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Sensitivity of Four Simple Methods to Screen Chinese Patients for Diabetic Peripheral Neuropathy
Abstract
Context:
Diabetic peripheral neuropathy (DPN) is a common complication associated with long-term type 2 diabetes mellitus, although early diagnosis can improve prognosis.
Objective:
Our objective was to develop a simple protocol for early diagnosis of DPN in Chinese type 2 diabetic patients.
Subjects and methods:
A total of 209 type 2 diabetic patients were included; these patients were categorized as symptomatic and asymptomatic group based on their symptoms. Clinical data of these patients were recorded and they were screened for DPN by vibration perception threshold test (VPT), 10-G nylon monofilament test, temperature identification, and the tendon reflex test.
Results:
The total combined rate of patients who were tested positive for DPN with all four screening methods was 68.7%. Patients tested positive for DPN were significantly older and had a longer disease duration than those who were tested negative (p<0.01); however, glycated hemoglobin levels, presence of hypertension, and gender did not differ significantly between them (p>0.05). Among screening methods, the highest positive rate observed among patients screened with the VPT test was 63.64% as compared to other tests. The total positive rate for temperature discrimination, 10-G monofilament and tendon reflex test were 26.79%, 11.96 % and 17.22 % respectively. In asymptomatic group VPT showed the highest positive rate for DPN (48.41%).
Conclusions:
The combination of four simple methods can improve the detection rate of DPN and identify subclinical cases. Abnormal vibration perception was the most common feature of DPN and it was associated with both disease duration and the age of the patient.
... The sample size estimation was done based on the following formula in Statistics and Sample size mobile application for the parent study, N > = z 2 1−α/2 X Sens (1-Sens)/d 2 x prevalence, where, d is absolute precision, z the value for 95% CI, and sens is sensitivity of biothesiometer. The sample size was calculated to be 384 (~ 400) patients with DPN, based on the positivity rate by biothesiometer as 48.4% and 17.5% by mono lament test, [20] 5% absolute precision and 5% alpha error. Considering the prevalence of DPN as 20%, a total of 1920 (~ 2000) diabetic individuals were planned for enrolment. ...
... In the study by Jie FY et al which compared the diagnostic accuracy of mono lament, VPT, temperature and tendon re ex, the total positive rate for VPT was 63% as compared to 12% for mono lament 26.8% for temperature and 17.2% for tendon re ex. [20] This study used a 10.5 cut-off for biothesiometry based on the cut-off suggested by Hou et al with NCS as reference standard. ...
Background and objectives: Of the several screening tests used in screening for Diabetic Peripheral Neuropathy (DPN), each one has its demerits which act a threat to reliability. There is no single optimal method for the early diagnosis of Diabetic Peripheral Neuropathy (DPN). This study was conducted to compare the diagnostic accuracy of monofilament, biothesiometer and symptom-based scoring in detecting DPN, to determine the optimal cut-off for biothesiometer score compared to Nerve conduction studies (NCS) as gold standard and to compare the time taken to screen with monofilament and biothesiometer. Methodology: The cross-sectional comparative diagnostic accuracy study was conducted in the Medicine OPD of a tertiary care institute in Central India. Among the patients with DM, those who were advised NCS between March - October 2023 were included in the study. All patients had undergone clinical Michigan neuropathy scoring, biothesiometer and monofilament and NCS. Results and discussion: A total of 78 limbs among 39 patients with diabetes were assessed for DPN. The sensitivity of clinical Michigan neuropathy scoring, monofilament and biothesiometer (10 cut-off) were 15.6% (5.3 to 32.8), 35.5% (23.7 to 48.7) and 71% (58.1 to 81.8) respectively. A biothesiometer score of 10 was identified as optimal with area under the curve: 0.7132 (0.56 to 0.87), and the time taken to administer the biothesiometer was about 2.5 times more compared to the monofilament assessment. Conclusions: Biothesiometry has higher sensitivity compared to other screening methods such as monofilament and clinical symptom score. The biothesiometer cut off at 10 had higher sensitivity compared to the existing standards of 15mV. The need for lower cut-off for biothesiometry has to be established with reference to nerve conduction study standards in larger studies.
... Patients with DPN often have larger shoe sizes, calluses, crevices, or skin changes [3]. The degree of pathological severity and clinical symptoms are often inconsistent and mismatched, and up to 50 % of DPN patients remain asymptomatic [30]. In this study, there were about 43% (170/394) of DPN patients who didn't have sensory abnormalities. ...
... Elder patients are inclined to be oblivious to the symptoms of pain, numbness or other paresthesia and take it for granted for old process [30,31]. Therefore, we should educate patients how to prevent diabetes from DPN. ...
... A review of the literature suggests that the monofilament test is sensitive and comparable to a nerve conduction test [23][24][25]. Due to the wide variation in DPN, some authors have suggested combining several simple screening methods to assess detectability, such as assessing temperature perception with pressure, vibration, and tendon reflex perception [38]. This area certainly needs further research. ...
BACKGROUND Diabetes-related foot disease (DFD) is a serious complication of diabetes, increasing the risk of amputation. Coimplications are preventable, but most diabetics do not receive proper screening and treatment, despite indications. This study was a pilot screening of diabetes-related foot disease in a group of people with glycemic disorders. MATERIAL AND METHODS We recruited 143 volunteers over 40 years of age. In the final analysis, we included 85 people diagnosed with glycemic disorders (diabetes or prediabetes), for whom we performed a total of 170 foot measurements. We screened for peripheral artery disease using: foot pulse, ankle-brachial index (manual and automatic), toe-brachial index, and transcutaneous oxygen pressure (TcPO2). To screen for diabetic peripheral neuropathy, we used indicators of loss of protective sensation: pressure perception and temperature perception, and plantar pressure distribution. RESULTS A history of diabetes was reported by 26 (30.6%) of the subjects. Disorders of at least 1 foot occurred in 20 (66.7%) subjects with diagnosed diabetes and in 10 (17%) subjects declaring no diabetes. Higher risk and DFD category were correlated with duration of diabetes (r=0.68, p=0.007), glycemic levels (r=0.56, p=0.001), age (r=0.57, p=0.007), and the presence of other diabetes complications. The best predictor of risk in DFD was manual ABI, p=0.001; followed by automatic ABI, p=0.006. CONCLUSIONS Our results showed that peripheral complications of diabetes, such as DFD, often remain undiagnosed and untreated despite the high risk of developing ulcers. There is a need for multi-center screening studies.
... Studies by Xie et al. (32,33) have shown that compared with oral or intramuscular injection, acupoint injection of mecobalamin can significantly increase the serum SP level in patients with DPN, thereby improving neurological function. The VPT is the most sensitive test for detecting DPN and is also a predictor of foot injury (42,43). Zhao et al. (35) found that acupoint injection of mecobalamin can significantly reduce VPT, thereby reducing the clinical symptoms of patients and the risk of foot ulcers. ...
Objective
Mecobalamin is a commonly used drug in the treatment of diabetic peripheral neuropathy (DPN). This study aimed to systematically evaluate the efficacy and safety of acupoint injection of mecobalamin for DPN.
Methods
Relevant clinical trials on acupoint injection of mecobalamin for DPN published before 31 January 2023 were searched in eight commonly used databases. After screening and confirming the included studies, meta-analysis and trial sequential analysis were performed.
Results
A total of 10 relevant studies were confirmed, and the total sample size was 927 cases. On the efficacy endpoints, meta-analysis showed that compared with other administration methods, acupoint injection of mecobalamin significantly increased the clinical effective rate by 27% [RR = 1.27, 95% CI = (1.19, 1.36), P < 0.00001], motor nerve conduction velocity (median nerve) by 5.93 m/s [MD = 5.93, 95% CI = (4.79, 7.07), P < 0.00001], motor nerve conduction velocity (common peroneal nerve) by 5.66 m/s [MD = 5.66, 95% CI = (2.89, 8.43), P < 0.0001], sensory nerve conduction velocity (median nerve) by 4.83 m/s [MD = 4.83, 95% CI = (3.75, 5.90), P < 0.00001], and sensory nerve conduction velocity (common peroneal nerve) by 3.60 m/s [MD = 3.60, 95% CI = (2.49, 4.71), P < 0.00001], and trial sequential analysis showed these benefits were conclusive. In terms of safety endpoints, meta-analysis indicated that the total adverse events for acupoint injection were comparable to other methods of administration, and trial sequential analysis suggested that the results needed to be validated by more studies. Subgroup analysis demonstrated that the benefits of acupoint injections of mecobalamin were not limited by the dose, duration of treatment, or number of acupoints reported in the included studies. Harbord's test showed no significant publication bias (P = 0.106).
Conclusion
The efficacy of acupoint injection of mecobalamin for DPN was significantly better than other administrations, and its safety was comparable to other administrations. Therefore, acupoint injection may be the optimal method of mecobalamin for DPN.
Systematic review registration
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=454120, identifier: CRD42023454120.
... Additionally, there is no single tool that can be used to objectively evaluate sensory, motor, and autonomic deficits associated with diabetic peripheral neuropathy [58]. Evidence suggests that combining multiple assessments increases sensitivity, specificity, and accuracy of detecting diabetic peripheral neuropathy [8,[75][76][77][78]. Therefore, multiphasic screening-where one or more tools for assessing the signs and symptoms of diabetic peripheral neuropathy are used concurrently or sequentially-may detect a greater proportion of deficits, thereby aiding clinical decision-making. ...
Background
Diabetic neuropathy is the most common microvascular complication of diabetes mellitus and a major risk factor for diabetes-related lower-extremity complications. Diffuse neuropathy is the most frequently encountered pattern of neurological dysfunction and presents clinically as distal symmetrical sensorimotor polyneuropathy. Due to the increasing public health significance of diabetes mellitus and its complications, screening for diabetic peripheral neuropathy is essential. Consequently, a review of the principles that guide screening practices, especially in resource-limited clinical settings, is urgently needed.
Main body
Numerous evidence-based assessments are used to detect diabetic peripheral neuropathy. In accordance with current guideline recommendations from the American Diabetes Association, International Diabetes Federation, International Working Group on the Diabetic Foot, and National Institute for Health and Care Excellence, a screening algorithm for diabetic peripheral neuropathy based on multiphasic clinical assessment, stratification according to risk of developing diabetic foot syndrome, individualized treatment, and scheduled follow-up is suggested for use in resource-limited settings.
Conclusions
Screening for diabetic peripheral neuropathy in resource-limited settings requires a practical and comprehensive approach in order to promptly identify affected individuals. The principles of screening for diabetic peripheral neuropathy are: multiphasic approach, risk stratification, individualized treatment, and scheduled follow-up. Regular screening for diabetes-related foot disease using simple clinical assessments may improve patient outcomes.
Aims:
To investigate the prevalence and risk factors of diabetic peripheral neuropathy (DPN) in Type 2 diabetes mellitus (T2DM) patients with overweight or obese in Guangdong province in China.
Methods:
A cross-sectional study was carried out on T2DM patients with overweight/obese in 60 hospitals in Guangdong province. Methods of data collection included questionnaire, clinical examination, blood draw and clinical measurement. Demographic characteristics, diagnosis of diabetes and DPN, disease history, life styles and self-management, most recent laboratory test results and physical examination were collected. Binary logistic regression was used to assess risk factors of DPN.
Results:
A total of 3359 T2DM patients (age range 20-90 years) were recruited. The overall prevalence of DPN was 33.1%. Binary logistic regression identified age (odds ratio [OR]: 1.016, 95% confidence interval [CI]: 1.008, 1.024), duration of diabetes mellitus (OR: 1.072, 95% CI: 1.056, 1.087) and HbA1c (OR: 1.053, 95% CI: 1.013, 1.095) as risk factors for the presence of DPN.
Conclusions:
DPN is prevalent in T2DM patients with overweight or obese in Guangdong province in China and is significantly associated with age, HbA1c and duration of diabetes.
DPN is an important complication and contributes to the morbidity of diabetes mellitus. Evidence indicates early detection of DPN results in fewer foot ulcers and amputations.
The purpose of this study was to compare different screening tests in the detection of DPN in primary care setting.
It is a cross-sectional study in a random sample (N = 242) of type 2 diabetes mellitus participants at primary care setting. Different screening tests for detecting DPN such as Michigan Neuropathy Screening Instrument (MNSI), Semmes-Weinstein Monofilament (SWM), vibration sensation and ankle reflex were performed for each patient and compare between them.
45% of the participant had DPN based on MNSI, The detection rate using the 128-Hz tuning fork and 10-g SWM was nearly same (32.6 & 31.4%) respectively and significantly higher than ankle reflexes (23.1%). Although, the prevalence of DPN determined by the combined two tests (38.79%) was higher than that through the single test.
this study showed different results of DPN screening tests, even in the same group of patients. However there was a significant correlation between them. 128-Hz tuning fork and 10-g SWM monofilament would appear to be an appropriate, cheap and easy to use tool for identifying patients at risk of having neuropathy in primary care setting.
Diabetic peripheral neuropathy (DPN), a common and troublesome complication in patients with type 2 diabetes mellitus (T2DM), contributes to a higher risk of diabetic foot ulcer and lower limb amputation. These situations can negatively impact the quality of life of affected individuals. Despite its high prevalence and clinical importance, most diabetes mellitus patients not only do not recognize the presence of diabetic neuropathy, but also do not report their symptoms to physicians or other health care providers. Therefore, DPN is usually under diagnosed and undertreated. For early detection and appropriate intervention for DPN, a careful history, physical with neurologic examination, and prompt treatment are needed in T2DM patients.
Vibration perception threshold (VPT) is considered as a gold standard for diagnosis of diabetic peripheral neuropathy. However, the data are sparse comparing the VPT with commonly used bedside modalities. This study was carried out to evaluate the usefulness of simple bed side screening modalities for peripheral neuropathy in patients with diabetes mellitus.
A total of 1044 patients with diabetes mellitus attending the Diabetes clinic from January 2007 to May 2008, were included in this study. All subjects had a detailed clinical assessment including Diabetic Neuropathy Symptom (DNS) score, Diabetic Neuropathy Examination (DNE) score, ankle reflex, vibration sensation with a 128 Hz tuning fork, 10 g Semmes-Weinstein monofilament and vibration perception threshold (VPT).
The prevalence of peripheral neuropathy was 34.9 per cent with VPT. Foot care practices were followed by only 214 (20.5%) of the study population. When compared with VPT, ankle reflex was the most sensitive (90.7%) but least specific (37.3%). The tuning fork and monofilament tests respectively had lower sensitivity (62.5 and 62.8%) but better specificity (95.3 and 92.9%) and accuracy (78.9 and 77.9%). Significant correlations were observed between the VPT score and the DNE (r = 0.532, P<0.001) and DNS (r = 0.546, P<0.001) scores and absent tuning fork sensation (r = 0.590; P<0.001), monofilament sensation (r = 0.573; P<0.001) and ankle reflex (r = 0.377, P = 0.01).
The present findings show that simple bed side tests are useful for assessing peripheral diabetic neuropathy, even in those subjects in whom foot care practices are not followed.
Diabetic ulcers are the most common foot injuries leading to lower extremity amputation. Family physicians have a pivotal role in the prevention or early diagnosis of diabetic foot complications. Management of the diabetic foot requires a thorough knowledge of the major risk factors for amputation, frequent routine evaluation and meticulous preventive maintenance. The most common risk factors for ulcer formation include diabetic neuropathy, structural foot deformity and peripheral arterial occlusive disease. A careful physical examination, buttressed by monofilament testing for neuropathy and noninvasive testing for arterial insufficiency, can identify patients at risk for foot ulcers and appropriately classify patients who already have ulcers or other diabetic foot complications. Patient education regarding foot hygiene, nail care and proper footwear is crucial to reducing the risk of an injury that can lead to ulcer formation. Adherence to a systematic regimen of diagnosis and classification can improve communication between family physicians and diabetes subspecialists and facilitate appropriate treatment of complications. This team approach may ultimately lead to a reduction in lower extremity amputations related to diabetes.
Chronic complications are the major outcome of type 2 diabetes mellitus progress, which reduce the quality of life of patients, incur heavy burdens to the health care system, and increase diabetic mortality. The aims of this study were to describe the prevalence of chronic complications among urban Chinese type 2 diabetic outpatients; and to analyze the associations between chronic complications and patients' demographics, diabetic related clinical characteristics.
This cross-sectional hospital-based study was carried out in 4 major Chinese cities: - Shanghai, Chengdu, Beijing and Guangzhou. The survey was conducted from March to July in 2007 among 1,524 type 2 diabetic outpatients. The subjects were interviewed face-to-face by trained interviewers using a questionnaire to capture information on demographics, disease presentations and complications. All the subjects were invited to have a HbA1c test free of charge by the standardized method with Bio-Rad Variant II.
Of the 1,524 study subjects, 637 (41.8%) were male, and the mean age was 63.3 +/- 10.2 years. At least one chronic complication was diagnosed in 792 individuals (52.0%) of the study subjects; 509 (33.4%) presented with macrovascular complications and 528 (34.7%) with microvascular complications. The prevalence of cardiovascular and cerebrovascular conditions, neuropathy, nephropathy, ocular lesions and foot disease were 30.1%, 6.8%, 17.8%, 10.7%, 14.8% and 0.8%, respectively. The prevalence of chronic complications varied between cities, and significantly increased with age and duration of diagnosed diabetes. The mean of HbA1c in diabetic patients with chronic complications was 8.2% +/- 1.6% and 63.0% of the subjects with type 2 diabetes related complications had a poor glycemic control with the HbA1c > 7.5%.
Chronic complications are highly prevalent among type 2 diabetic outpatients, the glycemic control of diabetic patients with chronic complications was poor, and future efforts should be directed at intensive blood glucose control, strengthening early diagnosis and improving case management to prevent and minimize the occurrence of complications.
Plantar ulcers and lower-extremity amputation are frequent, severe, and costly problems in patients with diabetes mellitus (DM).¹ Although there are many risk factors for developing foot problems, peripheral neuropathy is an important factor that seems to predispose patients to plantar ulcers and amputation.²
Patients with DM and peripheral neuropathy typically show a gradual loss of sensation on the plantar surface of their feet in a stocking-glove pattern.² They seem to reach a threshold of insensitivity that puts them at risk for developing unnoticed ulcers on the plantar surface of the foot. This threshold has been referred to as the level of “protective sensation.”³ Clinicians need a method of easily and reliably testing for protective sensation to identify patients who are at risk for foot problems. Identification of those patients may allow preventive intervention.
The utility of rapid and reliable sensory tests appropriate for the diagnosis of neuropathy in the diabetes clinic, rather than as prognostic tools for the prediction of foot complications, has been unclear because of limitations inherent in previous studies. Although clinical practice guidelines recommend annual screening for neuropathy, they are unable to support specific recommendations for screening maneuvers because of a lack of evidence for the validity of screening tests in the medical literature. The objective of this study was to assess the operating characteristics of four simple sensory screening maneuvers as compared with standardized electrophysiological tests in the diagnosis of distal symmetrical polyneuropathy.
We assessed four simple tests (the 10-g Semmes-Weinstein monofilament examination [SWME], superficial pain sensation, vibration testing by the on-off method, and vibration testing by the timed method) in 478 subjects with independent blinded evaluations compared against the criterion standard of nerve conduction studies. We present receiver-operating characteristic (ROC) curves, positive and negative likelihood ratios, and sensitivity and specificity values for each test.
The four simple screening maneuvers reveal similar operating characteristics. Cutoff points by ROC curve analyses reveal that a positive or abnormal test is represented by five incorrect responses of eight stimuli applied. A negative or normal test is represented by one or fewer incorrect responses of eight stimuli applied. By these criteria, the point estimates of the positive likelihood ratios for vibration testing by the on-off method, vibration testing by the timed method, the SWME, and superficial pain sensation test are 26.6, 18.5, 10.2, and 9.2, respectively. The point estimates of the negative likelihood ratios are 0.33, 0.51, 0.34, and 0.50, respectively The screening tests showed comparable sensitivity and specificity results. The 10-g SWME, superficial pain test, and vibration testing by the on-off method are rapid, each requiring approximately 60 s to administer. The timed vibration test takes longer, and the interpretation is more complicated. The combination of two simple tests (e.g., the 10-g SWME and vibration testing by the on-off method) does not add value to each individual screening test.
Annual screening for diabetic neuropathy should be conducted using superficial pain sensation testing, SWME, or vibration testing by the on-off method. The reported operating characteristics for each sensory modality can be applied to positive findings on the physical examination of individual patients to predict the likelihood of neuropathy.
Peripheral neuropathy is common among people with diabetes and can result in foot ulceration and amputation. The aim of this study was to quantify the annual medical costs of peripheral neuropathy and its complications among people with type 1 and type 2 diabetes in the U.S.
A cost-of-illness model was used to estimate the numbers of diabetic individuals in the U.S. who have diabetic peripheral neuropathy (DPN) and/or neuropathic foot ulcers (both those with no deep infection and those accompanied by cellulitis or osteomyelitis) at a given point in time, and/or a toe, foot, or leg amputation during a year. Prevalence and incidence rates were estimated from published studies and applied to the general U.S. population. All costs were estimated in 2001 U.S. dollars. In a sensitivity analysis, we varied the rates of complications to assess the robustness of the cost estimates.
The annual costs of DPN and its complications in the U.S. were 0.8 billion US dollars (type 1 diabetes), 10.1 billion US dollars (type 2 diabetes), and 10.9 billion US dollars (total). After allowing for uncertainty in the point estimates of complication rates, the range of costs were between 0.3 and 1.0 billion US dollars (type 1 diabetes), 4.3b and 12.7 billion US dollars (type 2 diabetes), and 4.6 and 13.7 billion US dollars (type 1 and type 2 diabetes).
The total annual cost of DPN and its complications in the U.S. was estimated to be between 4.6 and 13.7 billion US dollars. Up to 27% of the direct medical cost of diabetes may be attributed to DPN.
The goal of this study was to estimate the prevalence of diabetes and the number of people of all ages with diabetes for years 2000 and 2030.
Data on diabetes prevalence by age and sex from a limited number of countries were extrapolated to all 191 World Health Organization member states and applied to United Nations' population estimates for 2000 and 2030. Urban and rural populations were considered separately for developing countries.
The prevalence of diabetes for all age-groups worldwide was estimated to be 2.8% in 2000 and 4.4% in 2030. The total number of people with diabetes is projected to rise from 171 million in 2000 to 366 million in 2030. The prevalence of diabetes is higher in men than women, but there are more women with diabetes than men. The urban population in developing countries is projected to double between 2000 and 2030. The most important demographic change to diabetes prevalence across the world appears to be the increase in the proportion of people >65 years of age.
These findings indicate that the "diabetes epidemic" will continue even if levels of obesity remain constant. Given the increasing prevalence of obesity, it is likely that these figures provide an underestimate of future diabetes prevalence.
ropathic pain (7–10), and this and other putative mechanisms will be discussed. The clinical features, diagnosis, and management of the focal and multifocal neuropathies will be described. A major portion of this review will discuss the clinical features, assessment, and management of the patient with the most common form of DN, diabetic distal sensory polyneuropathy (DPN). The late sequelae of DPN and their prevention will also be described. Finally, practical guidelines for the screening of DPN in clinical practice will be provided. For further details on this topic, please refer to recent reviews (11– 18).
Objective:
To evaluate the diagnostic value of vibration perception threshold (VPT) in diabetic peripheral neuropathy (DPN) by the receiver operating characteristic curve (ROC) and to establish its cut-off threshold.
Methods:
All patients had the VPT examination and nerve conduction velocity (NCV) examination. NCV examination showed that 283 patients with Type 2 diabetes were divided into a DPN group (n=151) and an NDPN group (n=132). The VPT diagnosis was evaluated by Youden index, sensitivity, specificity and the area under ROC curve. The best cut-off threshold was defined by the Youden index.
Results:
1) The NCV was significantly slower, while the VPT was higher in the DPN group than those in the NDPN group (both P values <0.05). 2) The VPT and NCV of both sides of the limb had no difference in all patients. 3) With NCV as the golden diagnosis criterion, the area under ROC of VPT was 0.707, the best cut-off threshold was 10.54 V, the sensitivity was 0.596, the specificity was 0.848, and the Youden index was 0.445. 4) The diagnosis ratio of NCV combined with VPT was 60.4%, significantly higher than that of NCV alone (P<0.05).
Conclusion:
Compared with NCV examination, VPT has good diagnostic value for DPN. The best cut-off value is 10.54 V.
Diabetes mellitus is not only a clinical syndrome characterizing hyperglycemia, but is also a cause of debilitating problem known as peripheral neuropathy (PN). This review addresses the importance of diagnosing PN in a clinical setting as PN causes pain and discomfort in lower extremities, loss or absence of protective sensations in the lower extremities leading to balance problems, risk of foot ulcerations, and a reduced quality of life in adults with type 2 diabetes. A variety of modalities or methods are available to evaluate both subjective and objective measures of peripheral nerve functions, and have been discussed in detail in this review. It is of utmost importance to understand that evaluating PN as a routine practice in a simple way may also play a vitally important role in preventing foot ulcers or fall-related morbidity and mortality in adults with type 2 diabetes.
Neuropathic pain is the most common chronic complication of diabetes mellitus. The mechanisms involved in the development of diabetic neuropathy include changes in the blood vessels that supply the peripheral nerves; metabolic disorders, such as the enhanced activation of the polyol pathway; myo-inositol depletion; and increased non-enzymatic glycation. Currently, much attention is focused on the changes in the interactions between the nervous system and the immune system that occur in parallel with glial cell activation; these interactions may also be responsible for the development of neuropathic pain accompanying diabetes. Animal models of diabetic peripheral neuropathy have been utilized to better understand the phenomenon of neuropathic pain in individuals with diabetes and to define therapeutic goals. The studies on the effects of antidepressants on diabetic neuropathic pain in streptozotocin (STZ)-induced type 1 diabetes have been conducted. In experimental models of diabetic neuropathy, the most effective antidepressants are tricyclic antidepressants, selective serotonin reuptake inhibitors, and serotonin norepinephrine reuptake inhibitors. Clinical studies of diabetic neuropathy indicate that the first line treatment should be tricyclic antidepressants, which are followed by anticonvulsants and then opioids. In this review, we will discuss the mechanisms of the development of diabetic neuropathy and the most common drugs used in experimental and clinical studies.
The aim of this study was to evaluate the prevalence of diabetic peripheral neuropathy in children and adolescents with type 1 diabetes mellitus and examine whether the neurological examination validly diagnoses diabetic peripheral neuropathy as compared with the gold standard of nerve conduction velocity in these patients. Nerve conduction velocity was measured in an unselected consecutive series of patients aged 8-18 years who had been suffering from type 1 diabetes mellitus for at least 1 year. For the neurological examination, neuropathy disability scores and neuropathy sign scores were used. Of the 39 patients, six (15%) had clinically evident diabetic peripheral neuropathy, whereas nerve conduction velocity testing revealed diabetic peripheral neuropathy in 15 (38%) patients. Sensitivity and specificity of the neurological examination for the diagnosis of diabetic peripheral neuropathy were 40% and 100%, respectively. The corresponding positive and negative predictive values were 100% and 72.7%, respectively. This conclusions from this study are that in children and adolescents with type 1 diabetes mellitus, diabetic peripheral neuropathy is highly prevalent, but in the majority of patients it is subclinical. Sensitivity and negative predictive values of the neurological examination are low. Therefore, routine nerve conduction velocity measurement for the assessment of diabetic peripheral neuropathy appears to be warranted in these patients.
With economic growth and urbanization there have been significant changes in the life style and diet of urban residents in large cities of China, which is experiencing a rapid increase in the prevalence of diabetes. While high prevalence of diabetes has been reported, little is known of the long-term effects of diabetes in such a large population. The aim of this study was to estimate the morbidity rate of diabetic peripheral neuropathy (DPN) in a Chinese urban diabetic population with more than 10 years' disease duration, and evaluate the relevant risk factors. The clinical manifestation of DPN and pain status was also assessed.
Five hundred and sixty-five diabetes patients were recruited into the study. Symptoms and examination helped diagnose neuropathy. The clinical manifestation of DPN was assessed with a visual analog pain score (VAS). Diabetic complication status was determined from medical records. Serum lipids and lipoproteins, glycosylated hemoglobin (HbA1c), and the urinary albumin excretion rate were measured.
The morbidity rate of DPN was 46.6%. HbA1c, hyperlipidemia, and retinopathy were significantly associated with neuropathy, and these risk factors were correlated with other diabetic micro and/or macrovascular complications. The average VAS pain score of the DPN patients was 4.12 ± 2.07. Severe and moderate pain was experienced by 11.4% and 40.5% respectively of DPN patients. About 3.7% of diabetic subjects had lower limb ulcer or amputation.
The morbidity rate of DPN for diabetic patients with > 10 years duration is very high compared to the range reported for other populations in the world. The risk factors for DPN include HbA1c, hyperlipidemia, and retinopathy. In long-standing diabetic patients, DPN was not associated with diabetic duration, and half of the DPN patients experienced considerable daily suffering.
To assess peripheral neuropathy following a standardized foot examination protocol in a representative population-based cohort of subjects with type 2 diabetes.
In a geographically defined population, aged 40-70 years with diabetes prevalence of 3.5% according to medical records, we investigated 156 type 2 diabetic subjects, 95% Caucasian, mean age 61.7±7.2 years, duration of diabetes 7.0±5.7 years, and HbA(1c) 7.3±2.4% (6.4% Mono-S), by questionnaires, clinical examinations, blood sampling, and review of medical records. Foot examination included clinical signs of peripheral neuropathy and tests of sensibility with monofilament, tuning fork, and assessments of the vibration perception thresholds (VPT).
Peripheral autonomic neuropathy (PAN) as judged by two or more signs of dysfunction was the most common and affected 43%. The prevalence of peripheral sensory neuropathy (PSN) was 15% by monofilament, 24% by tuning fork, and 28% by VPT expressed as ZscoreVPT ≥2.0 S.D. Twenty-nine percent had a VPT ≥25 V. Signs of peripheral motor neuropathy (PMN) affected 15%. Peripheral neuropathy, at least one variable, affected 67%, whereas 25% were affected by more than one variable of neuropathy, i.e., polyneuropathy. Exclusion of other identified causes for neuropathy than diabetes reduced the prevalence of diabetic polyneuropathy to 23%. Concurrent diabetic complications were 29% for retinopathy, 14% for incipient nephropathy, and 8% for overt nephropathy. The prevalence of macrovascular complications was 62% for CVD, 26% for PVD, and 11% for cerebrovascular lesion (CVL).
Peripheral neuropathy was common in this representative type 2 diabetes population. Clinical signs of PAN were the most frequent followed by diminished perception of vibration and touch.
The global spread of diabetes (DM) and the importance of early therapeutic intervention determine the need of simple, inexpensive and sensitive methods for diagnosis of diabetic complications in the general practice. The aim of this study was to assess a new instrument - the plaster Neuropad in diagnosing the sudomotor diabetic dysfunction and to investigate the correlates of Neuropad data with diabetic complications.
In this cross-sectional study participated 264 inpatients (M/F=126/138) with DM type 1/2 (61/203), mean age 55.4+/-12.0 and DM duration of 9.3+/-7.1 years. According to hospital records were registered: anthropometric data; fasting plasma glucose and HbA1c; presence of micro-(retino-, nephro-, neuropathy), and macrovascular (arterial hypertension, coronary artery disease and/or brain vascular disease) complications, and neuropathic symptoms were evaluated. For investigation of somatic DN a modified Neuropathy Disability Score (NDS) and for sudomotor autonomic DN - Neuropad were used.
Neuropad showed the highest between-feet correlation of 0.91 compared to all other individual tests and the NDS. Neuropad was able to separate patients in groups with different general risk profile, including age, duration of DM, presence of coronary and/or brain vascular disease, nephropathy, and retinopathy. Moreover, Neuropad differentiated patient groups by their stage of DN, evaluated by symptoms, diagnosis, the individual somatic tests and with the highest significance - by NDS. Most sensitive for detecting DN was NDS > or = 3, followed by Achilles reflexes, vibration perception (128 Hz tuning fork) and Neuropad. A borderline or abnormal result of Neuropad showed sensitivity=76.3/79.3, specificity=56.1/42.9, positive=86.3/62.8 and negative=39.5/63.0 predictive values, and diagnostic accuracy 72.2/62.9%, compared to the indices for presence of somatic DN (NDS > or = 3)/foot at risk (NDS > or = 6) respectively.
Screening for DN must cover somatic and autonomic disturbances. Neuropad is a new sensitive and appropriate for everyday clinical use test for detecting sudomotor DN and identification of patients at higher risk for chronic diabetes complications.
We wanted to summarize evidence about the diagnostic accuracy of the 5.07/10-g monofilament test in peripheral neuropathy.
We conducted a systematic review of studies in which the accuracy of the 5.07/10-g monofilament was evaluated to detect peripheral neuropathy of any cause using nerve conduction as reference standard. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool.
We reviewed 173 titles and abstracts of articles to identify 54 potentially eligible studies, of which 3 were finally selected for data synthesis. All studies were limited to patients with diabetes mellitus and showed limitations according to the QUADAS tool. Sensitivity ranged from 41% to 93% and specificity ranged from 68% to 100%. Because of the heterogenous nature of the studies, a meta-analysis could not be accomplished.
Despite the frequent use of monofilament testing, little can be said about the test accuracy for detecting neuropathy in feet without visible ulcers. Optimal test application and defining a threshold should have priority in evaluating monofilament testing, as this test is advocated in many clinical guidelines. Accordingly, we do not recommend the sole use of monofilament testing to diagnose peripheral neuropathy.
Neuropathy needs to be diagnosed early to prevent complications, such as neuropathic pain or the diabetic foot. It is obvious that diagnosis of neuropathy needs to be improved. New peripheral nerve function tests that appear to facilitate diagnosis are now emerging. This review outlines the new tests that have been proposed for the diagnosis of diabetic distal symmetric polyneuropathy, the commonest form of neuropathy in diabetes. New tests are classified into those mainly assessing large-fiber function (tactile circumferential discriminator, steel ball-bearing, and automated nerve conduction study) and those mainly assessing small-fiber function (NeuroQuick and Neuropad). Emerging tests are promising but must be evaluated in prospective studies. Moreover, their cost-effectiveness needs more careful appraisal. The clinician should, therefore, still rely on established modalities to diagnose neuropathy, but wider use of the new tests is expected in the near future.
Diabetic peripheral neuropathy (DPN) is a common disorder that can lead to limb loss and death. Up to 50% of DPN patients can be asymptomatic. This fact contributes to making DPN the leading cause of lower limb amputation. The degree of heterogeneity in the clinical manifestations of DPN makes diagnosing this condition difficult. This article reviews the characteristics, diagnosis, electrodiagnosis, classification, pathogenesis, and treatment of DPN.
A 10-year post-trial monitoring of patients with newly diagnosed type 2 diabetes randomised in the "United Kingdom Prospective Diabetes Study" (UKPDS) demonstrated a continued reduction in microvascular risk (-24%, p = 0.001) and emergent risk reductions for myocardial infarction (-15%, p = 0.01) and death from any cause (-13%, p = 0.007), despite an early loss of glycaemic differences ("legacy effect"). A continued benefit after metformin therapy was evident during the ten-year post-trial follow-up among overweight patients (-33%, p = 0.005 for myocardial infarction and -27%, p = 0.002 for death from any cause). In contrast, the benefits of previously improved blood pressure control were not sustained when between-groups differences in blood pressure were lost during follow-up, except for a reduced risk for peripheral vascular disease. These observations are strong arguments in favour of an early optimisation of blood glucose control and of a sustained control of blood pressure in patients with type 2 diabetes.
We have studied risk factors for diabetic foot ulceration by comparing diabetic patients who had active foot ulcers (n = 86) with diabetic patients who had no history of foot ulcers (n = 49). Whereas there was a strong association of diabetic foot ulceration with abnormal vibratory perception (Odds Ratio = 10.77; p less than 0.001, which increased with worsening vibratory perception), there was little association with abnormality of the ankle-pressure index (Odds Ratio = 2.84, p = n.s.). Although foot ulceration and limited joint mobility were associated (Odds Ratio = 3.57, p less than 0.001), this relation was not significant when allowances for abnormal vibratory perception and diabetes duration were made. These data suggest that sensory neuropathy is of greater aetiological importance than peripheral vascular disease in the development of diabetic foot ulceration. The measurement of the vibratory perception threshold is clinically useful in identifying those diabetic patients at high risk of foot ulceration.
A cross-sectional multicentre study of randomly selected diabetic patients was performed using a standardised questionnaire and examination, to establish the prevalence of peripheral neuropathy in patients attending 118 hospital diabetes clinics in the UK. Vibration perception threshold was performed in two centres to compare with the clinical scoring systems. A total of 6487 diabetic patients were studied. 53.9% male, median age 59 years (range 18-90 years). 37.4% Type 1 (insulin-dependent) diabetes mellitus, with a median duration of diabetes 8 years (0-62 years). The overall prevalence of neuropathy was 28.5% (27.4-29.6%) (95% confidence interval) in this population. The prevalence in Type 1 diabetic patients was 22.7% (21.0-24.4%) and in Type 2 (non-insulin-dependent) diabetic patients it was 32.1% (30.6-33.6%). The prevalence of diabetic peripheral neuropathy increased with age, from 5% (3.1-6.9%) in the 20-29 year age group to 44.2% (41.1-47.3%) in the 70-79 year age group. Neuropathy was associated with duration of diabetes, and was present in 20.8% (19.1-22.5%) of patients with diabetes duration less than 5 years and in 36.8% (34.9-38.7%) of those with diabetes duration greater than 10 years. Mean vibration perception threshold measured at the great toe was 21.1 +/- 13.5 SD volts and correlated with the neuropathy disability score, r = 0.8 p < 0.001. In conclusion, diabetic peripheral neuropathy is a common complication associated with diabetes. It increases with both age and duration of diabetes, until it is present in more than 50% of Type 2 diabetic patients aged over 60 years.(ABSTRACT TRUNCATED AT 250 WORDS)