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Validation of Neuropad in the Assessment of Peripheral Diabetic Neuropathy in Patients with Diabetes Mellitus Versus the Michigan Neuropathy Screening Instrument, 10g Monofilament Application and Biothesiometer Measurement
Abstract
Purpose:
Sudomotor dysfunction is a feature of Diabetic Peripheral Neuropathy (DPN). The indicator plaster Neuropad can provide an easy and accurate way to diagnose DPN. The aim of the present study was to evaluate Neuropad's specificity, sensitivity and accuracy in detecting DPN in patients with Diabetes Mellitus (DM).
Patients-methods:
A total of 174 patients with DM (79 with type 1 DM, 88 women), mean age 49.8 ± 16.1 years and mean DM duration 17.3 ± 7.7 years were included in the present study. The following methods were used to diagnose DPN: the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE, respectively), application of 10 g monofilament (MONO) and measurement of vibration perception threshold with biothesiometer (BIO). Neuropad was applied to both feet in all patients and according to the presence or absence of color change of the sticker, patients were divided in two groups: group A (n = 82, complete change in color from blue to pink, depicting normal perspiration) and group B (n = 92, incomplete or no change, depicting abnormal perspiration) Results: MNSIQ and MNSIE were positive for DPN in 111 and 119 patients, respectively. BIO was abnormal in 109 and MONO in 59 patients. Sensitivity of Neuropad testing was 95% vs. MONO, 73% vs. BIO, 73% vs. MNSIE and 75% vs. ΜNSIQ. Specificity was 69, 81, 90 and 92%, respectively and accuracy of the test was 78, 76, 78 and 83%, respectively.
Conclusions:
Neuropad has a high sensitivity and specificity in detecting DPN vs. MNSIQ, MNSIE and BIO. Neuropad has a high sensitivity but moderate specificity vs. MONO. The accuracy of the test was high in all measurements.
... Sudomotor dysfunction was assessed by the Neuropad test. 25 Peripheral arterial status was assessed by palpating the dorsalis pedis and posterior tibial pulses on both feet. Quality of life was assessed with a neuropathy and foot ulcer-specific quality of life instrument, the NeuroQoL. ...
... These self-reports are surprising, because current literature on diabetic foot ulcer risk features mainly high pressures sustained during normal gait. However, these self-reports are consistent with conclusions from two studies 25,29 and might justify revisiting the nature of activities believed to be high risk for ulceration in future studies. ...
Background
Prevention of diabetic foot ulcer recurrence in high risk patients, using current standard of care methods, remains a challenge. We hypothesised that an innovative intelligent insole system would be effective in reducing diabetic foot ulcer recurrence in such patients.
Methods
In this prospective, randomised, proof-of-concept study, patients with diabetes, and with peripheral neuropathy and a recent history of plantar foot ulceration were recruited from two multidisciplinary outpatient diabetic foot clinics in the UK, and were randomly assigned to either intervention or control. All patients received an insole system, which measured plantar pressure continuously during daily life. The intervention group received audiovisual alerts via a smartwatch linked to the insole system and offloading instructions when aberrant pressures were detected; the control group did not receive any alerts. The primary outcome was plantar foot ulcer occurrence within 18 months. This trial is registered with ISRCTN, ISRCTN05585501, and is closed to accrual and complete.
Findings
Between March 18, 2014, and Dec 20, 2016, 90 patients were recruited and consented to the study, and 58 completed the study. At follow-up, ten ulcers from 8638 person-days were recorded in the control group and four ulcers from 11 835 person-days in the intervention group: a 71% reduction in ulcer incidence in the intervention group compared with the control group (incidence rate ratio 0·29, 95% CI, 0·09–0·93; p=0·037). The number of patients who ulcerated was similar between groups (six of 26 [control group] vs four of 32 [intervention group]; p=0·29); however, individual plantar sites ulcerated more often in the control group (ten of 416) than in the intervention group (four of 512; p=0·047). In an exploratory analysis of good compliers (n=40), ulcer incidence was reduced by 86% in the intervention group versus control group (incidence rate ratio 0·14, 95% CI 0·03–0·63; p=0·011). In the exploratory analysis, plantar callus severity (change from baseline to 6 months) was greater in re-ulcerating patients (6·5, IQR 4·0–8·3) than non-re-ulcerating patients (2·0, 0·0–4·8; p=0·040).
Interpretation
To our knowledge, this study is the first to show that continuous plantar pressure monitoring and dynamic offloading guidance, provided by an innovative intelligent insole system, can lead to a reduction in diabetic foot ulcer site recurrence.
Funding
Diabetes UK and Orpyx Medical Technologies.
... 30 Zick et al reported a significant correlation between the two methods (Neuropad and Sudoscan), confirming Neuropad's ability to detect diabetic neuropathy. [31][32][33][34] Our study revealed that sudomotor dysfunction was present not only in the prediabetes group (49.47%) but also in the normal glucose tolerance group (49.01%) and the newly diagnosed diabetes group (53.85%) ( Table 1). Although a gradual worsening trend in sudomotor dysfunction was noted from the normal glucose tolerance group to the prediabetes group and further to the newly diagnosed diabetes group, no statistically significant differences were observed among these groups. ...
Purpose
To evaluate the impact of metabolic indicators on plantar sudomotor function and to explore the relationships between metabolic and non-metabolic indicators and sudomotor function in a physical examination cohort using Neuropad.
Methods
In this cross-sectional study, 481 participants were randomly enrolled. Sudomotor function was evaluated using Neuropad and a handheld color analyzer for both qualitative (visual Neuropad) and quantitative (quantitative Neuropad) analyses. The slope (Slope[1–10]) was used as a quantitative measure of sudomotor function.
Additional data included age, BMI (body mass index), FPG (fasting plasma glucose), HbA1c (hemoglobin A1c), blood pressure, lipid levels, and liver and kidney function. Participants were categorized into four blood glucose groups: normoglycemia (FPG <6.1 mmol/L and HbA1c <6%), prediabetes (FPG 6.1–6.9 mmol/L or HbA1c 6.0–6.4%), newly diagnosed diabetes (FPG ≥7.0 mmol/L or HbA1c ≥6.5% with no prior diagnosis, diabetes was diagnosed on the day of the physical examination), and previously diagnosed diabetes.
Results
(1) The previously diagnosed diabetes group presented a lower slope than the normoglycemia group (6.96 vs 8.73) and a greater rate of incomplete color change (71.11% vs 49.01%). With increasing FPG and HbA1c levels, the 10-minute slope decreased progressively (P =0.003, P=0.006). (2) A multivariable linear mixed-effects model adjusted for confounders indicated that previously diagnosed diabetes was an independent predictor of reduced sudomotor function. (3) Adjusting for the same confounders, previously diagnosed diabetes was associated with a 3.480-fold greater risk of incomplete color change than was normoglycemia (OR = 3.480, 95% CI = 1.506–8.042). (4) Age, BMI, ALB, eGFR, and alcohol consumption history were closely associated with sudomotor function.
Conclusion
There is a progressive decline in sudomotor function with increasing blood glucose levels in a physical examination cohort, and previously diagnosed diabetes emerges as an independent risk factor for sudomotor dysfunction.
... Then simple, easy to operate and high diagnostic efficacy neuropathy scoring system is an effective screening tool for diabetic neuropathy in social welfare. The Michigan Neurological Screening Scale is a reliable and concise method with high applicability and high reliability in screening diabetic neuropathy [6][7], and the results can be used as a reference for the diagnosis of diabetic neuropathy in social welfare. In this study, the Michigan Neuropathy Screening Scale was applied in social welfare to achieve early detection, early intervention and early treatment of diabetic neuropathy in patients with type 2 diabetes mellitus, to improve patients' knowledge of diabetic neuropathy and their satisfaction with doctors, and to increase the contracting rate of the key population of family doctors. ...
... 14 The Neuropad is a non-invasive and convenient POCDs that evaluates the sweat gland secretion function. 15 The sudomotor function can be evaluated qualitatively and quantitatively by using Neuropad. Consequently, the objective of this research is to explore the correlation of sudomotor function assessed by Neuropad with comprehensive lower limb arterial ischemia assessed by ABI, TBI and TcPO2 in type 2 diabetes mellitus (T2DM). ...
Background
As an early manifestation of diabetic peripheral neuropathy (DPN), sudomotor dysfunction significantly increases the risk of diabetic foot ulcer. The pathogenesis of sudomotor dysfunction is still unclear. Lower limb ischemia may be related to sudomotor dysfunction, but few studies have explored it. The purpose of this study is to explore the relationship between sudomotor function and comprehensive lower limb arterial ischemia including large arteries, small arteries and microvascular in type 2 diabetes mellitus (T2DM).
Patients and Methods
511 T2DM patients were enrolled in this cross-sectional study. Sudomotor function was assessed qualitatively and quantitatively by Neuropad. Lower limb arterial ischemia was defined as any abnormality of the ankle brachial index (ABI), toe brachial index (TBI) or transcutaneous oxygen tension (TcPO2).
Results
In this study, 75.1% of patients had sudomotor dysfunction. Compared with normal sudomotor function, patients with sudomotor dysfunction had a higher incidence of lower limb arterial ischemia (51.2% vs 36.2%, p = 0.004). Similarly, compared with the non-arterial ischemia group, the proportion of sudomotor disorders was higher in the arterial ischemia group (p = 0.004). Low TBI and low TcPO2 groups also had a higher proportion of sudomotor disorders (all p < 0.05).Compare with normal groups, low ABI, low TBI, and low TcPO2 groups had lower Slop4 which quantitatively reflecting Neuropad discoloration. Arterial ischemia was an independent risk factor for sudomotor dysfunction [OR = 1.754, p = 0.024]. Low TcPO2 also independently increased the risk of sudomotor disorders [OR = 2.231, p = 0.026].
Conclusion
Lower limb arterial ischemia is an independent risk factor of sudomotor dysfunction. Especially below the ankle (BTA) small arteries and microvascular ischemia may also be involved in the occurrence of sudomotor disorders.
... According to these results, in another recent study enrolling a diabetic population, Neuropad showed good sensitivity, accuracy, and specificity in detecting DPN compared to the Michigan Neuropathy Screening Instrument Questionnaire and biothesiometer. In the same study, Neuropad showed high sensitivity but moderate specificity compared with 10 g monofilament [104]. ...
Diabetic neuropathy (DN) is one of the main microvascular complications of both type 1 and type 2 diabetes mellitus. Sometimes, this could already be present at the time of diagnosis for type 2 diabetes mellitus (T2DM), while it appears in subjects with type 1 diabetes mellitus (T1DM) almost 10 years after the onset of the disease. The impairment can involve both somatic fibers of the peripheral nervous system, with sensory-motor manifestations, as well as the autonomic system, with neurovegetative multiorgan manifestations through an impairment of sympathetic/parasympathetic conduction. It seems that, both indirectly and directly, the hyperglycemic state and oxygen delivery reduction through the vasa nervorum can determine inflammatory damage, which in turn is responsible for the alteration of the activity of the nerves. The symptoms and signs are therefore various, although symmetrical painful somatic neuropathy at the level of the lower limbs seems the most frequent manifestation. The pathophysiological aspects underlying the onset and progression of DN are not entirely clear. The purpose of this review is to shed light on the most recent discoveries in the pathophysiological and diagnostic fields concerning this complex and frequent complication of diabetes mellitus.
... The use of a biothesiometer test as a diagnostic tool for neuropathy has been recommended in several studies with sensitivity and specificity of 71.4% and 91.2%, respectively, as well as with high accuracy. [16][17][18] The independent variables were age, sex, Body Mass Index (BMI), abdominal circumference, blood pressure, HbA1c, lipid profile, ankle-brachial index, moisture status of foot, foot temperature, capillaroscopy score, neuropathy score, diabetes duration, and exercise habit. The age of patients with DM was continuous data, while sex (male/ female), diabetes duration (<5/≥5 years), and exercise for diabetes (regularly/irregularly) were dichotomous data. ...
Background:
Neuropathy in diabetic foot is the onset of diabetic foot complications. The COVID-19 pandemic has caused changes in the health service system. The lockdown decision can make it difficult for patients to get medication and consult with health workers due to physical activity restrictions. This research aimed to analyze the factors that contribute to peripheral neuropathy in diabetic foot during the COVID-19 pandemic.
Materials and methods:
The research is a cross-sectional study with a sample of 122 patients with type 2 diabetes mellitus who participated in the Chronic Disease Management Program at community health centers in Malang, Indonesia, and was selected using a purposive sampling method. Data were analyzed using multivariate linear regression.
Results:
Variables that contributed to the development of neuropathy were ankle-brachial index of the right foot (β = 7.35, p = 0.06), irregular exercise (β = 2.01, p = 0.07), glycated hemoglobin A (HbA1c) (β = 0.97, p < 0.001), and Low-Density Lipoprotein (LDL) (β = 0.02, p = 0.06). Meanwhile, the variables that contributed to reducing neuropathy were ankle-brachial index of the left foot (β = -1.62, p = 0.73) and being female (β = -2.62, p = 0.02). The regression model could explain the variation in the scores of neuropathy in diabetic foot during the COVID-19 pandemic (R2 = 20.10%).
Conclusion:
The factors that contributed to the incidence of neuropathy in diabetic foot during the COVID-19 pandemic were ankle-brachial index, exercise for diabetes, LDL, HbA1c, and sex.
... The first one was about the socio-demographic characteristics of the study participants and including age, gender, place of residence, and the participant's medical history with diabetes mellitus. The second section contained the International Restless Leg Syndrome Study Group consensus criteria (a validated 4-items for RLS diagnosis, the desire to move the limbs, worsen by rest, improved with movement, and more during the night [14,15]) and Michigan diabetic neuropathy questionnaire, a reliable 15-items tool for the diagnosis of peripheral neuropathy [16]. The questionnaire inquiries about numbness, burning pain, and prickling sensations in legs and feet, muscle cramps, too sensitivity to touch, and feeling weak or the legs hurt when walking. ...
Diabetic Peripheral Neuropathy (DPN) and restless leg syndrome are common among patients with
diabetes and might complicate each other’s deleterious consequences. The study assessed the rates of
peripheral neuropathy and restless leg syndrome in diabetes mellitus. This study is a case-control
carried out in king Fahad specialist hospital and primary healthcare centers in Tabuk city, Saudi
Arabia during the period from September to December 2020, 132 diabetic patients were selected as
cases, and 132 as controls. A structured, self-administered questionnaire based on the International
Restless Leg Syndrome Study Group consensus criteria and Michigan peripheral neuropathy
assessment questionnaire were used to obtain information from the participants. Moreover, the
Statistical Package for Social Sciences (SPSS) software was used for data analysis.
Out of 264 participants with a mean age (46 ± 14 years), males' dominance was obvious (73.5% and
75.0% in patients and the control group, respectively). Peripheral neuropathy was evident in 18.2%
of patients and 2.3% of the control group, P-value < 0.001). Ninety-one of the participants in both of
the study groups had restless leg syndrome, out of which 53.9% were from the diabetes mellitus
group. No significant association was found between having restless leg syndrome with neither
peripheral neuropathy nor diabetes mellitus, p values: 0.524, and 0.822, respectively. Peripheral
neuropathy and restless leg syndrome were common among patients with diabetes, however, no
significant association was found between restless leg syndrome with neither diabetes nor peripheral
neuropathy; So, raising the awareness of the public and clinicians is highly needed.
... The first one was about the socio-demographic characteristics of the study participants and including age, gender, place of residence, and the participant's medical history with diabetes mellitus. The second section contained the International Restless Leg Syndrome Study Group consensus criteria (a validated 4-items for RLS diagnosis, the desire to move the limbs, worsen by rest, improved with movement, and more during the night [14,15]) and Michigan diabetic neuropathy questionnaire, a reliable 15-items tool for the diagnosis of peripheral neuropathy [16]. The questionnaire inquiries about numbness, burning pain, and prickling sensations in legs and feet, muscle cramps, too sensitivity to touch, and feeling weak or the legs hurt when walking. ...
... This contrasted with Papanas [35], who observed correlation with the vibration perception threshold measured with a neurothesiometer. In another study, Didangelos et al. [36] showed that Neuropad ® has high sensitivity but only moderate specificity vs. the monofilament test in patients with DM. Another recent study reported that if the two tests (monofilament and Neuropad ® ) are used jointly as screening tools for patients with DM, plantar ulcers are less likely to appear and the cost to healthcare systems is reduced [37]. ...
Aim
To assess the concordance between variations in Neuropad® results and the those in different diagnostic criteria of Diabetic Peripheral Neuropathy, according to various clinical guidelines.
Methods
A descriptive observational study was conducted of 111 patients with a confirmed diagnosis of diabetes mellitus. The criteria for inclusion in the study were that patients should be aged 18 years or more and have at least 10 years’ history of diabetes mellitus.
Results
73 (65.8%) were male and 38 (34.2%) were female. Their mean age was 57.92 ± 13.24 years (95% CI 55.45–60.38). Healthy Neuropad® findings were obtained for 35 right feet (31.5%) and 31 left feet (27.9%).
Conclusion
Neuropad® is an effective instrument for detecting macro and microvascular complications such as early-stage neuropathy, although its use should always be accompanied by a clinical examination of the foot.
... However, those high-risk factors may be varied upon different demographic features and T2DM development. Human DPN is characterized by nerve fiber loss, axonal degeneration, and segmental demyelization with a decrease in nerve conduction velocity due to decreased intraepidermal nerve fiber density and reduced myelin thickness of the nerve sheath, so DPN is one of the most insidious, asymptomatic complications of diabetes, but it could results in irreversible foot ulcer, insensate foot injury, lower-extremity amputation and mortality in diabetic patients [6][7][8]. ...
Aims
Diabetic peripheral neuropathy (DPN) often coexists with sudomotor dysfunction, resulting in an increased risk of diabetic foot. This study aimed to explore an efficient method for early diagnosis of DPN by establishing a quantitative Neuropad.
Methods
We recruited 518 patients with type 2 diabetes. Neuropathy Symptoms Score (NSS) combined with Neuropathy Disability Score (NDS) was used to assess distal symmetrical peripheral neuropathy (DSPN). The area under the ROC curve (AUROC), sensitivity, and specificity were used to compare the diagnostic efficacy of quantitative Neuropad (the change rate of the chromatic aberration value per minute) and two types of visual Neuropad (visual Neuropad A: whether the time to complete colour change within 10 min, visual Neuropad B: the time to complete colour change) for DPN.
Results
We did not observe very good diagnostic efficacy of Neuropad (visual Neuropad A and B: 0.59 and 0.64, quantitative Neuropad AUROC: 0.62–0.64) when using standard DSPN diagnostic criteria (NDS 6–12 or NDS 3–5 combined with NSS 5–9). When DPN was assessed by NSS + NDS ≥ 4, visual Neuropad B improved the specificity (AUROC 0.72, 67.00%, specificity 71.70%) by extending the detection time compared with visual Neuropad A (AUROC 0.62, sensitivity 81.80%, specificity 41.70%). Quantitative Neuropad significantly improved the diagnostic effect (AUROC 0.81, sensitivity 80.0%, specificity 76.3%) and reduced the detection time (4 min).
Conclusions
This study provides a new quantitative Neuropad, which has great potential to be an extremely useful diagnostic tool for early screening of sudomotor dysfunction in the clinical practice.
Patients with peripheral neuropathy could have damaged peripheral nerves, which leads to sensory and motor dysfunction. Diabetes, infections, and trauma are the major causes of peripheral neuropathy. Vibratory perception threshold (VPT) tools are commonly used to detect peripheral neuropathy. This study aims to determine the assessment of peripheral neuropathy through the different diagnostic tools in the community in Malaysia. A total number of 1283 participants were recruited from the seven retail pharmacies located in Selangor, Malaysia. The peripheral neuropathy test was conducted based on VPT tools on both feet using the digital biothesiometer. Following that, Neurological Symptom Score (NSS) and Neurological Disability Score (NDS) were taken from the participants to assess the neurological symptoms. Participants had an average age of 40.6 ± 12.9 years and were mostly of Chinese ethnicity (54.1%). The findings show that increasing age was associated with more severe peripheral neuropathy across the various assessment tools, but gender differences were found with the biothesiometer test and ethnicity has severity in the biothesiometer and disability scores. The sensitivity and specificity of the biothesiometer test were 0.63 and 0.84, respectively. The combined tool NSS and NDS had high specificity and a high positive predictive value, suggesting that it could be a reliable indicator of peripheral neuropathy when both scores are elevated. The findings show that the biothesiometer test, NSS, and NDS are considered screening VPT tools for diagnosing peripheral neuropathy. However, further evaluation and diagnostic testing are necessary in cases of a positive test result.
Diabetic distal symmetric polyneuropathy (diabetic DSP) has variable clinical presentation that can complicate the diagnostic process. It is primarily identified by asymptomatic annual screening or from neuropathic symptoms. In this chapter, we present key considerations for findings on screening or clinical evaluation. First, identification of risk factors for diabetic DSP establishes a general pre-assessment probability. Second, identification of the other component causes (foot deformity, vascular impairment) of foot complications along with identifying the impaired protective sensation that is part of diabetic DSP is essential for preventing foot outcomes. Third, the clinician must recognize that there is heterogeneity in manifestations, involving small and large nerve fiber types. As in any process of diagnosis, a clinical evaluation considers each symptom or sign’s contribution to incrementally revising the clinician’s estimates of disease probability and it reduces clinical uncertainty. Simple screening methods are valid, as are clinical scales, adopted into research cohorts and trials, that can be implemented into practice. Once a chronically-progressive distal symmetric pattern of polyneuropathy is confidently identified, alternate causes can generally be accomplished by simple clinical considerations and simple laboratory testing. While uncommon, a typical features such as asymmetry, nonlength dependence, acute or subacute rather than chronic onset and progression, and motor predominance call for specialized testing and clinical expertise from a neurologist. Depending on the number and severity of deformity, vascular insufficiency, and diabetic DSP’s impairment in protective sensation, interventions are initiated including self-foot care education and professionally-fitted therapeutic footwear to referral for wound management and surgical consultation.KeywordsDiabetic distal symmetric polyneuropathyDiagnosis and screeningClinical scalesMichigan neuropathy screening instrumentToronto clinical neuropathy score
Diabetic peripheral neuropathy (DPN) is a common complication of both type 1 and 2 diabetes. It is a leading cause of lower-limb amputation and disabling neuropathic pain. Amputations in patients with diabetes have a devastating effect on quality of life and are associated with an alarmingly low life expectancy (on average only 2 years from the amputation). Amputation also places a substantial financial burden on health-care systems and society in general. With the introduction of national diabetes eye screening programmes, the prevalence of blindness in working-age adults is falling. This is not the case, however, with diabetes related amputations. In this Review, we appraise innovative point-of-care devices that enable the early diagnosis of DPN and assess the evidence for early risk factor-based management strategies to reduce the incidence and slow the progression of DPN. We also propose a framework for screening and early multifactorial interventions as the best prospect for preventing or halting DPN and its devastating sequelae.
Diabetes mellitus is a systemic disease affecting microvascular and macrovascular systems and is considered as the strongest risk factor for peripheral arterial disease. Although the prevalence of the peripheral arterial disease is high among people living with diabetes, its severity is not accurately detected with the prevalent diagnostic methodologies. The ankle-brachial index measurement is a simple, objective, and reliable tool for diagnosis of peripheral arterial disease. However, it is of limited value in the diagnosis of peripheral arterial disease among diabetic patients due to its low sensitivity among diabetic individuals. Diabetes mellitus results in atherosclerosis and calcification of peripheral arterial walls leading to false normal ankle-brachial index values. Therefore, healthcare practitioners should be careful not to misinterpret ankle-brachial index results among diabetic patients. A literature search was conducted using the keywords “ankle-brachial index,” “interpretation,” “limitations,” “diabetic foot,” and “peripheral arterial disease” on different medical search engines. The results were manually scanned and then further reviewed to select the articles related to our topic of discussion. This article will review the use of ankle-brachial index measurement among diabetic patients, its limitations and its prognostic value. In Conclusion, Ankle-brachial index can be used for diagnosis of peripheral arterial disease with some precautions (e.g. raising the threshold of diagnosis or using the lowest systolic pressure value measured at the ankle) and can also be a prognostic indicator for cardiovascular morbidity and mortality.
Purpose of review:
This article reviewed very recent papers (2016) discussing or bringing clinical evidences of the possible common pathways leading to diabetic foot syndrome (DFS) and increased mortality rates.
Recent findings:
Diabetic patients with diabetic foot syndrome have a mortality rate greater than twofold when compared with non-ulcerated diabetics. In addition, the 5-year mortality rate following amputation is estimated at 39-68%, a life expectancy comparable to aggressive types of cancer or advanced congestive heart failure. The majority of patients with diabetic foot ulcer also present insulin resistance, central obesity, dyslipidemia, and hypertension that characterize the metabolic syndrome that, in turn, is associated with an elevated risk of major cardiovascular events. Sensory neuropathy is the primary cause of more the 60% of diabetic foot ulcer. Diabetic peripheral neuropathy is a microvascular complication of diabetes mellitus and in type 2 diabetes, not only hyperglycemia but also other metabolic alterations and persistent inflammatory status due to adiposity play a major role in axon injury. Elevated triglycerides have been showed to be an independent risk factor for lower extremity amputation in diabetic patients. Also, toxic adiposity, oxidative stress, mitochondrial dysfunction, activation of the polyol pathway, accumulation of advanced glycation end products (AGEs), and elevation of inflammatory markers are also implicated in diabetic vascular disease and neuropathy. The hypotheses that the association between DFS and increased rates of mortality reflects the progression of micro- and macrovascular complications are reinforced by the additional association of DFU to renal failure and retinopathy.
Objective
This cross sectional study intended to evaluate two bedside tests (Neuropad and VibraTip) as screening tools for distal symmetrical polyneuropathy (DSPN) in Latin American patients with type 2 diabetes mellitus (T2D).
Subjects and methods
Ninety-three Colombian patients diagnosed with T2D were recruited. Anthropometric variables, glycemic control parameters, lipid profile and renal function were assessed for each patient. DSPN was defined by a Michigan Neuropathy Screening Instrument (MNSI) clinical score greater than 2. Both Neuropad and Vibratip tests were applied to each patient. Contingency analyses were performed to evaluate the diagnostic power of both tools.
Results
The prevalence of DSPN determined clinically by MNSI was 25.8%. DSPN in these patients was associated with age, worsening renal function, and insulin treatment. The sensitivity and specificity of the Neuropad test for DSPN was 66.6% and 63% respectively. Its negative predictive value (NPV) was 84.6%. The VibraTip test exhibited a sensitivity of 54.1% and specificity of 91.3%, with a NPV of 85.1%.
Conclusion
Neuropad and VibraTip are reliable screening tools for DSPN in Latin American population. VibraTip presents a considerable diagnostic power for DSPN in this population. Further studies regarding the cost-effectiveness of these tools in clinical practice are needed.
Background:
Diabetic foot ulcer is one of the chronic complications of diabetes mellitus (DM) with 25% of patients with diabetes developing a foot ulcer during their lifetime leading to amputation. Diabetic foot is classified into 2 main types: neuropathic ulcers (NPU) and neuro-ischemic ulcer (NIU) where in addition to neuropathy peripheral vascular disease (PVD) is also present.
Aims:
We aimed to a) assess the prevalence of Peripheral vascular disease (PVD) in patients of type 2 diabetes mellitus (T2DM) presenting with New Diabetic Foot ulcers (DFU). b) To compare the clinical profile and risk factors responsible for development of NPU and NIU in North Indian population.
Setting and design:
Cross sectional study conducted on first 100 T2DM patients presenting with new DFU in tertiary referral institute for one year period from August 2012 to July 2013.
Methods and material:
Detailed relevant clinical history including age, sex and duration of diabetes, history of smoking and hypertension (HTN) and prevalence of other complications like retinopathy, nephropathy, coronary artery disease (CAD) and stroke was obtained. Patients were examined for neuropathy, loss of pulsations, ankle brachial pressure index (ABI) and investigated for HbA1C, blood urea nitrogen (BUN) and serum creatinine. Statistical analysis used: t test, Fisher exact test and univariate analysis.
Results:
NIU was present in 30 and NPU in 70 out of 100 patients. NIU were commoner among males as compared to females (21/64 males vs 9/36 females). Strong association of smoking (20/30 patients), hypertension (24/30 patients) and longer duration of DM (14 vs 8 years) with NIU was found. Even other complications of DM like CAD (8/30 patients), stroke (4/30 patients), retinopathy (24/30 patients) and nephropathy (15/30 patients) were more prevalent in patients with NIU.
Conclusions:
Prevalence of PVD is 30% in our study which is more than previous studies showing an increasing trend. NPU are two times more common than NIU. Hypertensive male patients with smoking habits and longer duration of T2DM are most prone to develop NIU. NIU share the similar risk factors with CAD and coexist with other complications of DM which should be looked for and treated.
Diabetic polyneuropathy (DPN) encompasses multiple syndromes with a common pathogenesis. Glycemic control shows a limited correlation with DPN, arguing in favor of major involvement of other factors, one of which is alterations of lipid and lipoprotein metabolism. Consistent associations have been found between plasma triglycerides/remnant lipoproteins and the risk of DPN. Studies in cultured nerve tissue or in murine models of diabetes have unveiled mechanisms linking lipid metabolism to DPN. Deficient insulin action increases fatty acids flux to nerve cells, inducing mitochondrial dysfunction, anomalous protein kinase C signaling, and perturbations in the physicochemical properties of the plasma membrane. Oxidized low-density lipoproteins bind to cellular receptors and promote generation of reactive oxygen species, worsening mitochondrial function and altering the electrical properties of neurons. Supplementation with specific fatty acids has led to prevention or reversal of different modalities of DPN in animal models. Post hoc and secondary analyses of clinical trials have found benefits of cholesterol reducing (statins and ezetimibe), triglyceride-reducing (fibrates), or lipid antioxidant (thioctic acid) therapies over the progression and severity of DPN. However, these findings are mostly hypothesis-generating. Randomized trials are warranted in which the impact of intensive plasma lipids normalization on DPN outcomes is specifically evaluated.
Distal symmetric sensorimotor polyneuropathy (DSPN) is the most common neurological manifestation in diabetes. Major risk factors of DSPN include diabetes duration, hyperglycemia, and age, followed by prediabetes, hypertension, dyslipidemia, and obesity. Height, smoking, insulin resistance, hypoinsulinemia, and others represent an additional risk. Importantly, hyperglycemia, hypertension, dyslipidemia, obesity, and smoking are modifiable. Stringent glycemic control has been shown to be effective in type 1, but not to the same extent in type 2 diabetes. Antilipidemic treatment, especially with fenofibrate, and multi-factorial intervention have produced encouraging results, but more experience is necessary. The major comorbidities of DSPN are depression, autonomic neuropathy, peripheral arterial disease, cardiovascular disease, nephropathy, retinopathy, and medial arterial calcification. Knowledge of risk factors and comorbidities has the potential to enrich the therapeutic strategy in clinical practice as part of the overall medical care for patients with neuropathy. This article provides an updated overview of DSPN risk factors and comorbidities. © 2015, Society for Biomedical Diabetes Research. All rights reserved.
Objective
To systematically review studies reporting the prevalence in general adult inpatient populations of foot disease disorders (foot wounds, foot infections, collective ‘foot disease’) and risk factors (peripheral arterial disease (PAD), peripheral neuropathy (PN), foot deformity).
Methods
A systematic review of studies published between 1980 and 2013 was undertaken using electronic databases (MEDLINE, EMBASE and CINAHL). Keywords and synonyms relating to prevalence, inpatients, foot disease disorders and risk factors were used. Studies reporting foot disease or risk factor prevalence data in general inpatient populations were included. Included study's reference lists and citations were searched and experts consulted to identify additional relevant studies. 2 authors, blinded to each other, assessed the methodological quality of included studies. Applicable data were extracted by 1 author and checked by a second author. Prevalence proportions and SEs were calculated for all included studies. Pooled prevalence estimates were calculated using random-effects models where 3 eligible studies were available.
Results
Of the 4972 studies initially identified, 78 studies reporting 84 different cohorts (total 60 231 517 participants) were included. Foot disease prevalence included: foot wounds 0.01–13.5% (70 cohorts), foot infections 0.05–6.4% (7 cohorts), collective foot disease 0.2–11.9% (12 cohorts). Risk factor prevalence included: PAD 0.01–36.0% (10 cohorts), PN 0.003–2.8% (6 cohorts), foot deformity was not reported. Pooled prevalence estimates were only able to be calculated for pressure ulcer-related foot wounds 4.6% (95% CI 3.7% to 5.4%)), diabetes-related foot wounds 2.4% (1.5% to 3.4%), diabetes-related foot infections 3.4% (0.2% to 6.5%), diabetes-related foot disease 4.7% (0.3% to 9.2%). Heterogeneity was high in all pooled estimates (I2=94.2–97.8%, p<0.001).
Conclusions
This review found high heterogeneity, yet suggests foot disease was present in 1 in every 20 inpatients and a major risk factor in 1 in 3 inpatients. These findings are likely an underestimate and more robust studies are required to provide more precise estimates.
Diabetic foot ulcerations have been extensively reported as vascular complications of diabetes mellitus associated with a high degree of morbidity and mortality; in fact, some authors showed a higher prevalence of major, previous and new-onset, cardiovascular, and cerebrovascular events in diabetic patients with foot ulcers than in those without these complications. This is consistent with the fact that in diabetes there is a complex interplay of several variables with inflammatory metabolic disorders and their effect on the cardiovascular system that could explain previous reports of high morbidity and mortality rates in diabetic patients with amputations. Involvement of inflammatory markers such as IL-6 plasma levels and resistin in diabetic subjects confirmed the pathogenetic issue of the “adipovascular” axis that may contribute to cardiovascular risk in patients with type 2 diabetes. In patients with diabetic foot, this “adipovascular axis” expression in lower plasma levels of adiponectin and higher plasma levels of IL-6 could be linked to foot ulcers pathogenesis by microvascular and inflammatory mechanisms. The purpose of this review is to focus on the immune inflammatory features of DFS and its possible role as a marker of cardiovascular risk in diabetes patients.
Neuropad is currently a categorical visual screening test that identifies diabetic patients at risk of foot ulceration. The diagnostic performance of Neuropad was compared between the categorical and continuous (image-analysis (Sudometrics)) outputs to diagnose diabetic peripheral neuropathy (DPN). 110 subjects with type 1 and 2 diabetes underwent assessment with Neuropad, Neuropathy Disability Score (NDS), peroneal motor nerve conduction velocity (PMNCV), sural nerve action potential (SNAP), Deep Breathing-Heart Rate Variability (DB-HRV), intraepidermal nerve fibre density (IENFD), and corneal confocal microscopy (CCM). 46/110 patients had DPN according to the Toronto consensus. The continuous output displayed high sensitivity and specificity for DB-HRV (91%, 83%), CNFD (88%, 78%), and SNAP (88%, 83%), whereas the categorical output showed high sensitivity but low specificity. The optimal cut-off points were 90% for the detection of autonomic dysfunction (DB-HRV) and 80% for small fibre neuropathy (CNFD). The diagnostic efficacy of the continuous Neuropad output for abnormal DB-HRV (AUC: 91%, ) and CNFD (AUC: 82%, ) was better than for PMNCV (AUC: 60%). The categorical output showed no significant difference in diagnostic efficacy for these same measures.
An image analysis algorithm generating a continuous output (Sudometrics) improved the diagnostic ability of Neuropad, particularly in detecting autonomic and small fibre neuropathy.
Aims Identifying individuals with diabetes at high risk of cardiovascular disease (CVD) remains challenging. We aimed to establish whether peripheral neuropathy (PN) is associated with incident CVD events and to what extent information on PN may improve risk prediction among individuals with type 2 diabetes.
Methods We obtained data for individuals with type 2 diabetes, and free of CVD, from a large primary care patient cohort. Incident CVD events were recorded during a 30-month follow-up period. Eligible individuals had complete ascertainment of cardiovascular risk factors and PN status at baseline. The association between PN and incident CVD events (non-fatal myocardial infarction, coronary revascularisation, congestive cardiac failure, transient ischaemic attack and stroke) was evaluated using Cox regression, adjusted for standard CVD risk factors. We assessed the predictive accuracy of models including conventional CVD risk factors with and without information on PN.
Results Among 13 043 eligible individuals, we recorded 407 deaths from any cause and 399 non-fatal CVD events. After adjustment for age, sex, ethnicity, systolic blood pressure, cholesterol, body mass index, HbA1c, smoking status and use of statin or antihypertensive medication, PN was associated with incident CVD events (HR 1.33; 95% CI 1.02 to 1.75, p=0.04). The addition of information on PN to a model based on standard CVD risk factors resulted in modest improvements in discrimination for CVD risk prediction and reclassified 6.9% of individuals into different risk categories.
Conclusions PN is associated with increased risk for a first cardiovascular event among individuals with diabetes.
Neuropad is a simple visual indicator test, with moderate diagnostic performance for diabetic peripheral neuropathy. As it assesses sweating, which is a measure of cholinergic small nerve fibre function, we compared its diagnostic performance against established measures of both large and, more specifically, small fibre damage in patients with diabetes.
One hundred and twenty-seven participants (89 without diabetic peripheral neuropathy and 38 with) aged 57 ± 9.7 years underwent assessment with Neuropad, large nerve fibre assessments: (Neuropathy Disability Score, vibration perception threshold, peroneal motor nerve conduction velocity); small nerve fibre assessments: neuropathy symptoms using the Diabetic Neuropathy Symptoms score (corneal nerve fibre length and warm perception threshold).
Neuropad has a high sensitivity but moderate specificity against large fibre neuropathy assessments: Neuropathy Disability Score (> 2) 70% and 50%, vibration perception threshold (> 14 V) 83% and 53%, and peroneal motor nerve conduction velocity (< 42 m/s) 81% and 54%, respectively. However, the diagnostic accuracy of Neuropad was significantly improved against corneal nerve fibre length (< 14 mm/mm2) with a sensitivity and specificity of 83% and 80%, respectively. Furthermore, the area under the curve for corneal nerve fibre length (85%) was significantly greater than with the Neuropathy Disability Score (66%, P = 0.01) and peroneal motor nerve conduction velocity (70%, P = 0.03). For neuropathic symptoms, sensitivity was 78% and specificity was 60%.
The data show the improved diagnostic performance of Neuropad against corneal nerve fibre length. This study underlines the importance of Neuropad as a practical diagnostic test for small fibre neuropathy in patients with diabetes.
The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. T2DM is associated with both microvascular (neuropathy, nephropathy and retinopathy) and macrovascular complications [coronary artery disease (CAD), stroke, carotid artery disease and peripheral artery disease (PAD)]. Apart from acting on diabetic dyslipidemia, statins were shown to exert beneficial effects on several diabetic complications as well as other cardiovascular (CVD) risk predictors such as endothelial dysfunction, inflammation, oxidative stress, chronic kidney disease (CKD), non-alcoholic fatty liver disease (NAFLD), metabolic syndrome (MetS), obstructive sleep apnea syndrome (OSAS) and hyperuricemia. Several clinical trials involving T2DM patients have reported significant reductions in coronary and cerebrovascular events following statin treatment. However, a modest statin-related risk of new-onset diabetes (NOD) has been reported but that did outweigh the benefit of CVD risk reduction in high-risk individuals. Overall, statin use is beneficial and should be recommended in diabetic patients to target their increased CVD risk.
Ezetimibe, an inhibitor of intestinal cholesterol absorption, can decrease total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglycerides (TGs) and apolipoprotein (apo) B levels and increase high-density lipoprotein cholesterol (HDL-C) levels. Apart from lipid-lowering, ezetimibe may exert certain off-target actions (e.g. anti-inflammatory, anti-atherogenic and antioxidant) thus contributing to a further decrease of cardiovascular disease (CVD) risk. Ezetimibe trials resulted in controversial outcomes with some studies reporting atherosclerosis regression and reductions in CVD events following ezetimibe therapy in combination with a statin while others reported negative results. The results of the ongoing IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) which compares ezetimibe plus simvastatin with simvastatin monotherapy with regard to CVD outcomes after acute coronary syndromes should further elucidate the effect of ezetimibe on CVD events. This review presents the results of up-to-date clinical trials with ezetimibe and summarizes its potential pleiotropic effects. Furthermore, we comment on the administration of ezetimibe in treating high-risk patients [i.e. with diabetes mellitus (DM), metabolic syndrome (MetS), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease (CKD), peripheral artery disease (PAD) or carotid disease]. The use of ezetimibe either as monotherapy or as add-on therapy in daily clinical practice is also discussed.
Dyslipidemia, and especially atherogenic dyslipidemia, a combination of small low-density lipoproteins cholesterol (LDL-C), decreased high-density lipoprotein cholesterol (HDL-C) and increased triglyceride (TG) concentrations, represents a major cardiovascular (CV) risk factor. Nuclear receptor peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of lipid metabolism; PPAR ligands are used to treat dyslipidemias. Fibrates have a major impact on TG metabolism as well as on modulating LDL size and subclasses. Fibrates target atherogenic dyslipidemia by increasing plasma HDL-C concentrations and decreasing small dense LDL (sdLDL) particles and TGs, thus contributing to dyslipidemia management, particularly in patients with diabetes (DM) or the metabolic syndrome (MetS). Furthermore, fibrates exert beneficial effects on adipokines, inflammation and oxidative stress as well as neuroprotective properties. However, further studies are needed to define the role of fibrates in the prevention of CV events. We review the effects of fibrates on atherogenic dyslipidemia and CV risk reduction.
To estimate the accuracy of Neuropad for the diagnosis and staging of distal symmetric polyneuropathy (DPN) across different stages of neuropathy, using multiple-level likelihood ratios (LRs) to interpret the time necessary to complete the color change of the test.
We conducted a cross-sectional, cohort-type diagnostic accuracy study in 251 consecutive adult type 2 diabetic patients with no peripheral arterial disease or other potential causes of neuropathy, who were recruited between January 2005 and December 2008 from the diabetes outpatient clinics in Alexandroupolis Hospital, Greece. Patients were tested for DPN by means of the neuropathy disability score (NDS) and Neuropad. Multiple-level LRs for time to complete color change were calculated across different stages of neuropathy.
The areas under the curve for the diagnosis of any (NDS of ≥3), at least moderate (NDS of ≥6), or severe (NDS of ≥9) DPN were 0.91, 0.96, and 0.97, respectively. The calculation of multiple-level LRs showed that time to complete color change <360 s suggested the absence of neuropathy. Values between 360 and 1,000 s were indicative of mild neuropathy. Finally, values between 1,000 and 1,200 or >1,200 s were strongly suggestive of moderate or severe DPN, respectively.
Neuropad could be used as a triage test for the diagnosis and staging of DPN in patients with type 2 diabetes, prompting referral to specialized care setting.
Ezetimibe, an inhibitor of cholesterol intestinal absorption, is a lipid lowering agent with potential pleiotropic actions. Ezetimibe in combination with a statin is effective in decreasing low density lipoprotein cholesterol(LDL-C), lowering triglyceride and raising high density lipoprotein cholesterol levels. Ezetimibe plus statin achieve LDL-C targets in a greater proportion of patients than statin monotherapy. Ezetimibe also seems to improve renal function, insulin resistance and inflammatory markers. These actions are useful in patients with diabetes. Ezetimibe is a well-tolerated and effective (in terms of achieving LDL-C targets) option inpatients with hyperlipidemia with or without diabetes. This editorial will discuss several properties of ezetimibe, with special reference to diabetes.
To examine the association between the moisture status of the skin of the feet with foot ulceration in subjects with diabetes.
A total of 379 subjects with diabetes were examined. Assessment of peripheral neuropathy was based on neuropathy symptom score, neuropathy disability score, vibration perception threshold, and the 10-g monofilament perception. The moisture status of the skin of the feet was assessed using the visual test Neuropad.
Patients with foot ulceration had more severe peripheral neuropathy and more often an abnormal Neuropad response. Multivariate logistic regression analysis demonstrated that the odds of foot ulceration increased with measures of neuropathy but increased also with an abnormal Neuropad response.
An abnormal Neuropad response correlates with foot ulceration in subjects with diabetes. This finding, if confirmed prospectively, suggests that the Neuropad test may be included in the screening tests for the prediction of foot ulceration.
A series of 519 non-diabetic subjects had vibration thresholds at three points measured using a biothesiometer. Thresholds appeared to be log normally distributed and increased with age. Centile charts of this relation were derived from the data giving a range for normal thresholds. The biothesiometer provides a quick and reliable assessment of vibration thresholds, which when related to the centile charts gives an objective measure of the progress of diabetic peripheral neuropathy.
Peripheral neuropathy remains a major cause of morbidity and is a cardinal factor in the pathogenesis of diabetic foot ulceration. The aim of the present study was to compare the new indicator test for sudomotor function (Neuropad®) with the vibration perception threshold (VPT) and the clinical examination in the diagnosis of peripheral neuropathy in subjects with type 2 diabetes. This study included 154 type 2 diabetic patients (76 men) with a mean age of 64.3±7.3 years and a mean diabetes duration of 12.8±4.3 years. Neuropathy was diagnosed clinically using the Neuropathy Disability Score (NDS). The VPT was measured with a neurothesiometer, values25Volts being classified as abnormal. Sudomotor function was evaluated by the indicator test. Sensitivity of the indicator test for neuropathy was 97.8% and specificity was 67.2%. Sensitivity and specificity of VPT for neuropathy were 78.9% and 85.9% respectively. A significant correlation was shown between time to colour change of the indicator test and VPT (rs=0.889, p<0.001).
Conclusions: Both the indicator test and the VPT have a high sensitivity for neuropathy. Sensitivity is higher with the indicator test, but specificity is higher with VPT. Time until complete colour change of the indicator test shows a positive correlation with VPT. Thus, the indicator test appears to be a useful additional diagnostic tool of neuropathy, particularly suitable for screening and self-examination, in type 2 diabetes. The correlation between time to colour change of the indicator test and VPT is interesting and merits investigation in a prospective study.
The commercially available Neuropad test was developed as a simple visual indicator test to evaluate diabetic neuropathy. It uses a colour change to define the integrity of skin sympathetic cholinergic innervation. We compared the results of Neuropad assessment in the foot with established measures of somatic and autonomic neuropathy.
Fifty-seven diabetic patients underwent Neuropad assessment, quantitative sensory and autonomic function testing, and evaluation of intra-epidermal nerve fibre density in foot skin biopsies.
Neuropad responses correlated with the neuropathy disability score (r(s)=0.450, p<0.001), neuropathic symptom score (r(s)=0.288, p=0.03), cold detection threshold (r(s)=0.394, p = 0.003), heat-as-pain perception threshold visual analogue score 0.5 (r(s)=0.279, p=0.043) and deep-breathing heart rate variability (r(s)= -0.525, p<0.001). Intra-epidermal nerve fibre density (fibres/mm) compared with age- and sex-matched control subjects (11.06+/-0.82) was non-significantly reduced (7.37+/-0.93) in diabetic patients with a normal Neuropad response and significantly reduced in patients with a patchy (5.01+/-0.93) or absent (5.02+/-0.77) response (p=0.02). The sensitivity of an abnormal Neuropad response in detecting clinical neuropathy (neuropathy disability score >or=5) was 85% (negative predictive value 71%) and the specificity was 45% (positive predictive value 69%).
The Neuropad test may be a simple indicator for screening patients with diabetic neuropathy.
Introduction: Type 2 diabetes mellitus (T2DM) is associated with several cardiovascular (CV) risk factors such as insulin resistance, obesity, hypertension, dyslipidaemia, non-alcoholic fatty liver disease as well as platelet and haemostatic abnormalities increasing the risk of thrombosis. Therefore, T2DM patients are at an increased risk for CV disease (CVD).
Areas covered: This narrative review discusses the treatment of T2DM. This includes lifestyle measures (diet, exercise and smoking cessation) as well as hypolipidaemic, antihypertensive, weight reducing, antiplatelet and glucose lowering drugs. The focus is on the effects of these therapeutic strategies on CVD risk. Randomized controlled clinical trials (RCTs) reporting CVD outcomes with such drugs in T2DM patients are also reviewed.
Expert Opinion: Apart from current guidelines, the findings of RCTs on CVD outcomes in T2DM patients should be taken into consideration in daily clinical practice. Multiple risk factors should be targeted simultaneously in such high-risk patients in order to efficiently reduce the risk of CV events.
This study determined the prevalence of diabetic peripheral neuropathy (DPN) and subclinical DPN (sDPN) in patients with type 2 diabetes mellitus (T2DM) using nerve conduction study (NCS) as a diagnostic tool. We also investigated the factors associated with the development of sDPN and compared factors between the sDPN and confirmed DPN (cDPN). This cross-sectional study involved 240 T2DM patients who were successively admitted to the endocrinology wards of Wuhan Union Hospital over the period of January to December 2014. Data on the medical history, physical and laboratory examinations were collected. DPN was diagnosed using NCS. One-way ANOVA with least significant difference (LSD) analysis or chi-square tests was used to compare parameters among DNP-free, sDPN and cDPN patients. Independent factors associated with sDPN were determined using logistic regression. The results showed that 50.8% of the participants had DPN, and among them, 17.1% had sDPN. sDPN showed significant independent associations with age, height, HbA1c, presence of atherosclerosis and diabetic retinopathy. Patients with DPN differed significantly from those without DPN with respect to age, duration of disease (DOD), HbA1c, presence of atherosclerosis, diabetic retinopathy, nephropathy and hypertension. Patients with cDPN, relative to those with sDPN, had significantly longer DOD and higher prevalence of peripheral artery disease (PAD) and coronary artery disease (CAD). Our study suggests that a significant number of T2DM patients are affected by sDPN, and the development of this condition is associated with advanced age, tall stature, poor glycaemic control, presence of diabetic retinopathy and atherosclerosis. On the other hand, patients with cDPN tend to have a longer DOD and are more likely to suffer from PAD and CAD. © 2017, Huazhong University of Science and Technology and Springer-Verlag GmbH Germany.
Introduction:
The number of people with diabetes mellitus (DM) is estimated to exceed 640 million by the year 2040. Diabetic foot ulcer (DFU) is a debilitating illness that affects more than 2% of DM patients. DFU is caused by DM-induced neural and vascular lesions leading to a reduced sensation and microcirculation. The increase in the prevalence of DFU has prompted researchers to find new therapies for the management of DFU. Areas covered: This review presents the current status of novel biological therapies used in the treatment of DFU. Literature information and data analysis were collected from PubMed, the website of the American Diabetes Association, and ClinicalTrials.gov. The keywords used in the search were: DM, DFU, complications of DM. Expert opinion: Many biological agents have been investigated in a bid to find an effective therapy for DFU. These include growth factors (platelet-derived growth factor, vascular endothelial growth factor etc), stem cells (epithelial progenitor-, adipose-derived stem cells etc), anti-diabetic drugs (insulin, exendin-4), herbs, urokinase, dalteparin, statins and bio-agents such as acid peptide matrix. Biological agents that can reduce hyperglycaemia, increase sensation, microcirculation and oxygenation and repair lost tissue are the most ideal for the treatment of DFU.
Purpose of review:
Type 2 diabetes mellitus (T2DM) is associated with increased coronary heart disease (CHD) morbidity and mortality. These patients are also more prone to heart failure, arrhythmias and sudden cardiac death. Furthermore, coronary interventions performed in such high-risk patients have worse outcomes. In this narrative review, we discuss the role of diabetic dyslipidaemia on the risk of CHD in patients with T2DM. The effects of hypolipidaemic, antihypertensive and antidiabetic drugs on lipid and glucose metabolism in T2DM are also considered.
Recent findings:
Among CHD risk factors, diabetic dyslipidaemia characterized by moderately elevated low-density lipoprotein (LDL) cholesterol, increased triglycerides and small, dense LDL particles as well as decreased high-density lipoprotein cholesterol levels may contribute to the increased CHD risk associated with T2DM. Hypolipidaemic, antihypertensive and antidiabetic drugs can affect lipid and glucose parameters thus potentially influencing CHD risk. Such drugs may improve not only the quantity, but also the quality of LDL as well as postprandial lipaemia.
Summary:
Current data highlight the importance of treating diabetic dyslipidaemia in order to minimize CHD risk. Both fasting and postprandial lipids are influenced by drugs in patients with T2DM; physicians should take this into consideration in clinical decision making.
The indicator plaster neuropad®, using a shift in colour of a coblat-II-compound from blue to pink in the presence of water, for the first time presents the opportunity to investigate the altered perspiration of the diabetic foot as result of autonomic neuropahty by a simple and safe method. In a first clinical study we investigated the perspiration of the sole's skin of 20 diabetics with and without peripheral sensoric neuropathy at the metatarsal bones MTH I and II, the main sites of neuropathic ulcers, by using the indicator plaster. The study shows that in the group of healthy controls the standardised shift of colour was completed after ten minutes and that the altered perspiration could be identified even in those cases of diabetics without sensoric neuropathy. Thus the indicator plaster Neuropad® offers a chance of early detection of peripheral diabetic neuropathy as the major reason for the development of the diabetic foot and to prevent ist consequences.
Background:
Cardiovascular autonomic neuropathy (CAN) is a prevalent and neglected chronic complication of diabetes, with a large impact on morbidity and mortality. Part of the reason why it is not detected and treated opportunely is because of the complexity of the tests required for its diagnosis. We evaluated the Neuropad®, a test based on sudomotor function, as a screening tool for CAN in adult patients with type 2 diabetes in Bogotá, Colombia.
Methods:
This was a cross-sectional evaluation of Neuropad® for the detection of CAN. Patients were 20-75years of age and did not suffer from any other type of neuropathy. CAN was diagnosed using the Ewing battery of tests for R-R variability during deep breathing, Valsalva and lying-to-standing maneuvers. Additionally, distal symmetric polyneuropathy (DSP) was diagnosed using a sign-based scale (Michigan Neuropathy Disability Score - NDS) and a symptom-based score (Total Symptom Score - TSS). The primary outcome was the sensitivity and specificity of the Neuropad® for the diagnosis of CAN, and secondary outcomes were the sensitivity and specificity of Neuropad® for DSP.
Results:
We studied 154 patients (74 men and 80 women). Prevalence of CAN was extremely high (68.0% of study participants), but also DSP was prevalent, particularly according to the signs-based definition (45%). The sensitivity of the Neuropad® for any degree of CAN was 70.1%, being slightly higher for the deep breathing and Valsalva tests than for lying-to-standing. The specificity of the Neuropad® for any type of CAN was only 37.0%, as expected for a screening exam. The negative predictive value was higher for the deep breathing and Valsalva tests (69.4 and 81.6%, respectively). Neuropad showed also a good sensitivity and negative predictive value for DSP. The sensitivity and specificity of Neuropad were better among men, and among patients with diabetes duration above the group median.
Conclusions:
The Neuropad is a simple and inexpensive device that demonstrated an adequate performance as a screening tool for cardiovascular autonomic neuropathy in Latin American patients with DM2.
Approximately half of all patients with a diabetic foot ulcer have co-existing peripheral arterial disease. Identifying peripheral arterial disease among patients with foot ulceration is important, given its association with failure to heal, amputation, cardiovascular events and increased risk of premature mortality. Infection, oedema and neuropathy, often present with ulceration, may adversely affect the performance of diagnostic tests that are reliable in patients without diabetes. Early recognition and expert assessment of peripheral arterial disease allows measures to be taken to reduce the risk of amputation and cardiovascular events, while determining the need for revascularization to promote ulcer healing. When peripheral arterial disease is diagnosed, the extent of perfusion deficit should be measured. Patients with a severe perfusion deficit, likely to affect ulcer healing, will require further imaging to define the anatomy of disease and indicate whether a revascularization procedure is appropriate. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Background:
Despite the significant public health burden of lower-extremity amputations in diabetes mellitus, few data are available on the epidemiology of lower-extremity amputations in diabetes mellitus in the community setting.
Methods:
A retrospective incidence cohort study based in Rochester, Minn, was conducted.
Results:
Among the 2015 diabetic individuals free of lower-extremity amputation at the diagnosis of diabetes mellitus, 57 individuals underwent 79 lower-extremity amputations (incidence, 375 per 100 000 person-years; 95% confidence interval, 297 to 467). Among the 1826 patients with non—insulin-dependent diabetes mellitus, 52 underwent 73 lower-extremity amputations, and the subsequent incidence of lower-extremity amputation among these residents was 388 per 100 000 person-years (95% confidence interval, 304 to 487). Of the 137 insulin-dependent diabetic patients, four subsequently underwent five lower-extremity amputations (incidence, 283 per 100 000 person-years; 95% confidence interval, 92 to 659). Twenty-five years after the diagnosis of diabetes mellitus, the cumulative risk of one lower-extremity amputation was 11.2% in insulin-dependent diabetes mellitus and 11.0% in non— insulin-dependent diabetes mellitus. When compared with lower-extremity amputation rates for Rochester residents without diabetes, patients with non—insulin-dependent diabetes mellitus were nearly 400 times more likely to undergo an initial transphalangeal amputation (rate ratio, 378.8) and had almost a 12-fold increased risk of a below-knee amputation (rate ratio, 11.8). In this community, more than 60% of lower-extremity amputations were attributable to non—insulin-dependent diabetes mellitus.
Conclusions:
These population-based data document the magnitude of the elevated risk of lower-extremity amputation among diabetic individuals. Efforts should be made to identify more precisely risk factors for amputation in diabetes and to intervene in the processes leading to amputation.(Arch Intern Med. 1994;154:885-892)
Diabetes is a complex disease with many serious potential sequelae, including large vessel arterial disease and microvascular dysfunction. Peripheral arterial disease is a common large vessel complication of diabetes, implicated in the development of tissue loss in up to half of patients with diabetic foot ulceration. In addition to peripheral arterial disease, functional changes in the microcirculation also contribute to the development of a diabetic foot ulcer, along with other factors such as infection, oedema and abnormal biomechanical loading. Peripheral arterial disease typically affects the distal vessels, resulting in multi‐level occlusions and diffuse disease, which often necessitates challenging distal revascularisation surgery or angioplasty in order to improve blood flow. However, technically successful revascularisation does not always result in wound healing. The confounding effects of microvascular dysfunction must be recognised ‐ treatment of a patient with a diabetic foot ulcer and peripheral arterial disease should address this complex interplay of pathophysiological changes. In the case of non‐revascularisable peripheral arterial disease or poor response to conventional treatment, alternative approaches such as cell‐based treatment, hyperbaric oxygen therapy and the use of vasodilators may appear attractive, however more robust evidence is required to justify these novel approaches.
We examined the diagnostic utility of the indicator test Neuropad in the assessment of overall and small fibre dysfunction in 1 010 patients with type 2 diabetes mellitus (T2DM) (608 men, mean age 63.9±10.3 years) from 5 diabetes clinics. Sudomotor function was diagnosed by the Neuropad® test. Overall and small nerve fibre dysfunction was diagnosed through clinical examination and symptoms. Patients were divided into Groups A (441 patients with sudomotor dysfunction) and B (569 patients without sudomotor dysfunction). The former were older (p<0.05) and had longer T2DM duration (p<0.05) than the latter. For overall nerve fibre dysfunction, abnormal Neuropad defined as patchy/blue had 94.9% sensitivity, 70.2% specificity and 98.1% negative predictive value (NPV), while for small fibre dysfunction the corresponding values were 85.6%, 71.2% and 93.3%. For overall nerve fibre dysfunction, abnormal Neuropad defined as blue had 64% sensitivity, 96% specificity and 91% NPV, while for small fibre dysfunction the corresponding values were 52%, 96% and 85%. The odds ratios (ORs) of Neuropad patchy/blue for overall and for small fibre dysfunction were 43.7 and 14.7, respectively. The ORs of Neuropad blue for overall and for small fibre dysfunction were 45.7 and 24.9, respectively. In conclusion, Neuropad patchy/blue response exhibited better diagnostic performance both for overall and small nerve fibre dysfunction. Its very high NPV renders it an excellent screening tool primarily to exclude neuropathy in T2DM.
Objective:
Examination of sudomotor function is now recommended to assess peripheral autonomic dysfunction. The aim of this study was to evaluate the clinical usefulness of Neuropad, a simple visual indicator test, for assessment of diabetic polyneuropathy (DPN).
Methods:
This study examined 87 diabetic patients with a mean age of 61.1±8.8 years, a mean diabetes duration of 13.0±7.5 years and a mean HbA1c of 8.8±1.7%. Diagnosis of DPN was based on clinical examinations using modified Toronto Clinical Neuropathy Score (mTCNS). The patients also underwent 4-g monofilament test and heart rate variability by coefficient of variation of R-R intervals (CV(R-R)) was determined with the patients at rest. The Neuropad test was applied on the plantar aspect of the great toe and removed after 10 minutes to evaluate the color change as normal (blue to completely pink), patchy (patches of blue and pink) and abnormal (remained blue).
Results:
Twenty-eight patients showed a normal, 45 patchy and 14 abnormal response to the Neuropad test. Patients with an abnormal response had significantly longer diabetes duration than those with a normal or a patchy response, but HbA1c levels were similar among the three groups. The C(R-R) at rest was significantly lower in patients with an abnormal response than those of normal and patchy response, respectively. Abnormal responders showed significantly higher mTCNS and lower monofilament results as well as higher prevalence of orthostatic hypotension, retinopathy or nephropathy than normal responders.
Conclusion:
The Neuropad test is a useful screening test for detecting DPN.
The hazards of cobalt(II) chloride hexahydrate are discussed. Keywords (Audience): High School / Introductory Chemistry
Diabetic foot ulcers arise from neuropathy and/or ischaemia. The diabetic foot is associated with cardiovascular disease (CVD) and excess mortality. Lipid-lowering therapy reduces CVD morbidity and mortality in diabetic patients with foot ulcers. In particular, statins decrease CVD mortality and improve survival in diabetic foot patients, while fibrates benefit patients with a specific lipid profile. Statins reduce progression of the local disease, improving symptoms and reducing amputations, mainly due to their impact on peripheral arterial disease. Fibrates appear to reduce amputations by improving neuropathy. They also improve ulcer healing and reduce recurrence. This review assesses the role of hypolipidaemic treatment in diabetic foot patients.
Neuropad is a novel indicator test for sudomotor dysfunction, which has not been validated as a screening tool in a population-based study. This study aimed to evaluate the utility of Neuropad as a screening tool for distal symmetric polyneuropathy among elderly subjects with diabetes and pre-diabetes in the general population.
Eligible subjects aged 61–82 years (n = 940) from the KORA F4 survey were examined, 201 of whom had diabetes and 231 had pre-diabetes (WHO 1999 criteria). Polyneuropathy was defined by the Michigan Neuropathy Screening Instrument (MNSI) score >3.
Polyneuropathy was diagnosed in 60 (29.9%) subjects with diabetes and in 45 (19.5%) subjects with pre-diabetes, respectively (p = 0.013). The sensitivity and negative predictive value of Neuropad (reading time: 10 min) for the diagnosis of polyneuropathy were moderately high, reaching 76.7% and 78.1% in subjects with diabetes and 57.8% and 76.5% in those with pre-diabetes, respectively. Conversely, the specificity and positive predictive value for the diagnosis of polyneuropathy were rather low: 35.5% and 33.6% in diabetic individuals and 33.3% and 17.3% in subjects with pre-diabetes, respectively. Use of the >2 cut-off and MNSI combined with monofilament examination did not improve the diagnostic performance of Neuropad.
In the elderly general population with diabetes and pre-diabetes, Neuropad has reasonable sensitivity but rather low specificity for the diagnosis of polyneuropathy. It is a useful simple and inexpensive tool to screen for and to exclude polyneuropathy as desired, while its low specificity implies that a longer reading time merits consideration. Copyright
A simple non-invasive indicator test (Neuropad®) has been developed for the assessment of sweating and, hence, cholinergic innervation in the diabetic foot. The present review summarizes current knowledge on this diagnostic test. The diagnostic ability of this test is based on a colour change from blue to pink at 10 min, with excellent reproducibility, which lends itself to patient self-examination. It has a high sensitivity (65.1–100%) and negative predictive value (63–100%), with moderate specificity (32–78.5%) and positive predictive value (23.3–93.2%) for the diagnosis of diabetic peripheral neuropathy. It also has moderate to high sensitivity (59.1–89%) and negative predictive value (64.7–91%), but low to moderate specificity (27–78%) and positive predictive value (24–48.6%) for the diagnosis of diabetic cardiac autonomic neuropathy. There are some data to suggest that Neuropad can detect early diabetic neuropathy, but this needs further evaluation. It remains to be established whether this test can predict foot ulceration and amputation, thereby contributing to the identification of high-risk patients.
Diabet. Med. 30, 525–534 (2013)
It is well established that diabetes mellitus increases the risk of cardiovascular disease (CVD) and all-cause mortality. Observational studies suggest that a history of diabetic foot ulceration (DFU) may increase this risk further still. We sought to determine to what extent DFU is associated with excess risk over and above diabetes.
We identified studies reporting on associations of DFU with CVD and all-cause mortality. We obtained data on incident events of all-cause mortality, fatal myocardial infarction and fatal stroke. Study-specific estimates were pooled using a random-effects meta-analysis and the statistical heterogeneity of included studies was assessed using the I (2) statistic.
The eight studies included reported on 3,619 events of all-cause mortality during 81,116 person-years of follow-up. DFU was associated with an increased risk of all-cause mortality (RR 1.89, 95% CI 1.60, 2.23), fatal myocardial infarction (2.22, 95% CI 1.09, 4.53) and fatal stroke (1.41, 95% CI 0.61, 3.24). CVD mortality accounted for a similar proportion of deaths in DFU and non-DFU patients.
Patients with DFU have an excess risk of all-cause mortality, compared with patients with diabetes without a history of DFU. This risk is attributable, in part, to a greater burden of CVD. If this result is validated in other studies, strategies should evaluate the role of further aggressive CVD risk modification and ulcer prevention in those with DFU.
Aim: The aim of this prospective study was to evaluate the contribution of the indicator test for sudomotor function Neuropad® to the early diagnosis of peripheral neuropathy in patients with type 2 diabetes mellitus. Included were 109 type 2 diabetic patients (55 men, mean age 56.15±6.14 years), whose initial clinical examination (Neuropathy Disability Score, NDS) was negative for neuropathy. Patients were first examined between January and June 2004 and re-examined 5 years later by the NDS and Neuropad®. Initially, 70 patients (64.22%) had normal and 39 (35.78%) patients had abnormal Neuropad® (groups A and B, respectively). NDS was significantly higher in group B on both examinations (p<0.001). On the second examination, 2 patients (2.86%) in group A and 10 patients (25.64%) in group B had developed neuropathy (p=0.001). Neuropad® had 83.33% sensitivity and 68.04% specificity for neuropathy. There was a modest but significant agreement (kappa=0.259, p<0.001) between Neuropad® and NDS for neuropathy.
Conclusions: Among type 2 diabetic patients with normal NDS, development of neuropathy is significantly more frequent in those with abnormal Neuropad®. These results suggest a potential utility of Neuropad® for the earlier diagnosis of neuropathy in type 2 diabetes.
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.
The aim of the present study was to determine the diagnostic accuracy of the Neuropad sudomotor test for diabetic cardiovascular autonomic neuropathy (CAN) and diabetic polyneuropathy (DPN), the latter assessed using a multi-level diagnostic approach.
In 51 diabetic patients, CAN, symptoms and signs of DPN, vibration perception threshold (VPT), cold (CTT) and warm thermal perception thresholds (WTT) were measured. Neuropad response was determined as normal (complete colour change) or abnormal (absent or incomplete colour change). The time until the complete colour change (CCC time) was recorded.
CCC time showed significant correlations with all the neurological parameters, the strongest of which were with Valsalva ratio (rho = -0.64, P < 0.0001), symptoms of DPN (rho = 0.66, P < 0.0001), postural hypotension (rho = 0.54, P = 0.0001) and CTT (rho = -0.54, P = 0.0001). CCC time showed moderate diagnostic accuracy for both CAN and DPN: the areas under the receiver operating characteristic (ROC) curves were 0.71 and 0.76, respectively. The diagnostic characteristics of three cut-off values of CCC time, identified by ROC analysis (i.e. 10, 15 and 18 min), were analysed. Compared with 10 min, the 15-min cut-off value provided better specificity (from 27% to 52% and from 31% to 62% for CAN and DPN, respectively) and a better likelihood ratio for negative result (from 0.67 to 0.34 and from 0.58 to 0.33) without lowering sensitivity (from 82% to 82% and from 85% to 80%).
Neuropad is a reliable diagnostic tool for both CAN and DPN, albeit of only moderate accuracy. Extending the observation period to 15 min provides greater diagnostic usefulness.
A method for estimating the cholesterol content of the serum low-density lipoprotein fraction (Sf- 0.20)is presented. The method involves measure- ments of fasting plasma total cholesterol, tri- glyceride, and high-density lipoprotein cholesterol concentrations, none of which requires the use of the preparative ultracentrifuge. Cornparison of this suggested procedure with the more direct procedure, in which the ultracentrifuge is used, yielded correlation coefficients of .94 to .99, de- pending on the patient population compared. Additional Keyph rases hyperlipoproteinemia classifi- cation #{149} determination of plasma total cholesterol, tri- glyceride, high-density lipoprotein cholesterol #{149} beta lipo proteins
We determined the normal limits for various neuropathic tests in healthy subjects. The study, the Rochester Diabetic Neuropathy Study (RDNS), is noteworthy because of its size (more than 400 subjects), random selection of subjects, and selection of at least 15 men and 15 women without neuropathy, neurologic disease, or diseases predisposing to neuropathy from each hemidecade between 18 and 74 years of age from the population of a defined region (Rochester, MN). Subjects were classified into those with (nonhealthy subjects, RDNS-NS) and without (healthy subjects, RDNS-HS) neuropathy, neurologic or psychiatric disease, or diseases known to predispose to neuropathy. The study provides normal limits for tests used in the RDNS but it has broader uses as well. We found that (1) less than 10% of subjects in the third decade, approximately 20% in the fourth decade, and approximately 30% in the fifth or older decades were placed into the RDNS-NS category; (2) healthy subjects (RDNS-HS) retain their ability to walk on toes and heels regardless of age, excessive weight, or lack of physical fitness, but not their ability to arise from a kneeled position--lost in more than 5% of persons 60 years and older; (3) the frequency of decreased or absent ankle reflexes exceeds 5% in healthy subjects older than 50 years--limiting their value as a sign of diabetic polyneuropathy and necessitating a grading change with age in the neuropathy impairment score.(ABSTRACT TRUNCATED AT 250 WORDS)
Early diagnosis of distal symmetric sensorimotor polyneuropathy, a common complication of diabetes, may decrease patient morbidity by allowing for potential therapeutic interventions. We have designed an outpatient program to facilitate diagnosis of diabetic neuropathy.
Patients are initially administered a brief questionnaire and screening examination, designated the Michigan Neuropathy Screening Instrument (MNSI). Diabetic neuropathy is confirmed in patients with a positive assessment by a quantitative neurological examination coupled with nerve conduction studies, designated the Michigan Diabetic Neuropathy Score (MDNS). In this study, 56 outpatients with confirmed type I or II diabetes were administered the standardized quantitative components required to diagnose and stage diabetic neuropathy according to the San Antonio Consensus Statement (1) and the Mayo Clinic protocol (2). These same patients were then assessed with the MNSI and the MDNS.
Of 29 patients with a clinical MNSI score > 2, 28 had neuropathy. Twenty-eight patients with an MDNS of > or = 7 had neuropathy, while 21 non-neuropathic patients had a score < or = 6. Of 35 patients with diabetic neuropathy, 34 had > or = 2 abnormal nerve conductions. Twenty-one normal patients and one patient with neuropathy had < or = 1 abnormal nerve conduction.
The results indicate that the MNSI is a good screening tool for diabetic neuropathy and that the MDNS coupled with nerve conductions provides a simple means to confirm this diagnosis.
The magnitude of the health problem from diabetic neuropathies remains inadequately estimated due to the lack of prospective population-based studies employing standardized and validated assessments of the type and stage of neuropathy as compared with background frequency. All Rochester, Minnesota, residents with diabetes mellitus on January 1, 1986, were invited to participate in a cross-sectional and longitudinal study of diabetic neuropathies (and also of other microvascular and macrovascular complications). Of 64,573 inhabitants on January 1, 1986 in Rochester, 870 (1.3%) had clinically recognized diabetes mellitus (National Diabetes Data Group criteria), of whom 380 were enrolled in the Rochester Diabetic Neuropathy Study. Of these, 102 (26.8%) had insulin-dependent diabetes mellitus (IDDM), and 278 (73.2%) had non-insulin-dependent diabetes mellitus (NIDDM). Approximately 10% of diabetic patients had neurologic deficits attributable to nondiabetic causes. Sixty-six percent of IDDM patients had some form of neuropathy; the frequencies of individual types were as follows: polyneuropathy, 54%; carpal tunnel syndrome, asymptomatic, 22%, and symptomatic, 11%; visceral autonomic neuropathy, 7%, and other varieties, 3%. Among NIDDM patients, 59% had various neuropathies; the individual percentages were 45%, 29%, 6%, 5%, and 3%. Symptomatic degrees of polyneuropathy occurred in only 15% of IDDM and 13% of NIDDM patients. The more severe stage of polyneuropathy, to the point that patients were unable to walk on their heels and also had distal sensory and autonomic deficits (stage 2b) occurred even less frequently--6% of IDDM and 1% of NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)
While lower-extremity amputation (LEA) is a frequent complication of diabetes, effective strategies for the prevention of LEA in primary care settings have not been extensively studied.
This prospective study of American Indians with diabetes in a rural primary care clinic was divided into three periods: the standard care period (1986 to 1989), during which patients received foot care at the discretion of the primary care provider; the public health period (1990 to 1993), during which patients were screened for foot problems and high-risk individuals received foot care education and protective footwear; and the Staged Diabetes Management (SDM) period (1994 to 1996), during which comprehensive guidelines for diabetic foot management were adapted by the primary care clinicians to their practices and were systematically implemented.
A total of 639 individuals contributed 4322 diabetic person-years during the three periods of observation. Patient sex distribution, mean age, and mean duration of diabetes were similar i the three periods. The average annual LEA incidence was 29/1000 diabetic person-years for the standard care period (n = 42), 21/1000 for the public health period (n = 33), and 15/1000 for the SDM period (n = 20), an overall 48% reduction (P = .016). Overall, the incidence of a first amputation declined from 21/1000 to 6/1000 (P < .0001).
The customization and systematic implementation of practice guidelines by local primary care providers was associated with improved diabetic foot care outcomes. SDM has relevance to primary care organizations seeking to improve outcomes for patients with diabetes.
Diabetic foot ulceration represents a major medical, social and economic problem all over the world. While more than 5% of diabetic patients have a history of foot ulceration, the cumulative lifetime incidence may be as high as 15%. Ethnic differences exist in both ulcer and amputation incidences, with both being less common in patients of Indian subcontinent origin living in the UK. Foot ulceration results from the interaction of several contributory factors, the most important of which is neuropathy. With respect to the management of acute Charcot neuroarthropathy in diabetes, recent studies suggest that bisphosphonates reduce disease activity as judged not only by differences in skin temperature, but also by assessing markers of bone turnover. The use of the total-contact cast is demonstrated in the treatment of acute Charcot feet and of plantar neuropathic ulcers. Histological evidence suggests that pressure relief results in chronic foot ulcers changing their morphological appearance by displaying some features of an acute wound. Thus, repetitive stresses on the insensate foot appear to play a major role in maintaining ulcer chronicity. It is hoped that increasing research activity in foot disease will ultimately result in fewer ulcers and less amputation in diabetes.
A cross-sectional study has been performed in order to estimate the prevalence, severity, and current treatment of chronic painful peripheral neuropathy (CPPN) in people with diabetes in the community.
Using a structured questionnaire and examination we have assessed these factors in a community sample of people with diabetes (n=350) and compared them with 344 age- and sex-matched people without diabetes from the same locality.
The prevalence of CPPN was estimated to be 16.2%[95% confidence interval (CI): 6.8-16%] in people with diabetes compared with 4.9% (95% CI: 2.6-7.2%) in the control sample (P < 0.0001). Diabetic subjects with and without CPPN did not differ in age, sex, type and duration of diabetes, body mass index, smoking status and glycaemic control. However, CPPN diabetic subjects had significantly higher Visual Analogue Scale (VAS) scores for pain over the preceding 24 h [median (interquartile range) 3.5 (1.5-6.7) cm vs. 0.7 (0-3.9) cm, P < 0.0001]. Also, the total McGill Pain Questionnaire Score (a measure of pain quality and severity) was 18 (13-31.5) vs. 10 (4-16) (P < 0.0001). Of patients with diabetes and CPPN, 12.5% (7/56) had never reported their symptoms to their treating physician and 39.3% (22/56) had never received any treatment for their painful symptoms.
CPPN is common, often severe but frequently unreported and inadequately treated.
Recent findings have shed new light on the role of peripheral nerves in the skin and have established a modern concept of cutaneous neurobiology. There is bidirectional rather than unidirectional (conveying information from the periphery) signaling between central and peripheral nerves and the endocrine and immune systems. This interaction is mediated principally by cutaneous small nerve fibers and will influence a variety of physiologic and pathophysiologic functions central to wound healing, which include cellular development, growth, differentiation, immunity, vasoregulation, and leukocyte recruitment. Thus, disease of the small fibers in diabetic patients is frequent and may have a considerable impact on the predisposition and subsequent wound-healing response to foot ulceration. The authors review the basic pathophysiology, clinical consequences, and current methods to evaluate somatic and autonomic nerve fiber dysfunction and damage.
The objective of this study was to evaluate the sensitivity and specificity of a new indicator test (Neuropad) for the diagnosis of peripheral neuropathy in type 2 diabetes patients as compared with clinical examination and nerve conduction study (NCS).
This study included 120 type 2 diabetes patients (58 men) with a mean age of 67.3 +/- 5.9 years and a mean diabetes duration of 13.1 +/- 3.2 years. Diabetic neuropathy was diagnosed through the Neuropathy Disability Score. An NCS was performed on radial, ulnar, sural, and common and deep peroneal nerves. Patients were also examined with the new indicator test. The "time to complete color change of the test" from blue to pink was recorded. The test was considered abnormal in patients who exhibited a time to complete color change of the test exceeding 600 s in at least one foot.
Neuropathy was diagnosed by clinical examination in 83 (69.2%) patients. The sensitivity of the indicator test for clinical neuropathy was 95.2%, and its specificity was 67.6%. The sensitivity of NCS for clinical neuropathy was 94%, and its specificity was 62.1%. The sensitivity of the indicator test for abnormal NCS was 97.8%, and its specificity was 96.4%.
The new indicator test has a very high sensitivity not only for the diagnosis of clinical neuropathy but also for the diagnosis of neurophysiological neuropathy. Specificity is moderately high for the diagnosis of clinical neuropathy, while it is particularly high for the diagnosis of neurophysiological neuropathy. The indicator test has a validity comparable to that of NCS for the diagnosis of diabetic neuropathy. Finally, the time to complete color change of the test is associated with the severity of nerve conduction impairment.
To evaluate the inter-rater reliability between patient and health care provider of the indicator plaster neuropad (IPN) in the diagnosis of peripheral neuropathy and the feasibility of the IPN.
A total of 156 patients with diabetes were examined. At the same visit, the IPN was evaluated by the health care provider. Afterward, the IPN with written instructions for its use and evaluation for self-testing at home were provided together with a questionnaire asking for the easiness of the IPN.
Neuropathy was diagnosed in 56.9% of the participants by the health care provider. The k statistic to measure overall agreement between patient and health care provider of the IPN was very good: 0.88 (95% CI 0.85-0.91). The indicated instructions and the IPN were evaluated as easy by the patients.
The high degree of reliability and the easiness of the IPN suggest that it is proper for self-testing for the identification of peripheral neuropathy.