Study On Cognitive Impairment And Risk Factors And Predisposing Genes Among The Patients With Type 2 Diabetes Mellitus

Objective:To compare and analyze the clinical features and related factors between case group of cognitive impairment and control group of normal cognitive function among the patients with type 2 diabetes mellitus(T2DM).To explore the risk factors of cognitive impairment and analyze the relationships between cognitive impairment and polymorphisms of ApoE gene and TNF-αgene,and provide scientific basis for the prevention of cognitive decline and the development of dementia in patients with type 2 diabetes mellitus.Methods:A based hospital case-control study was conducted in Metabolic Disease Hospital of Tianjin Medical University between 2008 May and 2009 March.The subjects included 248 patients with type 2 diabetes mellitus,among which 60 cases with cognitive impairment as case group,188 cases without cognitive impairment as control group.The information was collected by using self-made questionnaire, including demographic data,disease history,disease family history,behavior pattern, clinical data,laboratory data,depression,anxiety and cognitive function,blood samples were collected from 60 cases of type 2 diabetes with cognitive impairment, 120 cases of type 2 diabetes without cognitive impairment.The polymorphisms of Apo E gene and TNF-αgene were detected by PCR-Restriction Fragment Length Polymorphism(PCR-RFLP).The risk factors were analyzed by non-conditional logistic regression and OR value and 95%CI were calculated.Results:1.Results of univariate logistic regression analysis showed that age,education,physical practice,family history of diabetes,depression,anxiety,DM course of disease, glycemia control,diabetic peripheral neuropathy,diabetic retinopathy,hypertension and serum total cholesterol were significantly associated with cognitive impairment in type 2 diabetic patients.The OR values and its 95%confidence interval(CI) were as follows:3.379(2.114-5.402),0.430(0.295-0.629),0.538(0.295-0.984),0.520(0.286- 0.947),2.321(1.269-4.246),3.062(1.666-5.627),1.980(1.302-3.011),2.191(1.252-3.834),2.039(1.047-3.972),1.927(1.071-3.469),2.244(1.136-4.434),1.306(1.040-1.641).Education,physical practice,DM family history are protect factors,others are all risk factors.After adjusting for possible confounding factors,the associations between diabetic peripheral neuropathy,diabetic retinopathy,hypertension and serum total cholesterol,family history of diabetes and cognitive impairment were not existed.No associations were found between cognitive impairment and gender,per capita monthly income,character,smoking,drinking,drinking tea,family history of hypertension,diabetic nephropathy,coronary artery disease,types of treatment for diabetes,body mass index,systolic pressure,diastolic pressure,fasting blood glucose, postprandial 2 hours blood glucose,triglycerides,low density lipoprotein cholesterol, high density lipoprotein cholesterol,uric acid,urea nitrogen and urine creatinine.2.The frequencies of Apo E gene types in case group were 0%,15.00%,6.67%, 41.66%,31.67%and 5.00%forε_2/2,ε_2/3,ε_2/4,ε_3/3,ε_3/4 andε_4/4 types;while 2.5%,22.50%,5.83%,55.83%,11.67%and 1.67%in control group,respectively.The difference of the frequencies of the Apo E gene types between the two groups was statistical significance(P=0.011).The frequencies of Apo E alleleε₂,ε₃ andε₄ were 10.83%,65.0%and 24.17%in case group and 16.67%,72.92%and 10.41%in control group,respectively.The difference of the frequencies of Apo E alleles between the two groups was statistical significance(χ²=12.646,P=0.002).Results of univariate logistic regression analysis showed that T2DM patients with Apo Eε₄ allele have high risk of cognitive impairment,its OR and 95%CI were 3.225(1.628～6.389),and still significant after adjusting for diabetes course.3.The frequencies of TNF-αgene types in case group were 68.33%,25.00%,6.67%, for GG,GA and AA types;while 85.00%,12.50%and 2.50%in control group, respectively.The difference of the frequencies of TNF-αgene types between the two groups was statistical significance(P=0.028).The frequencies of TNF-αallele G and A were 80.83%and 19.17%in case group and 91.25%and 8.75%in control group,respectively.The difference of the frequencies of the TNF-αalleles between the two groups was statistical significance(χ²=8.091,P=0.004).Results of univariate logistic regression analysis showed that T2DM patients with TNF-αA allele had high risk of cognitive impairment,its OR and 95%CI were 2.626(1.253～5.502), and still significant after adjusting for diabetes course.4.Main effects model of non-conditional logistic regression was analyzed by entering those risk factors aboved univariate logistic regression analysis.The 7 related factors in the equation were age,anxiety,diabetes course,education,Apo Eε₄ allele,giycemia control,TNF-αA allele.The OR and its 95%CI were as follows:5.889(2.744-12.639), 4.205(1.607-11.004),3.008(1.638-5.524),0.396(0.232-0.676),4.340(1.589-11.854), 3.323(1.419-7.783),3.323(1.419-7.783) and 3.931(1.366-11.315).High education was the protect factor,others were risk factors.5.The total scores of ADAS,memory score,language score,operation score, attention score,ADL score of case group were all higher than that of control group, and the differences between the two groups were statistical significance.The results of multi-stepwise regression showed that the factors associated with memory, language,operation,attention and daily life ability were age,education,depression, anxiety,practice,diabetes course,diabetic peripheral neuropathy,family history of diabetes and glycemia control.Conclusions:The memory,language ability,operation,attention,ability of daily life of T2DM patients with cognitive impairment were lower than that of T2DM patients with normal cognitive function.The risk factors of cognitive impairment were old, anxiety,longer diabetes course,ApoEε₄ allele,bad giycemia control,TNF-αA allele. High education was the protect factor for cognitive impairment in type 2 diabetic patients.