Autonomic Nervous System ; physiopathology ; Blood Pressure ; physiology ; Cardiovascular Diseases ; therapy ; Cardiovascular System ; physiopathology ; Diabetic Neuropathies ; therapy ; Humans

OBJECTIVE: To investigate the abnormalities in regional homogeneity of brain activity in patients with diabetic peripheral neuropathy (DPN) using resting-state functional magnetic resonance imaging (rs-fMRI) and explore the association between brain activity changes and DPN. METHODS: A regional homogeneity (ReHo) approach was used to compare the local synchronization of rs-fMRI signals among 20 patients with painful DPN, 16 patients with painless DPN, and 16 type 2 diabetic patients without DPN (non-DPN group). RESULTS: Compared with the those without DPN, the patients with painful DPN showed high ReHo in the left inferior temporal gyrus and the right central posterior gyrus, and low ReHo in the posterior cingulate gyrus, right inferior parietal gyrus, and the left superior parietal gyrus ( < 0.05);the patients with painless DPN group showed high ReHo in the left inferior temporal gyrus, the right middle temporal gyrus, and the right superior frontal gyrus, and low ReHo in the left thalamus ( < 0.05).No significant differences in ReHo were found between the patients with painful DPN and painless DPN (>0.05). CONCLUSIONS The patients with DPN have altered ReHo in multiple brain regions and impairment of a default mode network, for which the left temporal gyrus may serve as a functional compensatory brain area. ReHo disturbance in the central right posterior gyrus may play a central role in the pain symptoms associated with painful DPN.
Brain ; diagnostic imaging ; physiopathology ; Brain Mapping ; methods ; Diabetic Neuropathies ; physiopathology ; Gyrus Cinguli ; diagnostic imaging ; physiopathology ; Humans ; Magnetic Resonance Imaging ; methods ; Neuralgia ; physiopathology ; Temporal Lobe ; diagnostic imaging ; physiopathology

OBJECTIVETo compare the clinical efficacy between acupuncture and intravenous administration of lipoic acid and alprostadil for distal symmetric multiple peripheral neuropathy of diabetes mellitus.

METHODSSixty patients were randomly divided into an acupuncture group (31 cases) and a medication group (29 cases). Patients in the two groups received basic treatment to control blood sugar within a safe range. On this basis, patients in the acupuncture group were treated with acupuncture at Geshu (BL 17), Weiwanxiashu (EX-B 3), Ganshu (BL 18), Pishu (BL 20), Shenshu (BL 23), Zusanli (ST 36), Taixi (KI 3), ashi points, etc. Patients in the medication group were treated with intravenous administration of lipoic acid (0.6 g) and alprostadil (10 mg). The treatment was given once a day, 10 days for a course of treatment; there was an interval of 2 days between courses, and totally 3 courses were given. The score of peripheral neuropathy of diabetes mellitus, the change of nerve conduction: velocity and clinical efficacy before and after treatment in the two groups were observed.

RESULTSAfter treatment, the score of peripheral neuropathy was significantly reduced in the two groups (both P < 0.05), which was more significant in the acupuncture group (P < 0.05). After treatment, the sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity (MNCV) of median nerve and common peroneal nerve were significantly increased in the two groups (all P < 0.05). Compared between two groups, the SNCV and MNCV of common peroneal nerve in the acupuncture group were significantly superior to those in the medication group (both P < 0.05); the MNCV of median nerve in the acupuncture group was significantly superior to that in the medication group (P < 0.05); the SNCV of median nerve in the acupuncture group was not significantly different from that in the medication group (P > 0.05). The total effective rate was 83.9% (26/31) in the acupuncture group, which was significantly superior to 62.1% (18/29) in the medication group (P < 0.05).

CONCLUSIONAcupuncture and conventional medication both have satisfied effects for distal symmetric multiple peripheral neuropathy of diabetes mellitus, and acupuncture is superior to medication on improving clinical signs of sensory disorder, reflection disturbance and muscle weakness, nerve conduction and clinical curative effect.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Aged ; Diabetes Mellitus, Type 2 ; complications ; Diabetic Neuropathies ; etiology ; physiopathology ; therapy ; Female ; Humans ; Male ; Middle Aged ; Peripheral Nerves ; physiopathology ; Peripheral Nervous System Diseases ; etiology ; physiopathology ; therapy

To investigate the effects of Tongxinluo capsule on sciatic nerve apoptosis in spontaneous type II diabetic KK/Upj-Ay mice, in order to explore its mechanism for improving diabetic peripheral neuropathy (DPN). KK/Upj-Ay mice were selected as the DPN animal model and randomly divided into the model, Tongxinluo low, middle and high group (1, 2, 4 g x kg(-1)). C57BL/6 mice were selected as the control group. Mice were given intragastrically for 12 weeks. Paw withdrawal latency, motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) were detected. Apoptotic rate were detected by FCM. Bcl-2, Bax, Caspase-3 mRNA and protein expression in sciatic nerve were examined by Real-time PCR and Western blot. p38MAPK, p-p38MAPK expression were examined by Western blot. In this study,the authors found that Tongxinluo capsule could increase paw withdrawal latency, MNCV and SNCV. Apoptotic rate of sciatic, the expression of Bax and caspase-3 were lower, while Bcl-2 expression was higher in Tongxinluo group than those in model mice. The expression of p-p38MAPK significantly decreased in Tongxinluo group. The results showed that Tongxinluo capsule has protective effects on diabetic peripheral neuropathy of mice via inhibiting cell apoptosis and suppressing the expression of p-p38MAPK.
Animals ; Apoptosis ; drug effects ; Capsules ; administration & dosage ; Diabetic Neuropathies ; drug therapy ; physiopathology ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Sciatic Nerve ; cytology ; drug effects

OBJECTIVETo evaluate the small fiber function in patients with type 2 diabetes mellitus of the early stage by measuring the sensory threshold with the quantitative temperature testing technology.

METHODSTwenty cases of patients with type 2 diabetes with no neurological deficit (DM group) and twenty age and sex-matched healthy controls underwent the detecting of cold sensory threshold (CST), warm sensory threshold (WST), cold pain threshold (CPT), heat pain threshold (HPT) in both inside of their hands.

RESULTSThere was no significant difference in CST, WST, CPT and HPT between left and right inside of hand of the same sample among all the testers. But the four kinds of threshold showed significant difference in the right inside of hand between patients and healthy people ( P < 0.05). In addition, the CST and WST differed significantly in the left inside of hand between the patients and healthy controls while the CPT and HPT showed no significant difference in the left inside of hand between them. Patients group and control group with CST and WST on the left side of the comparison difference was statistically significant (P < 0.05).

CONCLUSIONQuantitative analysis of temperature sense threshold can not only reflect increase of the pain threshold value, also can reflect its decrease, i. e. hyperalgesia, which may help to diagnose small fibrous peripheral neuropathy recognition, especially in early diabetic peripheral neuropathy.

Case-Control Studies ; Cold Temperature ; Diabetes Mellitus, Type 2 ; physiopathology ; Diabetic Neuropathies ; diagnosis ; Hot Temperature ; Humans ; Hyperalgesia ; Pain Threshold ; Sensory Thresholds ; Thermosensing

OBJECTIVETo observe abnormalities in heart rate variability (HRV) in diabetic rats and to explore the effects of treatment with Guizhi Decoction ([symbols; see text]) on cardiac autonomic nervous (CAN) imbalance.

METHODSA radio-telemetry system for monitoring physiological parameters was implanted into rats to record electrocardiac signals and all indictors of HRV [time domain measures: standard deviation of all RR intervals in 24 h (SDNN), root mean square of successive differences (RMSSD), percentage of differences between adjacent RR intervals greater than 50 ms (PNN50), and standard deviation of the averages of RR intervals (SDANN); frequency domain measures: low frequency (LF), high frequency (HF), total power (TP), and LF/HF ratio]. The normal group was randomly selected, and the remaining rats were used to establish streptozocin (STZ)-induced diabetic model. After 4 weeks, the model rats were divided into the model group, the methycobal group, and the Guizhi Decoction group, 9 rats in each group. Four weeks after intragastric administration of the corresponding drugs, the right atria of the rats were collected for immunohistochemical staining of tyrosine hydroxylase (TH) and choline acetyltransferase (CHAT) to observe the distribution of the sympathetic and vagus nerves in the right atrium. The myocardial homogenate from the interventricular septum and the left ventricle was used for determination of TH, CHAT, growth-associated protein 43 (GAP-43), nerve growth factor (NGF), and ciliary neurotrophic factor (CNTF) levels using an enzyme-linked immunosorbent assay.

RESULTS(1) STZ rats had elevated blood glucose levels, reduced body weight, and decreased heart rate; there was no difference between the model group and the drug treated groups. (2) Compared with the model group, only RMSSD and TP increased in the methycobal group significantly (P<0.05); SDNN, RMSSD, PNN50, LF, HF, and TP increased, LF/HF decreased (P<0.05), and SDANN just showed a decreasing trend in the Guizhi Decoction group (P>0.05). TH increased, CHAT decreased, and TH/CHAT increased in the myocardial homogenate of the model group (P<0.05). Compared with the model group, left ventricular TH reduced in the methycobal group; and in the Guizhi Decoction group CHAT increased, while TH and TH/CHAT decreased (P<0.05). Compared with the model group, CNTF in the interventricular septum increased in the methycobal group (P<0.05); GAP-43 increased, NGF decreased, and CNTF increased (P<0.05) in the Guizhi Decoction group. There were significant differences in the reduction of NGF and elevation of CNTF between the Guizhi Decoction group and the methycobal group (P<0.05). (3) Immunohistochemical results showed that TH expression significantly increased and CHAT expression significantly decreased in the myocardia of the model group, whereas TH expression decreased and CHAT expression increased in the Guizhi Decoction group (P<0.05).

CONCLUSIONGuizhi Decoction was effective in improving the function of the vagus nerve, and it could alleviate autonomic nerve damage.

Animals ; Autonomic Nervous System ; drug effects ; physiopathology ; Choline O-Acetyltransferase ; metabolism ; Diabetes Mellitus, Experimental ; drug therapy ; physiopathology ; Diabetic Neuropathies ; drug therapy ; physiopathology ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Heart ; innervation ; physiopathology ; Heart Rate ; drug effects ; physiology ; Male ; Monitoring, Physiologic ; methods ; Rats, Wistar ; Telemetry ; methods ; Treatment Outcome ; Tyrosine 3-Monooxygenase ; metabolism ; Vagus Nerve ; drug effects ; physiopathology

Diabetes Mellitus ; Diabetic Neuropathies ; drug therapy ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Inventions

PURPOSE: We previously reported that insulin resistance, low high-density lipoprotein (HDL) cholesterol, and glycaemic exposure Index are independently associated with peripheral neuropathy in Korean patients with type 2 diabetes mellitus. We followed the patients who participated in that study in 2006 for another 6 years to determine the relationship between insulin resistance and neuropathy. MATERIALS AND METHODS: This study involved 48 of the original 86 Korean patients with type 2 diabetes mellitus who were referred to the Neurology clinic for the assessment of diabetic neuropathy from January 2006 to December 2006. These 48 patients received management for glycaemic control and prevention of diabetic complications in the outpatient clinic up to 2012. We reviewed blood test results and the nerve conduction study findings of these patients, taken over a 6-year period. RESULTS: Low HDL cholesterol and high triglycerides significantly influenced the development of diabetic neuropathy. Kitt value (1/insulin resistance) in the previous study affected the occurrence of neuropathy, despite adequate glycaemic control with HbA1c <7%. Insulin resistance affected the development of diabetic neuropathy after 6 years: insulin resistance in 2006 showed a positive correlation with a change in sural sensory nerve action potential in 2012. CONCLUSION: Diabetic neuropathy can be affected by previous insulin resistance despite regular glycaemic control. Dyslipidaemia should be controlled in patients who show high insulin resistance because HDL cholesterol and triglycerides are strongly correlated with later development of diabetic neuropathy.
Adult ; Diabetes Mellitus, Type 2/*metabolism/*physiopathology ; Diabetic Neuropathies/*metabolism/*physiopathology ; Female ; Humans ; Insulin Resistance/*physiology ; Logistic Models ; Male ; Middle Aged

OBJECTIVETo study the effects of Jinmaitong capsule on oxidative stress and cell apoptosis of dorsal root ganglion (DRG) in rats with diabetic peripheral neuropathy.

METHODSSixty male SD rats were randomly divided into normal group and model groups. The diabetic rat models were established using Streptozotocin (STZ) method (60 mg/kg of intraperitoneal injection), and then randomly divided Jinmaitong low, middle, and high-dose groups and vitamin C group. All the experimental rats were sacrificed at 16-week and then the DRG was isolated. The morphological changes of DRG were observed using the Nissl's staining, and the NADPH oxidase subunit p22-phox, Cyt C, Bcl-2, and Caspase-3 of DRG in rats were detected by immunohistochemistry and quantitative reverse transcription PCR (qRT-PCR). Cell apoptosis was detected by TUNEL.

RESULTSCompared with the model group, the expressions of NADPH oxidase subunit p22-phox protein, Cyt expression of C protein, Caspase-3 protein, and mRNA cell apoptosis rate in each treatment group significantly decreased whereas the expressions of Bcl-2 mRNA and protein significantly increased (P<0.05 or P<0.01). The Jinmaitong high-dose group had the best effect and was significantly different from that of the vitamin C group (P<0.01).

CONCLUSIONSJinmaitong capsule can prevent the nerve injury in rats with diabetic peripheral neuropathy by inhibiting oxidative stress and decreasing the apoptosis. The high-dose Jinmaitong capsule has the best effect and is superior to vitamin C.

Animals ; Apoptosis ; drug effects ; Capsules ; Caspase 3 ; metabolism ; Diabetes Mellitus, Experimental ; Diabetic Neuropathies ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Ganglia, Spinal ; physiopathology ; Male ; Oxidative Stress ; drug effects ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley

Diabetic peripheral neuropathy (DPN), one of the most common chronic complications of diabetes, is characterized by allodynia, hyperalgesia and spontaneous pain. Chinese epidemiological studies have shown that at least 25% diabetic patients suffered from painful DPN, which compromises patients' daily functioning and becomes a major health care problem. Although the pathogenesis of painful DPN is not fully understood and current treatment options are very limited, research in the field has advanced our understanding on the mechanism of painful DPN in the past Decade of Pain Research and Control. This review will mainly focus on evaluation of current diabetic animal models, possible molecular pathways and available therapies, with an emphasis on roles of purinergic receptor and its signaling transduction pathways. Common therapies address one or two DPN symptoms, while others offer wider symptom control, presumably by targeting pathophysiological mechanisms of DPN. Purinergic receptor signaling transduction pathways might become potential targets for treatment for painful DPN.
Animals ; Diabetes Mellitus ; physiopathology ; Diabetic Neuropathies ; physiopathology ; Humans ; Hyperalgesia ; physiopathology ; Pain ; physiopathology ; Receptors, Purinergic P2X ; physiology