2型糖尿病患者轻度认知功能障碍和血清AGEs水平的关系

? ???? 2 2 6 ???? ??????????????? ( W 6 ) 。 ???? ?? ( 6 ) ,? ,?? ,???? ,????????????? ,???????、????????。 ???? ??? ( 63 )? ,???? ,???????、????????。 2 q @ 　???? : 1671 - 7554 (2009) 09 - 0011 - 03 2 型 糖 尿 病 患 者 轻 度 认 知 功 能 障 碍 和 血 清 AGEs 水 平 的 关 系 ?? ,??? ,?? ,?? ,??? ,??? ,??? (?????????????? , ?? 250021) ?? :?? 　?? 2???????????????????????? (AGEs)????? 。?? 　? 2?? ???? 62????????????? 30 ? ,????????? 32 ? ,?????? 30 ?。? ELISA?? ??? AGEs ,????????? 、??、?? 、?????、24 h?????????。?? 　??????? ??? AGEs??????????????? ( P < 0.05)?????? ( P < 0. 01) ;2 ?????? MMSE?? ???、?????、??????、???????? AGEs ?????? ( r = - 0. 315 , - 0. 276 , - 0. 384 , - 0. 384 , - 0.282) 。?? 　?? AGEs??? 2????????????????????? ,?????? ?????。 ??? :2???? ;???????? ;?????? ;????? ????? :R587.1 　　　????? :A Correlation between mild cognitive impairment and advanced glycosylation end product level in type 2 diabetic patients GAO Xia , ZHANG Hong2xia , GAO Ling , CHEN Qing , J IANGXiu2yun , GUAN Qing2bo , ZHAO Jia2jun (Department of Endocrinology , Provincial Hospital Affiliated to Shandong University , Jinan 250021 , China) Abstra ct : Objective 　To determine the relationship between advanced glycosylation end products (AGEs) and mild cognitive im2 pairment in type 2 diabetic patients. Methods　Based on the Mini2Mental State Examination (MMSE) score , type 2 diabetic pa2 tients were divided into two groups : one group with 30 cases of cognitive impairment and the other with 32 cases of non2cognitive impairment. 30 normal participants served as the control group. AGEs was measured by ELISA in all subjects , also HbA1 c , blood lipids , uric acid , fibrinogen , urinary albumin of 24 hours , and other biochemical indicators were measured in all subjects. Results　The AGEs level of the cognitive impairment group was significantly higher than that of the non2cognitive impairment group ( P < 0.05) and the control group ( P <0. 01) . MMSE score of patients with type 2 diabetes negatively correlated with age , durationof diabetes , HbA1 c , body mass index , and serum levels of AGEs ( r = - 0. 315 , - 0. 276 , - 0. 384 , - 0. 384 , - 0. 282) . Conclusions 　Increased AGEs may be an important risk factor for cognitive impairment in type 2 diabetic patients. AGEs may be involved in the pathogenesis of diabetic encephalopathy. Key words: Type 2 diabetes mellitus ; Advanced glycosylation end products ; Cognitive impairment ; Diabetic encephalopathy 　　??????????????? ,???? ?????????? ,??????、????、 ?????、?????、??????????? ??。?????????????????。? ? ,????????? ,??????????? ???? ,??????????????[ 1] 。? ????????????????????? , ??????????????[223] 。????? 　? 47? 　? 9 ? 　Vol. 47 　 No. 9 　 　 　 　 　 ? 　? 　? 　? 　? 　? 　(? 　? 　?) JOURNAL OF SHANDONGUNIVERSITY(HEALTH SCIENCES) 　 　 　 　 　 2009 ? 9? 　 Sep. 2009　 : 2009 04 1 : 2009 H 0 7 : 197 - : 19 - E ma il :guan ingbo medmail . com. cn ? ?? 2 ????????????????? (advanced glycosylation end products , AGEs)???? ?????????? ,???? AGEs ???? ??????????。 1 　????? 1. 1 　???? 　92 ????????????? ??? 2 ?????????????????? ???。???????? ,??????、??? ????????????。2 ???????? ? 1999? WHO???????。??????? ????? Petersen ??[4 ] :????????? , ??????? ;?????? ,???????? ??????? ;???????? ;?????? ???? ; ???????? (Mini2Mental State Examination ,MMSE) 24?27?。 ????? 3? : ①???????? :?? 2 ?????? ,?????????? ,? 30? ,? ?? 12 ? ,? 18? ,51?73 ? ,?? (63. 43 ?6. 39) ? ; ②????????? :2 ?????? ,?? ????? (MMSE?? > 27 ?) ,? 32 ? ,??? 14? ,? 18 ? ,50?71 ? ,?? (61. 09?5. 57)? ; ③ ????? :?30 ? ,???13? ,? 17 ? ,50?70 ? ,?? (58. 73 ?5. 98) ? ,?????、???、? ??、????、???????。 ?????????????? : ①???? ????????????????????? ?、????????、???????、???? ??? ; ②????????????????? ?? ,??????????? ; ③??????? ??????????????? ; ④????? ?????????、??????????? ,? ??????、????? ; ⑤????? 2??? ??????????????。 1. 2 　?? 1. 2. 1　?????? 　????????? :? ?、??、??、?????、2 ??????、?? ??(???、???、????????) 、??? (??????????、????????) 、?? ??????????????????? (?? ??、???、???) 。????? (BMI) = ?? ? ( )Π?? 。 　 G ??? 　???????? ?? ???????? 3 L ,?????? ,? ? 3 000 r/ min?? 15 min(?????? B600 ??? ?????? ,???????) ,????? - 60 ????? ,??????? ,?????? ELIAS ??? AGEs ,??????????。???Lab2 systems?????? 450 nm ???? OD ? ,?? ???? ,???????。AGEs ??????? ? Uscnlife ??。 1. 2. 3　????? 24 h????????? 　? ? 1 ???????????? ( TC) 、???? (TG) 、????????? (LDL2C) 、?????? ??? ( HDL2C) 、??、????? ( Fib)????? ?? ( HbA1c) 。?? 24 h ? ,??????? 24 h ?????? (MA) ,???????????Orion Diagnostica ?? ,??????????。?? 24 h ? MA ?????30 mgΠL ??? ( Ⅰ) ,??30 mgΠL ??? ( Ⅱ) 。 1. 3 　????? 　????? SPSS 16. 0???? ?????。??????????????? , ???????????? �x ?s ?? ,???? ????? ,????? Bonferroni ??、???? ?? Games2Howell ?? ;???????χ2 ??? ?????。MMSE???????? Spearman ? ??????? , P <0. 05?????????。 2 　? 　? 2. 1 　???? 　?? 1。???????、??、 ??????????????? ( P > 0. 05) 。? ????????BMI、HbA1c、Fib、??、??、24 h ? MA???????????? ,?????? ?? ( P > 0. 05) 。?????????????? ??????????????? ( P <0. 05) 。 2. 2 　???????? AGEs????? 　?? 1。???????? AGEs ????????? ???? ,???????? ,????????? ????????? AGEs ??????? ( P < 0. 01 , P < 0. 05) ,?????? ,???????? AGEs ???? ( P <0. 05) 。 2. 3 　2????? MMSE ?????????? ?? 　? Spearman ?????? ,2 ?????? ? MMSE??? TC、TG、LDL2C、HDL2C、???、? ???????? ( P ? > 0. 05) ;MMSE ???? ?、 、G 、?????? BMI ???? ,?? ???????? ,?? 。?? , ? G ? ???( = 6 , < ) 。 　12　　　 ? 　? 　? 　? 　? 　? 　(? 　? 　?) 47? 9 ? 　 kg 2 1. 2. 2 A Es 12 h m 1 h HbA1c A Es 2 HbA1c A Es r 0. 4 4 P 0. 001 ? ? 1　???????????? (�x ?s) ? 　? ???? ???? ( n =30) ????? ???? ( n =32) ????? ( n = 30) ?? (?Π?) 12Π18 14Π18 13Π17 ?? (?) 63. 43?6. 39 61. 09 ?5. 57 58 . 73 ?5. 98 ?? (?) 11. 13?5. 74Δ 9. 21 ?6. 23 ? ????? (?) 7. 43?4. 84 8. 84?4. 97 8. 35?5. 28 HbA1 c( %) 10. 19 ?2. 63 3 3 9. 47 ?2. 45 3 3 4. 90?0. 44 BMI(kgΠm2) 25. 63 ?1. 87 3 3 24. 43 ?2. 37 3 21 . 00 ?2. 94 Fib ( mΠg?L - 1) 3 . 85 ?1. 17 3 3. 39?0. 94 3. 05?0. 59 TC( cΠmmol?L - 1) 5. 20?0. 95 5. 19?1. 32 4. 58?0. 73 TG( cΠmmol?L - 1) 1. 91 ?0 . 58 3 3 1. 90 ?0. 47 3 3 1. 34?0. 27 LDL2C( cΠmmol?L - 1) 2. 94?0. 66 3. 07?0. 80 3 2. 60?0. 43 HDL2C( cΠmmol?L - 1) 1. 37?0. 32 1. 23?0. 28 1. 28?0. 15 24 h? MA(ⅠΠⅡ) 16Π14 3 19Π13 3 26Π4 ???( PΠmmHg) 142. 80?24. 02 3 149. 78?22. 55 3 121 . 58 ?14 . 07 ???( PΠmmHg) 83. 87?15. 45 85. 31?13. 59 76 . 96 ?7. 46 ???( cΠmmol?L - 1) 311. 23?61. 32 293. 12 ?80. 20 268 . 58 ?68 . 21 AGEs (ρΠmg?L - 1) 16. 64 ?6. 45 3 3Δ 11. 70 ?4. 61 3 8. 48?2. 43 　　3P < 0. 05 , 33P <0. 01 vs ??? ;ΔP <0. 05 vs????? ???? ? 2 　AGEs?????? MMSΠE?????? ? 　? MMSE?? r P ?? (?) - 0. 315 0.013 ????? (?) 　0. 296 0.019 ????? (?) - 0. 384 0.002 BMI(kgΠm2 ) - 0. 282 0.027 HbA1c ( %) - 0. 276 0.030 AGEs(ρΠmg?L - 1) - 0. 384 0.002 3 　? 　? ?????????????????[5 ] ,? ?????????[ 6] ,60 ?????? 6 %? 12 %???? ,85 ???????? 20 %?48 %? ???。???? 400 ????? ,?????? ???? ,???????[7 ] 。???? ,???? ???????????????? ,????? ??????????????????? 3 ? , ???????? ,????????? (AD)?? ?????????? ,??????????? ?、AGEs ??、??????????[8 ] 。2 ?? ????????????????????? ? ,???????? ,?????、?????? ??????。 AGEs????????????????? ?? ,??????????????????? , ?????。Maillard ???????????? , ????????????????????? ? ,???? AGEs?? ,?????????。? ????AGEs??????????????? ?????。AGEs ????????????? ??[9 ] 。??????? ,????????? AGEs ?????????????? ,????? ??????? ;?????????? AGEs ? ???????。Spearman ?????? MMSE ? ??AGEs????。??????????AGEs ?? ,??? 2???????????????。 ??????????????? ,?????? ?????????? ,??????????? ??????。???? AGEs ?致?????? ??????????? : ①AGEs?? tau ??? Aβ,??AD ??????? ; ②AGEs ????? ??? ,?????????。Takeuchi ?[10 ] ?? ??????????????? AGEs???? ?? ,?致 BHK21 ???????、?????? ? (SH2SY5Y)??、????????、????? ?????? ( N9) ? ? ; ③AGEs ? AGE ?? (RAGE)?? ,?????? ,????????? ???? ,???????? ,???????? ; ④AGEs??????? ,??????????? ??? ,???????? ;?????????? ????????? ,??????[ 11 ] 。 HbA1c ????????????????? ???? ,?????????? 2?3 ????? ???。????????? ,AGEs? HbA1c ?? ?? , ?? AGEs ???????????? ; MMSE??? HbA1c ???? ,????[12] ??? ??? ,?? 2??????????????? ????? ,???????????????? ???。 Spearman ??????? ,MMSE?????、 ?????? BMI ???? ,????????? ? ,???、??、???????。?????? ????????。????????????? ?????。????????? ,30 ????? ???????? 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