Title: National Diabetes Research Group. Chin J Int Med 20:678,1981
1?????????
2? ?
- 2??????????????????
- ?????????,????,????
- ?????
- ????????
- ????????????
3???????????????
National Diabetes Research Group. Chin J Int Med
20678,1981 Pan XR, et al. Diabetes 201664,
1997 Gu D, et al. Diabetologia 461190,
2003Wenying Yang, et al. N Engl J Med
20103621090-101.
???????
4??????????????????
?????(?????)
?(????????)
??,????(???)
?(?????)
??????(???????)
??(??????)
????
- Diabetes Statistics. October 1995 (updated 1997).
NIDDK publication NIH 96-3926. - Harris MI. In Diabetes in America. 2nd ed.
19951-13.
5????????1,2
?????????
1 ?????(?????????,????????) ?
1)????(??????????,??????????) ? 11.1mmol/l (200mg/dl)
2)????(???????8????????) ? 7.0mmol/l (126mg/dl)
3)75g??????2???? 11.1mmol/l (200mg/dl)
2 ???????,?????????????
1.??2????????.2007?. 2.Organization WH.
Definition, Diagnosis and Classification of
Diabetes Mellitus and its Complications. Report
of a WHO Consultation.WHO/NCD/NCS/99.2.
GenevaWHO,1999 1999.
6??2???????????
??
HbA1c () lt6.5
???? (mmol/L) 4.4-6.1
????? (mmol/L) 4.4-8.0
??2????????.2007?.
7? ?
- 2??????????????????
- ?????????,????,????
- ?????
- ????????
- ????????????
8??2????????????
??70???2??????HbA1c???
27
73
Curr Med Res Opin. 2009 Jan25(1)39-45.
9IMPROVE????????2???????????????
??? ????????? ?OAD?? ??? OAD (???????lt1??)
???? 21,729 7,012 12,890 1,769
?????? - 32.3 59.3 8.1
??HbA1c SD () 9.5 2.1 9.9 2.2 9.2 1.9 9.6 2.3
??1??????? 24.0 11.1 29.6 34.1
??1???? ??? 40.5 21.6 49.2 52.5
????????,HbA1c????
????????????
102009 ADA/EASD?????????????????
???? ?????HbA1c ???() ??
????????????
???????
?????? 1.0-2.0 ????
???? 1.0-2.0 ????????
?????????
??? 1.5-3.5 ??????,????,?????
??? 1.0-2.0 ????
Nathan DM. Diabetes Care 2009 32 193-203.
112007???2????????2?????????????
???????(BMI24kg/m2)
????? (BMIlt24kg/m2)
?????????? ????
?????????? ???????????????????????????????(????
)?a-??????
3???HbA1cgt6.5
????????????? ??????? ????????(????)? a-??????
3???HbA1cgt6.5
3???HbA1cgt6.5
?????
?????
??BMI 24kg/m2,??BMI 28kg/m2
??2????????.2007?.
12DCCT/EDIC ???????????1????????????????
A
B
????????????????????????
????????????
Conventional treatment
P0.02
P0.02
??????42
??????57
Conventional treatment
Intensive treatment
Intensive treatment
Years since Entry
Years since Entry
- DCCT/EDIC group. N Engl J Med. 2005 353(25)
26432653.
13UKPDS???????????2?????????????????????
???????????
?????
????
????
?????????????
0
-6
-5
-9
-10
1997?
-12
-13
2007?
-15
-16
-15
-20
-24
-25
-25
??????,p lt0.05
- Holman RR et al. N Engl J Med 20083591577-1589.
- UKPDS Study Group. Lancet, 1998
14? ?
- 2??????????????????
- ?????????,????,????
- ?????
- ????????
- ????????????
15?????????
1920
1930
1940
1950
1960
1970
1980
1990
2000
16???????
- ?????
- ????
- ????
- ????
- ?????????
- ????
- ??????
17????????????????
S
S
GLy
LIe
Val
Glu
GLn
Cys
Thr
Ser
Lle
Cys
Ser
Leu
Tyr
Gln
Leu
Glu
Asn
Tyr
Cys
Asn
Cys
15
1
5
10
21
S
S
S
S
Phe
Val
Asn
Gln
His
Leu
Cys
Gly
Ser
His
Leu
Val
Glu
Ala
Lau
Tyr
Leu
Val
Cys
Gly
10
15
1
5
20
Glu
Arg
30
B30 A8 A10
???? ??? ??? ????
???? ??? ??? ????
???? ??? ??? ???
25
Gly
Phe
Phe
Tyr
Thr
Pro
Lys
Thr
18?????????
- ????
- ?????
- ???????????
- ????????
- ??(????)
19??????PH??????????????
????? ????
?? (?????) ????? ?????
?? ????lt100ppm ????lt1ppm
PH? ??,?? ??
???? ? ?
20?????????????????
??????????? (n48)
??????????? (n15)
0.9
0.9
IgG-?????(u/l)
IgG-?????(u/l)
0.7
0.7
0.5
0.5
0.3
0.3
0.1
0.1
????(gt0.1u/l)???
Peacock I.et al? The Lancet, January 1983 149-152
21???????????
?? ?????? - ????? R
?? ?????? - ????? N
???? - ?????30R? 50 R
22???,????,????,????
??? R
??? N
??? 30R
??? 50R
23??? ?????????
(?)??????????????????
?????? ?????? (??????) ?????? (????????)
?????????? (???????????????????????? ) ?? ???
?????? (????????) ????????? ??????
(?)???????????????GMP?? ????????????, ??????????
???????????
24??????
??????0.5?? ??????1?3?? ??????8??
????????? ?????? ???????????????? ?????
25??????
????????? ????? ??????? ????????
??????1.5?? ??????4?12?? ??????24??
26??????
???????????? ????? ??????? ????????
??????0.5?? ??????2?8?? ??????24??
27??????
???????????? ????? ???????
??????0.5?? ??????2?8?? ??????24??
28??? ,??????????,???????????1,2
(?)??????????? 2008????????????????????7
6.3?????
76.3
(?) 27????????????????
- 1982 ??????????????????
- 1985 ???????????????,????????
- 1986 ????????????????? 30R
- 1987 ??????????????????????
- ???200???????????????
1.2008 IMS Data. 2.Internal Sales Data, 2008
29 ?????????
- ??????
- ?????????????????????
- ????????????????
- ??????
- ????,???????,?????
- ???,??????
- ??????
- ??????????????,????????
- ??????????
- ???
30?????????????????
31????????????????
- ???????????
- ??? HbA1c
- ???????
- ???????
- ????????
- ???????????
32????????-???
-Asp
Pro
33?????????
- ????????????????????
- ?????????
- ????????????
- ????????1???2??????
- ?????HbA1c ???
- ???????
- ????????
- ????????,???????????????
34????????--???30
????30R
????30
????
30
30
???????
?????
????? (NPH)
????????
35??? 30?????30R??? ??????????
????????? ????????
25
20
???????? ????????? ????????
15
????? (mU/l)
10
5
???30
0
????30R
800
1100
1400
1700
2000
2300
200
500
800
????(??)
36????????
?????,???????????????
- ???????(24h)
- ????,??????
- ?????????
37????????-???
Karsholm Ludvigsen. Receptor 199551-8.
38????????
????? PH7.4
????
6?????? ?6????? ??????
Capillary membrane
???????
Capillary blood
???????
39???????
???????
??????? ???????
???? ?????
????
40????????,?????????24??
???
0.8 U/kg
0.4 U/kg
?????
3.0
2.5
2.0
?????? (mg/kg/min)
1.5
1.0
0.5
0
0
2
4
6
8
10
12
14
16
18
20
22
24
?? (??)
Klein O et al. Diabetes Obes Metab 20079290-299
41?????????
????? ???
IGF-IR/IR ??? ??
????? ??
IGF-I?? ???
????? ????
100
100
100
????
100
1
1.9
66
100
84
?????
156
58
0.9
81
81
92
?????
11
0.9
16
204
18
???
86
152
783
641
?????
7.5
P Kurtzhals P, et al. Diabetes 2000 49 999-1005
42???????
- ???????,??????
- ?????????
- ??????64??????
- ????????
- ??????
43? ?
- 2??????????????????
- ?????????,????,????
- ?????
- ????????
- ????????????
44??????????
800
600
400
????? (pmol/min)
200
0
0600
1000
1400
1800
2200
0200
0600
??
Polonsky KS et al. N Engl J Med 1996334777
45???????????
- ??????????-??????
- ?????????????
- ?????????
46???????????
- ??????????????
- ??????????
- ?????????????????????????????
- ???????
- ??????????????
- ???????????????????
Joslin????.?????????.39681
47??????
- 2????
- ???????????????????????????
- ???????????????????(??????2??????)
- ???????1?????????????????
- 1????
- ????????????,????????????
- ?????
- ??2????????????????
- ????
- ???
- ???????
48??????????
492????????????
- ??2?????????
- ?????????????????
- ???????????????????,??????????????????????
- ??????????,????????,?????????,????????????????????
?(??????)
??????????????/?????
50??????????
- ????????,?????
- ??????NPH??????,?FPG???4-6 mmol/L(???)
- ???????????30u,????????,?????????????
- ??gt2??????, ????????????
???.????????????????.7210
51????????? ___?????
- ??????????
- ?10????????????
- ?????0.2 U/kg
- ????,?????????????????
- 3-4???????,??????1-4 U
- ???????4-6 mmol/L(???)
2007?????????
52????????? ___?????
- ?????????????????,HbA1c???T2DM??,????????????
- ????????
- ?????0.4-0.6 U/kg??/?,?11????????????
- ????,????????????,???????????????????????
- 3-4???????,??????1- 4U????????????
2007?????????
53?????????????
- ????????????,??
- ????????????
- ? HbA1c gt 8, ???????????
- ? HbA1c gt 10, ???????????,
- ????????????
- ??????T2DM??
- HbA1c gt 8.5, ??????????????
AACE Guideline
54??????????
55??????????????
- ????????????????????
- ???????,???????
- ??????,????????(IR ??)??????,?????????
56??-???????????
75
Dinner
Breakfast
Lunch
50
Plasma Insulin µU/ml)
25
800
400
1600
2000
2400
400
1200
800
Time
57??????(1)
- ????/?
- ????????????????????
- ????
- ???
- 1)???2h?????-11Am?????????
- 2)????????????,???????
- 3)???NPH????,??????????
- 4)???NPH????,???FPG?????
58?????2?/?????
59??????(2)
- ????/?
- ??? ??? ???
- R R R
NPH - ??????
- ???
- ??? 12Am-3Am???
- NPH????
- ??? FBG????
60??????(3)
- ????/?
- R R R NPH ??
- ???????????
- ?????????
61???????4?/?????
62??????(4)
- ????/?
- R R R ???
- NPH 8Am?? NPH???
- ??NPH?30-50???,??R?????
- ???????????????????????
63??????(5)
- ??????
- ?????????????
- ??????
- ????????,??????????
- ???1??????
- ????
64??????? ___?????????????
- ???????
- HbA1c 6.5
- FBG lt 110mg/dL
- 2h PPG lt 140mg/dL
65??????????
- 1????
- ??????
- ??????????2??????(?????????????????????,???????)
- ???????
66???????????
- ?????????????
- ????????
- ??????????(???????)
- ?????????????????
- ???????????
- ?????????
67???????????
?? ??? ??? ???
?? ????? ??1 RI
RI RI NPH ??2
RI RI RIUL ??3
RIUL RI
RIUL ??4 RI
RI RI UL ??5
RINPH /-RI RI
NPH CSII RI
RI RI
68??????????????
- ????????????????40-50??
- ????????18-24????
- ????
- 1????0.5-0.8u/Kg??,???1.0
- 2??????0.3-0.8u/Kg??
69???????___????????
- ??? ??? ???? ???
- RI 25?30 RI15?20 RI 20?25 NPH20
- ????(CSII)
- 40????????
- ?????20,
- ????????15
- ??10(?????)
70???????????? ___???30 ??????
???30???????????????????????????? EMEA (European
Agency for the Evaluation of Medicinal
Products,???????)????
????????????????????
71??????
2007?????????
72? ?
- ??????????????????
- ?????????????
- ?????????????????????
??????????
73? ?
- 2??????????????????
- ?????????,????,????
- ?????
- ????????
- ????????????
74????-??
- ??- ????
- ??
- ??
- ??- ????
- ??????????
75???????
- ??2.5cm,
- (????????)
- ?????? 5 cm?????????
76???????
- ????????
- ????
- ????????,?????(????)
- ????,?4590???
- ???????10????
- ???????????????90???,???????????????????
- ?????????,?????
77???????
- ????????????,????????????????
- ??????????,???????,??,?????????????????????,?????
78???????????????????
?? ??? 32G 6mm ??? 32G 6mm ??? 30G 8mm ??? 30G 8mm
??/????(BMIgt18kg/m2) 45???? ????? ???? ??
??-???? 90???? ????? ???? ??
??-??(BMIgt27kg/m2) 90???? 1. ????????? 2. ??????,?????? 90???? ????? ????
79?????????
- ??, ?????
- ?????????????
- - ???????????
- - ??
- - ?????
- - ??????
- - ?????
- ????? ??, ?????????
- ?????????????
- ?????????????
- ?????????????????
- ????,??????,???????
80??? ??
??? 3,?????????
??? 4,????????????????
81???,????,????????????
??? 4
82??????????
- ????(CSII,??????????)
- ???????????????????????????????
- ????
- ??????????????????.???????????????????,????????
?????????
83