Can glyburide be advocated over subcutaneous insulin for perinatal outcomes of women with gestational diabetes? A systematic review and meta-analysis
- 作者列表："Helal, Khaled Fathy","Badr, Mohammad Samir","Rafeek, Mohamed El-Sayed","Elnagar, Walid Mohamed","Lashin, Mohamed El-Bakry
PURPOSE:To obtain precise findings from published studies about the efficacy and safety of glyburide versus subcutaneous insulin in patients with gestational diabetes mellitus (GDM). METHODS:We searched PubMed, Cochrane Library, Web of Science, and Scopus, up to January 2019, for relevant studies that compared glyburide with subcutaneous insulin for patients with GDM. We extracted maternal and neonatal outcomes from included studies, performed meta-analysis, evaluated heterogeneity, assessed the risk of bias of included studies, and conducted subgroup and sensitivity analyses. RESULTS:A total of 24 studies (11 randomized controlled trials (RCTs) and 13 observational cohort studies) with a total of 24,517 women were included in the present study. The pooled estimate showed that glyburide significantly decreased the need for cesarean section (OR = 0.87, 95% CI [0.82, 0.92], p < 0.0001), fasting blood glucose (MD - 5.63 mg/dL, 95% CI [- 10.97, - 0.28], p = 0.04), and Apgar score at 5 min (MD - 0.30, 95% CI [- 0.36, - 0.23], p < 0.001) than insulin. However, glyburide significantly increased the risk of neonatal hypoglycemia (OR = 1.42, 95% CI [1.03, 1.95], p = 0.03) and neonatal intensive care unit admission duration (NICU) (MD 4.26 days, 95% CI [2.65, 5.86], p < 0.01) compared to insulin. The overall results did not favor either group in terms of macrosomia (OR = 1.14, 95% CI [0.92, 1.41], p = 0.25) and large for gestational age (LGA) (OR = 1.38, 95% CI [0.99, 1.92], p = 0.06). While subgroup analysis of RCTs showed that maternal hypoglycemia and LGA rates were significantly higher in glyburide than insulin and cesarean section rates were comparable between both compared groups. CONCLUSION:Our study suggests that glyburide is an effective and well-tolerated drug compared to insulin in the management of women with GDM, provided neonates are monitored for hypoglycemia and Apgar score. In addition, glyburide was associated with lower cesarean sections, which may add to the potential clinically benefits of glyburide compared to insulin.
目的: 从已发表的关于格列本脲与皮下胰岛素治疗妊娠期糖尿病 (GDM) 患者的疗效和安全性的研究中获得精确的结果。 方法: 我们检索了截至 2019年1月的 PubMed 、 Cochrane 图书馆、 Web of Science 和 Scopus，寻找比较格列本脲与皮下胰岛素治疗 GDM 患者的相关研究。我们从纳入的研究中提取孕产妇和新生儿结局，进行荟萃分析，评价异质性，评估纳入研究的偏倚风险，并进行亚组和敏感性分析。 结果: 本研究共纳入 24 项研究 (11 项随机对照试验 (rct) 和 13 项观察性队列研究)，共计 24,517 名女性。汇总估计显示，格列本脲显著降低了剖宫产的需要量 (or = 0.87，95% CI [0.82，0.92]，p <0.0001),空腹血糖 (MD - 5.63 mg/dL，95% CI [- 10.97，-0.28]，p = 0.04)，5 min Apgar 评分 (MD-0.30，95% CI[- 0.36，-0.23]，p <0.001) 比胰岛素。然而，格列本脲显著增加了新生儿低血糖 (or = 1.42，95% CI [1.03，1.95]，p = 0.03) 和新生儿重症监护病房 (NICU) 的风险。(MD 4.26 天，95% CI [2.65，5.86]，p <0.01) 与胰岛素相比。总体结果在巨大儿 (or = 1.14，95% CI [0.92，1.41]，p = 0.25) 和大胎龄 (LGA) 方面不支持两组 (Or = 1.38，95% CI [0.99，1.92]，p = 0.06)。而 rct 的亚组分析显示，格列本脲的产妇低血糖和 LGA 发生率显著高于胰岛素，两组间剖宫产率相当。 结论: 我们的研究表明，只要监测新生儿低血糖和 Apgar 评分，与胰岛素相比，格列本脲在 GDM 妇女的管理中是一种有效且耐受性良好的药物。此外，格列本脲与较低的剖宫产术相关，与胰岛素相比，这可能增加格列本脲的潜在临床益处。
METHODS:Aims We aimed to develop a prediction model based on clinical and biochemical variables for gestational diabetes mellitus (GDM) based on the 2013 World Health Organization (WHO) criteria. Methods A total of 1843 women from a Belgian multi-centric prospective cohort study underwent universal screening for GDM. Using multivariable logistic regression analysis, a model to predict GDM was developed based on variables from early pregnancy. The performance of the model was assessed by receiver-operating characteristic (AUC) analysis. To account for over-optimism, an eightfold cross-validation was performed. The accuracy was compared with two validated models (van Leeuwen and Teede). Results A history with a first degree relative with diabetes, a history of smoking before pregnancy, a history of GDM, Asian origin, age, height and BMI were independent predictors for GDM with an AUC of 0.72 [95% confidence interval (CI) 0.69–0.76)]; after cross-validation, the AUC was 0.68 (95% CI 0.64–0.72). Adding biochemical variables, a history of a first degree relative with diabetes, a history of GDM, non-Caucasian origin, age, height, weight, fasting plasma glucose, triglycerides and HbA_1c were independent predictors for GDM, with an AUC of the model of 0.76 (95% CI 0.72–0.79); after cross-validation, the AUC was 0.72 (95% CI 0.66–0.78), compared to an AUC of 0.67 (95% CI 0.63–0.71) using the van Leeuwen model and an AUC of 0.66 (95% CI 0.62–0.70) using the Teede model. Conclusions A model based on easy to use variables in early pregnancy has a moderate accuracy to predict GDM based on the 2013 WHO criteria.
METHODS:Leveraging the availability of nationwide electronic health records from over 500,000 pregnancies in Israel, a machine-learning approach offers an alternative means of predicting gestational diabetes at high accuracy in the early stages of pregnancy. Gestational diabetes mellitus (GDM) poses increased risk of short- and long-term complications for mother and offspring^ 1 – 4 . GDM is typically diagnosed at 24–28 weeks of gestation, but earlier detection is desirable as this may prevent or considerably reduce the risk of adverse pregnancy outcomes^ 5 , 6 . Here we used a machine-learning approach to predict GDM on retrospective data of 588,622 pregnancies in Israel for which comprehensive electronic health records were available. Our models predict GDM with high accuracy even at pregnancy initiation (area under the receiver operating curve (auROC) = 0.85), substantially outperforming a baseline risk score (auROC = 0.68). We validated our results on both a future validation set and a geographical validation set from the most populated city in Israel, Jerusalem, thereby emulating real-world performance. Interrogating our model, we uncovered previously unreported risk factors, including results of previous pregnancy glucose challenge tests. Finally, we devised a simpler model based on just nine questions that a patient could answer, with only a modest reduction in accuracy (auROC = 0.80). Overall, our models may allow early-stage intervention in high-risk women, as well as a cost-effective screening approach that could avoid the need for glucose tolerance tests by identifying low-risk women. Future prospective studies and studies on additional populations are needed to assess the real-world clinical utility of the model.
METHODS::Repurposing of currently approved medications is an attractive option for the development of novel treatment strategies against physiological and infectious diseases. The antidiabetic sulfonylurea glyburide has demonstrated off-target capacity to inhibit activation of the NLRP3 inflammasome in a variety of disease models, including vaginal candidiasis, caused primarily by the fungal pathogen Candida albicans Therefore, we sought to determine which of the currently approved sulfonylurea drugs prevent the release of interleukin 1β (IL-1β), a major inflammasome effector, during C. albicans challenge of the human macrophage-like THP1 cell line. Findings revealed that the second-generation antidiabetics (glyburide, glisoxepide, gliquidone, and glimepiride), which exhibit greater antidiabetic efficacy than prior iterations, demonstrated anti-inflammatory effects with various degrees of potency as determined by calculation of 50% inhibitory concentrations (IC50s). These same compounds were also effective in reducing IL-1β release during noninfectious inflammasome activation (e.g., induced by lipopolysaccharide [LPS] plus ATP), suggesting that their anti-inflammatory activity is not specific to C. albicans challenge. Moreover, treatment with sulfonylurea drugs did not impact C. albicans growth and filamentation or THP1 viability. Finally, the use of ECE1 and Candidalysin deletion mutants, along with isogenic NLRP3-/- cells, demonstrated that both Candidalysin and NLRP3 are required for IL-1β secretion, further confirming that sulfonylureas suppress inflammasome signaling. Moreover, challenge of THP1 cells with synthetic Candidalysin peptide demonstrated that this toxin is sufficient to activate the inflammasome. Treatment with the experimental inflammasome inhibitor MCC950 led to similar blockade of IL-1β release, suggesting that Candidalysin-mediated inflammasome activation can be inhibited independently of potassium efflux. Together, these results demonstrate that the second-generation antidiabetic sulfonylureas retain anti-inflammatory activity and may be considered for repurposing against immunopathological diseases, including vaginal candidiasis.