Fatal Diabetic Ketoacidosis—A Potential Complication of MDMA (Ecstasy) Use

A 19‐year‐old woman with insulin‐dependent diabetes mellitus was found dead in bed having allegedly recently taken ecstasy and consumed alcohol. At autopsy, there were microhemorrhages in the brain with subnuclear vacuolization and Armanni–Ebstein changes in renal tubules. Biochemical analyses confirmed diabetic ketoacidosis (vitreous glucose—46.5 mmol/L; β‐OH butyrate—13.86 mmol/L.). Toxicological analyses of blood showed a low level of 3,4‐methylenedioxy‐methamphetamine (MDMA) (0.01 mg/L), with acetone but no alcohol or other common drugs. Death was attributed to diabetic ketoacidosis most likely provoked by mixed MDMA/alcohol ingestion. Although the use of illicit drugs by young individuals with diabetes mellitus is being increasingly recognized, it has been noted that there is minimal information about the relationship between drug use and acute diabetic complications. Toxicological screening of cases of lethal diabetic ketoacidosis in the young may clarify lethal mechanisms in individual cases and also help to determine the extent of this problem.     

桃红四物汤保护2型糖尿病模型大鼠血管损伤的实验研究

目的 观察桃红四物汤对2型糖尿病模型大鼠胸主动脉的保护作用,并探究其作用机制。方法 采用高糖高脂饲料联合链脲佐菌素复制2型糖尿病大鼠模型,桃红四物汤连续干预模型大鼠8周,观察模型大鼠胸主动脉的病理学变化,Western blot法检测胸主动脉核因子κB（nuclear factor κB,NF-κB）蛋白表达,RT-qPCR技术检测单核细胞趋化蛋白-1（monocyte chemoattractant protein 1,MCP-1）和血管细胞黏附分子-1（vascular cell adhesion molecule 1,VCAM-1）mRNA表达,ELISA法检测血清肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）和转化生长因子-β1（transforming growth factor-β1,TGF-β1）的含量。结果 桃红四物汤可显著改善模型大鼠胸主动脉损伤;显著抑制模型大鼠胸主动脉NF-κBp65蛋白和MCP-1、VCAM-1 mRNA的表达（P<0.05）,显著降低血清TNF-α、TGF-β1的含量（P<0.05）。结论 桃红四物汤可有效保护模型大鼠胸主动脉病理损伤,其作用机制与干预NF-κB信号通路,抑制MCP-1、VCAM-1、TNF-α和TGF-β1表达有关。     

糖尿病合并脑梗死急性期证候演变的聚类分析

目的 探究糖尿病合并脑梗死急性期患者证候的演变规律。方法 共纳入102例糖尿病合并脑梗死急性期患者,分别在发病第3天（72 h内）、第7天、第15天采集患者的四诊信息,对四诊变量进行层次聚类分析,对不同时点的证候要素进行动态分析。结果 层次聚类分析结果提示,发病第3天证候可聚为阴虚、内风、气虚血瘀、痰热四类,发病第7天的证候可聚为气阴两虚、痰热、血瘀、痰湿、内风五类,发病第15天的证候可聚为血瘀、气阴两虚、痰热、痰湿四类。结论 糖尿病合并脑梗死急性期不同时点的证候要素与文献报道相似,发病72 h内以内风较为突出,而后则以痰热、痰湿、血瘀证候为主,气阴两虚贯穿于糖尿病合并脑梗死的急性期。     

丹蛭降糖胶囊对2型糖尿病合并大血管病变患者糖脂代谢及生活质量的影响

目的 观察丹蛭降糖胶囊对2型糖尿病合并大血管病变患者糖脂代谢及生活质量的影响。方法 选取2型糖尿病合并大血管病变患者50例,随机分为对照组和治疗组各25例,对照组给予西药常规治疗,治疗组加服丹蛭降糖胶囊,治疗4周,检测并对比干预前后两组患者血清空腹血糖(fasting blood glucose,FPG)、餐后2小时血糖(2-hour postprandial blood glucose,2hPG)、稳态评估模型胰岛素抵抗指数(homeostasis model assessment of insulin resistance,HOMA-IR)、三酰甘油(triacylglycerol,TG)、总胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL)水平的变化情况;采用生存质量特异性量表(diabetes specific quality of life,DSQL)评价生存质量,根据临床症状和血糖改善情况综合判断疗效。结果 与治疗前比较,两组患者治疗后血清FPG、2hPG、TG、LDL水平均显著降低（P＜0.05）,HDL水平显著升高（P＜0.05),且治疗组治疗后血清TC水平显著降低（P＜0.05）,对照组患者治疗后血清TC水平变化无统计学意义（P＞0.05）;与对照组比较,治疗组患者血清2hPG、TC水平下降更显著(P＜0.05),HDL水平升高更显著（P＜0.05);与对照组比较,治疗组患者生理功能评分降低程度显著大于对照组（P＜0.05）;治疗组临床疗效优于对照组（P＜0.05）。结论 丹蛭降糖胶囊能显著降低2型糖尿病合并大血管病患者血清血糖血脂水平,有效拮抗患者胰岛素抵抗和血液脂毒性,提高患者生活质量和临床疗效。     

A Characterization of Sources of Isopropanol Detected on Postmortem Toxicologic Analysis

Abstract: Isopropanol is an important chemical to forensic pathologists in that intoxication can result in death yet presence does not necessarily indicate intoxication. Several reports have been published, which indicate that isopropanol can be created endogenously in certain situations including diabetes mellitus, starvation, dehydration, and chronic ethanol use; however, a large‐scale analysis addressing all of the possible causes of postmortem isopropanol detection has not been performed. A retrospective review of all cases examined at the Bexar County Medical Examiner’s Office between 1993 and 2008 in which isopropanol was detected in routine alcohol screening was undertaken. The cases were categorized by the source of the isopropanol, and the concentrations of isopropanol and acetone were analyzed. Analysis revealed isopropanol concentrations to be low (<100 mg/dL) in cases of antemortem and postmortem creation and in postmortem contamination and high (>100 mg/dL) in cases of antemortem exposure. These results are consistent with other published reports.     

电针对糖尿病大鼠胰腺组织CHOP、Bax、Bcl-2蛋白表达及胰腺超微结构的影响

目的观察针刺对糖尿病大鼠胰腺组织内质网应激及细胞凋亡的影响。方法高脂高糖饲料喂养加低剂量链脲佐菌素腹腔注射复制糖尿病大鼠模型,按血糖分层将模型复制成功的大鼠随机分为模型组、针刺组和二甲双胍组,另设空白组。干预4周后检测随机血糖、大鼠胰腺组织CHOP、Bcl-2、Bax蛋白含量,观察胰腺细胞超微结构。结果模型复制后,模型复制组随机血糖显著高于空白组(P0.05)。针刺组和二甲双胍组随机血糖均较治疗前明显降低(P0.05);与模型组比较,针刺组随机血糖水平呈降低趋势(P0.05)。模型组CHOP、Bax蛋白含量明显高于空白组(P0.05),Bcl-2蛋白含量显著低于空白组(P0.05);模型组、针刺组和二甲双胍组CHOP、Bax蛋白含量比较,差异无统计学意义(P0.05);针刺组和二甲双胍组Bcl-2蛋白含量均显著高于模型组(P0.05)。针刺组和二甲双胍组胰腺细胞线粒体排列整齐,在空泡变性,线粒体嵴断裂,粗面内质网变形,糖原颗粒减少方面,其异常变化较模型组明显减轻。结论针刺可通过改善糖尿病大鼠胰腺组织内质网应激,良性调节Bcl-2、Bax蛋白含量,从而保护胰腺细胞。     

Intentional overdose of glargine insulin: Determination of the parent compound in postmortem blood by LC-HRMS

Insulin glargine is a long-acting insulin analog that is converted after enzymatic cleavage of the arginine pair of the β-chain into its main metabolite M1 (21^A-Gly-insulin), which is responsible for the hypoglycemic activity. In all the overdose cases described in the literature, only M1 concentrations have been reported, whereas insulin glargine was always absent or below the limit of quantitation. In this study, we present a case of suicide of a young nurse by injection of insulin glargine in which the parent molecule was found at a toxic concentration in blood. The determination and the discrimination of insulin glargine from human insulin and other synthetic analogs in the blood specimen were performed by liquid chromatography coupled to high-resolution mass spectrometry (Waters XEVO G2-XS QToF) and extraction after precipitation in the presence of bovine insulin (internal standard), with a mixture of acetonitrile/methanol +1% formic acid followed by purification on solid phase extraction cartridges C18. Glargine insulin tested highly positive in the blood with a concentration of 1.06 mg/L. Due to the difficulty in obtaining a M1 pure standard, the metabolite could not be dosed. This unique presence of the parent molecule, reported for the first time, can be explained by inter-individual variability in the rate of conversion to metabolite. Intravenous injection versus subcutaneous injection can also explain the presence of insulin glargine. Finally, the dose injected may have been so high that saturation of the proteolytic enzymes responsible for conversion to M1 should have occurred.     

Infant Death Following Home Birth: A Case Report of Fatal Neonatal Hypoglycemia

Infants born to diabetic mothers are at increased risk for symptomatic hypoglycemia and death after birth. A 36-year-old G4P3 mother with a history of gestational diabetes and newly diagnosed type II insulin-dependent diabetes gave birth at home, in the care of a midwife, to a macrosomic infant girl (10 lbs.). Several hours after birth, the infant became lethargic and was found to be hypoglycemic (blood sugar: 28 mg/dL). Glucose and sugar water were administered by the midwife; however, the infant continued to decompensate. Emergency medical services were called, and the infant was transported to the hospital where, despite resuscitative efforts, she died. An autopsy and review of the literature was performed. At autopsy, characteristic features of maternal–fetal glucose dysregulation were identified, including fetal macrosomia, cardiomegaly, hepatomegaly, and severe pancreatic islet cell hypertrophy/hyperplasia. Developmental abnormalities and other potential causes of death were not identified. Although deaths due to hypoglycemia cannot be reliably diagnosed postmortem using vitreous glucose levels, a clinical history of maternal glucose dysregulation in combination with certain gross and histologic findings should prompt a pathologist to consider maternal–fetal glucose dysregulation as a diagnosis of exclusion and cause of death.     

Fatal Diabetic Ketoacidosis and Antipsychotic Medication

Hyperglycemia and new onset diabetes have been described with certain antipsychotic medications and some of the initial presentations are fatal diabetic ketoacidosis (DKA). We report 17 deaths due to DKA in psychiatric patients treated with second generation antipsychotic medications. Death certificates and toxicology data were searched for DKA and hyperglycemia. We reviewed the medical examiner records which included the autopsy, toxicology, police, and medical examiner investigators' reports. The decedents ranged in age from 32 to 57 years (average 48 years). There were 15 men and two women. The immediate cause of death was DKA in all. The psychiatric disorders included: 10 schizophrenia, three bipolar/schizophrenia, two bipolar, and two major depression. The most frequent atypical antipsychotic medications found were quetiapine and olanzapine followed by risperidone. In 16 deaths, we considered the medication as primary or contributory to the cause of death.     

川芎嗪和血塞通对糖尿病肾病患者尿微量白蛋白的作用

目的:观察川芎嗪和三七总皂苷对2型糖尿病肾病患者尿微量白蛋白的影响。方法:44例患者随机分为3组,即川芎嗪组(给予川芎嗪注射液)、三七总皂苷组(给予血塞通注射液,主要成分为三七总皂苷)和对照组(不用川芎嗪、血塞通)。疗程均为2周,3组基础治疗措施相同。治疗前后分别测定24 h尿微量白蛋白排泄率。结果:川芎嗪组和三七总皂苷组,治疗后24 h尿微量白蛋白排泄率明显下降,差异有显著性(P<0.01);对照组治疗前后24 h尿微量白蛋白排泄率比较,差异无显著性。结论:川芎嗪和三七总皂苷能够降低2型糖尿病肾病患者尿微量白蛋白排泄率,延缓糖尿病肾病的发展。