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Self-measurement of Blood Glucose and Continuous Glucose Monitoring - Is There Only One Future? 自我测量血糖和持续血糖监测-只有一个未来吗?
Q2 Medicine Pub Date : 2018-09-01 Epub Date: 2018-09-10 DOI: 10.17925/EE.2018.14.2.24
Lutz Heinemann, Andreas Stuhr, Adam Brown, Guido Freckmann, Marc D Breton, Steven Russell, Lutz Heinemann

Monitoring glycaemic control in patients with diabetes has evolved dramatically over the past decades. The introduction of easy-to-use systems for self-monitoring of blood glucose (SMBG) utilising capillary blood samples has resulted in the availability of a wide range of systems, providing different measurement quality. Systems for continuous glucose monitoring (CGM) - used mainly in patients with type 1 diabetes (T1D) - were made possible by the development of glucose sensors that measure glucose levels in the interstitial fluid (ISF) in the subcutaneous tissue of the skin. CGM readings might not correspond exactly to SMBG measurement results taken at the same time, especially during rapid changes in either blood glucose or ISF glucose levels. The mean absolute relative difference is the most popular method used for characterising the measurement performance of CGM systems. Unlike the International Organization for Standardization 15197:2013 criteria for SMBG systems, no accuracy standards for CGM systems exist. Measurement quality of CGM systems can vary based on several factors, limiting their safety and effective use in managing diabetes. Patients have to be trained adequately to make safe and efficient use of CGM systems (like with SMBG systems). Also, systems for CGM must be evaluated in terms of patient safety and the ability to provide accurate measurements regardless of the fluctuation of glucose levels. As new technological advancements in glucose monitoring are essential for improved management options of diabetes, such as automated insulin dosing systems, there is a need for a critical view of all such developments. It is likely that both, SMBG and CGM systems, will play important future roles in the treatment of diabetes.

在过去的几十年里,监测糖尿病患者的血糖控制已经发生了巨大的变化。利用毛细血管血液样本,引入易于使用的血糖自我监测系统(SMBG),导致了各种系统的可用性,提供不同的测量质量。连续血糖监测(CGM)系统主要用于1型糖尿病(T1D)患者,通过测量皮肤皮下组织间质液(ISF)中的葡萄糖水平的葡萄糖传感器的发展成为可能。CGM读数可能与SMBG测量结果不完全对应,特别是在血糖或ISF血糖水平快速变化时。平均绝对相对差是表征CGM系统测量性能最常用的方法。与国际标准化组织15197:2013 SMBG系统标准不同,CGM系统没有精度标准。CGM系统的测量质量可能因几个因素而有所不同,这限制了其在糖尿病管理中的安全性和有效性。必须对患者进行充分培训,以便安全有效地使用CGM系统(如SMBG系统)。此外,CGM系统必须在患者安全性和提供准确测量的能力方面进行评估,而不管血糖水平的波动。由于血糖监测方面的新技术进步对于改善糖尿病的管理选择至关重要,例如自动胰岛素给药系统,因此需要对所有这些发展持批判态度。很可能SMBG和CGM系统都将在未来的糖尿病治疗中发挥重要作用。
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引用次数: 14
Developments in the Management of Type 1 and Type 2 Diabetes. 1型和2型糖尿病的治疗进展。
Q2 Medicine Pub Date : 2018-09-01 Epub Date: 2018-09-10 DOI: 10.17925/EE.2018.14.2.13
Chantal Mathieu
Received: 10 July 2018 Published Online: 17 July 2018 Citation: European Endocrinology. 2018;14(2):13–4 Corresponding Author: Chantal Mathieu, Dept Endocrinology UZ Gasthuisberg Herestraat 49 3000 Leuven, Belgium. E: chantal.mathieu@uzleuven.be Poor glucose control resulting from diabetes is responsible for the deaths of millions of people worldwide each year, and reduces the quality of life for many more. As a result, research continues for new glucose-lowering drugs, as well as improved ways to manufacture and deliver insulin. In this expert interview, Chantal Mathieu, Professor of Medicine at the Catholic University of Leuven, Belgium, discusses some of the latest developments in the management of both type 1 (T1D) and type 2 (T2D) diabetes.
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引用次数: 1
Empagliflozin and Cardio-renal Outcomes in Patients with Type 2 Diabetes and Cardiovascular Disease - Implications for Clinical Practice. Empagliflozin 与 2 型糖尿病和心血管疾病患者的心肾功能结果--对临床实践的启示。
Q2 Medicine Pub Date : 2018-09-01 Epub Date: 2018-09-10 DOI: 10.17925/EE.2018.14.2.40
David H Fitchett

In patients with type 2 diabetes (T2D), the excretion of glucose by the kidney with sodium-glucose cotransporter 2 (SGLT2) inhibitors lowers glycosylated haemoglobin (HbA1c) levels, decreases body weight and visceral adiposity, as well as improving cardio-renal haemodynamics. Currently, four SGLT2 inhibitors are approved in the US and Europe to improve glycaemic control - empagliflozin, dapagliflozin, canagliflozin, and ertuglifozin. Recently, the SGLT2 inhibitor empagliflozin was approved by the FDA for the reduction of cardiovascular (CV) death in adults with T2D and CV disease (CVD). This approval was based on the findings of the Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) study, which was the first study to show a significant reduction of a primary CV endpoint with a glucose-lowering agent. In this study, the primary outcome (CV mortality, non-fatal myocardial infarction [MI] and non-fatal stroke) was reduced by empagliflozin (10.5%; 490/4,687) compared with placebo (12.1%; 282/2,333); hazard ratio (HR), 0.86 (95% confidence interval [CI]: 0.74, 0.99). The primary outcome was driven by a large reduction of CV mortality (relative risk reduction [RRR], 38%). Empagliflozin also reduced all-cause mortality (RRR, 32%). Furthermore, empagliflozin reduced the adjudicated outcome of heart failure (HF) hospitalisation by 35% (HR, 0.65; 95% CI: 0.50, 0.85). Other non-adjudicated measures of HF outcomes were similarly reduced including investigator reported HF, the introduction of loop diuretics and death from HF. In the analysis of renal outcomes, incident or worsening nephropathy was reduced for empagliflozin (12.7%) compared with placebo (18.8%); HR, 0.61 (95% CI: 0.53, 0.70). Empagliflozin significantly reduced the risk of progression to macroalbuminuria (38%) and doubling of creatinine (44%), as well as the need of starting renal-replacement therapy (55%). The benefits of empagliflozin for the reduction of CV death, all-cause death and hospitalisation for HF were observed across a range of baseline subgroups such as HbA1c level and renal function (down to estimated glomerular filtration rate [eGFR] 30 ml/min/1.73 m2). The rapid reduction of HF outcomes with empagliflozin is observed across the spectrum of CVD and HF risk and represents a therapeutic advance in the prevention and perhaps also in the treatment of HF, an often poorly recognised complication of T2D. This review discusses the EMPA-REG OUTCOME study and the implications for treating patients with T2D and CVD.

对于 2 型糖尿病(T2D)患者,钠-葡萄糖共转运体 2(SGLT2)抑制剂可通过肾脏排泄葡萄糖,降低糖化血红蛋白(HbA1c)水平,减轻体重和内脏脂肪,并改善心肾血流动力学。目前,美国和欧洲批准了四种 SGLT2 抑制剂来改善血糖控制,它们是 empagliflozin、dapagliflozin、canagliflozin 和 ertuglifozin。最近,SGLT2 抑制剂 empagliflozin 获得了美国食品及药物管理局(FDA)的批准,用于降低患有 T2D 和 CV 疾病(CVD)的成人的心血管疾病(CV)死亡率。这项批准是基于 Empagliflozin、心血管结局和 2 型糖尿病死亡率(EMPA-REG OUTCOME)研究的结果,该研究是首个显示降糖药物可显著降低主要心血管终点的研究。在这项研究中,与安慰剂(12.1%;282/2,333)相比,empagliflozin(10.5%;490/4,687)降低了主要结局(CV死亡率、非致死性心肌梗死[MI]和非致死性卒中);危险比(HR)为0.86(95%置信区间[CI]:0.74,0.99)。主要结果是CV死亡率大幅降低(相对风险降低率[RRR],38%)。恩格列净还降低了全因死亡率(相对风险降低率,32%)。此外,恩格列净还将心力衰竭(HF)住院的裁定结果降低了35%(HR,0.65;95% CI:0.50,0.85)。其他非判定的心力衰竭结果也同样减少,包括研究者报告的心力衰竭、使用襻利尿剂和因心力衰竭死亡。在肾脏结果分析中,与安慰剂(18.8%)相比,恩格列净(12.7%)减少了肾病的发生或恶化;HR为0.61(95% CI:0.53,0.70)。恩格列净大大降低了进展为大蛋白尿(38%)和血肌酐翻倍(44%)的风险,以及开始肾脏替代治疗的需要(55%)。在HbA1c水平和肾功能(低至估计肾小球滤过率[eGFR]30毫升/分钟/1.73平方米)等一系列基线亚组中,都观察到了empagliflozin在降低冠心病死亡、全因死亡和因高血压住院方面的益处。empagliflozin能迅速降低心血管疾病和心房颤动的风险,代表了预防和治疗心房颤动的治疗进步,而心房颤动是T2D的并发症之一,通常未得到充分认识。本综述将讨论 EMPA-REG OUTCOME 研究及其对治疗 T2D 和心血管疾病患者的意义。
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引用次数: 0
Updates in Diagnosis and Treatment of Acromegaly. 肢端肥大症诊断和治疗的最新进展。
Q2 Medicine Pub Date : 2018-09-01 Epub Date: 2018-09-10 DOI: 10.17925/EE.2018.14.2.57
Roula Zahr, Maria Fleseriu

Acromegaly is a rare disease, caused largely by a growth hormone (GH) pituitary adenoma. Incidence is higher than previously thought. Due to increased morbidity and mortality, if not appropriately treated, early diagnosis efforts are essential. Screening is recommended for all patients with clinical features of GH excess. There is increased knowledge that classical diagnostic criteria no longer apply to all, and some patients can have GH excess with normal GH response to glucose. Treatment is multifactorial and personalised therapy is advised.

肢端肥大症是一种罕见疾病,主要由生长激素(GH)垂体腺瘤引起。其发病率比以前想象的要高。如果得不到适当的治疗,发病率和死亡率都会增加,因此早期诊断至关重要。建议对所有具有 GH 过多临床特征的患者进行筛查。越来越多的人认识到,传统的诊断标准不再适用于所有人,有些患者可能存在 GH 过多,但对葡萄糖的反应正常。治疗是多因素的,建议采用个性化疗法。
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引用次数: 0
Second-Generation Insulin Analogues - a Review of Recent Real-World Data and Forthcoming Head-to-Head Comparisons. 第二代胰岛素类似物-对最近真实世界数据和即将进行的正面比较的回顾。
Q2 Medicine Pub Date : 2018-05-01 Epub Date: 2018-05-11 DOI: 10.17925/EE.2018.14supp1.2
Didac Mauricio, Irene Hramiak

Insulin analogues play a key role in the effective management of type 2 diabetes. However, there are several behavioural barriers to appropriate early initiation of insulin therapy, despite compelling evidence supporting the benefits of this strategy in those patients for whom oral anti-diabetes agents provide insufficient control. The development of second-generation insulin analogues (insulin glargine 300 U/mL and insulin degludec) has provided physicians with agents that can provide comparable glycaemic control to first-generation insulin, but with a reduced risk of hypoglycaemia and modes of action suited to once-daily regimens. These characteristics may help overcome patient and physician concerns about early insulin use in disease management. To date, there have been no head-to-head comparisons of second-generation insulins: here we consider recent real-world evidence and the forthcoming direct comparison in the BRIGHT randomised controlled study, as presented at the recent 11th International Conference on Advanced Technologies & Treatments for Diabetes (ATTD) 2018.

胰岛素类似物在2型糖尿病的有效治疗中起着关键作用。然而,尽管有令人信服的证据支持这种策略对那些口服抗糖尿病药物不能充分控制的患者的益处,但在适当的早期开始胰岛素治疗方面存在一些行为障碍。第二代胰岛素类似物(甘精胰岛素300u /mL和去gludec胰岛素)的发展为医生提供了能够提供与第一代胰岛素相当的血糖控制的药物,但降低了低血糖的风险,并且适合每日一次的治疗方案。这些特征可能有助于克服患者和医生对疾病管理中早期使用胰岛素的担忧。到目前为止,还没有第二代胰岛素的正面比较:在这里,我们考虑了最近的现实世界证据和即将在BRIGHT随机对照研究中进行的直接比较,该研究在最近的第11届国际糖尿病先进技术与治疗会议(ATTD) 2018上发表。
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引用次数: 20
Effect of Body Lotions on Capillary Blood Glucose Measurement - Interference of Hydroquinone-Containing Body Lotion with Capillary Glucose Measurement. 沐浴露对毛细血管血糖测定的影响——含对苯二酚沐浴露对毛细血管血糖测定的干扰。
Q2 Medicine Pub Date : 2018-04-01 Epub Date: 2018-04-18 DOI: 10.17925/EE.2018.14.1.44
Andrea Ma Omengue, Eugène Sobngwi, Mesmin Dehayem, Eric V Balt, Anne Mo Boli, Simeon P Choukem, Jean F Gautier, Jean-Claude Mbanya

The reliability of capillary blood glucose measurements is tremendously important for patients' care and follow-up. Some factors independent of glucose control could however affect readings during ambulatory monitoring of capillary glucose levels in patients with diabetes mellitus. We sought to evaluate the impact of three body lotions commonly used in Cameroon on different strata of glycaemia. We explored their influence over time on measured capillary glucose values. We enrolled 16 participants. Eligible individuals were adult patients with diabetes (n=12) stratified into three levels of capillary glucose values (100 ± 40 mg/dL [5.55 ± 2.22 mmol/L], 200 ± 40 mg/dL [11.1 ± 2.22 mmol/L] and 300 ± 40 mg/dL [16.65 ± 2.22 mmol/L]) and normoglycaemic individuals (n=4). We measured capillary blood glucose before application, immediately after, then 5, 30 and 60 minutes after application of sweet almond oil, corticosteroid cream and hydroquinone lotion. The measurements made on impregnated body lotion-permeated fingers were compared to that of a clean finger. We observed a significant increase (delta [95% confidence interval, CI]: 119.5% [77.4-222.1]) of capillary glucose level immediately after administration of hydroquinone-containing body lotion (p<0.001). Capillary glucose values after the use of corticoid cream and sweet almond oil was stable 5, 30 and 60 minutes after application (p=0.875 and p=0.883 respectively). In the case of the hydroquinone-containing body lotion, there was a significant difference between capillary glucose level at 5 minutes (delta [95%CI]: 81.6% [55.3-214.2]; p<0.001), 30 minutes (delta [95%CI]: 71.6% [21.8-134.6]; p<0.001) and 60 minutes (delta [95%CI]: 58.3% [2.8-133.3]; p=0.013) after application compared to the value obtained from the clean finger. We observed from our study that there were significant variations in capillary blood glucose measurements induced by the use of hydroquinone lotion.

毛细管血糖测量的可靠性对患者的护理和随访非常重要。然而,一些独立于血糖控制的因素可能影响糖尿病患者在动态监测毛细血管血糖水平时的读数。我们试图评估喀麦隆常用的三种身体乳液对不同血糖水平的影响。我们探索了它们随时间对测量的毛细血管葡萄糖值的影响。我们招募了16名参与者。符合条件的受试者为成年糖尿病患者(n=12),分为毛细血管血糖值(100±40 mg/dL[5.55±2.22 mmol/L]、200±40 mg/dL[11.1±2.22 mmol/L]和300±40 mg/dL[16.65±2.22 mmol/L])和血糖正常组(n=4)。分别在使用甜杏仁油、皮质类固醇乳膏和对苯二酚洗剂前、后、后5分钟、30分钟和60分钟测量毛细血管血糖。将浸渍过身体乳液的手指的测量值与干净手指的测量值进行比较。我们观察到,在给予含对苯二酚身体乳后,毛细血管葡萄糖水平立即显著增加(δ[95%置信区间,CI]: 119.5% [77.4-222.1])
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引用次数: 1
A Comparison of Insulin Pen Devices and Disposable Plastic Syringes - Simplicity, Safety, Convenience and Cost Differences. 胰岛素笔装置与一次性塑料注射器的比较——简单、安全、方便和成本差异。
Q2 Medicine Pub Date : 2018-04-01 Epub Date: 2018-04-18 DOI: 10.17925/EE.2018.14.1.47
Ripudaman Singh, Clarence Samuel, Jubbin J Jacob

Context: Managing diabetes efficiently demands a simple, safe, convenient and economical therapy. This study was done to understand the simplicity, safety, convenience and cost effectiveness of using pen versus syringe devices in patients on long-term insulin therapy. Design: This prospective observational study was conducted at the endocrine outpatient department of a universityaffiliated teaching hospital in North India. The investigator interviewed patients using a self-made questionnaire after obtaining consent; patients were scored based on their answers. A high score represented a poor response. A total of 90 completed questionnaires (45 from each group) were obtained. Results: Mean simplicity, safety and convenience score among the pen users was 5.31 ± 0.51, 5.4 ± 0.89 and 4.13 ± 1.04 respectively, as compared to 9.78 ± 1.43, 8.09 ± 2.02 and 8.67 ± 0.56 in syringe users respectively. The difference in these scores was statistically significant (p=0.0001). All patients felt that treatment using pen device was costlier when compared to using syringes, with pen users spending Rs1,756 per month on their insulin therapy, as compared to syringe users, who spent Rs590 per month. Among insulin pen users, 22.2% had optimal glycated haemoglobin levels (6-7.5%) as compared to 2.2% among syringe users, and this difference was statistically significant (p=0.007). Conclusions: An insulin pen is simple, safe and convenient to use, and may provide better glycaemic control. Treatment with a pen device is costlier, which may be due to the higher use of analogue insulin among pen users.

背景:有效管理糖尿病需要一种简单、安全、方便和经济的治疗方法。本研究旨在了解长期胰岛素治疗患者使用笔与注射器设备的简单性、安全性、便利性和成本效益。设计:本前瞻性观察研究在印度北部一所大学附属教学医院的内分泌门诊部进行。研究者在征得患者同意后,使用自制问卷对患者进行访谈;根据患者的回答进行评分。得分高代表反应差。共获得90份问卷,每组45份。结果:钢笔使用者的简易性、安全性和便利性平均得分分别为5.31±0.51、5.4±0.89和4.13±1.04,注射器使用者的简易性、安全性和便利性平均得分分别为9.78±1.43、8.09±2.02和8.67±0.56。这些评分的差异有统计学意义(p=0.0001)。所有患者都认为,与使用注射器相比,使用钢笔设备进行治疗更昂贵,钢笔使用者每月在胰岛素治疗上花费1756卢比,而注射器使用者每月花费s590卢比。在胰岛素笔使用者中,22.2%的人糖化血红蛋白水平最佳(6-7.5%),而注射器使用者中为2.2%,这一差异具有统计学意义(p=0.007)。结论:胰岛素笔使用简单、安全、方便,具有较好的血糖控制效果。使用笔式设备治疗更昂贵,这可能是由于笔使用者使用类似胰岛素的频率更高。
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引用次数: 14
Ischaemic Haemorrhagic Stroke in a Child with New Onset Type 1 Diabetes Mellitus. 1例新发1型糖尿病儿童缺血性出血性卒中
Q2 Medicine Pub Date : 2018-04-01 Epub Date: 2018-04-18 DOI: 10.17925/EE.2018.14.1.59
Noor Shafina Mohd Nor, Choong Yi Fong, Kartini Rahmat, Wan Mun Vanessa Lee, Azriyanti Anuar Zaini, Muhammad Yazid Jalaludin

Cerebral oedema is the most common neurological complication of diabetic ketoacidosis (DKA). However, ischaemic and haemorrhagic brain injury has been reported infrequently. A 10-year old girl who was previously well presented with severe DKA. She was tachycardic with poor peripheral perfusion but normotensive. However, two fast boluses totalling 40 ml/kg normal saline were given. She was transferred to another hospital where she was intubated due to drowsiness. Rehydration fluid (maintenance and 48-hour correction for 7.5% dehydration) was started followed by insulin infusion. She was extubated within 24 hours of admission. Her ketosis resolved soon after and subcutaneous insulin was started. However, about 48 hours after admission, her Glasgow Coma Scale score dropped to 11/15 (E4M5V2) with expressive aphasia and upper motor neuron signs. One dose of mannitol was given. Her symptoms improved gradually and at 26-month follow-up she had a near-complete recovery with only minimal left lower limb weakness. Serial magnetic resonance imaging brain scans showed vascular ischaemic injury at the frontal-parietal watershed regions with haemorrhagic transformation. This case reiterates the importance of monitoring the neurological status of patient's with DKA closely for possible neurological complications including an ischaemic and haemorrhagic stroke.

脑水肿是糖尿病酮症酸中毒最常见的神经系统并发症。然而,缺血性和出血性脑损伤的报道并不多见。一名10岁女孩,先前表现为严重的DKA。她心动过速外周灌注差但血压正常。然而,给予两次快速丸,总计40 ml/kg生理盐水。她被转移到另一家医院,在那里她因困倦而插管。开始补液(维持和48小时纠正7.5%的脱水),然后输注胰岛素。入院后24小时内拔管。她的酮症很快消失,并开始皮下注射胰岛素。入院后约48小时,格拉斯哥昏迷评分降至11/15 (E4M5V2),出现表达性失语和上运动神经元体征。给予一剂甘露醇。她的症状逐渐改善,在26个月的随访中,她几乎完全康复,只有轻微的左下肢无力。连续脑磁共振成像扫描显示在额顶叶分水岭区血管缺血性损伤伴出血性转化。本病例重申密切监测DKA患者神经系统状况的重要性,以防可能出现的神经系统并发症,包括缺血性和出血性中风。
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引用次数: 2
The Importance of the 2015 American Thyroid Association Guidelines for Adults with Thyroid Nodules and Differentiated Thyroid Cancer in Minimising Overdiagnosis and Overtreatment of Thyroid Carcinoma. 2015年美国甲状腺协会指南对成年甲状腺结节和分化型甲状腺癌患者减少甲状腺癌过度诊断和过度治疗的重要性
Q2 Medicine Pub Date : 2018-04-01 Epub Date: 2018-04-18 DOI: 10.17925/EE.2018.14.1.13
Valeriano Leite

The 2015 guidelines from the American Thyroid Association for adults with thyroid nodules and differentiated thyroid may be particularly important in minimising potential harm from overdiagnosis and overtreatment of thyroid tumours by providing more restrictive indications for biopsy of thyroid nodules, by considering active surveillance programs, as an alternative to surgery, for papillary microcarcinomas, and by recommending more conservative surgical approaches and a more judicious use of radioiodine.

美国甲状腺协会2015年针对甲状腺结节和分化甲状腺的成人指南,通过为甲状腺结节活检提供更严格的适应症,考虑主动监测方案,作为乳头状微癌手术的替代方案,可能在最大限度地减少甲状腺肿瘤过度诊断和过度治疗的潜在危害方面尤为重要。通过推荐更保守的手术方法和更明智地使用放射性碘。
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引用次数: 3
A LEMON a Day Keeps Fatigue Away - The ABCDE of Fatigue. 一天一个柠檬让疲劳远离——疲劳的基础知识。
Q2 Medicine Pub Date : 2018-04-01 Epub Date: 2018-04-18 DOI: 10.17925/EE.2018.14.1.15
Sanjay Kalra, Rakesh Sahay

Fatigue is a common symptom in clinical medicine. The complex and multifaceted etiopathogenesis of fatigue is a challenge for the differential diagnosis and management of fatigue. This brief communication shares two simple mnemonics - LEMON and ABCDE - which help in the evaluation of fatigue. These frameworks are as relevant to endocrinology and diabetes as to general practice. The mnemonic LEMON stands for lifestyle, endocrine, medical/metabolic, observer (physician) and nutrition-related factors which may cause fatigue; ABCDE lists the aetiology of fatigue in three columns related to physiological/nutritional, psychosocial and biomedical causes (each column includes one cause and how this relates to the ABCDE rubric).

疲劳是临床医学中常见的症状。疲劳的复杂和多方面的病因是对疲劳的鉴别诊断和管理的挑战。这篇简短的交流分享了两个简单的助记符——LEMON和ABCDE——它们有助于评估疲劳。这些框架与内分泌学和糖尿病的相关性不亚于一般实践。助记符号LEMON代表可能导致疲劳的生活方式、内分泌、医疗/代谢、观察者(医生)和营养相关因素;ABCDE在与生理/营养、社会心理和生物医学原因相关的三个栏目中列出了疲劳的病因(每个栏目包括一个原因以及它与ABCDE标题的关系)。
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引用次数: 0
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European Endocrinology
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