accumulation in agricultural soils is prone to crop uptake, posing risk to human health. Passivation shows potential to inactivate soil labile As and lower crop As uptake but often contributes little to improving the microbiota in As-contaminated soils. Here, the combined addition of ferrihydrite and Trichoderma asperellum SM-12F1 as a potential future application for remediation of As-contaminated soil was studied via pot experiments. The results indicated that, compared with the control treatment, the combined addition of ferrihydrite and T. asperellum SM-12F1 significantly increased water spinach shoot and root biomass by 134 and 138%, respectively, and lowered As content in shoot and root by 37 and 34%, respectively. Soil available As decreased by 40% after the combined addition. The variances in soil pH and As fractionation and speciation were responsible for the changes in soil As availability. Importantly, the combined addition greatly increased the total phospholipid fatty acids (PLFAs) and gram-positive (G+), gram-negative (G−), actinobacterial, bacterial, fungal PLFAs by 114, 68, 276, 292, 133, and 626%, respectively, compared with the control treatment. Correspondingly, the soil enzyme activities closely associated with carbon, nitrogen, and phosphorus mineralization and antioxidant activity were improved. The combination of ferrihydrite and T. asperellum SM-12F1 in soils did not reduce their independent effects.

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A comparison of the International Association of Diabetes and Pregnancy Study Groups Recommendations with Former Criteria for Diagnosing Gestational Diabetes Mellitus: A Retrospective Cohort Study

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0630-5118

Aim The aim of the study was to compare the frequency of gestational diabetes mellitus (GDM) and pregnancy outcomes in women diagnosed by WHO 1999 and IADPSG criteria. Methods This was a retrospective cohort study comprising 1508 women who underwent a 75-g OGTT after the 24th week of gestation at the University Hospital of Bialystok between 2004 and 2012. Results GDM was diagnosed by WHO 1999 criteria in 486 (32.2%) patients and by IADPSG criteria in 397 (26.3%) women. Three hundred fifty five (23.5%) patients fulfilled both criteria, whereas 111 (7.4%) and 39 (2.6%) subjects met only WHO 1999 or IADPSG criteria, respectively. Isolated fasting hyperglycemia was found in 3.4% of patients fulfilling WHO 1999 criteria and in 17.6% of women who met IADPSG criteria. In total, fasting glycemic value was diagnostic in 42.8% of the participants fulfilling the new criteria. The main risk factor for GDM was family history of diabetes (OR 2.285 [95%CI: 1.772-2.945], p=0.00001). The rates of cesarean section and macrosomia were higher in the group with GDM than in the healthy women (54.7% vs 41.9% and 18.9% vs 13.9%, respectively), but the differences were not significant. Three months postpartum the disturbances of glucose tolerance were found in 21% of the patients with GDM. Conclusions The introduction of the IADPS criteria did not increase the prevalence of GDM, but increased the number of patients with fasting hyperglycemia. Twelve weeks postpartum the patients with prior GDM had significantly higher post-load glucose levels than the healthy women.
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Expression of TIGIT and FCRL3 is Altered in T Cells from Patients with Distinct Patterns of Chronic Autoimmune Thyroiditis

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0597-8948

Background Co-inhibitory receptors (IR), such as TIGIT and FCRL3, provide a checkpoint against highly destructive immune responses. Co-expression of TIGIT and FCRL3, in particular, has been linked to the HELIOS+ subset of regulatory CD4+FOXP3+T-cells. Of these, CD4+FOXP3-exon(E)2+ cells have higher expression of IR and exhibit strongest suppressive properties. Nevertheless, how the expression of TIGIT, FCRL3, HELIOS, and FOXP3E2 is regulated in chronic autoimmune thyroiditis (AT), is not known. Methods Thirty patients with AT [encompassing spontaneously euthyroid (euAT), hypothyroid-untreated and L-thyroxine-treated cases)] and 10 healthy controls (HC) were recruited. FCRL3, TIGIT, HELIOS and FOXP3E2 mRNA expression levels in peripheral blood (PB) T cells were measured via quantitative real-time PCR and compared to clinicopathological factors. Results The TIGIT and FCRL3 expression levels from T cells of AT cases were inversely related to the thyroid volume, and were significantly increased in hypothyroid patients (on+off L-thyroxine), but not euAT cases. The FCRL3 expression in PB T cells positively correlated with thyroid-peroxidase autoantibody levels; by contrast, T cells from aged AT patients and combined samples (AT+HC) accumulated more TIGIT mRNA. The patients with higher TIGIT mRNA levels had a greater prevalence of hypothyroidism, showing higher peak thyrotropin levels at diagnosis or at follow-up. Conclusions Multiple IR, namely FCRL3 and TIGIT, but not the transcription factors HELIOS and FOXP3E2, showed increased mRNA levels in PB T cells from end-stage, long-standing and/or more aggressive AT, in proportion to disease severity. A relation with major clinical subphenotypes was observed, thereby identifying IR as potentially important players in AT.
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The Role of Different Molecular Markers in Papillary Thyroid Cancer Patients with Acromegaly

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0629-9223

Purpose Prevalence of papillary thyroid cancer (PTC) is increased in patients with acromegaly. We aimed to determine the protein expression of BRAF, RAS, RET, insulin like growth factor 1(IGF1), Galectine 3, CD56 in patients with PTC related acromegaly and to compare the extensity of these expressions with normal PTC patients and benign thyroid nodules. Methods We studied 313 patients with acromegaly followed in Cerrahpasa Medical Faculty, Endocrinology and Metabolism Clinic between 1998 and 2015. On the basis of availability of pathological specimen of thyroid tissues, thyroid samples of 13 patients from 19 with acromegaly related PTC (APTC), 20 normal PTC and 20 patients with multinodulary goiter (MNG) were histopathologically evaluated. Protein expressions were determined via immunohistochemical staining in ex-vivo tumor samples and benign nodules. Results The incidence of PTC in acromegaly patients were 6% (n=19). Among patients with PTC, APTC and MNG, all the immunohistochemical protein expressions we have studied were higher in papillary thyroid cancer groups (p<0.01, for all). Between PTC group without acromegaly and APTC, galectin 3 and IGF1 expression was significantly higher in acromegalic patients (p<0.01 for all) while RAS was predominantly higher in PTC patients without acromegaly (p<0.01). Conclusion BRAF expression was not higher in PTC with acromegaly patients compared to PTC patients without acromegaly. Galectine 3 and IGF1 were expressed more intensively in APTC. These positive protein expressions may have more influence on determining malign nodules among acromegaly patients.
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Assessment of the Dynamic Insulin Secretion and Sensitivity Test (DISST) Pre and Post Gastric bypass Surgery

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0603-3539

Objective To compare the dynamic insulin secretion and sensitivity test (DISST) with the euglycaemic clamp in individuals undergoing open Roux-en-Y gastric bypass (RYGB) surgery prior-to and one month after surgery. Methods Insulin sensitivity in individuals with obesity undergoing RYGB was studied with DISST and a euglycaemic hyperinsulinaemic clamp. Results Eleven participants, including nine females, mean(SD) age 51.2(12.1)yrs, with a preoperative BMI of 48.7(9.5)kg/m2 were studied. Weight reduced from a mean(SD) of 133.8(29.8)kg to 123.8(28.9)kg post-surgery (p<0.001). The mean(SD) insulin sensitivity index (ISI-DISST) was 3.07×10−4(2.18)L.pmol−1.min−1 preoperatively and 2.36 ×10−4(0.78)L.pmol−1.min−1 postoperatively (p=0.37). The mean(SD) clamp ISI was 2.14 ×10−2(1.80)mg.L.kg−1.min−1.pmol−1 and 2.00×10−2.(0.76)mg.L.kg−1.min−1.pmol−1 postoperatively (p=0.86). Correlation between ISI-DISST and ISI-Clamp preoperatively was r=0.81(95%CI 0.37-0.95) and post-operatively r=0.47(95%CI 0-0.88). Bland-Altman analysis demonstrates systematic bias between the two tests, where DISST underestimated insulin sensitivity compared with the clamp by 0.96×10-2.mg.L.kg−1.min−1.pmol−1 (95%CI -2.24 to 0.32). Conclusions There was a strong correlation between DISST and the clamp preoperatively and DISST can be used to estimate insulin sensitivity in individuals with morbid obesity. After RYGB surgery, DISST had a weaker correlation with the clamp suggesting the fundamental physiological determinants of insulin sensitivity being measured by each method change in different ways with changes in glucose homeostasis following RYGB surgery.
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Increased OGA Expression and Activity in Leukocytes from Patients with Diabetes: Correlation with Inflammation Markers

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0596-7337

O-linked-β-N-Acetylglucosaminylation (O-GlcNAcylation), a reversible post-translational modification involved in diabetic complications, is regulated by only two enzymes, O-linked N-acetylglucosamine transferase (OGT) and β-N-Acetylglucosaminidase (OGA). Increased OGA expression has been described previously in blood cells from patients with diabetes and was interpreted as an adaptative response to hyperglycemia-induced O-GlcNAcylation. OGA expression was thus proposed to have potential utility as a diagnostic marker. The present work was undertaken to determine whether determination of OGA enzymatic activity in blood cells could constitute a more rapidly accessible marker than OGA expression level measurements.Blood samples were obtained from patients with type 2 diabetes from the Department of Diabetology of the Cochin Hospital and healthy volunteers from the French blood Agency. OGA enzymatic activity and OGA mRNA expression levels were evaluated in leucocytes from patients with type 2 diabetes and from healthy donors.OGA activity was higher in leucocytes from patients with diabetes compared to control individuals. Surprisingly, OGA activity was not correlated hyperglycaemia markers (blood glucose, fructosamine, HbA1c) but was positively correlated with the inflammatory marker C-reactive protein. OGA mRNA levels were also increased in leucocytes from patients with diabetes and were correlated with mRNA coding for two pro-inflammatory proteins, TNFα and TxNIP.Therefore, OGA activity in leucocytes might be a more easily accessible biomarker than OGA expression levels. However, changes in OGA activity observed in patients with type 2 diabetes may reflect the inflammatory rather than the glycaemic status of these patients.
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A Novel c.125 T>G (p.Val42Gly) Mutation in The Human INS Gene Leads to Neonatal Diabetes Mellitus via a Decrease in Insulin Synthesis

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0603-3463

Background Neonatal diabetes mellitus is likely caused by monogenic mutations, several of which have been identified. INS mutations have a broad spectrum of clinical presentations, ranging from severe neonatal onset to mild adult onset, which suggests that the products of different mutant INS alleles behave differently and utilize distinct mechanisms to induce diabetes. In this study, a neonatal diabetes mellitus patient's INS gene was sequenced, and functional experiments were conducted. Methods The neonatal diabetes mellitus patient's genomic DNA was extracted, and the patient's KCNJ11, ABCC8, and INS genes were sequenced. A novel mutation was identified in INS, and the open reading frame of this human mutant INS gene was inserted into the pMSCV-PIG plasmid. The constructed pMSCV-PIG plasmid was combined with VSV-g and Gag-pol and transfected into 293T cells to package the lentivirus. To stably overexpress the mutant gene, INS-1 cells were infected with the virus. The levels of insulin in the cell culture medium and cytoplasm were determined by ELISA and immunocytochemistry, respectively. Results A heterozygous mutation, c.125T>G (p. Val42Gly), was identified in a neonatal diabetes mellitus patient's INS gene. The human mutant INS open reading frame was overexpressed in INS-1 cells, and the mutant insulin was undetectable in the cell culture medium and cytoplasm. Conclusions The novel heterozygous activating mutation c.125 T>G (p.Val42Gly) impairs the synthesis of insulin by pancreatic beta cells, resulting in diabetes.
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Altered microRNA expression during Impaired Glucose Tolerance and High-fat Diet Feeding

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0619-4576

Objective MicroRNAs (miRNAs) play a critical role in metabolic regulation. Recently, we identified novel miRNAs in the whole blood of South African women of mixed ethnic ancestry. The aim of this study was to investigate whether five of these novel miRNAs are expressed in serum and whether their expression is altered during metabolic dysregulation. Methods Expression levels of the five novel miRNAs (MYN08, MYNO22, MYN059, MYNO66 and MYNO95) were measured in the serum of women with Impaired Glucose Tolerance (IGT) and Normoglycemia (NGT) (n=24), and in the whole blood of vervet monkeys fed a high-fat or standard diet (n=16) using quantitative real-time PCR. Results Only three of the selected novel miRNAs (MYNO8, MYNO22 and MYNO66) were expressed in serum. The expression of MYN08 and MYNO22 were associated with fasting glucose and insulin concentrations, decreased during IGT and able to predict IGT. The expression of these miRNAs were similarly decreased in vervet monkeys fed a high-fat diet. In silico analysis identified a total of 291 putative messenger RNA targets for MYNO8 and MYNO22, including genes involved in gluconeogenesis, carbohydrate metabolism, glucose homeostasis and lipid transport. Conclusion Two novel miRNAs, MYNO8 and MYNO22, are associated with metabolic dysregulation in South African women of mixed ethnic ancestry and with high-fat diet feeding in vervet monkeys. Furthermore, putative gene targets were enriched in biological processes involved in key aspects of glucose regulation, which strengthens the candidacy of these miRNAs as biomarkers for dysglycemia, and warranting further studies to assess their clinical applicability.
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Pleiotropic Effect of Lipoprotein-Apheresis on the Soluble Form of Activated Leukocyte Cell Adhesion Molecule (sALCAM) in Familial Hypercholesterolaemia

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0630-0232

Introduction/Background Atherosclerosis is an inflammatory disorder in which several converging immune responses modulate and induce lipid accumulation in macrophages. Activated leukocyte cell adhesion molecule (ALCAM) has been described as a structural homologue of HDL-receptor and functions as a pattern recognition receptor (PRR), while its soluble form sALCAM is involved in ALCAM-dependent and -independent immune mechanisms. The aim of this study was to investigate the effect of aggressive removal of low density lipoprotein-cholesterol (LDL-C) and lipoprotein(a) (Lp [a]) by lipoprotein-apheresis (LA) on sALCAM and blood viscosity as well as to evaluate its association with lipoproteins and serum markers of inflammation.
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Transcriptomic Analysis of the Association Between Diabetes Mellitus and Myocardial Infarction

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0619-4412

Background Diabetes mellitus (DM) is a major risk factor for coronary artery disease (CAD), and the complications of CAD are the leading cause of deaths among people with DM. Herein, this study aims to identify the common genes and pathways between diabetes and myocardial infarction (MI) to provide more clues for the related mechanism studies. Methods Differentially expressed genes (DEGs) were identified using the cutoff (|log2(fold change)|>0.45 and P value<0.05) by the analysis of online datasets (GSE9006 and GSE48060) related to DM and MI respectively. Moreover, the overlapped DEGs between DM and MI were identified, followed by enriched Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. And the independent patient RNA samples were collected for qRT-PCR validation of the mRNA expression of these overlapped genes. Results PI3, ACSL1, MMD and MMP were altered in both T1DM and MI, and they were highly related to "regulation of cellular protein metabolic process". Meanwhile, six genes were identified in both T2DM and MI, which are ADM, NFIL3, PI3, SLPI, ACSL1 and MMP9 and significantly related to "negative regulation of endopeptidase activity". And the expression of these genes were validated. Conclusions In summary, we identified the common DEGs and pathways between T1DM or T2DM and MI, and further validated the changes of those DEGs, providing some clues for mechanism study and potentially therapeutic targets.
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Klotho Restraining Egr1/TLR4/mTOR Axis to Reducing the Expression of Fibrosis and Inflammatory Cytokines in High Glucose Cultured Rat Mesangial Cells

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0044-101601

Anti-aging protein Klotho is closely associated with a variety of chronic diseases and age-related diseases. And Klotho gene deficiency enhances the phosphorylation of mammalian target of rapamycin (mTOR), resulting in exacerbating streptozotocin-stimulated diabetic glomerular injury and promoting the progression of early diabetic kidney disease (DKD). However, it has not yet been elucidated that the mechanism of Klotho function on the pathogenesis of diabetic glomerular injury. What's more, insulin represents the antilipolytic effect via the mTOR-early growth response factor 1 (Egr1) regulatory axis in mammalian organism. Valsartan reduced the high glucose-activated toll like report 4 (TLR4) expression and inflammatory cytokines via inhibiting Egr1 expression. In this study, we aim to explore the effects of Klotho on Egr1 expression and TLR4/mTOR pathways activity in high glucose cultured rat mesangial cells (RMCs) in vitro. Our study revealed that high glucose upregulated Egr1 to aggravate the inflammation and fibrosis in RMCs. And high glucose activates Egr1/TLR4/mTOR regulatory axis in MCs, indicating that one coherent feedforward loop is formed. Anti-aging protein Klotho may attenuate glomerular inflammation and fibrosis to provide protection against diabetic kidney injury via inhibiting the activity of Egr1/TLR4/mTOR regulatory axis in high glucose conditions. This study complements the function mechanism of Egr1/TLR4/mTOR regulatory axis playing in the pathogenesis of DKD, and provides a new direction and theoretical basis for anti-aging protein Klotho in DKD treatment.
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Infected Diabetic Foot Ulcers: No Laterality?

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0584-6396

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The Effect of the Oral Administration of Leucine on Endothelial Function, Glucose and Insulin Concentrations in Healthy Subjects

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0597-8985

Objective The aim of our study was to investigate the potential differential effect of hyperglycaemia and hyperinsulinaemia induced by glucose infusion alone and in combination with leucine consumption on endothelial function in healthy individuals. Methods Ten male volunteers were examined in random order twice. In one visit, they consumed 250 ml water (baseline) and 30 min later glucose was infused iv. In the other visit, they consumed 250 ml water with 25 g of leucine and 30 min later the same amount of glucose was infused. Serum glucose and insulin were measured at baseline and every 10 min after glucose infusion for 1 h. Endothelial function was evaluated by measurement of flow mediated vasodilatation (FMD) at baseline, 10 and 60 min after glucose infusion. Results In both visits, glucose levels increased to the same degree, whereas insulin response was significantly higher after leucine administration. FMD values declined significantly compared to baseline 10 min after glucose infusion in the control visit (6.9±2.7 vs. 3.2±3.5%, respectively, p=0.006), while no significant change was observed when glucose infusion was followed by leucine consumption. Conclusions Acute hyperglycaemia impairs endothelial function in healthy male individuals. Leucine administration prevents hyperglycaemia-mediated endothelial dysfunction probably due to enhanced insulin secretion.
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The Effect of Metformin Therapy for Preventing Gestational Diabetes Mellitus in Women with Polycystic Ovary Syndrome: A Meta-Analysis

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0603-3394

Objective This study was to analyze the efficacy of metformin intervention in preventing gestational diabetes mellitus (GDM). Methods A systematic review and meta-analysis of clinical trials or observational studies of metformin intervention in preventing symptoms of GDM during pregnancy were performed. Medline, Embase, and Cochrane Library were searched through to now. The main evaluated primary outcomes were incident of GDM, miscarriage, preterm delivery, and neonatal mortality. The evaluated secondary outcomes were mean difference of gestational age at birth and birth weight between metformin group and control group. Results We included 6 studies including 3 randomized clinical trials (RCTs), 2 observational studies, and 1 non-RCT in our meta-analysis. A total of 643 patients were enrolled for a follow-up study with continued metformin therapy (n=341) or not (n=302) during pregnancy. Metformin therapy reduced the proportion of patients developing GDM (log Odds Ratio: -1.27; 95%CI: -2.24 to -0.30) but had no significant effect on reducing the proportion of abortion, preterm delivery, and neonatal death in pregnant women with polycystic ovary syndrome (PCOS). Also, it did not cause a significant difference in gestational age at birth and birth weight in metformin group versus control/placebo group. Conclusions Metformin was associated with less frequent GDM development than control diets, suggesting that it is the appropriate intervention to be prescribed to prevent GDM in patients with PCOS.
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Long Non-Coding RNA CASC2 Improves Diabetic Nephropathy by Inhibiting JNK Pathway

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0629-9958

It's known that long non-coding RNA CASC2 overexpression inhibit the JNK pathway in some disease models, while JNK pathway activation exacerbates diabetic nephropathy. Therefore we speculate that long non-coding RNA CASC2 can improve diabetic nephropathy by inhibiting JNK pathway. Thus, our study was carried out to investigate the involvement of CASC2 in diabetic nephropathy. We found that serum level of CASC2 was significantly lower in diabetic nephropathy patients than in normal people, and serum level of CASC2 showed no significant correlations with age, gender, alcohol consumption and smoking habits, but was correlated with course of disease. ROC curve analysis showed that serum level of CASC2 could be used to accurately predict diabetic nephropathy. Diabetes mellitus has many complications. This study also included a series of complications of diabetes, such as diabetic retinopathy, diabetic ketoacidosis, diabetic foot infections and diabetic cardiopathy, while serum level of CASC2 was specifically reduced in diabetic nephropathy. CASC2 expression level decreased, while JNK1 phosphorylation level increased in mouse podocyte cells treated with high glucose. CASC2 overexpression inhibited apoptosis of podocyte cells and reduced phosphorylation level of JNK1. We conclude that long non-coding RNA CASC2 may improve diabetic nephropathy by inhibiting JNK pathway.
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