Point-of-care beta-hydroxybutyrate testing for assessing diabetic ketoacidosis severity prior to treatment in the emergency department

We prospectively evaluated the correlation between point-of-care β-OHB values and DKA severity at time of initial diagnosis in 54 patients. The correlation coefficients between β-OHB and pH, bicarbonate and anion gap were 0.33, 0.25 and 0.16, respectively. We conclude that point-of-care β-OHB absolute values cannot reliably assess DKA severity.     

Association between sarcopenia and the severity of diabetic polyneuropathy assessed by nerve conduction studies in Japanese patients with type 2 diabetes mellitus

Aims/IntroductionThis study examined the association between the severity of diabetic polyneuropathy (DPN) based on the Baba classification, and sarcopenia and its related factors.Materials and MethodsThe participants were 261 patients with type 2 diabetes mellitus. DPN was classified as stages 0–4 according to the Baba classification. Sarcopenia was diagnosed based on measurements of the skeletal mass index, grip strength and walking speed, using the Asia Working Group for Sarcopenia 2019 diagnostic criteria.ResultsThe median age of the participants was 67 years, the proportion of men was 58.6%, the median estimated duration of diabetes was 10 years and the median values for glycated hemoglobin were 10.3%. With regard to DPN, the prevalence of Baba classification stages 0–2 was 90.8% (n = 237), and that of stage 3 or 4 was 9.2% (n = 24). The prevalence of sarcopenia was 19.9%. A trend toward an increase in the frequency of slow walking speed was seen as the stage of DPN progressed. The frequencies of sarcopenia and slow walking speed were higher in the group with the Baba classification stages 3 and 4 than in the group with stages 0–2. On multiple logistic regression analyses, however, DPN was not significantly related to sarcopenia and walking speed.ConclusionsAlthough severe DPN might be related to sarcopenia, the frequency of severe DPN is low in the clinical setting, indicating that its contribution to sarcopenia is modest.     

定量感觉检查在糖尿病周围神经病变诊断中的应用

目的 了解定量感觉检查在糖尿病周围神经病变诊断方面的应用。方法 使用温度觉分析仪及振动觉分析仪,用“极限”（limits)法测定22例正常人及45例糖尿病患者肢体四个部位的温度觉、振动觉阈值,并同时检查感觉传导速度。结果 糖尿病患者的温度觉阈值、振动觉阈值显著地高于年龄匹配的正常人;糖尿病患者温度觉阈值异常率显著地大于振动觉阈值,提示小神经纤维受损比大神经纤维更常见;定量温度觉检查对糖尿病周围神经病变的诊断敏感性高于定量振动觉检查及感觉神经传导速度;糖尿病患者温度觉阈值、振动觉阈值与血糖无显著相关性。结论 定量感觉检查（特别是定量温度觉检查）对糖尿病神经病变的诊断是一种敏感的方法。     

于世界糖尿病日重谈糖尿病足的诊治与预防

糖尿病足治疗困难，医疗费用高。临床处理时，首先要明确糖尿病足的主要病因因素，如神经性、缺血性或神经缺血性以及是否合并感染，并根据常用的糖尿病足Wagner分级法来判断糖尿病足的严重程度，以采取相应的治疗措施，如神经性溃疡应减轻局部压力和纠正局部的畸形，周围血管病变则采用内科治疗和介入或外科治疗，感染的局部处理和全身用药等。糖尿病足的防治必须强调多学科合作和综合治疗，预防的重点在于开展糖尿病足危险因素筛查并给予纠正。     

参麦活血饮对糖尿病大鼠坐骨神经和红细胞山梨醇水平及神经功能的影响

目的 探讨糖尿病（DM）大鼠坐骨神经和红细胞山梨醇含量与神经功能之间的关系。观察参麦活血饮进行短期干预的作用和可能机制。方法 采用链脲佐菌素诱发DM大鼠模型。造模1周后用中成药参麦活血饮（成分为红参，麦冬，红花）治疗。用药4周后测定神经电生理，坐骨神经和红细胞山梨醇水平。结果 DM大鼠神经传导速度减慢，坐骨神经和红细胞山梨醇水平升高；经参麦活血饮治疗后上述改变减轻。同时，红细胞和坐骨神经山梨醇水平呈正相关；感觉神经传导速度与坐骨神经和红细胞山梨醇水平呈负相关，H反射与坐骨神经和红细胞山梨醇水平呈正相关。运动神经传导速度与坐骨神经和红细胞山梨醇水平无明显相关。结论 DM时红细胞山梨醇水平可反映坐骨神经山梨醇水平，亦能反映周围神经的病变程度，中药参麦活血饮可明显缓解DM大鼠周围神经的早期病变。     

神经症状/神经缺陷评分与神经传导速度诊断糖尿病周围神经病变的相关性

目的 研究神经症状/神经缺陷评分（NSS/NDS）与神经传导速度（NCV）在诊断糖尿病周围神经病变（DPN）中的相关性,并探讨NSS/NDS的临床使用价值.方法 以679例同时测定了NSS/NDS评分和NCV的2型糖尿病患者为研究对象,男性404例,女性275例,平均年龄（59±ll）岁.以NCV作为诊断DPN的金标准,分析NSS/NDS评分诊断DPN的敏感度、特异度、阳性预测值、阴性预测值、准确度、约登指数、Kappa值（一致性）及相关性等.采用Spearman相关和多因素logistic逐步回归进行相关性分析.结果 NSS/NDS评分诊断DPN的敏感度、特异度、阳性预测值、阴性预测值、准确度、约登指数、一致性及相关性分别为68.0％、77.2％、86.5％、53.5％、71.0％、45.2％、0.405、0.424.当NSS≥5分或NDS≥6分时,患者有较高的NCV异常率（77.8％ ～ 100％）.NSS、NDS评分与NCV均呈正相关（r=0.292、0.358,均P＜0.01）,患者神经症状或体征越严重,越容易引起NCV的减慢.Logistic回归分析显示NSS/NDS评分诊断DPN的危险因素是病程、年龄和UAlb/Cr[比值比（OR）=1.085、1.051、1.002,均P＜0.01].与NCV诊断DPN的危险因素相关性较好.结论 NSS/NDS评分与NCV诊断DPN有相关性,尤其是神经症状、神经缺陷严重时相关性更好.NSS/NDS评分操作简单快速,方便有效,可在临床中作为DPN的筛查.     

Lumos for the long trail: Strategies for clinical diagnosis and severity staging for diabetic polyneuropathy and future directions

Diabetic polyneuropathy, which is a chronic symmetrical length‐dependent sensorimotor polyneuropathy, is the most common form of diabetic neuropathy. Although diabetic polyneuropathy is the most important risk factor in cases of diabetic foot, given its poor prognosis, the criteria for diagnosis and staging of diabetic polyneuropathy has not been established; consequently, no disease‐modifying treatment is available. Most criteria and scoring systems that were previously proposed consist of clinical signs, symptoms and quantitative examinations, including sensory function tests and nerve conduction study. However, in diabetic polyneuropathy, clinical symptoms, including numbness, pain and allodynia, show no significant correlation with the development of pathophysiological changes in the peripheral nervous system. Therefore, these proposed criteria and scoring systems have failed to become a universal clinical end‐point for large‐scale clinical trials evaluating the prognosis in diabetes patients. We should use quantitative examinations of which validity has been proven. Nerve conduction study, for example, has been proven effective to evaluate dysfunctions of large nerve fibers. Baba’s classification, which uses a nerve conduction study, is one of the most promising diagnostic methods. Loss of small nerve fibers can be determined using corneal confocal microscopy and intra‐epidermal nerve fiber density. However, no staging criteria have been proposed using these quantitative evaluations for small fiber neuropathy. To establish a novel diagnostic and staging criteria of diabetic polyneuropathy, we propose three principles to be considered: (i) include only generalizable objective quantitative tests; (ii) exclude clinical symptoms and signs; and (iii) do not restrictively exclude other causes of polyneuropathy.     

F-wave latency serves as the most reproducible measure in nerve conduction studies of diabetic polyneuropathy: multicentre analysis in healthy subjects and patients with diabetic polyneuropathy

Aims/hypothesis. For use in future drug development for diabetic polyneuropathy, we conducted multicentre trials to assess the reproducibility of nerve conduction studies.¶Methods. All measurements were repeated twice at a time interval of 1–4 weeks in 132 healthy subjects (63 men) and 172 patients (99 men) with diabetic polyneuropathy. Using a standardised method, 32 centres participated in the study of control subjects and 65, in patients with diabetic polyneuropathy. Motor nerve conduction studies consisted of stimulating the left median and tibial nerves and recording the compound action potential from abductor policis and adductor hallucis for measuring amplitude, terminal latency and minimal F-wave latency. For sensory conduction studies, sensory nerve action potentials were recorded antidromically from the second digit and the posterior aspect of the lateral malleous after distal stimulation of the left median and sural nerves. We also calculated motor conduction velocity, F-wave conduction velocity and sensory conduction velocity. The relative intertrial variation and intraclass correlation coefficient were used as an index of reproducibility.¶Results. Of all the measurements, F-wave latency yielded the highest intraclass correlation coefficient with the smallest relative intertrial variation for both median and tibial nerves in both groups.¶Conclusion/interpretation. Median and tibial F-wave latency provide the most reproducible measures for a nerve conduction study, serving as one of the best measures in multicentre drug trials for diabetic polyneuropathies. [Diabetologia (2000) 43: 915–921]     

Point-of-care method for total white cell count: an evaluation of the HemoCue WBC device

Point-of-care testing (POCT) is becoming an important adjunct to haematology laboratory practice. An important component of the blood count is the total white cell count (WBC). Previously, this required laborious microscopic cell counting, but it can now be performed by means of automation; however, in many under-resourced countries, costly automated counters are only available in very few central hospitals. Moreover, neither method is practical in most POCT situations. The HemoCue WBC has been developed as a simplified alternative method, consisting of a reagent pre-loaded disposable cuvette together with basic image analysis technology. This report describes an assessment of its utility. The WBC of 500 routine blood samples from the hospital were tested in parallel by the HemoCue WBC and by a reference analyser to assess accuracy and utility of the former. The tests included precision, linearity, type of blood sample and anticoagulant and potential interfering substances in blood specimens. In the tests for accuracy, 192 of the 200 showed percentage difference from the NEQAS reference of <10% whilst the remaining eight samples differed by <12%, thus meeting the requirements of Clinical laboratory improvement amendments (CLIA)-88 regulations. Of the samples tested with potential interfering substances only those with >2% normoblasts or reticulocytosis showed significant differences from the reference measurements. The HemoCue WBC is reliable for WBC counts within the analytical range of 0.4-30.0 x 10(9)/l, except in samples where there are significant numbers of normoblasts or reticulocytes. It is simple to use and provides a valuable advance in the facilities available for POCT in haematology.     

Exercise-induced conduction velocity increment: a marker of impaired peripheral nerve blood flow in diabetic neuropathy

Summary Severe microvascular disease exists at the stage of clinical diabetic neuropathy. A non-invasive test that will identify those diabetic subjects who will eventually develop neuropathy is essential for early intervention. Sural sensory conduction velocity was recorded (x 3) in 12 non-neuropathic diabetic subjects, 15 diabetic subjects with established neuropathy and 16 age-matched normal control subjects, before and after exercise to 80% age/sex predicted maximum heart rate. Fixed sural electrodes were used. Subcutaneous temperature was recorded by a needle thermocouple placed near the sural nerve. Sural sensory conduction velocity increased significantly after exercise in normal subjects (p<0.01, mean increase 5.07 m/s) and non-neuropathic diabetic subjects (p<0.02, mean increase 3.99 m/s) but not in neuropathic subjects (mean increase 0.99 m/s). Subcutaneous temperature rose significantly in normal subjects (p<0.01, mean increase 2.07°C) and non-neuropathic diabetic subjects (p<0.001, mean increase 2.52 °C) but not in neuropathic subjects (mean increase 0.15 °C). However, sural sensory conduction velocity increased by 1.2 m · s^–1. °C^–1 following direct warming of the limb in six neuropathic subjects which was comparable to that of normal and non-neuropathic subjects (1.49 and 1.48 m · s^–1. °C^–1). The impairment of exercise conduction increment in diabetic neuropathy suggests impaired nerve blood flow in diabetic neuropathy.     

Methods for assessing diabetic polyneuropathy: validity and reproducibility of the measurement of sensory symptom severity and nerve function tests

The usefulness of sensory symptoms in the assessment of diabetic polyneuropathy is unclear. In the present study, we studied the hypothesis that pain is associated with small nerve fibre function, and that sensory alteration is associated with large nerve fibre function. In addition, we assessed the reproducibility and the ability to detect changes in clinical status over time of the nerve function tests currently used in clinical trials. Patients (78) with stable diabetic polyneuropathy were examined on three separate occasions with a test-retest interval of 17 and 52 weeks. Small nerve fibre function was measured using temperature discrimination thresholds for warmth (TDTwarmth) and cold (TDTcold). Large nerve fibre function was measured by testing sensory and motor nerve conduction velocities (SNCV and MNCV) and vibration perception thresholds (VPT). Neuropathic pain was only significantly associated with TDTcold, and with the MNCV of the tibial nerve. Sensory alteration was associated with almost all nerve function tests except the SNCV and MNCV of the ulnar nerve. The measurements of symptom severity and the nerve function tests all proved to be sufficiently reproducible. The standardized smallest detectable difference on group level (SDD) of the measurement of sensory alteration and neuropathic pain were almost the same (9% and 12%, respectively). Among the nerve function tests, the SNCV and MNCV had the smallest SDD (3-4%), and were, therefore, potentially the most responsive instruments. The SDD of the TDT was greater than the VPT (9-14% vs 21-28%, respectively). In conclusion, neuropathic pain was not associated with small nerve fibre function, and sensory alteration was associated with both large and small fibre function. In addition, the standardized measurement of symptom severity, the SNCV and MNCV tests, and the VPT test appear to be useful for monitoring the course of polyneuropathy in clinical trials.     

复合维生素B对糖尿病周围神经病变大鼠坐骨神经的传导速度及cAMP、cGMP含量的影响

目的探讨复合维生素B对糖尿病周围神经病变（DPN）大鼠坐骨神经的传导速度及cAMP、cGMP含量的影响。方法95只健康wistar大鼠,随机选取正常对照30只,其余65只以STZ腹腔注射建立糖尿病（DM）大鼠模型。将DM大鼠随机分为糖尿病对照组32只和复合维生素B治疗组33只,分别给予生理盐水和复合维生素B（20mg／kg）灌胃,连续8周,观察药物对DPN大鼠坐骨神经的传导速度及cAMP、eGMP含量的影响。结果复合维生素B治疗组大鼠坐骨神经传导速度明显提高,坐骨神经内cAMP、eGMP含量明显增加。结论复合维生素B对DPN大鼠周围神经功能有明显的保护作用。     

Screening and diagnosis of diabetic polyneuropathy in clinical practice: A survey among German physicians (PROTECT Study Survey)

AimsWe sought to obtain detailed information on the procedures and appraisal of screening for and diagnosing diabetic sensorimotor polyneuropathy (DSPN) in clinical practice.MethodsThis cross-sectional survey included 574 physicians from 13 federal states across Germany who responded to a tripartite questionnaire.ResultsThe vast majority of the respondents reported to screen for DSPN at least once a year (87 %), while 65 % reported to examine the feet of DSPN patients at least twice a year. However, only 28 % and 20 % of the respondents used questionnaires and scores to assess the severity of neuropathic symptoms and signs, respectively. The rates of participants reporting that they do not use a standardized testing procedure were 58 % for pressure sensation, 62 % for pain sensation, and 54 % for thermal sensation. The rates of respondents reporting that they do not deploy a standardized assessment were 41 % for vibration sensation, 73 % for pressure sensation, 77 % for pain sensation, and 66 % for thermal sensation. Half of the physicians oriented themselves towards clinical guidelines when diagnosing DSPN.ConclusionsDespite relatively high screening rates, the willingness to implement both standardized testing procedures and assessment and to follow guidelines is low among physicians when screening for and clinically diagnosing DSPN.     

Na/K ATP酶活性及其ATP1A1基因多态性与2型糖尿病周围神经病变的相关性

目的研究大连地区汉族人Na／KATP酶活性及ATP1A1基因多态性与2型糖尿病（T2DM）周围神经病变（DPN）的关系。方法用聚合酶链反应-限制性片段长度多态性方法对大连地区的106例T2DM患者和45例正常对照者（NC）的ATP1A1基因进行扩增，对其基因多态性进行研究，并用比色法测定其红细胞的Na／KATP酶活性。结果与NC组相比，T2DM组红细胞Na／KATP酶活性降低，在伴有DPN组，Na／KATP酶活性的降低更为明显。在T2DM患者中，有DPN组与无DPN组相比，基因型分布差异有统计学意义（P〈0．05）。T2DM患者携带有限制性等位基因A与非携带者Na／KATP酶活性的差异有统计学意义（P〈0．05）。结论Na／KATP酶活性的降低在DPN的发病中起重要作用，Na／KATP酶的基因ATP1A1多态性与T2DM患者发生DPN相关。T2DM携带有限制性等位基因A的患者DPN的发生率低于非携带者。     

Advances in the monitoring of oral anticoagulation: Point-of-care testing, patient self-monitoring, and patient self-management

Oral anticoagulation with warfarin sodium has proven to be an effective therapy for patients at risk for thromboembolic disease, but due to its high risk/benefit ratio, many physicians are reluctant to prescribe the drug. The development of capillary whole-blood prothrombin time (PT) monitors provides a potential means to decrease this risk/benefit ratio and to encourage the use of warfarin. Studies show that this technology is accurate, precise, and correlates closely with standard laboratory methods. Given that these monitors are simple and portable, investigators have conducted studies to determine their suitability for patient self-testing and home monitoring. Investigations show that patients can accurately and precisely perform the PT test at home, and that this mode of therapy appears to be at least as safe and effective as standard management. Furthermore, limited studies also suggest that patients can also manage their own dosing based on personalized guidelines designed by a physician. Given the theoretical potential for improved patient outcomes and overall cost reduction, patient self-monitoring and self-management are not far off. Large randomized prospective trials are now needed to confirm that the future of anticoagulation management should include patient self-monitoring and patient self-management of therapy.     

Numbness and paresthesia in bilateral toes and soles,and disproportional sweating restricted to face and trunk are suitable symptoms useful for the diagnosis of diabetic symmetric polyneuropathy

Aims/Introduction: In order to diagnose diabetic symmetric polyneuropathy (DSPN) more simply and accurately, we identified symptoms that correlated with neurological functions and existed more frequently in diabetic than non‐diabetic subjects. Materials and Methods: The relationships between 10 symptoms (numbness or paresthesia in toe and sole, numbness in hand, pain in foot or hand, coldness in legs, painful leg cramp, dizziness on standing, sweating restricted to face/trunk and frequent constipation/diarrhea) and clinical background, defined as DSPN and cardiovascular autonomic neuropathy (CAN) by the criteria proposed in the statement of the American Diabetes Association, and seven quantitative nerve function data were evaluated in 593 diabetic patients in Wakayama Medical University Hospital (WMUH). Furthermore, the prevalence of various symptoms was examined by three questionnaires: a WMUH survey (999 diabetic outpatients), a Nationwide survey (1524 male diabetic outpatients under a primary‐care physician) and a Control survey (501 non‐diabetic subjects). Results: Bilateral ‘numbness in toe and sole’, ‘paresthesia in toe and sole’, ‘pain in foot’ and ‘sweating restricted to face/trunk’ were significantly associated with diabetes duration, retinopathy, probable and confirmed DSPN, possible and advanced CAN, and all or six nerve functions. Questionnaire surveys clarified that symptoms that are not rare (>15%) and more frequent in diabetic than non‐diabetic subjects were bilateral ‘numbness in toe and sole’, ‘paresthesia in toe and sole’, ‘coldness in legs’, ‘dizziness on standing’ and ‘sweating restricted to face/trunk’. Conclusions: Therefore, bilateral ‘numbness in toe and sole’, ‘paresthesia in toe and sole’ and ‘sweating restricted to face/trunk’ are suitable symptoms useful for the diagnosis of DSPN. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00124.x, 2011)     

A comparison of the Neuropen against standard quantitative sensory-threshold measures for assessing peripheral nerve function.

AIMS: To investigate the efficacy of the Neuropen, a new clinical device that assesses both pain and pressure perception, to evaluate peripheral nerve function in diabetic patients compared with standard clinical testing methods. METHODS: Peripheral nerve function was assessed in 124 diabetic patients attending a multidisciplinary diabetes clinic, using (i) the modified Neuropathy Disability Score (NDS), derived from assessment of vibration, pinprick (pain), temperature sensation plus ankle reflexes, and (ii) vibration perception threshold (VPT) measured at the hallux. Patients were stratified into various neuropathic groups according to their NDS score. In addition, nerve function was assessed using the Neuropen, a device combining a 10-g monofilament and a weighted Neurotip. Inability to feel sensation on either or both feet for each test of the Neuropen (i.e. the monofilament or the Neurotip) was defined as an abnormal response. RESULTS: The sensitivity of the Neuropen to detect neuropathy compared with the NDS (score > or = 6/10) was high using either an abnormal monofilament response (87.8%), an abnormal Neurotip response (91.8%) or a combination of the two (82.0%). Neuropen specificity improved, however, when the combination of abnormal monofilament and abnormal Neurotip responses was used (68%), rather than the individual tests (57% and 41%, respectively). CONCLUSIONS: The Neuropen is a sensitive device for assessing nerve function and may provide an inexpensive alternative screening method to identify patients with moderate to severe neuropathy.     

The diabetic heart: A review of the lifework of Sophie Maria Koltai

It is well known that cardiovascular alterations are the principal causes of mortality in patients with diabetes. Premature and accelerated atherosclerosis cannot be the sole cause of diabetic heart disease because functional disorders develop both in experimental and in clinical diabetes before the onset of the detectable morphological changes of the vessel wall. Namely, altered adrenergic responses and prostaglandin metabolism and diminished vasodilatory ability can be seen in diabetic vessels. This leads to enhanced vasoconstriction, which – combined with increased sympathetic activity – may induce myocardial edema and an increase in myocardial stiffness, resulting in diminished heart function. Increased myocardial stiffness due to myocardial dehydration caused by hyperglycemic hyperosmolality can also result in impaired heart function. Thus, myocardial water content plays a key role in the development of diabetic heart dysfunction. Disturbances in the myocardial energy metabolism may also contribute to the diminished cardiac performance in the diabetic state. Some antidiabetic agents may also have deleterious cardiovascular effects. Whether the functional abnormalities observed in the reviewed studies lead to clinically manifest heart disease in diabetes may depend on the superimposition of the classical cardiovascular risk factors. Thus, adequate control of carbohydrate and lipid metabolism and the possible concomitant hypertension may prevent the further impairment of heart function and the development of overt heart disease.