Deterministic nonlinear features of cutaneous perfusion are lost in diabetic subjects with neuropathy

The aim of this study was to analyze and compare the deterministic nonlinear structure of cutaneous laser Doppler flowmetry signals obtained from the forearm and foot of normal subjects and diabetic patients without neuropathy (D), with peripheral neuropathy (DPN) and with combined autonomic and peripheral neuropathy (DAN). Flow oscillations were evaluated under baseline conditions, after local warming of the skin to 44 °C and after warming plus iontophoresis of phenylephrine. The presence of nonlinearity was investigated by three complementary approaches: (i) attractor reconstruction, (ii) calculation of largest Lyapunov exponents (LLEs), and (iii) correlation dimension analysis. Conclusions were validated against surrogate stochastic time series generated by randomizing the Fourier phase of the raw data. In the control and D groups, the combination of phenylephrine and warming unmasked flowmotion with a prominent component at 0.1 Hz. Attractor reconstruction revealed toroidal structure and estimated LLEs were positive. LLEs decreased to zero and dimension estimates increased for surrogate data, consistent with loss of determinism. In diabetic subjects with neuropathy estimates of LLE were not significantly different from zero and dimensions were unaffected by phase randomization. Evidence for nonlinear structure was also obtained under baseline conditions in normal and D subjects, but was lost on warming alone. We conclude that deterministic control mechanisms contribute to cutaneous flowmotion, particularly when pseudo-quasiperiodic behavior is enhanced by phenylephrine. Nonlinear analysis of laser Doppler signals may provide previously unrecognized insights into the effects of diabetic neuropathy on perfusion because it can identify loss of complexity independently of the amplitude of the signals recorded.     

糖尿病足危险因素分析

目的探讨糖尿病（DM）患者发生糖尿病足（DF）的危险因素。方法利用病案查询系统检索1996年1月至2009年12月四川大学华西医院DF患者的总出院人数为662例,男371例,291例,平均年龄（664-11）岁;同期入院无DF的DM患者353例,男205例,女148例,平均年龄（66±9）岁。根据是否合并DF将所有患者分为DF患者组（DFP组）和非DF患者组（non．DFP组）。用卡方检验和单、多因素logistic回归分析方法对常见危险因素进行分析。结果与non—DFP组相比,DFP组糖尿病慢性并发症糖尿病肾病（DN）、糖尿病视网膜病变（DR）、周围动脉病变（PAD）、糖尿病周围神经病变（DPN）、糖尿病自主神经病变（DAN）的发生率均明显高于non—DFP组,组间差异均有统计学意义（X。=34．133、11．694、165．727、85．852、72．021,均P〈0．05）;且其肺部感染、骨质疏松的发生率更高,差异亦均有统计学意义（X2=32．619,23．932,均P〈0．05）。单因素分析显示吸烟、DN、DR、PAD、DPN、DAN是DF的危险因素（Wald=4．874、33．516、11．581、146．356、82．446、67,686,均P〈0．05）;高密度脂蛋白胆固醇（HDL—C）（Wald=25．532,P=0．000）是DF的保护性因素。多因素非条件logistic回归分析显示DN、DPN、DAN、PAD是DF的危险因素（Wald=11．007、21．484、11．963、87．427,均P〈0．05）;而HDL—C（Wald=14．971,P=0．000）是DF的保护性因素。结论DN、DPN、DAN、PAD是DF的危险因素,而HDL—C是DF的保护因素。     

Elevation of von Willebrand factor in plasma in diabetic patients with neuropathic foot ulceration.

AIMS: The present study examines the relationship between markers of endothelial dysfunction and diabetic neuropathy or consequent neuropathic foot ulceration in patients with Type 2 diabetes mellitus. METHODS: We studied 65 Type 2 diabetic patients including 25 diabetic patients without neuropathy, 27 with neuropathy but no history of foot ulceration, and 13 with neuropathic ulceration. Plasma concentrations of von Willebrand factor (vWF) and soluble thrombomodulin (TM), measures of endothelial dysfunction, were determined by enzyme immunoassays. We performed various tests quantifying aspects of diabetic neuropathy including vibration perception threshold (VPT; for sensory neuropathy), coefficient of variation of R-R intervals (CVR-R; for cardiac autonomic neuropathy), and cold-induced vasodilation in the great toe for peripheral sympathetic neuropathy. RESULTS: CVR-R and cold-induced vasodilation were significantly diminished in patients with neuropathic foot ulceration compared with patients with neuropathy but no history of foot ulceration. Plasma vWF concentrations were positively correlated with VPT and cold-induced vasodilation test, and were inversely correlated with CVR-R. Multivariate analysis disclosed that VPT and percentage vasodilation were independent factors for plasma vWF. Plasma vWF was significantly elevated in patients with foot ulceration compared with patients without neuropathy or those with neuropathy but not foot ulceration. However, plasma TM concentrations did not differ between the three groups. CONCLUSIONS: Diabetic patients with neuropathic foot ulceration had severe impairment of cardiac autonomic and peripheral sympathetic nerves. Elevation of vWF in plasma was associated with neuropathic foot ulceration, linking endothelial dysfunction to foot ulceration.     

Detecting and treating the protean manifestations of diabetic autonomic neuropathy

The manifestations of diabetic autonomic neuropathy (DAN) are protean and clinically involve multiple systems, including the cardiovascular system, the gastrointestinal system, the genitourinary system as well as the sweat glands (sudomotor dysfunction) and the gallbladder. In addition, cardiac autonomic neuropathy (CAN) is associated with a correctible inability to appreciate and correct hypoglycaemia. While not a clinical problem, pupillary involvement should be the clue and the catalyst to investigate for other manifestations of DAN. This review outlines a practical approach to detecting and investigating the manifestations of DAN. Of particular importance is early detection of cardiovascular involvement where prompt therapy through glycaemic control can decrease the severity of CAN and decelerate the frequency and severity of retinopathy and nephropathy in addition to decreasing cardiovascular events and mortality. CAN also plays a role in accelerating other diabetic complications such as acute ischaemic stroke, heart failure, medial artery calcinosis, foot ulcers, peripheral artery disease and Charcot joints. Many therapies of DAN are available, which should not only decrease morbidity and mortality from DAN, but also improve the patient's quality of life. However, the therapies available are largely symptomatic.     

Autonomic neuropathy and transcutaneous oxymetry in diabetic lower extremities

Summary Transcutaneous oxygen tension is a useful method with which to assess the functional status of skin blood flow. The reduced values observed in diabetic patients have been interpreted as a consequence of peripheral vascular disease. However, diabetic patients show lower transcutaneous oxygen tension values than control subjects with equivalent degrees of peripheral vascular disease, suggesting that additional factors are involved. Since the autonomic nervous system influences peripheral circulation, we studied the relationship between autonomic neuropathy and foot transcutaneous oxymetry in non-insulin-dependent diabetic (NIDDM) patients without peripheral vascular disease. The following age-matched patients were selected and evaluated: control subjects, C, (n=20), NIDDM patients without autonomic neuropathy, D, (n=16) and with autonomic neuropathy, DN, (n=20). All diabetic patients showed lower transcutaneous oxygen tension values than control subjects, while no differences were observed between the diabetic patients with and without autonomic neuropathy. In addition the saturation index that increases in the presence of autonomic neuropathy does not correlate with foot TcPO₂. In conclusion autonomic neuropathy does not influence foot TcPO₂ and therefore it is unlikely that it contributes to development of foot lesions during induction of foot skin ischaemia.Abbreviations NIDDM Non-insulin-dependent diabetes mellitus - TcPO₂ transcutaneous oxymetry - A-V arterio-venous shunts - PVD peripheral vascular disease - HbA_1c glycated haemoglobin - SI saturation index     

Visual sensitivity loss in the central 30° of visual field is associated with diabetic peripheral neuropathy

Aims/hypothesis  

Impaired central vision has been shown to predict diabetic peripheral neuropathy (DPN). Several studies have demonstrated diffuse retinal neurodegenerative changes in diabetic patients prior to retinopathy development, raising the prospect that non-central vision may also be compromised by primary neural damage. We hypothesise that type 2 diabetic patients with DPN exhibit visual sensitivity loss in a distinctive pattern across the visual field, compared with a control group of type 2 diabetic patients without DPN.     

Incipient cardiovascular autonomic imbalance revealed by wavelet analysis of heart rate variability in Type 2 diabetic patients.

AIM: Incipient cardiovascular autonomic imbalance is not readily diagnosed by conventional methods. Spectral analysis of heart rate variability (HRV) by wavelet transform (WT) was used to measure cardiovascular autonomic function in patients with Type 2 diabetes. METHODS: Thirty-two diabetic patients without (D), 26 with cardiovascular autonomic neuropathy (DAN) and 72 control subjects (C) participated. A 30-min HRV time series was analysed by wavelet transformation and four characteristic frequency intervals were defined: I (0.0095-0.021 Hz), II (0.021-0.052 Hz), III (0.052-0.145 Hz) and IV (0.145-0.6 Hz). RESULTS: When compared with C, in both D and DAN the normalized power and amplitude of interval II were increased and of interval IV decreased, resulting in a significantly higher II/IV ratio. Furthermore, in DAN the normalized power and amplitude of interval I were increased and of interval III decreased when compared with the D and C groups. The diabetic patients were divided in two equal subgroups according to HbA(1c) < 8.0% and >or= 8.0%. In the subgroup with HbA(1c) >or= 8.0%, normalized power in interval II was significantly higher and in interval IV significantly lower than in the subgroup with HbA(1c) < 8.0%. In D, but not in DAN patients prescribed ACE inhibitors, the absolute amplitude and power of oscillations were significantly higher than in patients not taking ACE inhibitor therapy. CONCLUSIONS: Patients with diabetes have increased sympathetic and decreased parasympathetic cardiac activity regardless of the presence of autonomic neuropathy. Glycaemic control and treatment with ACE inhibitors may favourably influence HRV in diabetic patients without autonomic neuropathy.     

Insulin resistance is independently associated with peripheral and autonomic neuropathy in Korean type 2 diabetic patients

In addition to chronic hyperglycemia, insulin resistance itself has been proposed to cause a diabetic neuropathy. We evaluated the role of insulin resistance in the pathogenesis of peripheral and autonomic neuropathy in patients with type 2 diabetes. Eighty-six patients with type 2 diabetes were evaluated for the anthropometric and biochemical profiles, and Kitt value was calculated from insulin tolerance test to assess the insulin resistance. Various autonomic function tests, nerve conduction velocity, and quantitative sensory tests were performed to assess autonomic and peripheral neuropathy. In univariate analysis, both autonomic and peripheral neuropathy were significantly associated with glycemic exposure index (GE index), HDL-cholesterol, duration of DM, and Kitt value. In stepwise linear regression analysis, GE index was an independent predictor of autonomic and peripheral neuropathy (β = 0.643, P < 0.001; β = 0.207, P = 0.013, respectively), and Kitt value was also an independent factor for the autonomic and peripheral neuropathy (β = − 0.306, P < 0.001; β = − 0.329, P < 0.001, respectively). Low HDL-cholesterol increased the odds ratio for peripheral neuropathy. Insulin resistance is independently associated with peripheral and autonomic neuropathy in Korean Type 2 diabetic patients along with hyperglycemia and HDL-cholesterol.     

Glycemic profile variability: An independent risk factor for diabetic neuropathy in patients with type 2 diabetes

BackgroundImpaired glycemic control is a potential predictor for macro- and microvascular complications of diabetes, which could be recognized by glycemic variability. The aim of this 10-year prospective cohort study presented here is to gain a better understanding of the correlation between GV and diabetic peripheral neuropathy (DPN) as one of the most common complications of T2DM.MethodsSince February 2010, 1152 adult patients with T2DM have been followed-up. Baseline features, anthropometric measurements, and laboratory findings were collected and documented during ten years. The association between DPN incidence and glycemic profile variability was evaluated using cox regression analysis. The coefficient of variation of glycemic indices within subjects was calculated and compared using an independent sample t-test.ResultsIndividuals who developed neuropathy had significantly higher mean levels of glycemic indices (HbA1c, FBS, and 2hpp), urinary albumin excretion, mean creatinine levels, and a longer duration of diabetes. A significant positive correlation between incidence of DPN and glycemic profile variability (cv-FBS10 %, cv-FBS20 %, cv-2hpp20 %, cv-HbA1c5 % and cv-HbA1c10 %) was revealed. Results also showed that higher variability of FBS was associated with the higher risk of neuropathy incidence (HR: 12.29, p-value: 0.045), which indicates that glycemic profile variability is an independent risk factor for DPN in patients with T2DM.ConclusionVariability of glycemic profiles from a visit to visit, regardless of sustained hyperglycemia, was indeed a significant risk factor for DPN in diabetic type 2 patients. CV-FBS was the most critical glycemic variability indices for DPN development.     

糖尿病周围神经病变和血管病变对糖尿病足溃疡的相互作用及相关性探讨

目的 探讨糖尿病足溃疡（DFU）发生的危险因素,分析糖尿病周围神经病变（DPN）和糖尿病血管病变（PAD）与DFU的相互作用.方法 选取T2DM患者278例,按其是否合并DFU分成糖尿病足溃疡组（DFU,102例）和糖尿病非足溃疡组（NDFU,176例）,回顾性分析两组生化特征和并发症情况.采用Logistic回归分析DFU发生的危险因素,并通过相对超额危险度比（RERI）,归因比（AP）和相互作用指数（S）评价DPN与PAD的相加相互作用.结果 与NDFU组比较,DFU组HbA1c和纤维蛋白原（FIB）水平,DR、DPN和PAD发生率均升高,血红蛋白（Hb）、血白蛋白（Alb）、TC和LDL-C降低（P＜0.05）.Logistic回归分析显示,DFU相关影响因素有：HbA1 c、DPN、PAD、Hb、Alb和FIB（OR分别为1.41、3.66、3.00、0.98、0.79和2.51）.DPN和PAD对DFU的相加相互作用指标RERI、AP和S分别为3.45（95％CI：1.22～8.56）、0.29（95％CI：0.02～0.58）和1.45（95％CI：1.03～4.96）.结论 血糖控制欠佳、合并DPN和PAD、营养不良及FIB代谢失衡是DFU发生的主要危险因素.DPN和PAD对DFU存在相加相互作用,同时患有DPN和PAD可增加DFU的患病风险.     

The effect of a cognitive or motor task on gait parameters of diabetic patients,with and without neuropathy

Aims To compare gait parameters of older people with diabetes and no peripheral neuropathy (DM) and people with diabetes and diabetic peripheral neuropathy (DPN) and to investigate the effect of a secondary motor or cognitive task on their gait. Methods Thirty subjects were recruited: 15 with DPN (mean age 69 ± 3.0 years) and 15 with diabetes and no neuropathy (70 ± 2.9 years). The temporal and spatial parameters of gait were determined using the GAITRite walkway. Subjects undertook four walks: under normal walking conditions (single task); four times while simultaneously undertaking an additional motor task, carrying a tray with cups of water (dual task); and four times whilst undertaking a cognitive dual task, counting backwards in sevens. This arithmetic task was also completed sitting. Results For all gait variables, there was a statistically significant difference between the groups. Subjects with DPN walked more slowly and with smaller steps compared with those with DM. In general, the secondary task had a significant and adverse effect on the gait parameters and this effect was greater for those with DPN in both absolute and relative terms. Both groups had poorer arithmetic ability when walking compared with sitting. Discussion Patients with DPN have different gait parameters to diabetic patients without neuropathy. Problems with divided attention when walking were more evident in the DPN group and may increase their risk of falls.     

Levels of three distinct p75 neurotrophin receptor forms found in human plasma are altered in type 2 diabetic patients

Aims/hypothesis The p75 neurotrophin receptor (p75NTR) has been shown to appear in the plasma of diabetic rats, possibly indicating diabetic neuropathy. The aim of this study was to use a semi-quantitative assay for human plasma p75NTR to investigate whether this receptor is a marker of peripheral diabetic neuropathy (DPN) and autonomic cardiovascular neuropathy (CAN) in type 2 diabetic patients. Subjects and methods Eighty type 2 diabetic patients and 25 controls without diabetes were analysed for p75NTR immunoreactivity by western blot analysis. DPN was assessed using the Neuropathy Disability Score (NDS). Cardiovascular autonomic function was detected using a standardised analysis of heart rate variability. Results Three distinct p75NTR signals were detectable in human plasma at ∼75, ∼51 and ∼24 kDa, representing the full length receptor (FL) and its intracellular domain (ICD) and extracellular domain (ECD), respectively. Levels of total plasma p75NTR immunoreactivity in patients with type 2 diabetes were similar to those in controls. Type 2 diabetic patients had significantly higher plasma levels of ICD and lower levels of ECD. However, there were no correlations of total p75NTR immunoreactivity or ECD or ICD immunoreactivity with NDS or aspects of CAN. Conclusions/interpretation Levels of the ECD of p75NTR are reduced and levels of the ICD are increased in the plasma of type 2 diabetic patients. None of the p75NTR subunits identified in human plasma seem to be a marker of peripheral or autonomic neuronal function in patients with type 2 diabetes. P. M. Humpert and S. Kopf contributed equally to this study.     

Association of diabetic foot ulcers with chronic vascular diabetic complications in patients with type 2 diabetes

ContextDiabetes mellitus is a common disease which is prevalent globally, presenting with chronic complications and constitutes a major risk to the patient. Diabetic foot ulcers are the single biggest risk factor for non-traumatic lower limb amputations in persons with diabetes. We aimed to screen for the chronic vascular diabetic complications in patients with diabetic foot ulcers (DFUs) and to assess the association of diabetic foot ulcers with these complications in the study group.Subjects and methodsThis cross-sectional study included 180 type 2 diabetic patients (aged 30–70 years) with diabetic foot ulcers who attended the Outpatient Clinic of Diabetes in Alexandria Main University Hospital. Full diabetic foot examination was done to all study subjects. DFUs were assessed using University of Texas Diabetic Wound Classification System. HbA1c, LDL-C, serum creatinine, and urinary albumin creatinine ratio (ACR) were measured for all study subjects. Estimated glomerular filtration rate (eGFR) was calculated using CKD-EPI equation. Fundus examination was done for all study subjects.ResultsThe prevalence of diabetic kidney disease (DKD) and diabetic retinopathy (DR) was 86.1% and 90% respectively among the study group. 86.7% of patients had neuropathic DFUs, 11.1% of them had ischemic DFUs and 2.2% had neuro-ischemic DFUs. Regarding diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) as risk factors for developing DFU, the prevalence of both of them respectively was 82% and 20% among the study group. There was statistically significant association between both DKD, DR and peripheral neuropathy. There was also statistically significant association between both DKD, DR and peripheral arterial disease (PAD).ConclusionChronic vascular diabetic complications are common among type 2 diabetic patients with diabetic foot ulcers. There is statistically significant association between these complications and diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD).     

Symptomatic diabetic autonomic neuropathy in type 1 diabetes (T1D): Findings from the T1D exchange

AimsWe aimed to evaluate the contemporary prevalence of and risk factors for symptomatic diabetic autonomic neuropathy (DAN) in participants with type 1 diabetes (T1D) enrolled in the T1D Exchange Clinic Registry.MethodsDAN symptoms and severity were assessed with the Survey of Autonomic Symptoms (SAS) in adults with ≥5 years of T1D participating in the T1D Exchange from years 2010–2017. Associations of demographic, clinical, and laboratory factors with symptomatic DAN were assessed.ResultsOf the 4919 eligible T1D participants, 965 (20%) individuals completed the SAS questionnaire [mean age 40 ± 17 years, median diabetes duration 20 years (IQR: 13,34), 64% female, 90% non-Hispanic White, and 82% with private insurance]. DAN symptoms were present in 166 (17%) of responders with 72% experiencing moderate severity symptoms or worse. Symptomatic DAN participants had higher hemoglobin A1c (p = 0.03), longer duration (p = 0.004), were more likely to be female (p = 0.03), and more likely to have lower income (p = 0.03) versus no DAN symptoms. Symptomatic DAN was associated with diabetic peripheral neuropathy (p < 0.0001), smoking (p = 0.002), cardiovascular disease (p = 0.02), depression (p < 0.001), and opioid use (p = 0.004).ConclusionsDAN symptoms are common in T1D. Socioeconomic factors and psychological comorbidities may contribute to DAN symptoms and should be explored further.     

Cardiovascular response to exercise in diabetic patients: influence of autonomic neuropathy of different severity

Summary We investigated cardiovascular function and plasma catecholamine response during incremental exercise and recovery in diabetic patients with (DAN+) and without autonomic neuropathy (DAN–). The former group was divided according to the presence of parasympathetic (DAN+PH–) or associated parasympathetic and sympathetic (DAN+PH+) damage to the autonomic nervous system. A group of healthy volunteers was studied as a control group. All the patients and control subjects underwent a submaximal or symptom-limited incremental exercise test using a cycle-ergometer. Air flow and respiratory gas fractions were sampled at the level of the mouth allowing a breath-by-breath analysis of oxygen consumption (VO₂). Heart rate and systolic blood pressure were recorded and venous blood samples were obtained from the patients at rest and during each minute of exercise and recovery to measure norepinephrine and epinephrine plasma levels. Haemodynamic parameters and plasma catecholamines were computed at rest and at 25, 50, 75 and 100% of the peak VO₂ (VO_{2 max}). The breath-by-breath relationships among VO₂, heart rate and VO₂/heart rate against work were assessed during exercise for patients and control subjects. While VO_{2 max} in absolute values was not significantly different among the diabetic groups, VO_{2 max} was much less in diabetic patients than in control subjects (p<0.01). During exercise the rate of heart rate, systolic blood pressure, norepinephrine and epinephrine increase was different among the diabetic groups, being significantly blunted in DAN+PH+. The VO₂/work relationship of the three diabetic groups was similar but markedly reduced in respect to that of control subjects (p<0.001). The relationship between oxygen pulse (VO₂/heart rate) and work showed no differences among the diabetic groups, whereas its slope was significantly steeper in control subjects (p<0.01 vs DAN–; p<0.05 vs DAN+PH– and DAN+PH+). In conclusion during incremental exercise both DAN+PH– and DAN+PH+ exhibit abnormal heart rate, systolic blood pressure and catecholamine responses which, however, appear clearly distinct between the two groups of DAN+. In DAN+ the VO₂ increment is reduced during exercise. Since DAN–show the same impairment, this particular finding seems most likely to be influenced by factors (i.e.: diabetic cardiomyopathy) other than overt autonomic neuropathy.Abbreviations C Control subjects - DAN– diabetic patients without autonomic neuropathy - DAN+ diabetic patients with autonomic neuropathy - DAN+PH– diabetic patients with autonomic neuropathy without postural hypotension - DAN+PH+ diabetic patients with autonomic neuropathy with postural hypotension - V_E minute ventilation - VO₂ oxygen consumption - VCO₂ carbon dioxide production - AT anaerobic threshold - SaO₂ arterial oxygen saturation - HR heart rate - SBP systolic blood pressure - CW cardiac work - VO_{2 max} peak VO₂     

Peripheral neuropathy in prediabetes and the metabolic syndrome

Peripheral neuropathy is a major cause of disability worldwide. Diabetes is the most common cause of neuropathy, accounting for 50% of cases. Over half of people with diabetes develop neuropathy, and diabetic peripheral neuropathy (DPN) is a major cause of reduced quality of life due to pain, sensory loss, gait instability, fall‐related injury, and foot ulceration and amputation. Most patients with non‐diabetic neuropathy have cryptogenic sensory peripheral neuropathy (CSPN). A growing body of literature links prediabetes, obesity and metabolic syndrome to the risk of both DPN and CSPN. This association might be particularly strong in type 2 diabetes patients. There are no effective medical treatments for CSPN or DPN, and aggressive glycemic control is an effective approach to neuropathy risk reduction only in type 1 diabetes. Several studies suggest lifestyle‐based treatments that integrate dietary counseling with exercise might be a promising therapeutic approach to early DPN in type 2 diabetes and CSPN associated with prediabetes, obesity and metabolic syndrome.     

The effect of obesity on the assessment of diabetic peripheral neuropathy: A comparison of Michigan patient version test and Michigan physical assessment

ObjectiveNerve conduction studies (NCS) and Michigan Neuropathy Screening Instrument (MNSI) are commonly used to make the diagnosis of diabetic peripheral neuropathy. The objective of this study was to compare the diagnostic values of MNSI patient version test and physical test for the assessment of the diabetic peripheral neuropathy in obese vs. non-obese patients.MethodThis study was conducted on 70 type 2 diabetic patients. We carried out the MNSI patient version test and MNSI physical assessment test. Nerve conduction studies were performed for the diagnosis of the diabetic peripheral neuropathy.ResultsIn diabetic peripheral neuropathy (DPN) determined by NCS, the independent prediction of peripheral neuropathy was the score of Michigan physical assessment (odds 2.0; CI: 1.3–3.0). In BMI (body mass index) ≥30 diabetic patients who have peripheral neuropathy, Michigan patient version test is not significant. But the score of Michigan physical assessment is significantly increased in these patients compared to patients without peripheral neuropathy. In BMI < 30 diabetic patients who have peripheral neuropathy, scores of both Michigan patient version and physical assessment instruments are significantly increased.ConclusionTo screen diabetic peripheral neuropathy, Michigan physical assessment may be more useful instrument than Michigan patient version test in obese diabetic patients.     

Autonomic denervation may be a prerequisite of diabetic neuropathic foot ulceration

Studies using visceral (cardiovascular) autonomic function testing have left doubt as to the importance of autonomic neuropathy in the development of diabetic neuropathic foot ulceration. A test for peripheral autonomic denervation has been developed (acetylcholine sweatspot test), dependent on intradermal acetylcholine causing secretion by innervated sweat glands, detected by starch/iodine discoloration. The response is photographed and quantified using a grid (normal score = 0 or 1; abnormal = 5 to 60). The sweatspot test was applied to the feet of 19 diabetic patients with a history of foot ulceration, 17 with neuropathic pain, 8 complaining of numbness, and to 15 diabetic control patients. The sweatspot test score of the foot ulcer patients (median 54) was very much greater than that of the other groups (pain group, 4, p less than 0.005; numbness group, 2, p less than 0.01; diabetic control group, 2, p less than 0.0001). All the patients with neuropathic foot ulceration had peripheral autonomic denervation. The results suggest that autonomic denervation in the feet is always present in patients with diabetic neuropathic foot ulceration. Tests of peripheral autonomic denervation such as the acetylcholine sweatspot test may be useful to identify patients at risk of neuropathic foot ulceration.     

Predictors of diabetes foot complications among patients with diabetes in Saudi Arabia

AimsTo identify risk factors and clinical biomarkers of prevalent diabetes foot complications, including foot ulcers, gangrene and amputations among patients with diabetes in Jeddah, Saudi Arabia.Methods598 diabetes patients from Jeddah participated in the current study. Patients were considered to have diabetes foot complications if they reported diagnosis of foot ulcers or gangrene or amputations in a questionnaire administered by a physician and confirmed by clinical exams. Information on socio-demographic and lifestyle variables was self-reported by patients, and several clinical markers were assessed following standard procedures.ResultsThe prevalence of diabetes foot complications in this population was 11.4%. In the multivariable model without adjustment for PAD (peripheral artery disease) and DPN (diabetes peripheral neuropathy), non-Saudi nationality, longer diabetes duration and insulin use was significantly associated with higher diabetes foot complications prevalence. Each 1 g/L increase of hemoglobin was associated with 2.8% lower prevalence of diabetes foot complications. In the multivariable model adjusting for PAD and DPN, the previously observed associations except for nationality were no longer significant. Patients with both DPN and PAD had 9.73 times the odds of diabetes foot complications compared to the patients with neither condition.ConclusionIn this population, longer diabetes duration, insulin use, lower hemoglobin levels and non-Saudi nationality were associated with higher prevalence of foot complications. These associations were largely explained by the presence of DPN and PAD except for non-Saudi nationality. Diabetes patients with both DPN and PAD had nearly 10-fold increased risk of foot complications than those with neither condition.     

Association of peripheral neuropathy with subclinical left ventricular dysfunction in patients with type 2 diabetes

ObjectivesThe impacts of diabetic peripheral neuropathy (DPN) on clinical manifestations of left ventricular (LV) function in patients suffering from type 2 diabetes mellitus (T2DM) and the preserved LV ejection fraction (LVEF) lack a full evaluation. This study was carried out to investigate the correlation of peripheral neuropathy with subclinical LV systolic dysfunction, accompanied by the exploration of the relevant clinical features of peripheral neuropathy in these patients.MethodsA retrospective analysis was conducted depending on the data of 101 consecutive inpatients with T2DM and preserved LVEF (all ≥ 50 %), without coronary artery disease and other histories of heart disease. All subjects received both a nerve conduction assessment and a speckle-tracking echocardiography examination. Global longitudinal strain (GLS) was conducted to assess the subclinical LV systolic function.ResultsForty-six (46 %) patients were diagnosed as DPN according to electrophysiological examination and clinical assessment. A significant difference was revealed in GLS between patients with and without DPN (16.5 ± 2.8 vs. 19.3 ± 3.4, p < 0.001). Multiple logistic regression analysis indicated GLS as one of the independent determinative factors for DPN (odds ratio, 0.68; P < 0.001). In addition, motor-sensory nerve conduction exhibited a significant positive correlation with GLS, which may not be revealed between the types of peripheral nerve damage.ConclusionsDespite the preserved LVEF, the subclinical LV myocardial dysfunction may have occurred in T2DM patients with DPN. Peripheral nerve conduction was significantly correlated with GLS. An early assessment of nerve conduction may exert a dual warning significance for the progression of subclinical LV dysfunction in asymptomatic patients with T2DM.