| Objectives:In this study,high specific antibody was used to measure plasma proBDNF level in patients with cognitive impairment in T2DM,to analyze the correlation between plasma proBDNF level and cognitive impairment,blood glucose metabolism and inflammatory factors,and to explore the possible biological role and mechanism of plasma proBDNF in T2DM and cognitive impairment.Methods:1.Patients admitted to the Department of Neurology in the Second Affiliated Hospital of Kunming Medical University in Yunnan Province on December 14,2019 and December 2020 were recruited and divided into four groups according to the presence or absence of T2DM and cognitive impairment.The first group(no T2DM and no cognitive impairment),The second group(no T2DM and no cognitive impairment),The third group(T2DM and no cognitive impairment)and The fourth group(T2DM and cognitive impairment),Included a total of 130 participants(there are 39 in the first group,38 in the second group,26 in the third group and 27 in the fourth group).2.Collect general demographic data(included age,sex,years of education,history of hypertension,waist circumference and body mass index).3.Assessment of cognitive function:Mmontreal cognitive assessment,Wechsler memory scale,Stroop color word test,connection A and B test,and comparison of differences in cognitive function between the four groups.4.Glucose metabolism indicators:including fasting blood glucose,fasting insulin,2 hours postprandial blood glucose,glycated hemoglobin,Homeostasis model assessment of insulin resistance(HOMA-IR)and compared the differences in glucose metabolism indexes among the four groups.5.Inflammatory response indicators:including white blood cell count,neutrophil count,neutrophil percentage,lymphocyte count,lymphocyte percentage,monocyte count,monocyte percentage,platelet count,interleukin-6 and C-reactive protein,compare the differences in inflammatory response from the four groups.6.Plasma proBDNF level determination:Enzyme-linked immunosorbent assay(ELISA)was used to determine the concentration of proBDNF in plasma,to compare the differences in the concentration of proBDNF between the four groups,and to analyze the correlation between plasma proBDNF and inflammatory factors and glucose metabolism indicators in T2DM with cognitive impairment,Results:1.There was no statistically significant difference in hypertension,waist circumference and BMI among the four groups(P>0.05),the second group were older than the first group(P=0.00).When Other the random combination comparisons between two groups,theres were no statistical significance(P>0.05).If people over 45 years old are not complicated with T2DM,the older they are,the more likely they are to suffer cognitive impairment.However,If people over 45 years old are complicated with T2DM,such an age trend does not exist.T2DM may accelerate the process of cognitive impairment in people over 45 years of age.2.MOCA overall cognitive score,visuospatial and executive ability,naming,attention,computing ability,language(retelling+understanding),abstraction,delayed recall and orientation tests showed that compared with the first group,the above cognitive abilities of the second group and the fourth group were significantly decreased(P<0.05),Compared with other groups,cognitive abilities of the fourth group(including MoCA overall cognitive scores,visual space and execution,naming,attention,language,abstract,delayed recall and directional force level)were decreased(P<0.05).When Other the random combination comparisons between two groups,theres were no statistical significance(P>0.05).Suggesting T2DM patients may be prone to extensive cognitive impairment.3.In the wechsler memory scale of picture recalled,visual recognition,visual regeneration,associative learning,logical memory,backward memorization of numbers and backward memorization of numbers the above cognitive abilities in groups the second group and the fourth group were decreased compared with those in the first group(P<0.05),indicating that T2DM patients may be prone to extensive cognitive impairment.Compare with the other three groups,the fourth group worst performance in the field of cognitive tests(P<0.05).Suggesting the degree of cognitive impairment may worsen when patients with pre-existing cognitive impairment are combined with T2DM.4.In the connection test,compared with the first group,the time consuming of part A,part B and part(B-A)from/with the second group and the fourth group were prolonged(P<0.05),compared with the first group,the scores of part A and part B in groups 2,3 and 4 were decreased(P<0.05),indicating that T2DM patients may be prone to extensive cognitive impairment.Compare with the other three groups,the time consuming of the part A,part B and part(B-A)with group 4 was the longest(P<0.05),suggesting that T2DM may aggravate further impairment of executive function in patients with existing executive dysfunction combined with T2DM.5.In Stroop evaluation,compared with the first group and the third group,the fourth group had the longest time for Part A,B and C,the lowest correct number,the most error number and the value of time-consuming interference.Indicating T2DM patients may be prone to extensive the ability attention and anti-interference.Compare with the other three groups,the fourth group had the longest time for parts A,B and C(P<0.05),and the time interference value was the largest(P<0.05),suggesting that T2DM may aggravate the impairment of executive ability(attention and anti-interference ability)in patients with existing executive ability(attention and anti-interference ability).6.Comparison of the levels of fasting blood glucose,glycated hemoglobin,2-hour postprandial blood glucose,fasting insulin and HOMA-IR in the four groups showed that the above glucose metabolism indexes of the fourth group were higher than those in the first group(P<0.05).It is suggested that T2DM is prone to cognitive impairment,which may be related to the increase of glucose metabolism disorders(fasting blood glucose or HbAlc or 2 hours postprandial blood glucose or fasting insulin or HOMA-IR levels).The above indexes of glucose metabolism of the fourth group were higher than those of the second group(P<0.05).Suggesting that the above glucose metabolism indexes may be further increased in patients with cognitive impairment combined with T2DM.7.The inflammatory indexes of the four groups were analyzed.Compared with the first group,the lymphocyte count(P=0.04),monocyte count P=0.00),monocyte percentage(P=0.02),interleukin-6(P=0.00)and C-reactive protein(P=0.00)levels in the fourth group were all increased.It suggests that T2DM is prone to cognitive impairment,which may be related to the enhancement of inflammatory response(lymphocyte or monocyte or interleukin 6 or C-reactive protein levels).8.Plasma proBDNF level was determined by ELISA.Compared with the first group,plasma proBDNF level was increased to the third group and the fourth group,and the fourth group had the highest plasma proBDNF level(P<0.05).Suggesting the increase of plasma proBDNF level may be related to the glucose metabolism disorder of T2DM,and T2DM is easy to be combined with cognitive impairment,and may also be related to the increase of plasma proBDNF.The level of plasma proBDNF in the fourth group was higher than that in the second group(P<0.05).Suggesting when patients with original cognitive impairment combined with T2DM,the increase of plasma proBDNF may aggravate the further deterioration of their cognitive impairment and glucose metabolism disorder.9.The level of plasma proBDNF of group 4 was negatively correlated with MOCA total score(r=-0.25,P=0.04),language(r=-0.25,P=0.04),delayed recall(r=-0.26,P=0.04),directivity(r=-0.32,P=0.01),and backward memorization of numbers and backward memorization of numbers(r=-0.39,P=0.03).The level of plasma proBDNF of group 4 was positively correlated with the time consuming of part(B-A)(r=0.29,P=0.04).It is suggested that the higher the level of plasma proBDNF is,the worse the overall cognitive level is in T2DM patients with cognitive impairment,especially related to the ability impairment of language(retelling and understanding),instantaneous recall,orientation and executive.In group 4 the level of plasma proBDNF was positively correlated with the tow hour postprandial blood glucose(r=0.31,P=0.02).Suggesting that when T2DM patients combined with cognitive impairment,the higher the level of plasma proBDNF was,the higher the level of blood glucose 2 hours after prandial was.The level of plasma proBDNF of the fourth group was positively correlated with the level of lymphocyte counted(r=0.27,P=0.01)and monocyte count(r=0.30,P=0.01).Suggesting that when T2DM patients combined with cognitive impairment,the higher the level of plasma proBDNF was,the higher the level of lymphocyte count or monocyte count was.Conclusions:1.Persons over the age of 45,the greater the age may be more susceptible to cognitive impairment,and T2DM may accelerate the process of cognitive impairment.T2DM often show multiple cognitive domains,such as the visual space structure and execution ability(attention and anti-interference power)named language(repeat+)memory(including short-term memory,instantaneous memory,understanding memory,episodic memory)and directivity are impaired.2.T2DM is easy to be complicated with extensive cognitive impairment,which may be related to the vicious circle between the interaction of plasma proBDNF increasing,glucose metabolism disorder(fasting blood glucose or HbAlc or 2 hours postprandial blood glucose or fasting insulin or HOMA-IR levels)and inflammatory effect(lymphocyte or monocyte or interleukin 6 or C-reactive protein levels).It is mainly manifested as,the higher the level of plasma proBDNF,the worse the overall cognitive level may be,especially with language(retold and understanding),instantaneous recall orientation and executive ability damage degree is positively correlated,may be positively correlated with the increase of 2 hours postprandial blood glucose level is positively correlated and with the increase of lymphocyte count level or monocyte count level is positively correlated. |
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