brain - derived neurotrophic factor ( bdnf ) is a member of the neurotrophin family , which includes nerve growth factor , neurotrophin-3 , and neurotrophin-4/5 [ 14 ] . the role of bdnf in cell differentiation , neural growth , synaptic connectivity , and maintenance of target neurons is well established ; it has also been implicated in synaptic plasticity of brain function , such as learning and memory [ 5 , 6 ] . in addition to the role of bdnf in neurological disorders , recent studies reported that peripheral injection of bdnf exerts hypophagic and hypoglycemic effects on obese hyperglycemic animals but not on normal animals , pointing to antiobesity and antidiabetic effects [ 710 ] . bdnf mutant mice developed mature onset obesity , characterized by an increase in body weight . in the same study , the mutant mice displayed elevated serum leptin , insulin , glucose , and cholesterol . data from animal experiments and human studies suggested that bdnf may contribute to glucose metabolism and have a pathogenic role in the development of type 2 diabetes mellitus ( t2 dm ) in humans . according to recent studies , bdnf is associated with systemic inflammatory conditions , such as diabetes , acute coronary syndrome , and atherosclerosis [ 13 , 14 ] . the aim of this study was to evaluate the relationship between serum bdnf levels and various metabolic parameters and inflammatory markers in patients with t2 dm . this study was performed at the gop taksim education and research hospital outpatient department of internal medicine . it included 88 patients ( 38 males and 50 females ) and 33 control subjects ( 17 males and 16 females ) . the presence of diabetes was based on a previous diagnosis of t2 dm or a random plasma glucose level of 200  mg / dl or higher , together with classical features of dm , such as polyuria , polydipsia , polyphagia , and weight loss , or a fasting blood glucose level of > 126  mg / dl or higher or a hba1c level of 6.5% or higher . exclusion criteria were the presence of systemic diseases : neoplastic , inflammatory , and infectious diseases . the study protocol was approved by gop taksim research and education hospital ethics committee , istanbul . informed written consent was obtained from all the participants ( patients and controls ) after receiving a full explanation about the study and its purpose . hypertension was defined as antihypertensive drug use or systolic blood pressure 140  mmhg and/or diastolic blood pressure 90  mmhg . body mass index ( bmi ) was obtained using the formula weight ( kg)/height ( m ) . serum cholesterol , triglyceride , and high - density lipoprotein cholesterol ( hdl - c ) were measured by enzymatic colorimetric methods with commercially available kits ( cobas 311 , roche diagnostics gmbh , mannheim , germany ) , and low - density lipoprotein cholesterol c ( ldl - c ) was calculated according to the friedewald formula . serum glucose measures were determined enzymatically using the hexokinase method ( roche diagnostics gmbh , mannheim , germany ) . blood hba1c was determined with a cobas 311 analyzer using the particle - enhanced immunoturbidimetric method ( roche diagnostics , mannheim , germany ) . final results were expressed as percent hba1c of the total hb according to the protocol of the diabetes control and complications trial / national glycohemoglobin standardization program ( dcct / ngsp ) . the particle - enhanced immunoturbidimetric method with a behring nephelometer bn-100 ( behring diagnostic , frankfurt , germany ) was used to measure c - reactive protein ( crp ) . white blood cell ( wbc ) levels were measured with an automatic hematology analyzer ( beckman coulter , brea , ca , usa ) . the erythrocyte sedimentation rate ( esr ) was determined with the westergren method using an established normal range of 020  mm/1  hr . ferritin was measured with an electrochemiluminescence immunoassay ( roche hitachi modular e 170 ) . the insulin level was determined with an electrochemiluminescence immunoassay ( roche diagnostics , mannheim , germany ) on an automated roche cobas e 411 ( roche diagnostics ) . the homeostasis model assessment of insulin resistance ( homa - ir ) index was calculated from the fasting blood glucose and fasting serum insulin concentrations by the formula : homa - ir = fasting serum insulin ( u / ml )  fasting blood glucose ( mmol / l)/22.5 . serum bdnf was quantified using an elisa ( chemikine bdnf sandwich elisa kit , cyt306 ; millipore bioscience research reagents ; usa and canada ) following the instructions of the manufacturer . the intra - assay and interassay coefficients of variation were 3.7 and 8.5% , respectively . number cruncher statistical system ( ncss ) 2007 and power analysis and sample size ( pass ) 2008 statistical software ( utah , usa ) programs were used for the statistical analysis . descriptive statistical methods ( mean , standard deviation , frequency , ratio , minimum , and maximum ) were used to evaluate the study data . mann - whitney u test was used for quantitative parameters that were not normally distributed . values of p < 0.05 , p < 0.01 , and p < 0.001 were accepted as statistically significant . there were no significant differences in the age and gender or triglyceride , total cholesterol , hdl , ldl , wbc , and ferritin levels between the t2 dm patients and control subjects . the t2 dm patients had a significantly higher bmi , waist circumference , systolic pressure , diastolic pressure , fasting plasma glucose , fasting insulin , homa - ir , hba1c , esr , and crp levels than the control subjects ( p < 0.001 ) . among the patients , 64% were using oral antidiabetic drug only , 18% were using oral antidiabetic drug plus insulin , and 18% were using insulin only . on the whole , 30% of patients were taking lipid lowering drug , 61% of patients were taking antihypertension drug , and 9% were taking none . mean diabetes duration for enrolled subjects is 4.03  3.38 ( not shown in table ) . the serum bdnf levels showed a positive correlation with homa - ir ( r = 0.28 ; p < 0.05 ) , the triglyceride level ( r = 0.265 ; p < 0.05 ) , and the wbc level ( r = 0.35 ; p < 0.001 ) in t2 dm as shown in table 2 . in the logistic regression analysis , age ( p < 0.05 ) , bmi ( p < 0.05 ) , crp ( p < 0.05 ) , and bdnf ( p < the serum bdnf levels were significantly higher in the t2 dm patients compared to the healthy controls ( 206.81  107.32  pg / ml versus 130.84  59.81  pg / ml , p < 0.001 ) . a receiver operating characteristic curve ( roc ) analysis and diagnostic screening tests were used to determine the cut - off point for bdnf ( table 4 ) . patients , who had a bdnf level more than 137  pg / ml , were catching study group levels with a sensitivity of 71.79% , a specificity of 68% , a positive predictive value of 87.5% , and a negative predictive value of 43.59% . the area under the roc and the standard deviation were 71.8% and 5.6% , respectively . hba1c was the best predictor , followed by fasting blood glucose and homa - ir ( figure 1 ) . in this study , we investigated changes in the plasma bdnf level and correlations between bdnf and clinical and biochemical parameters in t2 dm patients . we found that the serum bdnf of t2 dm patients was significantly higher than that of control subjects . a previous study showed that serum bdnf levels were elevated in newly diagnosed female t2 dm patients compared to healthy subjects . similarly , a recent study reported that serum bdnf was significantly elevated in t2 dm patients compared to healthy controls . there are various potential mechanisms that link bdnf and development of type 2 diabetes . in animal experiments , it is shown that , by suppressing ppar - alpha and fibroblast growth factor 21 , bdnf might facilitate insulin resistance and dyslipidemia and thus has antidiabetic and lipid lowering effects . furthermore , some researchers claim that bdnf treatment reported to lower blood glucose in diabetic models . similarly , yamanaka et al . demonstrated that treatment with bdnf prevents age - related increase in blood glucose and development of diabetes in prediabetic db / db mice . together with the data derived from animal experiments , authors suggest that exogenous bdnf administration shows its antidiabetic and antilipidemic effects similar to thiazolidinediones . however , the diabetic patients in our study were not newly diagnosed ; thus , the duration of diabetes alone could not explain the elevated level of serum bdnf . on the other hand , fujinami et al . reported that serum bdnf levels were significantly lower in patients with advanced t2 dm compared to control subjects . plasma bdnf levels were decreased in humans with t2 dm and were independent of obesity in a study by krabbe et al . . in the same study , plasma bdnf levels were inversely associated with fasting plasma glucose . . this situation may be the result of ethnic differences . in a previous study , bdnf heterozygous knockout ( bdnf + / ) mice showed obesity and insulin resistance . it is possible that the increase recorded in bdnf in the current study of t2 dm may compensate for hyperinsulinemia and insulin resistance . reported a relationship between fasting blood glucose , triglycerides , and homa - ir and serum bdnf values . a previous study found that serum bdnf was associated with fasting insulin and homa - ir in t2 dm . our study demonstrated that serum bdnf levels were significantly positively correlated with homa - ir and triglyceride . other studies showed that bdnf improved hepatic insulin resistance in diabetic animals   and that bdnf was positively correlated with triglyceride , total cholesterol , and ldl - c in humans . some authors observed that bdnf treatment of obese and diabetic animals has a positive effect on glucose and lipid metabolism , with one study demonstrating that subcutaneous administration of bdnf reduces food intake and ameliorates impaired glucose tolerance in diet - induced obese mice . the results of these studies show that bdnf may have a role in the treatment of diabetes and dyslipidemia . previous studies described an association of plasma bdnf with inflammatory conditions [ 25 , 26 ] . some studies demonstrated increased bdnf expression in inflamed bladder tissue and in airway epithelium during allergic airway inflammation [ 27 , 28 ] . shin et al . showed that the plasma bdnf level was positively correlated with inflammatory cytokines in hemodialysis patients , suggesting that plasma bdnf might reflect uremic inflammation in patients undergoing hemodialysis . in our study , inversely , a previous study reported a correlation between bdnf and crp in t2 dm patients . the increase in bdnf levels may be associated with protecting neurons from inflammatory injury . in the logistic regression analysis , bdnf was independently associated with t2 dm , irrespective of age , bmi , and crp . patients who had a serum bdnf level more than 137  pg / ml were a predictive value like hba1c for the diabetes diagnosis with a sensitivity of 71.79% and a specificity of 68% . it had a positive predictive value of 87.5% and a negative predictive value of 43.59% . this novel research suggests that serum bdnf may be used as a prediction data for t2 dm like hga1c in future . more importantly , the standardization and cut - off values of serum bdnf had been controversial in previous studies . for the first time , current study suggests a cut - off point for serum bdnf of type 2 diabetes mellitus . first , this was a cross - sectional study of a relatively small number of patients . third , we measured levels of wbcs and crp to determine the association between bdnf values and inflammation but not those of other serum inflammatory markers , such as interleukin-6 or tumor necrosis factor . in conclusion , serum bdnf level was higher in patients with t2 dm , and the cut - off predictive value of bdnf was 137  pg / ml . the findings of this study suggest that bdnf may contribute to glucose and lipid metabolism and inflammation .
background and aim . studies have suggested that brain - derived neurotrophic factor ( bdnf ) plays a role in glucose and lipid metabolism and inflammation . 
 the aim of this study was to evaluate the relationship between serum bdnf levels and various metabolic parameters and inflammatory markers in patients with type 2 diabetes mellitus ( t2 dm ) . 
 materials and methods . 
 the study included 88 t2 dm patients and 33 healthy controls . 
 fasting blood samples were obtained from the patients and the control group . 
 the serum levels of bdnf were measured with an elisa kit . 
 the current paper introduces a receiver - operating characteristic ( roc ) generalization curve to identify cut - off for the bdnf values in type 2 diabetes patients . 
 results . 
 the serum levels of bdnf were significantly higher in t2 dm patients than in the healthy controls ( 206.81    107.32 
 pg / ml versus 130.84    59.81  pg / ml ; p < 0.001 ) . 
 they showed a positive correlation with the homeostasis model assessment of insulin resistance ( homa - ir ) ( r = 0.28 ; p < 0.05 ) , the triglyceride level ( r = 0.265 ; p < 0.05 ) , and white blood cell ( wbc ) count ( r = 0.35 ; p < 0.001 ) . in logistic regression analysis , age ( p < 0.05 ) , body mass index ( bmi ) ( p < 0.05 ) , c - reactive protein ( crp ) ( p < 0.05 ) , and bdnf ( p < 0.01 ) were independently associated with t2 dm . in roc curve analysis , bdnf cut - off was 137 . 
 conclusion . 
 the serum bdnf level was higher in patients with t2 dm . the bdnf had a cut - off value of 137 . 
 the findings suggest that bdnf may contribute to glucose and lipid metabolism and inflammation .