综合分析法诊断糖尿病周围神经病变对其临床特点和发病危险因素的影响

目的:通过临床和仪器等检查,综合分析诊断糖尿病周围神经病变,探讨其临床特点与发病相关危险因素的变化。方法:筛选434例2型糖尿病患者,收集其一般临床数据,如病史、身高、体重、血压、空腹血糖(FPG)、餐后2h血糖(PPG)、空腹血浆胰岛素(FIns)水平和血脂指标等,结合神经传导速度(NCV)、定量感觉检查(QST)(包括温度觉、振动觉、触觉和痛觉)结果,将其分为有或非糖尿病神经病变组,统计分析神经病变发病情况以及与这些指标的关系。结果:入选糖尿病患者的NCV检查异常率为52.3%,QST异常为62.9%,综合分析结果异常为63.6%,随着年龄和糖尿病病程的增长,神经病变的发生率增加;神经病变组的年龄、糖尿病病程、糖尿病家族史、吸烟史、饮酒史、身高、体重指数、收缩压、PPG、FIns水平、尿微量蛋白、血肌酐(Scr)等数据明显高于非神经病变组,并与神经病变发病相关(P<0.05),这些指标中年龄、身高、糖尿病病程、PPG、FIns水平、Scr是神经病变发病的危险因素(P<0.05)。结论:结合临床和仪器检查综合分析诊断糖尿病神经病变符合疾病的实际特点,最大限度地减少漏诊;分析后的发病相关危险因素与其他诊断方法相似。     

Prevalence of peripheral neuropathy in type 2 diabetic patients attending a diabetes center in Turkey

The aim of this study was to determine the prevalence and risk factors for neuropathy in type 2 diabetic patients attending a major Turkish diabetes center. Eight hundred and sixty-six consecutive type 2 diabetic patients were included in the study. A single observer performed biothesiometry studies on these patients. The presence of diabetic neuropathy was investigated using neurological symptom scale (NSS) and neurological disability score (NDS) performed. Neuropathy was determined with standardized neurological examinations and defined as the presence of abnormal NSS and NDS together with abnormal sensory or motor signs and symptoms as well as decreased great toe vibration perception. Overall, 60% (n = 520) of the patients were diagnosed as having neuropathy. The prevalence of neuropathy increased with age (p < 0.001) and duration of diabetes (p < 0.001). Multiple logistic regression analysis revealed the duration of diabetes (p < 0.001) and HbA1c levels (p < 0.001) as the risk factors for neuropathy. The overall prevalence of neuropathy in Turkish type 2 diabetic population was 60%. Age, duration of diabetes, and poor glycemic control were considered to be the risk factors for neuropathy.     

Exercise training can modify the natural history of diabetic peripheral neuropathy

BACKGROUND: Diabetes is the most important cause of peripheral neuropathy (DPN). No definitive treatment for DPN has been established, and very few data on the role of exercise training on DPN have been reported. AIM OF THE STUDY: We sought to examine the effects of long-term exercise training on the development of DPN in both Types 1 and 2 diabetic patients. PARTICIPANTS AND METHODS: Seventy-eight diabetic patients without signs and symptoms of peripheral DPN were enrolled, randomized, and subdivided in two groups: 31 diabetic participants [15 f, 16 m; 49+/-15.5 years old; body mass index (BMI)=27.9+/-4.7], who performed a prescribed and supervised 4 h/week brisk walking on a treadmill at 50% to 85% of the heart rate reserve (exercise group: EXE), and a control group of 47 diabetic participants (CON; 24 f, 23 m; 52.9+/-13.4 years old; BMI=30.9+/-8.4). Vibration perception threshold (VPT), nerve distal latency (DL), nerve conduction velocity (NCV), and nerve action potential amplitude (NAPA) in the lower limbs were measured. RESULTS: We found significant differences on Delta (delta) in NCV for both peroneal and sural motor nerve between the EXE and CON groups during the study period (P<.001, for both). The percentage of diabetic patients that developed motor neuropathy and sensory neuropathy during the 4 years of the study was significantly higher in the CON than the EXE group (17% vs. 0.0%, P<.05, and 29.8% vs. 6.45%, P<.05, respectively). In addition, the percentage of diabetic patients who developed increased VPT (25 V) during the study was significantly higher in the CON than the EXE group (21.3% vs. 12.9%, P<.05). Change on Hallux VPT from baseline to the end of the study was significantly different between the EXE and CON groups (P<.05); no significant change in Malleolus VPT between the two groups occurred. CONCLUSIONS: This study suggests, for the first time, that long-term aerobic exercise training can prevent the onset or modify the natural history of DPN.     

Nerve growth factor and expression of its receptors in patients with diabetic neuropathy

Aims Low serum nerve growth factor (NGF) levels have been reported in patients with diabetic peripheral neuropathy (DPN), but the role of NGF in the development of neuropathy is unclear. Thus, we investigated the associations of serum NGF level and NGF receptor activity with the presence and severity of DPN. Methods One hundred and thirty‐six patients with Type 2 diabetes were included in this cross‐sectional study. Serum NGF levels were measured by ELISA. Expressions of NGF receptors (TrkA and p75^NTR) were measured by immunohistochemical staining. The presence and severity of DPN were assessed by neuropathy disability score (NDS) and by corneal nerve fibre length (cNFL) and nerve branch density (cNBD) using in vivo confocal microscopy. Results Patients with DPN had higher serum NGF levels (56–451 pg/ml) than patients without DPN (4–54 pg/ml). However, in DPN patients, serum NGF was negatively associated with neuropathy severity (mild 222 ± 64 pg/ml; moderate 114 ± 17 pg/ml; severe 89 ± 20 pg/ml). This negative association was consistent in all severity indices (NDS, P < 0.001; cNFL, P < 0.001; cNBD P = 0.010) even after adjustment for age, sex, diabetes duration, insulin use, fasting glucose and glycated haemoglobin. Although NGF receptor activities had significantly (P < 0.05) negative associations with the presence and severity of neuropathy, these associations were not significant when adjusted for other factors. Conclusions Serum NGF level was positively associated with the presence of DPN but negatively associated with neuropathy severity in DPN patients. The change in serum NGF might be a consequence of, rather than a contributor to, the early development of DPN.     

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.     

Cardiac autonomic neuropathy in diabetic patients: influence of diabetes duration,obesity, and microangiopathic complications--the French multicenter study

The current study sought to examine in a large series of diabetic patients the prevalence of symptoms of autonomic neuropathy and subclinical cardiac autonomic neuropathy (CAN) and their determinants, particularly the influence of diabetes duration, obesity, and microangiopathic complications. Three hundred ninety-six patients, 245 type 1 and 151 type 2, were recruited in 7 French departments of diabetology. CAN was detected by measuring heart rate variability during 3 standardized tests: deep-breathing, Valsalva, and lying-to-standing tests. At least 24.5% of the patients had one or more symptoms suggesting overt autonomic neuropathy. They were older than those free of dysautonomic symptom (P<.001). The deep-breathing test correlated negatively with body mass index (BMI) in type 2 diabetic patients (P<.0001). In the whole population, the deep-breathing and Valsalva tests correlated negatively with diabetes duration (P=.0004 and.019, respectively) and the log urinary albumin/creatinine ratio (P<.002 and.001, respectively). The prevalence of CAN (51%) was higher than the prevalence of other diabetic complications. The rate of moderate and severe CAN (defined by 2 or 3 abnormal CAN function tests) was higher in type 1 than in type 2 diabetic patients (P=.031). It correlated with diabetes duration (P=.026) and was higher in the patients with retinopathy than in those without (P=.035). Among type 2 diabetic patients, the prevalence of CAN was higher in the obese ones (P=.033); in a logistic regression taking age, diabetes duration, and obesity as independent variables, CAN was associated independently with obesity (P=.034). Mild or moderate CAN was found in 33.8% and 13.0% of the 80 patients with diabetes duration less than 18 months. We conclude that CAN is found early in the course of diabetes and should be considered as a prognostic marker of microangiopathic complications. Obesity could be involved in the impairment of CAN function in type 2 diabetics and body weight control could provide an approach to reducing neuropathic complications.     

血管内皮生长因子基因3'-非翻译区936C/T多态性与2型糖尿病外周神经病变相关

目的 探讨血管内皮生长因子(VEGF)基因3'-非翻译区936C/T多态性与山东地区汉族人2型糖尿病合并周围神经病变(DPN)之间的关系.方法 194例糖尿病患者分为单纯糖尿病组(n=92)和糖尿病神经病变组(n=102),另120名健康个体设为健康对照组.采用PCR-限制性片段长度多态性(RFLP)方法确定全部个体的基因型;对不同基因型间及病例组间的临床与生化参数、血清VEGF浓度以及VEGF基因936C/T多态性进行了统计分析.结果 糖尿病神经病变组C等位基因及CC基因型频率显著高于对照组(x2为9.406和9.677,P＜0.05)和糖尿病组(x2为5.578和5.614,P＜0.05),而携带T等位基因的基因型(CT+TT)频率及T等位基因频率显著低于对照组(x2为9.406和9.677,P＜0.05)和糖尿病组(x2为5.578和5.614,P＜0.05).Logistic多元回归分析显示血清低密度脂蛋白胆固醇(LDL-C)、总胆固醇、HbA1c水平以及VEGF浓度与DPN发生呈正相关,而VEGF基因936C/T多态性与糖尿病周围神经病变发病危险呈负相关(β=-1.046,OR=0.457,P=0.006,95%CI:0.166～0.741).结论 中国山东地区汉族人群中存在VEGF基因936C/T多态性,C等位基因及CC基因型患者可能是糖尿病易于发生神经病变危险性的遗传标志,而T等位基因和携带T等位基因的基因型(936TF基因型和936CT基因型)可能是降低糖尿病发生神经病变风险的遗传标志.

Abstract：

Objective To elucidate the relationship between a 936C/T mutation at 3'-untranslated region of human vascular endothelial growth factor(VEGF) gene and diabetic peripheral neuropathy ( DPN ). Methods All subjects recruited in this study were assigned into DM (n = 92, diabetes without neuropathy, retinopathy or nephropathy), DPN (n = 102, diabetes with peripheral neuropathy only ), and healthy control (n = 120 ) groups,respectively. The gene polymorphism was determined by PCR-RFLP, as well as the other clinical parameters including serum VEGF by ELISA. Results The frequencies of both genotype CC and allele C were significantly higher in DPN group than those in either DM group(x2 = 5.578 and 5.614, P＜0. 05 ) or control group (x2 = 9. 406 and 9. 677, P＜0. 05 ). However, the frequencies of genotype(CT+TT) and allele T were significantly lower in DPN group than that in either DM group(x2 =5.578 and 5.614, P＜0. 05) and control group (x2=9.406 and 9.677, P＜0.05). The multivariate logistic regression analysis showed that the levels of HbA1c, total cholesterol, low-density lipoproteincholesterol( LDL-C ), and serum VEGF positively correlated with DPN, while the 936C/T polymorphism of VEGF gene negatively correlated with DPN(β= -1. 046, OR=0. 457, P=0. 006, 95% CI: 0. 166-0. 741 ). Conclusions Allele 936C of VEGF gene may serve as a genetic marker susceptible to DPN, while allele 936T may be a protective genetic marker of DPN.     

神经症状/神经缺陷评分与神经传导速度诊断糖尿病周围神经病变的相关性

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

Median neuropathy at the wrist as an early manifestation of diabetic neuropathy

Aims/Introduction

To elucidate the clinical significance of median neuropathy at the wrist (MN) in patients with diabetes.

Materials and Methods

In total, 340 patients with diabetes who were hospitalized for glycemic control were enrolled in the present study. The diagnoses of MN and diabetic polyneuropathy (DPN) were based on electrophysiological criteria. A total of 187 patients were divided into four subgroups: patients without MN or DPN; patients with MN without DPN; patients with MN and DPN; and patients with DPN without MN. Intergroup comparisons of clinical characteristics and results of nerve conduction studies were carried out.

Results

A total of 71 patients had neither MN nor DPN; 25 had MN, but no DPN; 55 had MN and DPN; and 36 had DPN, but no MN. In comparison with the MN and DPN group, the MN without DPN group included more patients in the early phase of diabetes (diagnosed within the past 5 years) and fewer patients with diabetic microangiopathy. Comparative median nerve conduction studies showed significantly lower motor and sensory nerve conduction velocities, longer F-wave latencies, and smaller sensory nerve action potentials in patients with MN and DPN than in those without DPN.

Conclusions

MN in patients with diabetes could be attributed to an impairment in axonal function at common entrapment sites, and could be used to identify an early manifestation of diabetic neuropathy.     

Evaluation of three screening tests and a risk assessment model for diagnosing peripheral neuropathy in the diabetes clinic

OBJECTIVE: with the aim of evaluating predictive power, three simple screening tests as alternates to nerve conduction tests for diagnosing diabetic peripheral neuropathy (DPN) were investigated. Results of the screening tests, along with the subjects' demographic and clinical characteristics, were planned as the variables for the development of a risk assessment tool for predicting DPN. DESIGN: this is a cross-sectional multi-group comparison study. The study utilized a predictive model derived from one subset of the study population, and prospectively tested in the other subset to predict the presence of neuropathy. SETTING: Diabetic Neuropathy Research Clinic of the Toronto General Hospital and University Health Network in Toronto, Ontario, Canada from June 1998 to August 1999. SAMPLE POPULATION: data come from 478 subjects consisting of non-diabetic reference subjects, and patients with type 1 and type 2 diabetes mellitus. OUTCOMES MEASURES: nerve conduction studies (NCS) comprised the primary defined outcome. The three screening sensory tests examined in the study were the Semmes-Weinstein 10 g monofilament examination (SWME), superficial pain sensation, and vibration by the on-off method. RESULTS: the three screening tests are significantly and positively correlated with NCS. An increase in the number of insensate responses in the screening test is associated with an increase in the abnormal NCS score. The strength of the association between NCS and each sensory test was greater when the neuropathy severity stage of the subject was added to the model. Both the SWME and vibration by the on-off method tests demonstrated sufficient statistical power to differentiate non-diabetic control subjects from subjects with diabetes, as well as to differentiate subjects with diabetes with and without neuropathy. These two tests, when compared with NCS, also demonstrated acceptable diagnostic performance characteristics in terms of high sensitivity and specificity, total number of correctly predicted cases, and receiver-operating characteristic curves. CONCLUSION: this data, through the development of a model involving training and validation sets, demonstrates that the knowledge of clinical risk factors alters the interpretation of sensory tests for DPN. This finding lends further support to the validity of simple sensory testing maneuvers in the conditional diagnosis of DPN. We recommend annual screening with either the SWME or vibration by the on-off method in the primary care and diabetes clinics.     

Retinal Microcirculation in Type 1 Diabetic Patients With and Without Peripheral Sensory Neuropathy

In patients with diabetes mellitus (DM), early retinal microvascular alterations can be observed even before the clinical diagnosis of diabetic retinopathy. This study aimed to investigate morphological and functional changes in retinal microvascular blood flow in type 1 diabetic patients with and without peripheral neuropathy (PNP) as compared to nondiabetic controls. Retinal microvascular blood flow (RBF) was assessed using scanning laser Doppler flowmetry (Heidelberg Retina Flowmeter, Heidelberg Engineering, Germany) before and after stimulation with flicker light. PNP was assessed using the neuropathy disability score (NDS) and by the evaluation of the vibration perception threshold (VPT). A total of 41 subjects were recruited for study participation and were stratified to 3 different groups according to their metabolic and neurological status: 14 nondiabetic subjects without PNP, 14 diabetic patients without PNP, and 13 diabetic patients with PNP. All subjects were free from diabetic retinopathy as assessed by fundoscopy. In diabetic patients with PNP, baseline and stimulated RBF was higher compared with diabetic patients without PNP and the nondiabetic control group. No difference with regard to RBF could be observed between the nondiabetic control subjects and patients with type 1 DM without PNP. No difference in the arterial WLR could be observed between the 3 groups. A linear correlation was found for VPT and RBF (r = .38, P < .001) and for NDS and RBF (r = .44, P < .0001). In our study population of patients with type 1 diabetes, PNP was associated with functional but not morphological changes in RBF.     

Usefulness of the vibration perception thresholds measurement as a diagnostic method for diabetic peripheral neuropathy: Results from the Rio de Janeiro type 2 diabetes cohort study

Aims

To investigate the associated factors with the vibration threshold perception (VPT) in patients with type 2 diabetes and to assess whether it is useful for detection of diabetic peripheral neuropathy (DPN).

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.     

Prevalence of diabetic complications in fibrocalculous pancreatic diabetic patients and type 2 diabetic patients: a cross-sectional comparative study

OBJECTIVE: To determine the prevalence of diabetes-related complications in subjects with fibrocalculous pancreatic diabetes (FCPD) and compare them with subjects with type 2 diabetes mellitus matched for age, sex, and duration of diabetes. METHODS: The study group comprised of 277 FCPD patients and 277 age, sex, and duration of diabetes-matched type 2 diabetic patients. All the study subjects underwent a detailed clinical examination, and fasting blood samples were obtained for biochemical studies. Peripheral Doppler was used for diagnosis of peripheral vascular disease (PVD). Vibratory perception threshold (VPT) was determined using biothesiometry for diagnosis of neuropathy. Diagnosis of coronary artery disease (CAD) was based on medical history and 12-lead resting ECG. Retinal photographs were used for diagnosis of retinopathy using a modified version of Early Treatment Diabetic Retinopathy Study (ETDRS) grading system. RESULTS: FCPD patients had lower body mass index (BMI) (P<.001), systolic blood pressure (P<.0001), diastolic blood pressure (P<.001), serum cholesterol (P<.001), serum triglyceride (P<.001), and serum creatinine (P<.01) but higher glycosylated hemoglobin (P<.001) levels compared to patients with type 2 diabetes. Prevalence of CAD was significantly higher among type 2 diabetic patients (11.9%) compared to FCPD patients (5.1%), P<.003. There was no significant difference in the prevalence of other diabetic complications between the two study groups (type 2 diabetes vs. FCPD: retinopathy-37.2% vs. 30.1%, PVD-4.3% vs. 4.7%, Neuropathy-25.3% vs. 20.9%, Nephropathy-15.0% vs. 10.1%). Multiple logistic regression analysis revealed the following risk factors for diabetes complications among type 2 diabetic subjects-retinopathy: BMI (P=.028), duration of diabetes (P<.001), and glycosylated hemoglobin (P=.026); nephropathy: diastolic blood pressure (P=.016) and glycosylated hemoglobin (P=.040); neuropathy: age (P<.001), duration of diabetes (P=.003), and glycosylated hemoglobin (P=.001). Among subjects with FCPD, systolic blood pressure (P=.013), glycosylated hemoglobin (P=.021), and duration of diabetes (P<.001) were associated with retinopathy; BMI (P=.057), glycosylated hemoglobin (P=.010), and duration of diabetes (P=.024) with nephropathy and age (P=.011) and BMI (P=.010) with neuropathy. Conclusion: The prevalence of retinopathy, nephropathy, neuropathy, and PVD was similar among FCPD patients and type 2 diabetic patients, but the prevalence of CAD was lower among FCPD patients.     

Transforming growth factor beta 1 as a biomarker of diabetic peripheral neuropathy: cross-sectional study

BackgroundSimple and efficient screening methods are lacking for diabetic peripheral neuropathy (DPN), the most common and most difficult to treat of the long-term diabetic complications. Increased levels of transforming growth factor beta 1 (TGFβ1) in type 2 diabetic patients (T2DM) plays an immunomodulatory role in diabetic nephropathy and, possibly, in atherosclerotic evolution. Since preliminary interrelationships between experimental DPN and TGFβ1 have been observed, we sought to assess whether TGFβ1 could be a biomarker molecule for human DPN.Materials and MethodsCross-sectional cohort study focused on the assessment of the interrelationships between TGFβ1 levels, cardiovascular disease (CVD), diabetic nephropathy (DNF), and neuropathy (DPN) in a group of T2DM patients (N=180; male 117, female 63) randomly selected from the North Catalonia Diabetes Study. DPN was diagnosed using clinical and neurophysiology evaluation. Incipient DNF was assessed by microalbuminuria (MAU). Total TGFβ1 (without acidification) was measured by immunoassay by ELISA (Promega).ResultsDPN correlated with age, time of diabetes duration, MAU, CVD, and TGFβ1 (P<.0001). Log-transformed TGFβ1 (logTGβ1) was significantly higher in patients with DPN than in those without (P<.0005). LogTGFβ1 (OR=7.5; P=.006), age (OR=1.1; P<.0005), and logMAU (OR=2.0; P=.016) appear as significant estimators of the occurrence of DPN in our series. The integrated ROC curve evaluation with these three parameters expressed an important sensitivity (78.1%), specificity (76.0%), positive predictive value (79.2%), and negative predictive value (70.3%) in relation to DPN presence.DiscussionTGFβ1 stands as an important biomarker molecule for DFN and DPN screening in our series. Further prospective studies are warranted.     

Tear production and corneal sensitivity in diabetes

AIM: Diabetic patients are at significant risk of developing corneal lesions such as superficial punctate keratitis, recurrent corneal erosions, persistent epithelial defects, and microbial keratitis. The aim of this study was to investigate whether diabetes mellitus is correlated with both reduced corneal sensation and reduced tear production. METHODS: In 25 type II diabetic patients with a history of retinopathy only and in 25 nondiabetic control subjects (age and sex matched), we performed noncontact corneal aesthesiometry and assessed basal tear production using Schirmer's test with topical anesthesia. The noncontact corneal aesthesiometer (NCCA) is a new noninvasive device for quantifying threshold corneal sensitivity. RESULTS: The diabetic patients demonstrated a significantly reduced Schirmer's test result (P<.001) and significantly reduced corneal sensitivity (P<.01). CONCLUSION: Our study supports previous reports of reduced basal tear production, lending more support to the theory of a peripheral neuropathy affecting lacrimal gland function in diabetes. We also confirmed reduced threshold corneal sensitivity in diabetic patients using the NCCA.     

Prevalence and risk factors for diabetic neuropathy and painful diabetic neuropathy in primary and secondary healthcare in Qatar

Aims/IntroductionThis study determined the prevalence and risk factors for diabetic peripheral neuropathy (DPN) and painful DPN (pDPN) in patients with type 2 diabetes in primary healthcare (PHC) and secondary healthcare (SHC) in Qatar.Materials and MethodsThis was a cross‐sectional multicenter study. Adults with type 2 diabetes were randomly enrolled from four PHC centers and two diabetes centers in SHC in Qatar. Participants underwent assessment of clinical and metabolic parameters, DPN and pDPN.ResultsA total of 1,386 individuals with type 2 diabetes (297 from PHC and 1,089 from SHC) were recruited. The prevalence of DPN (14.8% vs 23.9%, P = 0.001) and pDPN (18.1% vs 37.5%, P < 0.0001) was significantly lower in PHC compared with SHC, whereas those with DPN at high risk for diabetic foot ulceration (31.8% vs 40.0%, P = 0.3) was comparable. The prevalence of undiagnosed DPN (79.5% vs 82.3%, P = 0.66) was comparably high, but undiagnosed pDPN (24.1% vs 71.5%, P < 0.0001) was lower in PHC compared with SHC. The odds of DPN and pDPN increased with age and diabetes duration, and DPN increased with poor glycemic control, hyperlipidemia and hypertension, whereas pDPN increased with obesity and reduced physical activity.ConclusionsThe prevalence of DPN and pDPN in type 2 diabetes is lower in PHC compared with SHC, and is attributed to overall better control of risk factors and referral bias due to patients with poorly managed complications being referred to SHC. However, approximately 80% of patients had not been previously diagnosed with DPN in PHC and SHC. Furthermore, we identified a number of modifiable risk factors for PDN and pDPN.     

Early diabetic neuropathy： Triggers and mechanisms

Peripheral neuropathy, and specifically distal peripheral neuropathy (DPN), is one of the most frequent and troublesome complications of diabetes mellitus. It is the major reason for morbidity and mortality among diabetic patients, It is also frequently associated with debilitating pain. Unfortunately, our knowledge of the natural history and pathogenesis of this disease remains limited. For a long time hyperglycemia was viewed as a major, if not the sole factor, responsible for all symptomatic presentations of DPN. Multiple clinical observations and animal studies supported this view. The control of blood glucose as an obligatory step of therapy to delay or reverse DPN is no longer an arguable issue. However, while supporting evidence for the glycemic hypothesis has accumulated, multiple controversies accumulated as well.It is obvious now that DPN cannot be fully understood without considering factors besides hyperglycemia. Some symptoms of DPN may develop with little, if any, correlation with the glycemic status of a patient. It is also clear that identification of these putative non-glycemic mechanisms of DPN is of utmost importance for our understanding of failures with existing treatments and for the development of new approaches for diagnosis and therapy of DPN. In this work we will review the strengths and weaknesses of the glycemic hypothesis, focusing on clinical and animal data and on the pathogenesis of early stages and triggers of DPN other than hyperglycemia.     

Peripheral neuropathy does not invariably coexist with autonomic neuropathy in diabetes mellitus

Background: Peripheral somatic and autonomic neuropathies are the most common types of diabetic polyneuropathy. Although duration and degree of hyperglycemia are considered to be risk factors for both autonomic and peripheral neuropathy, recent studies have raised the question of a different development and natural history of these neuropathies in diabetes. In addition, a few studies have investigated the relationship between chronic painful and autonomic neuropathy. The aim of this study was to investigate to what extent autonomic and peripheral neuropathy coexist, as well as whether painful neuropathy is more common in diabetic patients with autonomic neuropathy. Methods: Subjects with type 1 (n=52; mean age 31.7 years) and type 2 diabetes (n=53; mean age 54.5 years) were studied. Evaluation of peripheral neuropathy was based on clinical symptoms (neuropathic symptom score), signs (neuropathy disability score), and quantitative sensory testing (vibration perception threshold). Assessment of autonomic neuropathy was based on the battery of standardized cardiovascular autonomic function tests. Results: Prevalence rates of pure autonomic and of pure peripheral neuropathy in patients with type 1diabetes were 28.8 and 13.5%, respectively. The respective rates in patients with type 2 diabetes were 20.7% (P=0.33 vs. type 1 diabetes) and 20.7% (P=0.32). Peripheral and autonomic neuropathy coexisted in 28.8% of type 1 and in 45.3% of type 2 diabetic subjects (P=0.08). Prevalence rates of chronic painful neuropathy in subjects with type 1 diabetes, with and without autonomic neuropathy, were 16.6 and 22.7%, respectively (P=0.85) and in type 2 diabetic subjects 20 and 22.2%, respectively (P=0.58). Multivariate analysis after adjustment for age, sex, blood pressure, duration of diabetes, HBA(1c), and presence of retinopathy or microalbuminuria showed that neither the indices of peripheral nerve function (neuropathic symptom score, neuropathy disability score, vibration perception threshold) nor the presence of peripheral neuropathy or chronic painful neuropathy are associated with the presence of autonomic neuropathy in individuals with either type 1 or type 2 diabetes. Conclusions: Peripheral and autonomic neuropathies do not invariably coexist in diabetes. In addition, chronic painful neuropathy may be present irrespective of the presence of autonomic neuropathy.