Updates in the Management of Diabetic Ketoacidosis

Diabetic ketoacidosis (DKA) is an emergency for people with diabetes characterized by hyperglycemia, metabolic acidosis, and ketosis. DKA onset and recurrence can largely be prevented through patient education. Nurse practitioners are well positioned to promote patient education, self-management, and individualized patient care. This article outlines updates in the clinical management of patients with DKA to optimize care and reduce costs.     

2型糖尿病患者酮症酸中毒风险预测模型的构建与验证

目的 通过2型糖尿病酮症酸中毒风险预测模型的构建与验证,早期识别2型糖尿病酮症酸中毒的高危人群,进行针对性的预防及控制,有效降低2型糖尿病酮症酸中毒的发生率。方法 选取大理州人民医院2019年1月—2020年12月住院治疗的2型糖尿病患者943例,采用Logistic回归分析筛选出独立危险因素并构建风险预测模型。选取2020年3月—2020年12月大理大学第一附属医院住院治疗的2型糖尿病患者393例对模型进行验证。结果 最终急性感染（OR=8.210）、应激事件（OR=129.267）、随机静脉血糖（OR=1.986）、糖化血红蛋白（OR=1.421）4个因素构建出风险预测模型。建模组受试者操作曲线下面积为0.994,最大约登指数为0.929,灵敏度为0.954,特异度为0.975,Hosmer-Lemeshow检验P=0.975。验证组受试者操作曲线下面积为0.901,最大约登指数为0.754,灵敏度为0.889,特异度为0.865。结论 急性感染、应激事件、随机静脉血糖、糖化血红蛋白是2型糖尿病酮症酸中毒发生的独立危险因素,据此构建的风险预测模型预测性能良好。     

An Unusual Case of Butcher's Broom Precipitating Diabetic Ketoacidosis

Background

Herbal medicines are readily available and commonly perceived to be relatively harmless. Butcher's Broom is used in various medicinal preparations and contains substances having α-adrenergic−stimulating properties.

Objective

Our aim was to report a case of toxicity associated with Butcher's Broom in a diabetic patient.

Case Report

A 39-year-old woman developed diabetic ketoacidosis 5 days after beginning therapy with Butcher's Broom for mild ankle swelling. Her diabetic ketoacidosis was complicated by hyperkalemia and acidosis with a pH of 7.02. After management with intravenous fluid, insulin, and calcium gluconate, her condition stabilized and she was discharged several days later.

Conclusions

This case represents a small but potentially serious public health concern in a diabetic woman taking Butcher's Broom.     

糖尿病酮症酸中毒36例临床分析

目的:总结糖尿病酮症酸中毒(DKA)的临床特点和小剂量胰岛素治疗的疗效.方法:回顾性分析2007年1月至2010年12月收治的36例DKA的临床资料.结果:36例中治愈34例,死亡2例,死于脑血管意外和急性心肌梗死各1例.结论:及时明确DKA诊断、消除诱因和采取以小剂量胰岛素、液体复苏为主的综合治疗是提高DKA的治愈率,降低死亡率的关键.     

Review article: Ketoacidosis in the emergency department

Diabetic ketoacidosis, a life‐threatening complication of type 1 diabetes mellitus, is a common cause of presentation to EDs. Two new drug classes have been found to cause ketoacidosis with distinctive presentations. The sodium‐glucose transport protein 2 inhibitors used in the management of type 2 diabetes mellitus may present with ketoacidosis with normal glucose levels. Ketoacidosis with these medications may be prolonged and recur after initial resolution. Checkpoint inhibitors may present with fulminant diabetic ketoacidosis in individuals with previously normal glucose tolerance. Ketoacidosis may also occur as a result of starvation and alcohol excess, as well as a number of rare causes. Other causes of metabolic acidosis with both high and normal anion gap need to be considered in the differential diagnosis of ketoacidosis. Diabetic ketoacidosis may also present with biochemical changes suggestive of myocardial ischaemia and pancreatitis in the absence of these pathologies. The present paper reviews ketone body metabolism, ketone testing and the causes and differential diagnosis of ketoacidosis with particular relevance to emergency medicine.     

以酮症起病的青少年糖尿病患者的临床特征

[目的]探讨以酮症起病的青少年糖尿病患者的临床特征.[方法]将94例新发青少年糖尿病患者,分为酮症起病组和非酮症起病组,比较两组患者的年龄、性别、家族史和胰岛功能等方面的差异,并比较两组患者在随访6个月时的代谢控制和治疗方式的差异.[结果]酮症起病组的起病年龄、BMI、FCP、2hPCP、TG要显著低于非酮症组,FPG、体重下降的比例和自身抗体阳性率要显著高于非酮症组.随访6个月时,酮症起病组的HbAlc高于非酮症组,FCP、2hPCP和体重上升的比例低于非酮症组.酮症起病组单独使用胰岛素的比例高于非酮症组,单独使用药物和饮食运动治疗的比例,酮症起病组显著低于非酮症组.[结论]以酮症起病的青少年糖尿病患者与非酮症起病者临床特征明显不同,而且二者在随访6个月时的胰岛功能、治疗方式存在明显差异.     

Arterial Blood Gas Results Rarely Influence Emergency Physician Management of Patients with Suspected Diabetic Ketoacidosis

OBJECTIVES: To test the hypothesis that arterial blood gas (ABG) results for patients with suspected diabetic ketoacidosis (DKA) do not influence emergency physicians' management decisions and to assess correlation and precision between venous pH and arterial pH. METHODS: Prospective, observational study of emergency physicians' decision making for consecutive ED patients with suspected DKA. Inclusion criteria were capillary blood glucose equal to or greater than 200 mg/dL, ketonuria, and clinical signs and symptoms of DKA. Venous pH, chemistry panel, and ABGs were drawn before treatment. Attending emergency physicians indicated planned management and disposition on a standardized form before and after reviewing ABG and venous pH results. This study was powered to detect a 10% difference in management decisions (n = 195). Pearson's correlation and Bland-Altman bias plot were used to compare venous pH and arterial pH. RESULTS: ABG analysis changed the emergency physicians' diagnosis in 2/200 cases (1.0%; 95% confidence interval [95% CI] = 0.3% to 3.6%), altered treatment in 7/200 cases (3.5%; 95% CI = 1.7% to 7.1%), and changed disposition in 2/200 cases (1.0%; 95% CI = 0.3% to 3.6%). The pH value of the ABGs changed the treatment or disposition in 5/200 patients (2.5%; 95% CI = 1.1% to 5.7%). The Po(2) and Pco(2) results of the ABGs altered treatment and disposition in 2/200 patients (1.0%; 95% CI = 0.3% to 3.6%). Venous pH correlated well with arterial pH (r = 0.951), and bias plotting yielded a bias value of -0.015 (+/- 0.006 pH units). CONCLUSIONS: ABG results rarely influenced emergency physicians' decisions on diagnosis, treatment, or disposition in suspected DKA patients. Venous pH correlated well and was precise enough with arterial pH to serve as a substitute.     

PD-1抑制剂致胰岛β细胞功能急剧丧失后糖尿病2例报告

本文报道2例程序性死亡受体1(programmed death-1,PD-1)抑制剂导致的1型糖尿病。一例患者为53岁男性,因食管癌接受信迪利单抗联合艾越奈达铂治疗,使用6个周期后突然出现糖尿病酮症酸中毒；另一例为46岁女性,因恶性黑色素瘤接受卡瑞利珠单抗治疗14次后随访血糖过程中出现血糖明显升高,及时给予治疗。这2例患者空腹及葡萄糖负荷后血清Ｃ肽均处于极低水平,糖尿病相关抗体及自身抗体阴性,提示胰岛β细胞完全丧失。这两例患者均诊断为PD-1抑制剂相关1型糖尿病,需要长期餐时胰岛素及长效胰岛素强化治疗；但一例治疗过程中未随访血糖,突然以糖尿病酮症酸中毒起病；一例治疗中随访血糖,发现血糖高及时治疗,避免出现糖尿病急性并发症。因此对于使用PD-1抑制剂治疗的患者需要定期监测患者的血糖,及时发现血糖升高,给予相应治疗,避免出现严重并发症。     

Measurement of IgG levels can serve as a biomarker in newly diagnosed diabetic children

This study was undertaken to determine humoral immune response to the presence of anti-immunoglobulin antibodies in children with newly diagnosed type 1 diabetes mellitus, using as a target cow immunoglobulins, in an attempt to elucidate further complex immuno-pathogenetic interactions of the disease. Serum immunoglobulin G (IgG) concentrations were measured by ELISA in 30 children with type 1 diabetes mellitus and 30 healthy matched normal children. It was found that normal children had a mean IgG level of 7.41 mg/ml while diabetic individuals had a mean IgG level of 8.52 mg/ml (p<0.00004). On the contrary, the mean level of IgG in diabetic sera after purification from anti-cow immunoglobulins was determined to be 7.52 mg/ml. Therefore, there was no significant difference in IgG level in patients with type 1 diabetes mellitus after removal of anti-cow immunoglobulin antibodies compared to normal children (p<0.58). Visualization of IgG and immuno-precipitation confirm that anti-cow immunoglobulins antibodies, which were unrelated to antigen, were co-precipitated with the antigen-antibody complex. A circulating immunoglobulin reacting with other immunoglobulins is thus present in children with type 1 diabetes and may well play a part in the complex immuno-pathogenetic interactions.     

Fulminant type 1 diabetes mellitus with remarkable elevation of serum pancreatic enzymes

Fulminant type 1 diabetes mellitus progresses extremely rapidly and is accompanied by ketoacidosis. Patients with the disease present at emergency departments with non-specific symptoms, including fever, nausea, vomiting, and abdominal pain. Here, we present a case of fulminant type 1 diabetes mellitus where the patient was initially misdiagnosed with gastroenteritis and acute pancreatitis. A 50-year-old Japanese woman was referred to our hospital with coma and shock. She had presented with nausea, vomiting, abdominal pain and thirst from 5?days before admission, and had been misdiagnosed with gastroenteritis by her primary care physician. Upon examination, metabolic acidosis and remarkable elevation of pancreatic exocrine enzymes were found (amylase 4322?IU/L, lipase 1046?IU/L). Acute pancreatitis was initially suspected because of the high pancreatic enzyme levels and abdominal pain. However, her plasma glucose level was markedly elevated at 1357?mg/dL. The patient was diagnosed with fulminant type 1 diabetes mellitus. Computed tomography showed no radiological evidence of acute pancreatitis. In conclusion, fulminant type 1 diabetes mellitus is often referred to hospital with flu-like or gastrointestinal symptoms and elevation of serum pancreatic enzymes. Physicians must be sure not to misdiagnose it as gastroenteritis or acute pancreatitis.     

Exenatide Once Weekly: Effectiveness,Tolerability, and Discontinuation Predictors in a Real-world Setting

PurposeThe goal of this study was to evaluate the effectiveness and safety of exenatide once weekly (EOW) and to determine predictors of treatment response and drug discontinuation in patients with type 2 diabetes mellitus (T2DM) followed up for 18 months in a real-world setting.MethodsThis retrospective cohort study included patients with T2DM who initiated EOW 2 mg between 2014 and 2019 in an outpatient diabetes clinic in Italy. Data were collected at baseline and at follow-up visits (6, 12, and 18 months after EOW). We estimated glycosylated hemoglobin (HbA_1c) and body weight mean changes from baseline to follow-up visits and assessed the proportion of patients reaching HbA_1c target ≤7% and a 5% weight loss after 12 months of treatment. We then attempted to establish predictors of glycemic and weight response, and compared patient characteristics between subjects who persisted on treatment versus those who discontinued EOW.FindingsOne-hundred eighty-six patients (46.2% male) were included in the study. The mean (SD) age and diabetes duration were 63.2 (8.9) years and 10.7 years (18.3), respectively. Significant reductions in HbA_1c values (−0.9%; 95% CI, −1.1 to −0.8) and body weight (−2.8 kg; 95% CI, −3.4 to −2.2) were observed after 6 months. Sixty-one percent of patients (87 of 143) achieved target HbA_1c values ≤ 7% after 12 months, and 34% (45 of 134) exhibited a weight loss of at least 5% of baseline body weight. Blood glucose and weight reductions were maintained after an 18-month follow-up. Predictors of adequate glycemic and weight response were shorter diabetes duration and nonuse of a different GLP-1RA, respectively. Patients on sulfonylureas failed to reach metabolic and body weight targets. The most common adverse events were gastrointestinal side effects (7.5%) and injection site reactions (6.4%), followed by headache (1.1%) and allergic reactions (1.1%). Forty-three percent of patients (79 of 186) discontinued EOW. The main reasons for discontinuation were insufficient HbA_1c improvement and/or limited weight reduction (19.9%), side effects (16.1%), or patient decision (6.5%). Predictors of discontinuation were higher HbA_1c levels at baseline and use of basal insulin therapy before EOW treatment.ImplicationsEOW treatment, in a real-world setting, offers sustained and effective glycemic control and weight loss over 18 months in patients with T2DM. Diabetes duration and basal insulin therapy, however, may affect the outcome of EOW treatment, suggesting that early initiation of EOW could improve glycemic control and reduce the risk of treatment discontinuation.     

1型糖尿病酮症酸中毒并发非甲状腺疾病病态综合征者3型脱碘酶mRNA水平研究

目的:探讨1型糖尿病(T1DM)合并酮症酸中毒(DKA)及正常甲状腺病态综合征(ESS)患者3型脱碘酶(D3) mRNA水平的变化及其发生机制.方法:T1DM并DKA及ESS患者28例,于确诊24 h内及DKA纠正后7d及14 d采血,选取同期住院的不伴感染、甲状腺疾病、缺氧、手术或禁食的同年龄同性别患者30例为对照组.采用放射免疫分析法检测血清T3、T4、FT3、FT4及TSH,采用Real-time PCR法测定血液D3 mRNA的表达水平.结果:DKA患者T3、FT3及FT4水平明显低于对照组,随着DKA的纠正,其水平逐渐回升,直至DKA后14d,FT3及FT4恢复至对照组水平,而T3仍未恢复至对照组水平.与之相对应,DKA者D3mRNA水平明显高于对照组,随着DKA的纠正,D3 mRNA水平逐渐下降,14 d仍未降至对照组水平.结论:D3 mRNA水平的变化可能是T1 DM合并DKA患者发生ESS的关键.     

The Role of Adiponectin as a Compensatory Mediator for the Primary Secretory Defect in Latent Autoimmune Diabetes in Adults

Background

Increased adiposity in patients with newly diagnosed type 2 diabetes mellitus (DM), as well as in patients who do not have DM, affects the regulation of insulin sensitivity and the metabolic effects of adiponectin.

Objective

The goal of this study was to investigate the relationship between plasma adiponectin levels and obesity in patients developing DM mainly due to an early decline in β-cell function.

Methods

We studied 29 patients with latent autoimmune diabetes in adults (LADA), 38 patients with type 1 DM, and 55 healthy volunteers.

Results

Plasma adiponectin levels, adjusted for body mass index (BMI), were higher in patients with type 1 DM than in controls (P < 0.001) and similar to those in patients with LADA (P = 0.464). Plasma adiponectin levels were higher in LADA patients compared with controls (P < 0.001). In LADA patients, plasma adiponectin levels, adjusted for BMI, correlated significantly with insulin resistance (β coefficient, –6.453 [2.772]; P = 0.028). Interestingly, this relationship in LADA patients was significant in more overweight patients (β coefficient, –7.142 [3.249]; P = 0.048) but not in leaner patients (P = 0.571), a finding that was not confirmed through the results in the controls (P = 0.520 and P = 0.992, respectively).

Conclusions

In patients with LADA, increases in plasma adiponectin levels, after adjustment for BMI, could act as a mediator for improvement in insulin sensitivity and thus compensate for the primary secretory defect. This effect seems more profound in more overweight subjects than in leaner subjects.     

糖化血红蛋白水平对糖尿病并发缺血性脑卒中患者再次脑血管事件的预测价值

目的:探讨糖化血红蛋白水平(HbA1c)对糖尿病(DM)并发缺血性脑卒中(IS)患者再次脑血管事件(SCE)的预测作用。方法:连续收集2008年6月至2011年6月DM并发IS患者168例。入院后测定HbA1c水平,收集临床资料。依据HbA1c水平将患者分为HbA1c升高组(HbA1c≥6.1%)和HbA1c正常组(HbA1c<6.1%)。对所有患者出院后18个月内SCE进行随访(每2个月一次),依据是否发生SCE将患者分为事件组和非事件组。采用受试者工作特征(ROC)曲线评价HbA1c水平对SCE的预测价值。结果:与HbA1c正常组(n=75)相比,HbA1c升高组(n=93)入院时空腹血糖、2 h餐后血糖、收缩压、胆固醇、甘油三酯及低密度脂蛋白胆固醇水平均升高,高密度脂蛋白胆固醇水平和Barthel指数均明显降低(均P<0.01)。事件组49例,HbA1c水平为(9.57±1.93)%;非事件组119例,HbA1c水平为(6.96±2.40)%,前者高于后者(P<0.01)。ROC曲线下面积为0.784(P<0.01,95%CI为0.713~0.855),取HbA1c水平6.55%为预测临界值的灵敏度和特异度分别为86.80%和64.30%。Kaplan-Meier生存曲线提示HbA1c水平≥6.55%时,SCE发生率增高(P<0.01)。结论:DM合并IS患者首次入院时HbA1c水平可能对出院后18个月内SCE进行预测。     

SGLT2抑制剂对2型糖尿病患者心血管结局影响的网状meta分析

目的 2型糖尿病是一种慢性疾病,而心血管事件是2型糖尿病常见的并发症,已有大型研究表明钠-葡萄糖共转运体抑制剂(SGLT2i)对改善2型糖尿病患者心血管结局具有一定作用。本文通过系统评价,间接比较了5种不同的SGLT2i对2型糖尿病并发不良心血管事件的疗效作用。方法 检索PubMed、Web of science、Cochrane Library、中国知网、万方、维普数据库,收集相关文献,检索时限为建库至2022年7月,由两位研究员独立筛选文献,并提取相应数据,以心力衰竭住院和心血管死亡复合结局为主要结局指标,以心力衰竭住院、心血管死亡和全因死亡为次要结局指标,使用Stata 16.0以及network程序包进行网状meta分析。结果 共检索到340篇文献,最终纳入11篇文献,包括62 904例患者,涉及5种干预手段,分别为:恩格列净、索格列净、达格列净、埃格列净和卡格列净。5种不同的SGLT2i在改变2型糖尿病患者的心力衰竭住院和心血管死亡复合结局、心血管死亡、心力衰竭住院和全因死亡方面差异无统计学意义(P>0.05)。与安慰剂相比,5种不同的SGLT2i均可显著改善2型糖尿病患者心力衰竭住院结局;恩格列净和索格列净在改善心力衰竭住院和心血管死亡复合结局方面差异有统计学意义;而在改善心血管死亡或全因死亡结局方面,安慰剂和5种不同的SGLT2i之间的差异均无统计学意义。结论 在改善2型糖尿病患者心力衰竭住院和心血管死亡复合结局和心力衰竭住院结局方面,恩格列净和索格列净有较显著的获益趋势,而针对心血管死亡或全因死亡结局,5种不同的SGLT2i与安慰剂间的差异无统计学意义,具体机制和原因仍需大型研究进行探索和验证。     

西格列汀联合二甲双胍对2型糖尿病患者血糖水平及心血管事件发生率的影响

目的探讨西格列汀联合二甲双胍治疗2型糖尿病(T2DM)的临床疗效及安全性。方法将208例T2DM患者随机分为二甲双胍+西格列汀组(MET/SITA组)105例和二甲双胍+阿卡波糖组(MET/DM组)103例,分别于服药前、服药后第12、24、48周检测患者体质量指数(BMI)、空腹血糖(FBG)、餐后2 h血糖(2h PPG)、糖化血红蛋白(Hb A1c)、三酰甘油(TG)、胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)和胰岛素抵抗指数(HOMA-IR)。随访记录不良反应和心血管事件发生率。结果 MET/SITA组BMI显著低于治疗前和MET/DM组(P0.01)。治疗24和48周后,MET/SITA组FBG、2h PPG和Hb A1c显著低于治疗前和MET/DM组,差异有统计学差异(P0.01)。随访发现,MET/SITA组心血管事件发生率显著低于MET/DM组,且生存周期较长。结论西格列汀联合二甲双胍治疗T2DM疗效佳,且安全性高。     

Association of immune-related adverse events induced by nivolumab with a battery of autoantibodies

BackgroundThe aim of this study was to assess the diagnostic performance of an autoantibody battery in patients receiving immune checkpoint inhibitors who experienced immune-related adverse events (irAEs).MethodsWe retrospectively analyzed several variables potentially related to irAEs, namely, demographic, clinical, and laboratory characteristics, including an autoantibody battery (antinuclear, anti-neutrophil cytoplasmic, anti-thyroid antibodies and rheumatoid factor).ResultsSixty-nine patients (48 men; 61.8 ± 10.9 years at baseline) diagnosed with stage-4 solid-organ cancer and treated with nivolumab were followed up for 12 ± 10.3 months. Thirty-two irAEs were detected in 26 patients (37.5%). Adverse events occurred more commonly in women (62% vs. 27%, p = .006), and younger patients (irAEs: 58.1 ± 9.8, no irAEs: 64.1 ± 10.9 years, p = .024). Autoantibody battery results were available for 26 patients and were more frequently positive in patients with irAEs (87% vs. 30%, p = .009). The positive predictive value, negative predictive value, and diagnostic accuracy of the battery were 82.3%, 77.8%, and 80.8%, respectively. Among the 64 patients with an evaluable response, 23 (38.5%) experienced tumour progression, this being less frequent in patients with irAEs (19% vs. 48.5%, p = .03). Overall survival was higher in patients developing irAEs (HR = 1.88, p = .05).ConclusionPositivity in a readily available autoantibody battery may be associated with the occurrence of irAEs.

KEY MESSAGES

• Positivity in an accessible and inexpensive autoantibody battery including antinuclear, anti-neutrophil cytoplasmic, anti-thyroid antibodies and rheumatoid factor may be associated with the occurrence of immune-related adverse events.
• Patients with cancer on immune checkpoint inhibitors experiencing immune-related adverse events showed a lower risk of progression and better overall survival than patients not experiencing this type of adverse effect.

     

不同年龄层次糖尿病患者并发周围神经病变的危险因素比较

目的:探讨不同年龄层次的2型糖尿病并发周围神经病变(DPN)患者的危险因素的差异。方法:2型糖尿病患者178例纳入研究。根据有无并发周围神经病变,分为非DPN组54例和DPN组124例;再根据年龄差异将124例DPN组分为老年DPN组(年龄≥60岁)和普通DPN组(年龄<60岁);收集各组一般资料及血液检测结果,并进行统计分析。结果:非DPN组和DPN组患者的年龄、糖尿病病程、糖化血红蛋白(HbA1c)、2 h餐后血糖(PG)、3 h PG、尿微量白蛋白(ALB)、尿肌酐(UCr)、尿A/C差异有统计学意义(均P<0.05);Logistic多因素回归分析显示患者的年龄、糖尿病病程是发生DPN的影响因素。非DPN组、普通DPN组和老年DPN组的年龄、HbA1c、3h PG、Cr、尿A/C差异均有统计学意义(均P<0.05);老年DPN组和普通DPN组患者的Cr和尿A/C差异均有统计学意义(均P<0.05)。结论:年龄及糖尿病病程是2型糖尿病并发DPN的影响因素;老年DPN患者出现糖尿病肾病的几率会增大。     

青少年1型糖尿病患者抑郁状况及影响因素调查

目的调查青少年1型糖尿病患者抑郁状况并探讨其影响因素,为制订治疗方案提供科学依据。方法采用抑郁自评量表和影响因素调查表对106例青少年1型糖尿病患者进行调查,分析影响青少年1型糖尿病患者抑郁状况的因素。结果青少年1型糖尿病患者抑郁阳性检出率为40．57％,患者起病年龄、出现酮症次数是患者抑郁发生的危险因素,文化程度、糖化血红蛋白是患者抑郁发生的保护因素。结论针对研究得出的因素,可定期对青少年1型糖尿病患者进行集中健康教育、开展咨询工作、举办集体活动、建立患者信息管理系统,增加与患者沟通,从而改善其心理状况。