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Enzyme May ID Nerve Injury in Diabetes


An enzyme associated with neural injury increased significantly in patients with diabetes and with diabetic neuropathy, suggesting potential as a biomarker for peripheral neuropathy in diabetic patients, investigators reported.


Levels of serum neuron-specific enolase (NSE) in diabetic patients differed slightly but significantly ( P=0.037) from those of nondiabetic patients. An even greater difference existed between diabetic patients with neuropathy and those without ( P<0.001).


The association of NSE to diabetic neuropathy was independent of glycemic state, age, sex, and kidney function, Li Jianbo, MD, PhD, of Nanjing Medical University in China, and colleagues reported online in Diabetes Care.


"We have observed for the first time that serum NSE levels are elevated in diabetes and are related to diabetic neuropathy," the authors concluded. "This may provide a potential blood marker for diabetic neuropathy. If future studies confirm our results, an increase in serum NSE as an indicator of diabetic neuropathy would aid timely prediction, diagnosis, and treatment of the diabetic population."


Several diagnostic tools have been developed for diabetic neuropathy, but a biomarker specific to neural damage is not among them. NSE recently emerged as a promising biomarker candidate.


NSE is a highly soluble intracellular enzyme normally located in the cytoplasm in neuroendocrine cells; it catalyzes the conversion of 2-phosphoglycerate into phosphoenolpyruvate. NSE is released into cerebrospinal fluid and blood following tissue injury.


Few studies have examined the relationship between NSE and diabetic peripheral neuropathy, the authors noted in their introduction. To address the issue, Jianbo and colleagues prospectively enrolled patients with type 1 or type 2 diabetes and healthy controls into a cross-sectional study.


Diabetes status was based on World Health Organization diagnostic criteria. An experienced physician performed a neuropathy assessment of all study participants, using age-related reference values. Patients with hyperglycemia, hypoglycemia, or ketonuria were excluded or the conditions were corrected prior to the neuropathy assessment.


Investigators used American Diabetes Association recommendations to classify diabetic neuropathy, which was assessed by means of a standardized test protocol. They defined stage 0 as no evidence of neuropathy, stage 1 as two or more asymptomatic abnormalities, stage 2 as two or more symptomatic abnormalities, and stage 3 as disabling neuropathy.


The final analysis comprised 568 participants, consisting of 136 healthy volunteers, 218 diabetic patients without neuropathy, and 214 diabetic patients with neuropathy.


As compared with diabetic patients without neuropathy, those with neuropathy had a higher fasting glucose level (305 versus 286 mg/dL, P=0.032), higher glycosylated hemoglobin (7.5% versus 6.8%, P=0.006), longer duration of diabetes (7.2 versus 5.9 years, P<0.001), and higher incidence of diabetic retinopathy (18.5% versus 10.2%, P=0.024). Other baseline characteristics did not differ significantly between the two groups of diabetic patients.


Diabetic patients had a mean NSE value of 9.1 mcg/L compared with 8.7 mcg/L. Diabetic patients with neuropathy had a mean NSE level of 10.8 mcg/L. Serum NSE levels increased with neuropathy stage 3 as compared with stage 0 ( P=0.004 to P=0.000). Moreover, NSE levels correlated significantly with neuropathy stage ( P<0.001).


Using receiver operating characteristic (ROC) analysis, Jianbo and colleagues found that the optimal cut to distinguish patients with diabetic neuropathy from those without was 10.10 µg/L, which was associated with a sensitivity of 66.3%, specificity of 72.5%, and maximal area under the curve of 0.73 ( P<0.001).


The authors cited several potential limitations of the results, including possible influence of ethnicity, the small difference in NSE values between diabetic patients without neuropathy and the control group, and the relatively low sensitivity of the NSE value identified by ROC analysis. The low test sensitivity might limit the clinical and research utility of the test, they acknowledged.


The study was supported by the National Natural Science Foundation of China and the Jiangsu Provincial Natural Science Foundation of China.


The authors reported no disclosures.


Title : Enzyme May ID Nerve Injury in Diabetes
Published on : Tuesday, July 16, 2013
Category : Diabetes
Post URL : http://internal-med.blogspot.com/2013/07/enzyme-may-id-nerve-injury-in-diabetes.html

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