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

Impaired wound healing in diabetes is a significant clinical problem which is thought to be associated with neuropathy and angiopathy previously . The present study indicates that accumulation of glucose and glycometabolic products in skin tissue, as the result of glycometabolic disorders, which contributes to cutaneous environmental alterations in diabetes mellitus, and subsequently induces the abnormal cell behaviors, cytokine alteration and matrix modification. Thus, diabetic neuropathy and angiopathy might be regarded as the pathological outcome of cutaneous environmental alterations. In conclusion, glycometabolism disorders could be described as one of the initial events for the alteration involving in the underlying cutaneous disorder which impair healing process. The related research focuses on the initial event of controlling disorders in wound healing and therefore contribute to providing the strategy of treatment as based on these approaches.
Diabetes Mellitus ; metabolism ; physiopathology ; Humans ; Skin ; metabolism ; Wound Healing

Patients with type 2 diabetes mellitus experience a complete and comfirm diabetic remission after bariatric surgery. Although weight-loss, reduction of food intake and other factors may play important roles in diabetic resolution after bariatric surgery, the major mechanism is the change in gastrointestinal hormones. Further research is essential to better understand these mechanisms and bariatric surgery may ultimately become a major tool in the treatment of type 2 diabetes mellitus.
Bariatric Surgery ; Diabetes Mellitus, Type 2 ; physiopathology ; surgery ; Humans

The changes in excitability and autorhthmicity of bladder detrusor in experimental non-insulin dependent diabetes mellitus (NIDDM) rats were observed. Sixty-nine NIDDM rats as NIDDM group and 69 normal rats as control group were enrolled into this experimental study. At 6th, 10th, 14th, 18th, 22nd and 26th week after the rats were injected last time, the changes in the excitability and autorhthmicity of detrusor strips in vitro were observed. The results showed that the threshold of the tension which made the detrusor strips contract was significantly higher in NIDDM group (0.716 +/- 0.325 g) than in control group (0.323 +/- 0.177 g) (F = 59.63, P < 0.001). At different stages, the threshold of the tension resulting the contract of the detrusor strips in NIDDM group was also higher than in control group. At 18th week after STZ injection, the frequency of spontaneous contract of the detrusor strips in NIDDM was significantly higher than in control group (P < 0.05), whereas at 22nd week, that in NIDDM group was significantly lower than in control group (P < 0.05). It was concluded that the decreased excitability of the bladder detrusor was the earliest and most obvious changes in bladder function in diabetes rats and the autorhthmicity had also changed at the early stage of diabetic bladder.
Diabetes Mellitus, Experimental/*physiopathology ; Diabetes Mellitus, Type 2/physiopathology ; Muscle Contraction/physiology ; Muscle Relaxation/physiology ; Rats, Wistar ; Urinary Bladder/*physiopathology ; Urinary Bladder Diseases/etiology ; Urinary Bladder Diseases/*physiopathology

OBJECTIVEThe prevalence of obesity and of type 2 diabetes mellitus in children have increased in the Chinese population over the past two decades, and thus diabetes prevention has become a major concern of public health agencies. Identification of individuals at risk for diabetes is an essential first step in designing and implementing intervention programs. Insulin resistance is the hallmark of the pathophysiology of type 2 diabetes mellitus. Subjects with hyperinsulinemia and impaired glucose tolerance are well accepted as being at high risk for diabetes. Acanthosis nigricans (AN) has been proposed as a reliable marker of hyperinsulinemia, but its utility for predicting hyperinsulinemia has not been systematically evaluated in obese children. In order to further explore the relationship between obese childhood with benign acanthosis nigricans and insulin resistance and type 2 diabetes mellitus, we examined 19 obese children with benign acanthosis nigricans.

METHODSNineteen of seventy six obese children (25%) with BMI over 25 enrolled in the Children' Hospital of Zhejiang University School of Medicine fromJune 1st to September 1st in 2003 were studied. Skin biopsies were performed in these 19 obese children with acanthosis nigricans for final diagnosis. Levels of glucose, insulin, and glucose/insulin ratio were measured on fasting blood specimens and anthropometric parameters including waist/hip ratio, fat mass, body fat percentage and body mass index were examined. Oral glucose tolerance tests were also performed in these 19 children with benign acanthosis nigricans.

RESULTSAnthropometric parameters including waist/hip ratio, fat mass, body fat percentage and body mass index as well as fasting insulin level in acanthosis nigricans group were significantly higher than that of healthy controls (P < 0.01). Fasting glucose to insulin ratio (FGIR) of these 19 obese children with benign acanthosis nigricans was 4.27 +/- 0.53, indicating apparent insulin resistance. One of them was diagnosed as type 2 diabetes mellitus and ten of them showed impaired oral glucose tolerance.

CONCLUSIONChildhood benign acanthosis nigricans is tightly associated with obesity, hyperinsulinemia, insuline resistance and type 2 diabetes mellitus, and may be used as a reliable index of insulin resistance.

Acanthosis Nigricans ; complications ; physiopathology ; Child ; Diabetes Mellitus, Type 2 ; complications ; physiopathology ; Humans ; Hyperinsulinism ; complications ; physiopathology ; Insulin Resistance ; Obesity ; complications ; physiopathology

In vitro electrical neurophysiological and behavioural studies have shown that diabetes mellitus negatively affects hippocampal function. In this study, by using in vivo extracellular recording, the spontaneous neural activity was obtained from hippocampus of anaesthetized rats in both streptozotocin-induced diabetes group and normal control group. Temporal relationship between neuronal firing and slow oscillation (1-4 Hz) of local field potentials (LFPs) in hippocampus was analyzed using coherence and phase locking measurement. Lower coherence value (0.617+/-0.028) was observed in diabetic rats than that in control rats (0.730+/-0.024) (P=0.005). Furthermore, phase-locking measurement using von Mises fitting parameterized by a concentration parameter kappa showed a lower degree (kappa= 0.347+/-0.113) of temporal coordination between neuronal spiking and slow oscillation of LFPs in the hippocampus of diabetic rats than that of normal ones (kappa= 1.174+/-0.134) (P<0.001). Both approaches demonstrated that diabetes can indeed impair the temporal coordination between neuronal spiking and slow oscillation of population activity in hippocampus. This observed neural coordination impairment may serve as a network level mechanism for diabetes-induced memory deterioration.
Action Potentials ; Animals ; Diabetes Mellitus, Experimental ; physiopathology ; Hippocampus ; physiopathology ; Memory ; Oscillometry ; Rats

OBJECTIVETo explore the values of vestibular evoked myogenic potential (VEMP) in the diagnosis of vestibular nerve impairment in type 2 diabetes mellitus patients.

METHODSForty-two cases (84 ears) of diabetes mellitus patients and 42 cases (84 ears) normal subjects as the control group were enrolled from 2014 to 2015.Both the patients and normal subjects underwent conventional air-conducted ocular vestibular evoked myogenic potential (oVEMP) and cervical vestibular evoked myogenic potential (cVEMP) in bilateral ears.The results were compared between the patients and normal subjects. A commercially available software package, SPSS19.0, was used for statistical analysis.

RESULTSIn 84 ears of the normal subjects, oVEMP was present in 70 ears, the educible rate was 83.3% (70/84). cVEMP was present in 74 ears, and the educible rate was 88.1% (74/84). In 84 ears of the diabetes mellitus patients, oVEMP was present in 49 ears, with the educible rate of 58.3% (49/84). cVEMP was present in 52 ears, with the educible rate of 61.9% (52/84). The educible rate in the control group was significantly higher than the diabetic group (oVEMP: χ(2)=12.71, P<0.05; cVEMP: χ(2)=15.37, P<0.05). In the diabetic group, the mean values of both oVEMP and cVEMP P1, N1 latencies were significantly longer when compared to the control group (P<0.05). No significantly statistical difference was found in oVEMP and cVEMP parameters (threshold, latency interval and amplitude) between groups (P>0.05).

CONCLUSIONSVestibular nerve was impaired in diabetes mellitus patients in some degree. VEMP examinations could be useful in the diagnosis of vestibular nerve impairment in type 2 diabetes mellitus patients.

Case-Control Studies ; Diabetes Mellitus, Type 2 ; physiopathology ; Humans ; Vestibular Evoked Myogenic Potentials ; Vestibular Nerve ; physiopathology

OBJECTIVETo investigate the association between diabetes and risks of primary liver cancer.

METHODSA Meta-analysis was performed to estimate the pooled relative risk (RR) to evaluate the relationship between diabetes and the risk of primary liver cancer from cohort studies, which were identified by searching in Medline, Chinese CNKI and Wanfang databases from January 1989 to February 2010. A total of 28 publications were found according to this method. Adjusted RRs and their corresponding 95% confidence intervals (95%CI) were calculated by using the fixed-effect and random-effect model in our analysis. We also conducted a number of sub-groups analysis stratified by some important variables, such as source, gender, region and quality of study.

RESULTSA total of 3800 cases of liver cancer and 3 672 248 study subjects from 14 prospective cohorts were included in our analysis. The pooled RR of primary liver cancer was 3.33 (95%CI: 1.82 - 6.10) for persons with diabetes when compared to subjects without diabetes. The results showed a significant association between diabetes and the risk of primary liver cancer based on these cohort studies. Subgroup analysis indicated that the pooled RRs for diabetes were 3.76 (95%CI: 1.69 - 8.38) in the population-based cohorts and 2.41 (1.34 - 4.32) in the hospital-based cohorts. In terms of the sex groups, the pooled RRs for diabetes were 2.32 (95%CI: 1.70 - 3.17) for males and 1.63 (95%CI: 1.08 - 2.47) for females, respectively.

CONCLUSIONAs one of independent risk factors, diabetes was associated with an increased risk of primary liver cancer.

China ; epidemiology ; Cohort Studies ; Diabetes Complications ; physiopathology ; Diabetes Mellitus ; epidemiology ; physiopathology ; Female ; Humans ; Liver Neoplasms ; epidemiology ; Male ; Risk Factors

OBJECTIVETo investigate the effect of hyperglycemia induced by different doses of strepzotozocin (STZ) on the liver, kidneys and eyes in rats.

METHODSFifty SD rats were divided equally into 5 groups to receive intraperitoneal injections with a single dose of STZ (40, 50, or 60 mg/kg), 3 doses of 25 mg/kg STZ (given at the interval of 24 h), or no treatment (blank control). The dynamic change of blood glucose was observed within 72 h after the first injection. Blood glucose was then monitored every 3 days and the general conditions of the rats were recorded. In the 9th week, fasting blood samples were collected for biochemical analysis and the pancreas, kidney, liver, and eye were examined for pathologies.

RESULTSWithin 72 h after STZ injection, blood glucose first slightly increased and then decreased and again increased to maintain a high level. Death occurred in rats receiving injections with 50 and 60 mg/kg STZ on the third day. In the surviving rats in the 4 STZ-injected groups, the success rate of modeling was 70%, 89%, 100%, and 100%, respectively. Blood glucose showed an inverse correlation with the body weight of the rats. Cataract was observed in the 10th week in rats injected with 40 mg/kg STZ and in the 8th week in the other groups. In the 9th week, the rats receiving 40 mg/kg STZ showed normal insulin, C-peptide, urea, UA, Cr, ALT, AST, TP, and ALB levels, but the rats in the other groups all showed variations in these biochemical indices, which corresponded to the pathological findings in the pancreas, kidneys, and liver.

CONCLUSIONSThree STZ doses of 25 mg/kg is optimal and efficient for inducing diabetes in rats with stable hyperglycemia. Both fasting and random blood glucose tests contribute to the evaluation of the complications of diabetes. The eyes are the most sensitive to hyperglycemia, followed by the kidneys and then by the liver.

Animals ; Blood Glucose ; Body Weight ; Diabetes Mellitus, Experimental ; physiopathology ; Eye ; physiopathology ; Hyperglycemia ; physiopathology ; Kidney ; physiopathology ; Liver ; physiopathology ; Pancreas ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Streptozocin

Erectile dysfunction (ED) is a common complication of diabetes mellitus. Diabetes mellitus can cause oxidative stress, which plays a key role in the pathogenesis of diabetes-associated ED by acting on blood vessel endothelia, peripheral nerves and smooth muscles and inducing cell apoptosis. Recent progress in the researches on the correlation of oxidative stress with diabetic ED is briefly reviewed in this article.
Animals ; Diabetes Mellitus, Type 2 ; complications ; physiopathology ; Diabetic Neuropathies ; etiology ; physiopathology ; Erectile Dysfunction ; etiology ; physiopathology ; Humans ; Male ; Oxidative Stress ; Rats