糖尿病病人血D-3-羟丁酸与尿酮体关系的研究

目的 探讨糖尿病时血D-3-羟丁酸与尿酮体定性测定的关系。方法 观察我院住院治疗的糖尿病无酮症患者42例,糖尿病酮症酸中毒患者19例以及健康体检者60例的血D-3-羟丁酸、尿酮体的变化;11例糖尿病酮症酸中毒患者治疗前及治疗后D-3-羟丁酸、尿酮体的变化。结果 糖尿病无酮症组D-3-羟丁酸阳性率与酮体阳性率有显著差异,糖尿病无酮症组与糖尿病酮症酸中毒组D-3-羟丁酸水平有很显著差异;糖尿病酮症酸中毒组在治疗前D-3-羟丁酸水平明显升高,而尿酮体的升高幅度低于D-3-羟丁酸,治疗后D-3-羟丁酸水平开始直线下降,而尿酮体却在明显升高后降低。结论 D-3-羟丁酸是糖尿病的重要监测指标,可对糖尿病酮症酸中毒提供早期诊断,可避免治疗过程中单纯测定尿酮体给人造成的误导,可对治疗效果提供准确判断。     

18例糖尿病酮症酸中毒血液β-羟丁酸/乙酰乙酸变化规律分析

我们用自行研制的酶法测定β－羟丁酸,乙酰乙酸试剂盒,全自动生化分析仪对１８例糖尿病酮症酸中毒患者血团体变化规律进行了分析,现介绍如下。１材料与方法１．１对象经临床诊断的糖尿病患者４８例,跟踪其血糖浓度高,同时测血酮体,最后转化为酮症酸中毒且资料完整者１８例。其中男１０例,女８例,年龄３１～６１岁。１．２方法使用自行研制的酶法测定β－羟丁酸,乙酰乙酸试剂盒,美国贝克曼ＣＸ－五全自动生化分析仪,非急诊患者早晨空腹采血,急诊患者随时采血,从血酮体开始超过正常值（β－羟丁酸,乙酰乙酸均小于０．３ ｍｍｏ…     

血清1,5-脱水葡糖苷浓度变化与糖尿病酮症酸中毒监测的研究

目的 检测糖尿病酮症酸中毒患者血清1,5-脱水葡糖苷(1,5-AG),评价对糖尿病酮症酸中毒患者血糖(BG)、血酮体的控制效果,对糖尿病酮症酸中毒患者的治疗及判定预后提供科学依据.方法 将确诊为糖尿病酮症酸中毒患者(n=23例),使用酶法测定1,5-脱水葡萄血糖、乙酰乙酸(AcAc)、β-羟丁酸(β-HBA)1次/d,连续观察4 d;正常体检者对照组(n=58例),所得数据进行统计学分析比较.结果 对照组与糖尿病酮症酸中毒组1,5-脱水葡糖苷、血糖、β-羟丁酸 乙酰乙酸差异均有统计学意义(P＜0.01).在糖尿病酮症酸中毒组内1,5-脱水葡糖苷与血糖在连续观察监测的4 d内,呈高度的负相关(r=-0.889);1,5-脱水葡糖苷与β-羟丁酸 乙酰乙酸呈高度负相关(r=-0.9207).结论 1,5-脱水葡糖苷检测可以做为较短时间内血糖、血酮体控制的灵敏指标.     

β-羟丁酸在糖尿病酮症酸中毒诊断中的应用

目的探讨β-羟丁酸测定在糖尿病酮症酸中毒诊断中的应用。方法检测96例糖尿病非酮症患者(糖尿病非酮症组)、28例糖尿病酮症酸中毒患者(糖尿病酮症酸中毒组)、60例正常体检人员(正常组)血清中的β-羟丁酸、空腹血糖(FBG)及尿酮体,并对结果进行比较分析。结果糖尿病酮症酸中毒组血β-羟丁酸(1.75±1.77)mmol/L、FBG(14.27±5.1mmol/L、尿酮体阳性率85.7%;糖尿病非酮症组血β-羟丁酸(0.275±0.34)mmol/L、FBG(11.34±3.65)mmol/L、尿酮体阴性;正常组血β-羟丁酸(0.16±0.09)mmol/L、FBG(4.69±0.36)mmol/L、尿酮阴性。糖尿病酮症酸中毒组血β-羟丁酸、FBG、尿酮体与糖尿病非酮症组相比,差异均有统计学意义(P<0.05)。结论检测血β-羟丁酸有助于糖尿病酮症酸中毒的早期诊断和治疗,其敏感性高于尿酮体检测。     

1例糖尿病酮症酸中毒昏迷伴多脏器功能衰竭患者的抢救与护理

糖尿病酮症酸中毒(DKA)特点是糖尿病代谢紊乱加重时,脂肪分解加速,大量脂肪酸经β氧化产生大量乙酰乙酸、β-羟丁酸和丙酮(三者统称为酮体).血清酮体超过正常水平时称为酮血症.尿酮体排出增多称为尿酮.临床上统称为酮症[1].     

糖尿病患者血清β-羟丁酸与血清酮体粉剂半定量法检测间的关系及价值研究

目的探讨糖尿病患者血清β-羟丁酸与酮体粉剂半定量法检测间关系及应用价值。方法对该院36例糖尿病无酮症(NDK)患者、30例糖尿病酮症酸中毒(DKA)患者、51例健康体检人员进行血清β-羟丁酸、血清酮体粉剂半定量法检测,并观察13例糖尿病酮症酸中毒患者治疗前、治疗中血清β-羟丁酸、酮体粉剂半定量法检测值的变化。结果 DKA组与NDK组、DKA组与健康对照组、NDK组与健康对照组的血清β-羟丁酸水平差异有统计学意义(P值均小于0.05),前者明显高于后者;DKA组与NDK组、DKA组与健康对照组的酮体粉剂法检测值差异有统计学意义(P值均小于0.01),NDK组与健康对照组酮体粉剂法检测值差异无统计学意义(P0.05);NDK组血清β-羟丁酸阳性率明显高于酮体粉剂法阳性率(P0.01);DKA组在治疗前血清β-羟丁酸明显升高,酮体粉剂法结果升高幅度低于血清β-羟丁酸;治疗中血清β-羟丁酸水平开始直线下降,酮体粉剂法值却在明显升高后降低。结论血清β-羟丁酸检测比血清酮体粉剂半定量法在糖尿病酮症酸中毒早期诊断、病情监测方面具有明显优势。     

血清β-羟丁酸测定在糖尿病患者中的临床意义

目的探讨血清β-羟丁酸测定在糖尿病酮症或酮症酸中毒诊断中的意义。方法采用酶速率法测定并比较非酮症糖尿病组(NDK)、糖尿病酮症酸中毒组(DKA)、健康对照组(NC)血清β-羟丁酸的浓度变化。同时应用亚硝基铁氰化钠法进行血酮体定性分析。结果血清β-羟丁酸在糖尿病患者中明显升高,升高程度与病情相关,酮症酸中毒患者高于无酮症糖尿病患者(t=28.92,P<0.01),在无酮症糖尿病患者中β-羟丁酸阳性率(36.7%,11/30)高于酮体定性阳性率(10.0%,3/30)。结论血β-羟丁酸测定对于糖尿病患者病情监测和酮症酸中毒的早期诊断等方面具有重要的临床意义。     

血清β-羟丁酸在糖尿病酮症酸中毒和妊娠剧吐中的诊断价值

目的 探讨血清β-羟丁酸测定在糖尿病酮症酸中毒(DKA)和妊娠剧吐中的诊断价值.方法 采用酶速率法测定血清β-羟丁酸浓度,对糖尿病酮症酸中毒、糖尿病无酮症(NDK)、健康对照、妊娠剧吐孕妇、正常孕妇组进行β-羟丁酸检测,同时对其进行尿酮体和血糖检验.结果 DKA的β-羟丁酸浓度和阳性率显著高于NDK组(P＜0.01)和对照组(P＜0.01);NDK组的β-羟丁酸浓度与对照组比较差异有统计学意义(P＜0.05);DKA尿酮体阳性率显著高于NDK组(P＜0.01)和对照组(P＜0.01).妊娠剧吐组的β-羟丁酸浓度和阳性率显著高于正常孕妇组(P＜0.01);妊娠剧吐组的尿酮体阳性率显著高于正常孕妇组(P＜0.01).结论 β-羟丁酸对DKA和妊娠剧吐的早期诊断具有重要的诊断价值,对鉴别诊断和治疗的疗效观察具有重要意义,联合血糖、尿酮体等同时检测更能全面诊断和分析疾病.     

血清β-羟丁酸酶法测定的方法学和临床应用评价

目的 评价酶法测定血清β-羟丁酸的方法 学性能及其在糖尿病酮症酸中毒早期预防和治疗中的作用.方法 用NCCLS的评价方案对本法的精密度、准确性、线性、方法相关性和干扰作评价.并用ROC曲线评价血清β-羟丁酸诊断糖尿病酮症酸中毒的准确性.结果 酶法测定β-羟丁酸具有良好的精密度(批内、批间、及总变异系数均小于3%)和准确度(回收率为97.5%),灵敏度为0.01mmol/L,检测线性范围为0.03～4.50 mmol/L,与其它商品化试剂的相关性良好(R=0.937),不受溶血、黄疸和脂血干扰.糖尿病控制不良酮症酸中毒组、糖尿病控制不良但无酮症酸中毒组、糖尿病控制良好组、无糖尿病史健康人对照组四组病例的血清β-羟丁酸水平分别为2.71±1.46 mmol/L、1.28±0.73 mmol/L、0.21±0.16 mmol/L、0.14±0.07 mmol/L.用ROC曲线评价当血清β-羟丁酸水平为2.1 mmol/L时诊断糖尿病酮症酸中毒的灵敏度89.2%,特异性94.3%.结论 酶法测定血清β-羟丁酸快速、准确、精密度高,可用于糖尿病酮症酸中毒的早期、特异、快速诊断及治疗监测.     

血清β-羟丁酸酶法测定的方法学和临床应用评价

目的评价酶法测定血清β-羟丁酸的方法学性能及其在糖尿病酮症酸中毒早期预防和治疗中的作用。方法用NCCLS的评价方案对本法的精密度、准确性、线性、方法相关性和干扰作评价。并用ROC曲线评价血清β-羟丁酸诊断糖尿病酮症酸中毒的准确性。结果酶法测定β-羟丁酸具有良好的精密度(批内、批间、及总变异系数均小于3%)和准确度(回收率为97.5%),灵敏度为0.01mmol/L,检测线性范围为0.03～4.50mmol/L,与其它商品化试剂的相关性良好(R=0.937),不受溶血、黄疸和脂血干扰。糖尿病控制不良酮症酸中毒组、糖尿病控制不良但无酮症酸中毒组、糖尿病控制良好组、无糖尿病史健康人对照组四组病例的血清β-羟丁酸水平分别为2.71±1.46mmol/L、1.28±0.73mmol/L、0.21±0.16mmol/L、0.14±0.07mmol/L。用ROC曲线评价当血清β-羟丁酸水平为2.1mmol/L时诊断糖尿病酮症酸中毒的灵敏度89.2%,特异性94.3%。结论酶法测定血清β-羟丁酸快速、准确、精密度高,可用于糖尿病酮症酸中毒的早期、特异、快速诊断及治疗监测。     

Sodium-glucose co-transporter-2 inhibitor-associated euglycemic diabetic ketoacidosis that prompted the diagnosis of fulminant type-1 diabetes: A case report

BACKGROUNDFulminant type 1 diabetes mellitus (FT1DM) is a subtype of type 1 diabetes mellitus characterized by an abrupt onset and a rapid and complete functional loss of islet β cells. It is a very rare disease generally associated with ketoacidosis and the absence of circulating pancreatic islet-related autoantibodies. Diabetic ketoacidosis with normal blood glucose levels has been reported during sodium-glucose co-transporter 2 (SGLT2) inhibitor therapy.CASE SUMMARYThe patient was a 43-year-old woman that consulted a medical practitioner for malaise, thirst, and vomiting. Blood analysis showed high blood glucose levels (428 mg/dL), a mild increase of hemoglobin A1c (6.6%), and increased ketone bodies in urine. The patient was diagnosed with type 2 diabetes mellitus. The patient was initially treated with insulin, which was subsequently changed to an oral SGLT2 inhibitor. Antibodies to glutamic acid decarboxylase were negative. Four days after receiving oral SGLT2 inhibitor, she consulted at Mie University Hospital, complaining of fatigue and vomiting. Laboratory analysis revealed diabetic ketoacidosis with almost normal blood glucose levels. The endogenous insulin secretion was markedly low, and the serum levels of islet-related autoantibodies were undetectable. We made the diagnosis of FT1DM with concurrent SGLT2 inhibitor-associated euglycemic diabetic ketoacidosis. The patient''s general condition improved after therapy with intravenous insulin and withdrawal of oral medication. She was discharged on day 14 with an indication of multiple daily insulin therapy.CONCLUSIONThis patient is a rare case of FT1DM that developed SGLT2 inhibitor-associated diabetic ketoacidosis with almost normal blood glucose levels. This case report underscores the importance of considering the diagnosis of FT1DM in patients with negative circulating autoantibodies and a history of hyperglycemia that subsequently develop euglycemic diabetic ketoacidosis following treatment with a SGLT2 inhibitor.     

酮症酸中毒起病的糖尿病患者的实验室指标比较

目的 提高临床医师对糖尿病酮症酸中毒(DKA)起病的暴发性1型糖尿病(FT1DM)的认识。方法 93例DKA起病的糖尿病患者根据糖尿病分型分为3组: 2型糖尿病（A）组、非暴发性1型糖尿病（B）组、FT1DM（C）组,对3组年龄、血糖、血钠、血钾、糖化血红蛋白、血pH值进行比较。结果 与2型糖尿病组相比,FT1DM组的血糖、血钾更高,HbA1c、血钠、血pH值更低,随着病程缩短,血pH值的比较无统计学意义。与非暴发性1型糖尿病组相比,FT1DM组的血糖、血钾更高,HbA1c更低,在血钠和血pH值的比较差异无统计学意义。结论 DKA起病的FT1DM患者具有更高的血糖和血钾,注意重视。除糖尿病类型外,糖尿病病程也影响酸中毒的实验室指标。     

Head-space gas-chromatographic determination of 3-hydroxybutyrate in plasma after enzymic reactions, and the relationship among the three ketone bodies

In this sensitive, reproducible method for determination of D-3-hydroxybutyrate (3-OHB) in plasma, it is converted to acetone by use of 3-hydroxybutyrate dehydrogenase (EC 1.1.1.30)/lactate dehydrogenase (EC 1.1.1.27) coupled with acetoacetate decarboxylase (EC 4.1.1.4). The resulting acetone is detected by head-space gas chromatography. The lowest concentration of 3-OHB detectable in plasma was 2 mumol/L. The calibration curve showed a linear relationship for 3-OHB concentration from 0 to 5 mmol/L (r = 0.999). Analytical recovery of 3-OHB (50 mumol/L) was 97.9 (SD 3.8)%. The method was developed for determination of the three ketone bodies in plasma. The ratio of acetone to acetoacetate was not significantly different (p greater than 0.2) between normals (n = 31) and diabetics (n = 86). In normal subjects, the ratio of 3-OHB to acetoacetate was 1.20 (SD 0.44). In diabetic patients, the ratio correlated with the logarithm of the total ketone body concentration (r = 0.828).     

Ketone body transport in the human neonate and infant.

Using a continuous intravenous infusion of D-(-)-3-hydroxy[4,4,4-2H3]butyrate tracer, we measured total ketone body transport in 12 infants: six newborns, four 1-6-mo-olds, one diabetic, and one hyperinsulinemic infant. Ketone body inflow-outflow transport (flux) averaged 17.3 +/- 1.4 mumol kg-1 min-1 in the neonates, a value not different from that of 20.6 +/- 0.9 mumol kg-1 min-1 measured in the older infants. This rate was accelerated to 32.2 mumol kg-1 min-1 in the diabetic and slowed to 5.0 mumol kg-1 min-1 in the hyperinsulinemic child. As in the adult, ketone turnover was directly proportional to free fatty acid and ketone body concentrations, while ketone clearance declined as the circulatory content of ketone bodies increased. Compared with the adult, however, ketone body turnover rates of 12.8-21.9 mumol kg-1 min-1 in newborns fasted for less than 8 h, and rates of 17.9-26.0 mumol kg-1 min-1 in older infants fasted for less than 10 h, were in a range found in adults only after several days of total fasting. If the bulk of transported ketone body fuels are oxidized in the infant as they are in the adult, ketone bodies could account for as much as 25% of the neonate's basal energy requirements in the first several days of life. These studies demonstrate active ketogenesis and quantitatively important ketone body fuel transport in the human infant. Furthermore, the qualitatively similar relationships between the newborn and the adult relative to free fatty acid concentration and ketone inflow, and with regard to ketone concentration and clearance rate, suggest that intrahepatic and extrahepatic regulatory systems controlling ketone body metabolism are well established by early postnatal life in humans.     

Diabetic Ketoacidosis as a Delayed Immune-Related Event after Discontinuation of Nivolumab

BackgroundNivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody with immune checkpoint inhibitory activity, represents a novel treatment for several cancers. Immune checkpoint inhibitors cause side effects, known as immune-related adverse events (irAEs) or delayed immune-related events (DIRE), after immunotherapy discontinuation. Type 1 diabetes mellitus (T1DM) and diabetic ketoacidosis have been reported to develop as an irAE during the treatment with nivolumab. Here, we report on a patient who developed T1DM and diabetic ketoacidosis after discontinuation of treatment with nivolumab as a DIRE.Case ReportA 59-year-old man, who received nivolumab for an alpha fetoprotein-producing gastric cancer, presented with acute fatigue 4 months after discontinuation of nivolumab. Throughout therapy with nivolumab, the patient's hemoglobin A1c (HbA1c) level was ≤ 6%. However, 1 month prior to the patient's emergency department visit, he noticed weight loss, and 3 weeks prior to that, his HbA1c was 7.1%. Urinalysis showed ketone bodies, and arterial blood gas analysis suggested metabolic acidosis with hyperglycemia (690 mg/dL), which established the diagnosis of diabetic ketoacidosis. An endogenous insulin deficiency without verifiable anti-islet autoantibodies was confirmed; the patient had a human leukocyte antigen haplotype that does not increase the risk of acute-onset T1DM. We considered that T1DM in this patient developed possibly due to nivolumab.Why Should an Emergency Physician Be Aware of This?This case highlights the need for clinicians to be vigilant of the fact that a history of anti-PD-1 monoclonal antibody therapy may increase the risk of diabetic ketoacidosis, whether treatment is ongoing or discontinued.     

In vitro glycation of brain aminophospholipids by acetoacetate and its inhibition by urea

Amino groups of amino acids, nucleic acids and lipids can react non-enzymatically with reducing sugars to form unstable Schiff bases that can then undergo the Amadori rearrangement to form irreversible advanced glycation end products (AGEs). Ketoacidosis is a life-threatening complication in patients with untreated diabetes mellitus and it is characterized by increased circulating ketone body concentrations. Recently, the in vitro glycation of hemoglobin by beta-hydroxybutyrate and acetone was described by our laboratory. This study was designed to evaluate the in vitro effect of acetoacetate on brain aminophospholipids at similar concentrations to that observed in ketoacidosis (16.13 mM total ketone bodies). The effect of acetoacetate was compared to that of glucose and the other ketone bodies; beta-hydroxybutyrate and acetone. The antiglycating activity of urea and glycylglycine was also investigated. The incubation of aminophospholipids with acetoacetate results in the formation of a new compound with an absorption peak at 280 nm. When this reaction product was analyzed by thin layer chromatography using an elusion system of methanol:chloroform:acetic acid:water (8:1:1:0.4), the R(f) value obtained (0.24-0.26) was similar to that of the compound formed by aminophospholipids with glucose. In contrast, this reaction product was not detected in those samples containing beta-hydroxybutyrate and acetone. The formation of this new compound was inhibited by urea more effectively than glycylglycine. In conclusion, this study provides the evidence that brain aminophospholipids react with acetoacetate forming AGEs and that this glycating effect of acetoacetate was remarkably decreased by urea, suggesting a protective physiological role for urea in the body as it was previously stated. Finally, this information adds knowledge about the contribution of ketoacidosis in the pathophysiology of diabetic complications, especially in type 1 diabetic patients.     

Euglycemic Diabetic Ketoacidosis with Elevated Acetone in a Patient Taking a Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitor

Background

Sodium-glucose cotransporter-2 (SGLT2) inhibitor medications are a class of antihyperglycemic agents that increase urinary glucose excretion by interfering with the reabsorption of glucose in the proximal renal tubules. In May of 2015, the U.S. Food and Drug Administration released a warning concerning a potential increased risk of ketoacidosis and ketosis in patients taking these medications.

Foreign bodies of the upper gastrointestinal tract: current management

The popularity of the flexible esophagogastroduodenoscope prompted us to reevaluate our management of foreign bodies. In this paper we report our experience and update treatment guidelines. In our series (from December 1975 to May 1982), 74 foreign bodies were removed: 12 with the rigid endoscope, 60 with the flexible endoscope, and two surgically. There was no morbidity or mortality. In the age group 1 to 10 years, there were 15 patients, while the age group 11 to 88 years had 59 patients. Although the rigid endoscope is less expensive and has a larger operating channel, the advantages of the flexible instrument are numerous. Foreign bodies of the pharynx and at the level of the cricopharyngeus muscle are best managed with a rigid endoscope; foreign bodies of the esophagus can be managed with rigid or flexible instruments, but are more easily managed with the latter. Foreign bodies of the stomach and duodenum that require removal can be managed only with the flexible panendoscope.     

食品交换法对儿童糖尿病的治疗效果

目的探讨食品交换疗法应用于儿童糖尿病饮食治疗的临床效果。方法选取2005-2007年采用食品交换法治疗的20例糖尿病患儿作为实验组，2003-2005年采用主食固定法治疗的20例糖尿病患儿作为对照组，比较两组患儿在饮食治疗12个月后的空腹血糖、餐后2h血糖和糖化血红蛋白代谢指标以及酮症酸中毒的发生率。结果饮食治疗后，实验组患儿空腹血糖、餐后2h血糖及糖化血红蛋白比对照组均显著降低（P〈0．01）；酮症酸中毒的发生率也明显低于对照组（P〈0．01）。结论食品交换法简单易学、便于掌握，可使食品种类多样化，不仅符合儿童的饮食习惯，有助于饮食治疗的有效落实，而且满足了儿童生长发育的需要。