Association of glycated hemoglobin at an early stage of pregnancy with the risk of gestational diabetes mellitus among non‐diabetic women in Japan: The Japan Environment and Children’s Study

Aims/IntroductionGestational diabetes mellitus (GDM) is one of the most common complications of pregnancy and is associated with adverse pregnancy outcomes. This study aimed to explore the associations between glycated hemoglobin (HbA1c) levels at the early stage of pregnancy and the GDM risk among non‐diabetic women in a nationwide study in Japan. In addition, the relationship between GDM and adverse pregnancy outcomes was also analyzed.Materials and MethodsThis cohort study (n = 89,799) used data from the Japan Environment and Children’s Study. We stratified the participants into four groups according to HbA1c levels at an early stage of pregnancy. We investigated the association of HbA1c at an early stage of pregnancy with the risk of GDM, and of GDM with the risk of some representative adverse pregnancy outcomes, using the multiple logistic regression model with adjustment for potential confounders.ResultsThe adjusted odds ratio for GDM per 0.1 percentage point increase in HbA1c (%) was 1.20. The adjusted odds ratio for developing GDM was significantly increased in women from the HbA1c 5.0–5.4% category. GDM significantly increased the adjusted odds ratio for adverse pregnancy outcomes, such as hypertensive disorders of pregnancy, polyhydramnios and premature birth.ConclusionsHigh‐normal HbA1c levels at the early stage of pregnancy are significantly associated with GDM risk in women in Japan. GDM was significantly associated with adverse pregnancy outcomes.     

创伤性脑损伤急性期高血糖对葡萄糖转运蛋白1表达的影响

目的探讨大鼠创伤性脑损伤急性期高血糖对皮层葡萄糖转运蛋白1(glucose transporter1,GLUT-1)表达的影响。方法成年雄性SD大鼠180只,随机分成正常对照组,创伤性脑损伤(traumatic brain injury,TBI)组,胰岛素治疗组,分别测定各组伤前伤后血糖值,采用RT-PCR法和Western-blot法测定各组伤侧及健侧皮层GLUT-1基因和蛋白的表达,应用TUNEL法测定各组伤侧及健侧皮层凋亡细胞数。结果TBI组伤后血糖明显升高,伤侧皮层GLUT-1表达明显减少,凋亡细胞数明显增多;胰岛素治疗组血糖变化不明显(P0.05),伤后12h,24h,48h,72hGLUT-1表达明显多于TBI组(P均0.01),凋亡细胞数明显少于TBI组(P均0.01);各组健侧皮层GLUT-1表达和凋亡细胞数未见明显变化(P0.05)。结论TBI急性期高血糖可增加伤后脑细胞凋亡,其机制可能与TBI急性期高血糖下调GLUT-1表达有关。     

超负荷血糖对鼠局灶性脑缺血侧皮质内皮抑素表达的影响

目的观察超负荷血糖对鼠局灶性脑缺血侧皮质区内皮抑素(endostatin)表达的影响,进一步探讨超负荷血糖加重脑缺血损伤的分子机制。方法用SD大鼠腹腔内注射链脲佐菌素首先建立糖尿病高血糖大鼠模型,继而应用栓线法建立永久性局灶性脑缺血模型。随机分为3大组:假手术组、脑缺血组和糖尿病脑缺血组。于缺血24h时间点行神经功能评分、TTC染色测梗死面积、TUNEL法检测细胞凋亡数目、免疫组化及Western blot检测ES表达,并进行图像分析。结果糖尿病脑缺血组的神经功能评分为(4.73±0.35)、梗死面积为(50.12±3.54)、细胞凋亡数为(26.22±2.35)、免疫组化检测ES为(99.35±3.25)及Western blot检测ES为(1.193±0.045)。脑缺血组的神经功能评分为(3.18±0.65)、梗死面积为(39.98±2.02)、细胞凋亡数为(17.28±1.01)、免疫组化检测ES为(113.17±1.35)及Western blot检测ES为(1.033±0.032)。与脑缺血组相比,糖尿病脑缺血组的神经功能评分、梗死面积、细胞凋亡数、ES蛋白表达均明显增加(P<0.05)。结论血管再生可能参与了超负荷血糖加重脑缺血损伤的过程,上调ES表达可能是超负荷血糖加重脑缺血损伤的机制之一。     

非酮症高血糖性舞蹈症

目的对非酮症高血糖性舞蹈症患者的临床表现、影像学特征及发病机制进行分析。方法结合相关文献对5例非酮症高血糖舞蹈症患者的临床资料进行分析。结果 5例均急性起病,可表现为单侧或双侧肢体的舞蹈症状;血糖和血渗透压明显增高;影像学表现为特异性斑片状脑出血和纹状体T1高信号;联合应用降糖药物和多巴胺受体阻滞剂可控制舞蹈症状。结论非酮症性高血糖、舞蹈症以及MRI显示为纹状体T1高信号,可能构成舞蹈症临床综合征;影像学改变可能表示由代谢紊乱引起的斑片状脑出血,后者导致基底神经节运动环路受损,从而产生舞蹈样症状。     

高血糖对树鼩脑皮层局灶性缺血时海马微环境离子稳态及神经元继发性损伤的影响

 目的：研究高血糖对树鼩脑皮层血栓性缺血时海马微环境离子稳态的影响,探讨高血糖在缺血后神经元继发性损伤中的作用及机制。方法：用链脲佐菌素复制树鼩高血糖模型,并用光化学方法诱导脑皮层局部血栓性缺血,用单泵等速微灌流系统和离子分析仪测定缺血4 h、24 h及72 h海马离子微环境（细胞外pH值、K+、Na+、Ca2+、Cl-）的动态变化,并观察脑组织的病理形态学改变及海马神经元密度变化。结果：树鼩脑皮层缺血后,其海马微环境内出现了pH值、Na+、Ca2+及Cl-含量的降低,K+含量升高,变化以缺血后4 h为著,24 h次之,72 h无显著差异;高血糖加缺血进一步加重离子稳态的紊乱,缺血后4 h的pH值、K+和Ca2+含量,以及缺血后24 h的pH值和Na+含量与正常血糖缺血组同期值相比,变化显著（P<0.05）。形态学观察显示,光化学反应后4 h照射区皮层可见梗死灶,且患侧海马CA1区也存在缺血损伤性改变;24 h病损达高峰;72 h伴随胶质细胞增生等修复性反应。相应时点高血糖加缺血组皮层及海马的损伤均大于缺血组,以缺血后24 h(P<0.01)和72 h(P<0.05)尤为显著。结论: 树鼩脑皮层血栓性缺血形成后,缺血中心区扩布所导致的微环境内酸碱平衡及离子稳态性异常可能是海马神经元继发性损伤的重要原因,高血糖可加剧缺血脑区离子微环境的紊乱。     

Novel appearance of hyperglycemia/diabetes,associated with COVID-19

In a recent meta-analysis the prevalence of coronavirus disease 2019 (COVID-19)-associated hyperglycemia was 25%, and that of COVID-19-associated new-onset diabetes was 19%. An association between hyperglycemia or new-onset diabetes and COVID-19 has been suggested. In a recent relevant study of critically and non-critically ill patients with COVID-19, we found that indeed beta-cell function was compromised in critically ill patients with COVID-19 and that these patients showed a high glycemic gap. Nevertheless, one quarter of critically ill patients with no history of diabetes have stress hyperglycemia, a finding which could obscure the prevalence of hyperglycemia or new-onset diabetes that could be attributed to COVID-19 per se.     

芝麻素对高脂、高糖饲养大鼠血脂血糖及血管重构的影响

目的：探讨芝麻素对高脂、高糖饲养大鼠血脂血糖及血管重构的影响。方法：大鼠高脂高糖饮食24周，于第9周开始连续口服芝麻素(120、60、30 mg·kg^-1·d^-1)16周。测血糖、血脂、血压、血清与血管总抗氧化能力和过氧化氢含量。主动脉HE染色和Masson染色分别观察主动脉组织学和胶原纤维变化。肠系膜动脉HE染色，病理图像分析系统测定血管中膜厚度(media thickness，M)、血管内径(luminal radius，L)和中膜厚度与内径比值（M/L）。免疫组化法观察主动脉诱导型一氧化氮合酶蛋白表达。结果：与模型组相比，芝麻素高中剂量组血糖、血脂和血压明显下降（P<0.01）；总抗氧化能力显著提高，过氧化氢含量明显降低（P<0.01或P<0.05）；主动脉iNOS蛋白表达和胶原纤维沉积明显减少；血管内膜和平滑肌细胞增殖减轻；系膜动脉血管M与M/L明显减少，L明显增加(P<0.01)。结论：芝麻素能纠正高脂、高糖诱导大鼠糖脂代谢异常,并抑制血压升高、改善血管重构。     

危重患者高血糖反应与炎症细胞因子及预后的相关性研究

目的 探讨危重患者高血糖反应与炎症细胞因子及预后的关系。方法 选择65例危重患者，随机分为胰岛素治疗组和常规治疗组，在人院24h内测定空腹血糖、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）水平，追踪观察1个月后的疗效。结果 危重患者血糖、TNF-α、IL-6水平明显升高，与正常对照组比较差异有统计学意义（P〈0．01或P〈0．001），与APACHEⅡ评分、预后相关（P〈0．01）；血糖与TNF-α、IL-6水平呈正相关（r=0．6256、0．5674）；胰岛素治疗组与常规治疗组预后比较差异无统计学意义（P〉0．05）。结论 拮抗TNF-α、IL-6等炎症因子，提高胰岛素的敏感性是治疗危重患者高血糖反应的关键。     

Lowering of glucose in critical care: a randomized pilot trial

BACKGROUND: Similar to cardiac surgery patients, medical-surgical critically ill patients may benefit from intensive insulin therapy. The objectives of this pilot trial were to evaluate the feasibility of a randomized trial of intensive insulin therapy with respect to (a) achieving target glucose values in the 2 ranges of 5 to 7 and 8 to 10 mmol/L and (b) uncovering problems with the protocol in anticipation of a larger trial. SETTING: The trial was conducted in a 15-bed medical-surgical university-affiliated intensive care unit (ICU). METHODS: We included patients older than 18 years, expected to be in ICU for more than 72 hours, with a glucose value of more than 10 mmol/L within 48 hours of ICU admission. Exclusion criteria were diabetic ketoacidosis, severe hepatic failure or hepatic resection, pancreatitis, glucose of less than 2.2 mmol/L on admission to hospital, insulin infusion on admission to ICU, planned withdrawal of life support, and inability to obtain informed consent. Patients underwent concealed random allocation to a target glucose range of 5 to 7 or 8 to 10 mmol/L using pretested algorithms of insulin infusions. Dedicated glucometer measurement of arterial glucose values was calibrated daily to values measured in the laboratory. RESULTS: We enrolled 20 patients with a mean (SD) Acute Physiology and Chronic Health Evaluation (APACHE) II score of 32 (10.2); 14 were insulin-dependent pre-ICU, and all were medical admissions. Mean glucose values were different in the 2 groups (7.1 +/- 2.6 vs 9.4 +/- 2.1 mmol/L, P < .001). Although the intensive insulin therapy group had more glucose measurements performed than the control group, a similar proportion of values were within the target range (682 [42.4%] of 1607 values in the 5- to 7-mmol/L range; 250 [38.7%] of 660 values in the 8- to 10-mmol/L range, P = .35). Glucose values of less than 2.5 mmol/L developed 7 times in 5 patients, 4 of whom were in the intensive insulin therapy group; however, no adverse consequences were documented. As expected, there were no differences in clinically important outcomes. CONCLUSIONS: In this pilot trial of ICU patients with high illness severity, glucose values were in the 2 target ranges only 40% of the time, using well-accepted initiation and maintenance insulin infusion algorithms. A large randomized trial of glycemic control is feasible in this population to examine clinically important outcomes, but will require refined insulin algorithms and more comprehensive behavior change strategies to achieve target values.     

Chronopharmacology of dapagliflozin-induced antihyperglycemic effects in C57BL/6J mice

Chronopharmacology is the study of the varying responses of drugs to changes in biological timing and endogenous periodicities. The selective sodium-glucose cotransporter 2 inhibitor, dapagliflozin, is a globally prescribed antihyperglycemic drug. Although dapagliflozin is usually administered once a day, the specific intake time is generally not mentioned. Therefore, this study aimed at investigating the diurnal effects of dapagliflozin on high-fat diet (HFD)-induced obesity in mice. Five-week-old male C57BL/6J mice were fed a normal (control) diet or HFD for 10 weeks. During the last 2 weeks, the mice were administered olive oil/ethanol emulsion or dapagliflozin (1 mg/kg, p.o.) in the light or dark phase. At the end of the experiment, the mice were euthanized after an 18 h fasting period, and plasma and tissue samples (epididymal white adipose tissues, liver, and kidney) were collected. Dapagliflozin administration in the light phase significantly decreased plasma glucose levels, insulin levels, adipose adipokines, and decreased the size of adipocytes, compared with the HFD group. In contrast, these parameters remained unchanged in the mice treated during the dark phase. Our data therefore suggests that dapagliflozin portrays definite chronopharmacology, which may provide valuable information on the importance of drug administration timing for maximal pharmacological effects.