Prevalence and clinical implications of painful diabetic peripheral neuropathy in type 2 diabetes: Results from a nationwide hospital-based study of diabetic neuropathy in Korea

Aims

To determine the prevalence and risk factors for painful diabetic peripheral neuropathy (PDPN) and evaluate sleep impairment and quality of life in patients with PDPN.

Methods

Data from the Korean Diabetes Association Neuropathy Study Group were used to evaluate 3999 patients with type 2 diabetes. PDPN was diagnosed using visual analogue scales (VAS) and medical history. The patients were asked to answer the Brief Pain Inventory-Short Form (BPI-SF), Medical Outcomes Study Sleep (MOS-Sleep) Scale, EuroQol (EQ-5D), and VAS.

Results

Among the patients with diabetic peripheral neuropathy (n = 1338), 577 (43.1%) were diagnosed with PDPN (14.4% of all patients with type 2 diabetes). PDPN was independently associated with age, female gender, fasting plasma glucose, hypertension, and previous cerebrovascular events. All pain severity and interference measures were higher in patients with PDPN than in non-PDPN patients, and patients with PDPN reported more impaired sleep and lower EQ-5D and VAS scores.

Conclusions

The prevalence of PDPN in Koreans was comparable to that in Western populations. PDPN may impair sleep and quality of life compared with non-PDPN, and physicians should carefully consider pain symptoms in patients with diabetic peripheral neuropathy.     

2型糖尿病患者振动觉阈值检测及影响因素

目的 探讨振动觉阈值检测对2型糖尿病患者下肢神经病变的诊断意义及其影响因素.方法 测定2008年8月至2009年4月在我院内分泌代谢科门诊就诊的1018例2型糖尿病患者振动觉阈值,根据振动觉阈值风险度将其分为低风险组(<15 V)484例、中风险组(15～25 V)302例、高风险组(>25 V)232例.比较患者下肢神经病变症状、基本情况和血糖控制指标,分析其影响因素.采用卡方检验、t检验、单因素方差分析等进行统计学分析.结果 低风险组、中风险组、高风险组分别占47.54%、29.67%、22.79%,中风险组、高风险组有神经病变症状者所占比例明显高于低风险组(分别为61.26%、65.52%、39.26%).各组年龄、糖尿病病程、收缩压、糖化血红蛋白及糖化血清蛋白差异有统计学意义(均P<0.05),男性振动觉阈值明显高于女性(P<0.01).振动觉阈值与年龄、性别、糖尿病病程、收缩压、糖化血红蛋白、糖化血清蛋白、空腹血糖呈正相关(P<0.05).多元回归分析显示年龄(P=0.000)、糖化血红蛋白(P=0.046)及糖化血清蛋白(P=0.030)是振动觉阈值的独立影响因素.结论 采用振动觉阈值检测筛查门诊2型糖尿病患者糖尿病周围神经病变的患病率为22.79%,年龄、糖化血红蛋白、糖化血清蛋白是振动觉阈值的独立影响因素.     

2型糖尿病患者周围神经病变危险因素分析

目的 探讨T2DM住院患者糖尿病周围神经病变（DPN）患病率及危险因素. 方法 选取T2DM住院患者205例,以多伦多临床评分系统（TCSS）评分作为DPN诊断标准,分为DPN组和无DPN（NDPN）组,比较两组各项指标. 结果 DPN患病率43.9％.DPN组年龄（57.76±12.50）vs（49.50±13.28）岁]、病程[（8.12±2.50）vs（5.67±1.99）年]、体重[（62.50±10.46） vs （67.03±13.43）kg]、DBP[（82.79±13.69）vs（86.98±12.18） mmHg]、BUN[（10.15±1.52）vs（41.35±5.66）μmol/L]、Scr[（102.79±61.56）vs（74.61±34.26）μmol/L]、UAlb/Cr[（211.66±26.78）vs（44.21±9.77）mg/24 h]和DR患病率[41（45.5％） vs 20（17.4％）]与NDPN组比较差异有统计学意义（P＜0.01）.Logistic多元回归分析显示,年龄、病程、UAlb/Cr、合并DR与DPN发生呈正相关. 结论 年龄、病程、UAlb/Cr、合并DR可能是T2DM住院患者发生DPN的危险因素.     

Association between a MIR499A polymorphism and diabetic neuropathy in type 2 diabetes

Aims

Diabetic polyneuropathy (DPN) and cardiovascular autonomic neuropathy (CAN) affect a large percentage of diabetic people and impact severely on quality of life. As it seems that miRNAs and their variations might play a role in these complications, we investigated whether the rs3746444 SNP in the MIR499A gene could be associated with susceptibility to DPN and/or CAN.

Variability of fasting plasma glucose and the risk of painful diabetic peripheral neuropathy in patients with type 2 diabetes

Aim

The relationship between glycaemic variability and painful diabetic peripheral neuropathy (PDPN) in patients with type 2 diabetes (T2D) is unclear. The aim of this study was to investigate whether variations in fasting plasma glucose (FPG), as represented by the coefficient of variation (CV), were associated with the risk of PDPN in patients with T2D.

Current perception thresholds: a new,quick, and reproducible method for the assessment of peripheral neuropathy in diabetes mellitus

Summary The Neurometer is a variable constant current sine wave stimulator, and has recently been proposed as a simple non-invasive and quantitative measure of peripheral nerve function. The device is portable and battery operated; assessment of upper and lower extremities takes only a few min, in contrast to conventional assessment techniques. In order to assess its potential in the quantification of diabetic neuropathy, detection thresholds for constant current electric sine wave stimulation were measured at three different frequencies in different sites in 31 healthy control subjects and 90 diabetic patients with and without neuropathy. The device provides good discrimination between neuropathic and non-neuropathic groups (p<0.001) and is quick and easy to use. Comparisons with results of conventional tests of nerve function show that high frequency detection thresholds correlate best with tests of large fibre function (r= 0.42–0.69, p<0.001), and low frequency detection thresholds correlate with tests of small fibre function (r=0.34–0.46, p<0.005). It is concluded that the device may be a simple and comprehensive way of assessing peripheral nerve function.     

Transcutaneous oxygen pressure (TcPO2): A novel diagnostic tool for peripheral neuropathy in type 2 diabetes patients

Aims

The assessment of transcutaneous oxygen pressure (TcPO₂) may serve as a non-invasive and lower-cost alternative to nerve conduction studies (NCSs) for the diagnosis of diabetic peripheral neuropathy (DPN). The aim of this study was to determine whether the measurement of TcPO₂ is useful for evaluating DPN.

Methods

We performed a cross-sectional study of 381 consecutive hospitalized diabetic patients classified by clinical examination and NCS as having DPN. Anthropometric and metabolic parameters were assessed. The TcPO₂ examination was performed in both supine and sitting positions.

Results

Three hundred and one patients had DPN. The TcPO₂ in both the supine and sitting positions was highest in the Non-DPN group and lower in the confirmed DPN group than the other three groups (p < 0.001). The Non-DPN group had the lowest sitting-supine position difference in TcPO₂ among the groups (p < 0.001). The risk factors strongly associated with DPN included sitting-supine position difference in TcPO₂ (OR = 4.971, p < 0.001), diabetic retinopathy (DR) (odds ratio [OR] = 3.794, p = 0.002), and HbA1c (OR = 1.534, p = 0.033). The area under the curve (AUC) of the sitting-supine position difference in TcPO₂ was 0.722 and revealed an optimal cut-off point for the identification of DPN (19.5 mmHg) that had a sensitivity of 0.611 and a specificity of 0.738 based on AUC analysis.

Conclusions

This large study of diabetic patients confirms that the sitting-supine position difference in TcPO₂ is higher in DPN patients than control subjects, indicating that TcPO₂ examination is a promising valuable diagnostic tool for DPN.     

Lipid-lowering therapy and peripheral sensory neuropathy in type 2 diabetes: the Fremantle Diabetes Study

Aims/hypothesis The aim of this study was to assess the relationships between lipid-lowering therapy and the prevalence and incidence of peripheral sensory neuropathy in type 2 diabetes mellitus. Methods We analysed data from an observational cohort study, the Fremantle Diabetes Study (FDS), specifically, (1) a cross-sectional sample comprising 1,237 FDS participants with type 2 diabetes mellitus, and (2) a longitudinal subgroup of 531 individuals who had attended six consecutive annual assessments. Neuropathy was identified using the clinical portion of the Michigan Neuropathy Screening Instrument. Results At entry, the cross-sectional sample had a mean ± SD age of 63.8 ± 11.3 years, 48.7% were men, median (interquartile range) diabetes duration was 4.0 (1.0–9.0) years, and 30.9% had peripheral neuropathy. Fibrates and statins were used by 3.5 and 6.8%, respectively. Multiple logistic regression analysis showed that older age, longer diabetes duration, central adiposity, increased height, higher fasting serum glucose, albuminuria and aboriginality were significant independent positive predictors of prevalent neuropathy, while systolic blood pressure and fibrate use (odds ratio 0.30, 95% CI 0.10–0.86; p = 0.025) were negatively associated. In the longitudinal subgroup, fibrate and statin use increased to 10.4 and 36.5%, respectively, over 5 years. In time-dependent Cox proportional hazards modelling, fibrate use [hazard ratio (HR) 0.52, 95% CI 0.27–0.98] and statin use (HR 0.65, 95% CI 0.46–0.93) were significant determinants of incident neuropathy (p ≤ 0.042). Conclusions/interpretation These preliminary observational data suggest that therapy with a statin or a fibrate may protect against the development of diabetic peripheral sensory neuropathy, but there is a need for additional confirmatory evidence, preferably from randomised clinical trials. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Hidden dangers revealed by misdiagnosed diabetic neuropathy: A comparison of simple clinical tests for the screening of vibration perception threshold at primary care level

Aim

Diabetic peripheral neuropathy is an important complication and contributes to the morbidity of diabetes mellitus. Evidence indicates early detection of diabetic peripheral neuropathy results in fewer foot ulcers and amputations. The aim of this study was to compare different screening modalities in the detection of diabetic peripheral neuropathy in a primary care setting.

血压控制不佳是痛性糖尿病周围神经病变的危险因素:前瞻性队列研究

目的通过前瞻性研究设计明确血压控制不佳是否为痛性糖尿病周围神经病变(DPN)发病的危险因素。方法本研究为前瞻性研究。自2014年起从上海5家社区卫生中心纳入年龄≥18岁未诊断DPN的患者。记录所有患者在基线纳入和随访结束时的基本资料、实验室检查和密西根神经病变筛查量表检查结果,并在随访结束时接受神经病理性疼痛问卷评估和神经传导功能检查。根据痛性DPN标准,将患者分为非DPN组、痛性DPN组和无痛性DPN组。比较非DPN组、痛性DPN组和无痛性DPN组患者基线及随访时临床资料,分析痛性DPN组和无痛性DPN组患者基线(收缩压、舒张压)、随访(收缩压、舒张压)以及随访和基线时血压差值的差异,并采用χ²检验比较血压控制不佳组(≥130/80 mmHg,1 mmHg=0.133 kPa)和血压控制良好组(<130/80 mmHg)痛性DPN发生率的差异,采用多因素logistic回归模型进一步分析血压控制不佳与痛性DPN之间的关系。结果最终纳入315例T2DM患者,随访(5.06±1.14)年,将患者分为非DPN组152例、痛性DPN组74例和无痛性DPN组89例。与非DPN组患者相比,痛性DPN组和无痛性DPN组患者基线的年龄、腰围和空腹血糖明显升高,差异有统计学意义(P<0.05);痛性DPN组患者基线时的糖尿病病程、收缩压和舒张压明显高于非DPN组患者(P<0.05)。痛性DPN组患者随访时的收缩压(P=0.030)和舒张压(P=0.007)明显高于无痛性DPN组,差异有统计学意义(P<0.05)。基线血压控制不佳组患者132例,血压控制良好组患者30例,基线血压控制不佳组痛性DPN的发生率49.24%(65/132)高于基线血压控制良好组26.67%(8/30),差异有统计学意义(P=0.025)。校正体重指数、糖化血红蛋白、年龄、性别、吸烟、饮酒、T2DM病程、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、服用血管紧张素转化酶抑制剂、其他降压药及二甲双胍后,血压控制不佳仍然与痛性DPN相关(OR=17.921,95%CI为1.497~214.593)。结论血压控制不佳为T2DM患者痛性DPN的危险因素。     

Sensitivity and specificity of a new indicator test (Neuropad) for the diagnosis of peripheral neuropathy in type 2 diabetes patients: a comparison with clinical examination and nerve conduction study

OBJECTIVE: 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). PATIENTS AND METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.     

Angiotensin-converting enzyme (ACE) gene II genotype protects against the development of diabetic peripheral neuropathy in type 2 diabetes mellitus

Background: Diabetic peripheral neuropathy (DPN) is one of the complications of type 2 diabetes mellitus (T2DM) that decreases the quality of life of T2DM patients. Very few studies have found an association between the development and progression of DPN in T2DM and angiotensin‐converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms. Methods: Using gene‐specific primers in a polymerase chain reaction, the presence of ACE I/D polymorphisms was screened for in 276 T2DM patients with DPN, 496 T2DM patients without DPN, and 331 control (non‐diabetic) subjects. Results: The distribution of the I/D genotypes was in Hardy–Weinberg equilibrium. The II genotype was significantly more prevalent in T2DM patients without DPN than the DD genotype (P < 0.05); however, there was no significant difference in the prevalence of the II and DD genotypes in T2DM patients with DPN (P = 0.78). Conclusion: The II genotype of the ACE gene has a protective effect against the development of DPN in T2DM patients. This suggests a role for the renin–angiotensin system in modulating neuropathy in T2DM.     

Impact of chronic kidney disease definition on assessment of its incidence and risk factors in patients with newly diagnosed type 1 and type 2 diabetes in the UK: A cohort study using primary care data from the United Kingdom

AimTo estimate the incidence and risk factors of chronic kidney disease (CKD) in patients with newly-diagnosed diabetes using different CKD definitions.MethodsUsing UK primary care data, patients with diabetes (type 1, 4691; type 2, 109,365) and no CKD were followed to identify newly-diagnosed CKD, classified by a broad and narrow CKD definition (to capture diabetes-induced CKD, termed diabetic kidney disease, DKD). Adjusted incidence rates of CKD/DKD were calculated, and risk factors identified using Cox regression.ResultsThere were 404 CKD cases and 147 DKD cases among patients with type 1 diabetes (T1D), and 29,104 CKD cases, 9284 DKD cases among patients with type 2 diabetes (T2D). Adjusted incidence rates of CKD per 100 years were 5.4 (T1D) and 5.5 (T2D); for DKD they were 1.9 and 1.5, respectively. Risk factors for CKD/DKD were older age, high social deprivation, obesity, cardiovascular disease, hypertension and smoking. Poor glycaemic control in the year after diabetes diagnosis was a strong predictor of CKD/DKD occurrence beyond this first year, and a risk factor for CKD/DKD in T2D.ConclusionsCKD and DKD remain common in diabetics in the decade after diagnosis. Early prevention of T2D and aggressive treatment of risk factors is urgent.     

High-dose thiamine therapy for patients with type 2 diabetes and microalbuminuria: a randomised, double-blind placebo-controlled pilot study

Aims/hypothesis  High-dose supplements of thiamine prevent the development of microalbuminuria in experimental diabetes. The aim of this pilot study was to assess whether oral supplements of thiamine could reverse microalbuminuria in patients with type 2 diabetes. Methods  Type 2 diabetic patients (21 male, 19 female) with microalbuminuria were recruited at the Diabetes Clinic, Sheikh Zayed Hospital, Lahore, Pakistan, and randomised to placebo and treatment arms. Randomisation was by central office in sequentially numbered opaque, sealed envelopes. Participants, caregivers and those assessing the outcomes were blinded to group assignment. Patients were given 3 × 100 mg capsules of thiamine or placebo per day for 3 months with a 2 month follow-up washout period. The primary endpoint was change in urinary albumin excretion (UAE). Other markers of renal and vascular dysfunction and plasma concentrations of thiamine were determined. Results  UAE was decreased in patients receiving thiamine therapy for 3 months with respect to baseline (median −17.7 mg/24 h; p < 0.001, n = 20). There was no significant decrease in UAE in patients receiving placebo after 3 months of therapy (n = 20). UAE was significantly lower in patients who had received thiamine therapy compared with those who had received placebo (30.1 vs 35.5 mg/24 h, p < 0.01) but not at baseline. UAE continued to decrease in the 2 month washout period in both groups, but not significantly. There was no effect of thiamine treatment on glycaemic control, dyslipidaemia or BP. There were no adverse effects of therapy. Conclusions/interpretation  In this pilot study, high-dose thiamine therapy produced a regression of UAE in type 2 diabetic patients with microalbuminuria. Thiamine supplements at high dose may provide improved therapy for early-stage diabetic nephropathy. Trial registration: CTRI (India) CTRI/2008/091/000112 Funding: Pakistan Higher Education Commission     

Screening for type 2 diabetes after a diagnosis of gestational diabetes by ethnicity: A retrospective cohort study

AimsTo estimate rates and identify determinants of post-partum glucose screening attendance in women with a history of gestational diabetes mellitus (GDM).MethodsRetrospective cohort study using the Clinical Practice Research Datalink linked to Hospital Episode Statistics, to identify women diagnosed with GDM between 01/01/2000 and 05/11/2018. Age adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression models.ResultsIn 10,868 women with GDM, with an average follow-up of 5.38 years (95% CI 5.31,5.45), there was an average of 3.79 (95% CI 3.70,3.89) screening episodes per individual, with a mean time to first screening test of 1.22 (95% CI 1.18, 1.25) years. South Asian women had a significantly greater likelihood of being screened compared to White women within the first 5 years post-partum, aOR: 1.89 95% CI (1.20,2.98). A low proportion of women received at least one test per year of follow-up (23.87%). Older age at GDM diagnosis, polycystic ovary syndrome, prescribed medication for GDM, and living in England, were all associated with a greater likelihood of being screened.ConclusionWhile the majority of women with previous GDM receive at least one glucose screening test within the first 5 years post-partum, fewer than a quarter of them receive on average one test per year of follow-up. Developing strategies to motivate more women to attend screening in primary care is essential.     

Gender differences in the incidence and progression of diabetic retinopathy among Japanese patients with type 2 diabetes mellitus: A clinic-based retrospective longitudinal study

A clinic-based retrospective longitudinal study conducted for 5.8 ± 2.5 years, including 383 (M/F 245/138) Japanese patients with type 2 diabetes mellitus showed that females exhibit a significantly higher prevalence of proliferative diabetic retinopathy (DR) at baseline and that female gender is an independent risk factor for the development of DR.     

A 6-year nationwide cohort study of glycaemic control in young people with type 1 diabetes. Risk markers for the development of retinopathy, nephropathy and neuropathy. Danish Study Group of Diabetes in Childhood

The study aimed to identify risk markers (present at the start of the study in 1989) for the occurrence and progression of microvascular complications 6 years later (in 1995) in a Danish nationwide cohort of children and adolescents with Type 1 diabetes (average age at entry 13.7 years). Probabilities for the development of elevated albumin excretion rate (AER), retinopathy, and increased vibration perception threshold (VPT) could then be estimated from a stepwise logistic regression model. A total of 339 patients (47% of the original cohort) were studied. Sex, age, diabetes duration, insulin regimen and dose, height, weight, HbA_1c, blood pressure, and AER were recorded. In addition, information on retinopathy, neuropathy (VPT), and anti-hypertensive treatment was obtained at the end of the study. HbA_1c (normal range 4.3–5.8, mean 5.3%) and AER (upper normal limit <20 μg min⁻¹) in two, timed overnight urine collections were analysed centrally. Eye examination was performed by two-field fundus photography. Determination of VPT was assessed by biothesiometry. Increased AER (≥20 μg min⁻¹) was found in 12.8% of the patients in 1995, and risk markers for this were increased AER and high HbA_1c, in 1989 (both p<0.001). Retinopathy was present in 57.8% of patients in 1995, for which the risk markers were long duration of diabetes (p<0.0001), age (p<0.01), and high HbA_1c (p<0.0001) in 1989. Elevated VPT (>6.5 V) was found in 62.5% of patients in 1995, for which the risk markers were male sex (p<0.05), age (p<0.0001), and increased AER (p<0.05) in 1989. This study confirms that hyperglycaemia plays a major role for the development of microvascular complications in kidneys and eyes, and emphasises the need for optimal glycaemic control in children and adolescents with Type 1 diabetes.