ACE,????????????

1
ACE,????????????

• Take hyperglycemia management to a new era

??? ?????????????? ????????? ? ??????????? 2008?10
?24
2
? ?

• IGT?????????????
• ????????????IGT??
• ACE????????????

3
??????????

• Each year 3.8 million deaths worldwide are
  attributable to diabetes
• Diabetes is associated with complications such
  as
• Diabetic neuropathy
• Renal failure
• Blindness
• Macrovascular disease
• Macrovascular complications are a major cause of
  death in people with diabetes

Diabetes Atlas, 3rd edition, International
Diabetes Federation, 2006
4
??????
FPG (mmol/L)

???
7.0

6.1

I-IGT
????
OGTT 2???? (mmol/L)
7.8 11.1
Shaw JE, et al. Diabetologia 421050,1999Resnick
HE, et al. Diabetes Care 23176,2000 Barrett-Conne
r E, et al. Diabetes Care 211236,1998Genuth S
,et al. Diabetes Care. 200326(11)3160-7.
5
????????????
Peoples Republic of China
Prediabetes 2003 33 million (4) 2025 54
million (5)
Diabetes 2003 23 million (3) 2025 46
million (4)
Prediabetes is defined by elevated blood glucose
levels below those used to diagnose
diabetes Elevated post OGTT levels IGT
(7.811.0 mm/L) Elevated fasting levels IFG
(5.6/6.06.9 mm/L)
Sicree, Shaw, Zimmet. Diabetes Atlas. IDF.
www.idf.org.2006
5
6
????????????
?????????????(???)
?????????
7
??????????IGT
??????
??????
European Heart Journal (2004) 25, 18801890
Da-Yi Hu, et al. European Heart Journal
2006272573-2579.
8
IGT???????
301?????
N 97(NGT), 51(IGT), 73(DM) ??????? Plt0.05,
?Plt0.005, v.s. NGT
Jing WS, Pan Cy,Lu Jm et al.Chin J Endocrinol
Metab 200420(2)136-139
9
IGT and the risk of CVD

• Da Qing IGT intervention Study
• 577 IGT
• 519 Control
• 4 IGT
• 0.4 NGT

The appearance of ECG consistent with CHD
Diabetes Care 199316.150-156
10
Relationship between of Coronary Lumen Diameter
and 2-hour Glucose
Angiographic coronary disease progression as
measured by change in minimum coronary luminal
diameter. Data from Mellen et al. Diabet Med
241156-1159, 2007.
10
11
? ?

• IGT?????????????
• ????????????IGT??
• ACE????????????

12
???????????????
13
?????????????????
ACCORD (N10251)
VADT (N1791)
UGDP (N600)
ADVANCE (N11140)
UKPDS (N5012)
Pioglitazone
SU, metformin,insulin
PROactive(N5238)
1970
1998
RECORD (N5447)
Rosiglitazone
2005
2007
2008
1970
1990
2000
2010
14
????????
UKPDS ACCORD ADVANCE VADT
??? 4,208 10,251 11,140 1791
?? 62 62 66 60
?? ??? 10??? 7??? 11???
15
ACCORD??

• ACCORD ???NIH?????????
• ???????????????(??HDL,??LDL)?????????????????
• ???10,251??????2??????
• ??????????????HbA1c???6.0??,???????HbA1c???7.0-7
  .9??
• ??6?

15
16
??????????? Action to Control Cardiovascular Risk
in Diabetes
17
ADVANCE??

• 11140?2??????,??????66?,????8?,??HbA1c??7.5
• ???????(HbA1c????lt6.5)??????(HbA1c????????????)
• ??????????????(????????,???????????????)?????,????
  ??????????????

18
ADVANCE???????????????????
New Eng J Med 2008358(24)2560-2572
19
ADVANCE???????????????????
New Eng J Med 2008358(24)2560-2572
20
VADT ??
N1791

• ????2????
• ?????????
• ????

????(A1c ?? lt6)
????(A1c ?? 8 - 9)
??????????? (???? 5-7 ?)
20
21
VADT?????????????????????
VADT??????????????????????
22
VADT ?????????????????
????? ????? ????? ????? ????? ?????
N CV????? N CV????? P
899 263 29.3 892 231 25.9 0.11
23
UKPDS??
1997 in survivor cohort
2002
2007 with final year data
2,118 ???/???
Clinic
Questionaire
1,010 ???/???
880 ????
Clinic
Questionaire
379 ????
279 ????
Clinic
Questionaire
136 ????
Mean age 62 8 years
Mortality 44(1,852) Lost-to-follow-up 3.5(146)
UKPDS 80. N Eng J Med 2008 359.
24
UKPDS?????HbA1c????
UKPDS results presented
UKPDS results presented
25
????????????Legacy Effect of Earlier Glucose
Control
After median 8.5 years post-trial follow-up
???? 1997 2007
????????? RRR P 12 0.029 9 0.040
????? RRR P 25 0.0099 24 0.001
???? RRR P 16 0.052 15 0.014
????? RRR P 6 0.44 13 0.007
RRRRelative Risk Reduction Plog Rank
25
26
UKPDS???????

• Despite an early loss of glycemic differences, a
  continued reduction in microvascular risk and
  emergent risk reductions for myocardial
  infarction and death from any cause were observed
  during 10 years of post-trial follow-up

27
IGT????????????
Janka HU. Fortschr Med 199211063741.
28
Readout

• Dysglycemia Time Complication
• Early detection Long-term safety intervention
  Benefits to comlications

29
????20????????????????lt???
Plt0.05
Lancet. 2008 May 24371(9626)1783-9.
30
???????????????????????

• ???????????????????,????????????????,????
  
• ?????????
• ??????????????

30
31
??????IGT????????
???OGTT????
Intent-to-treat population Cox proportional
hazards model time to single OGTT gt 11.1 or lt
7.8 mmol/L acarbose vs placebo
32
????/???????????IGT??2????????
43
87.8
76.8
??????50 mg ??3 ?,??????0. 25 g ??3 ?
?????????, 2001, 17(3) 131-4.
33
??????IGT???2???????????????
34
?????????????????????

• IDF2????????
• ???????????????????????????,??????????

• ?????????????????????????????????
• ????????,??????????????,?????????????????

lthttp//diabetes.webmd.com/news/20080723/ prediabe
tes-new-recommendationsgt  
35
? ?

• IGT?????????????
• ????????????IGT??
• ACE????????????

35
36
??????????? (Acarbose Cardiovascular Evaluation)

• ??
• ????????????????????
• ????
• 150??????????7500??????(IGT)????CHD,???????????(AC
  S)???
• ????4?
• ??
• ??????????????????????IGT??????????????

37
ACE?????????

• ???????????IGT?????????
• ?2002?8?6?????????,???????26??????
• ???IGT?????2?????????????
• ??????????,??????????,????????????

38
??????
39
??????

• ???????????????????
• ?????
• ???????
• ??????
• ??????????

40
? ?

• ????????????,??80??,????????
• ?????????????????IGT ?????,IGT????????????,???????
  ????
• ??????????,???????????????????
• ??????????????????????????
• ACE??,????????????????????????

40
41
? ?
Although cost will remain an important factor in
determining prevention of DM and CVD, early
detection and intervention of Prediabetes
(lifestyle modification and pharmacological
intervention) is ultimately much less expensive
than treating the complications of
diabetes. Early Diagnosis of IGT is essential
IGT might be Optimal Time for Intervention of
Diabetes and CVD Prevention
42
Thanks!
43
? ?

• ????????????????,????????????????
• IGT????????????,???????????
• ??????????????????????????
• ACE??,????????????????????????

44
??????????????
Intensive N () Standard N () HR (95 CI) P
Primary 352 (6.86) 371 (7.23) 0.90 (0.78-1.04) 0.16
Secondary
Mortality 257 (5.01) 203 (3.96) 1.22 (1.01-1.46) 0.04
Nonfatal MI 186 (3.63) 235 (4.59) 0.76 (0.62-0.92) 0.004
Nonfatal Stroke 67 (1.31) 61 (1.19) 1.06 (0.75-1.50) 0.74
CVD Death 135 (2.63) 94 (1.83) 1.35 (1.04-1.76) 0.02
CHF 152 (2.96) 124 (2.42) 1.18 (0.93-1.49) 0.17
45
????????
The benefits of previously improved
blood-pressure control were not sustained when
between-group differences in blood pressure were
lost. Early blood-glucose control bring
a long-term cardiovascular benefits.
46
?????????????????
????????
????????
47
??IGT??????????
Sicree, Shaw, Zimmet. Diabetes Atlas. IDF
www.idf.org.2006
48
???IGT????????
143.2

Sicree, Shaw, Zimmet. Diabetes Atlas. IDF
www.idf.org.2006
49
Growing prevalences of diabetes and
prediabetes in China
Screening with FPG only
National Diabetes Research Group. Chin J Int Med
20678,1981 Pan XR, et al. Diabetes 201664,
1997 Gu D, et al. Diabetologia 461190, 2003
50
????????

• 246 million people with diabetes worldwide
• roughly 6 of the adult population
• In 2007, the five countries with the largest
  numbers of people with diabetes are
• India, China, United States, Russia, Germany
• By 2025, the largest increases in diabetes
  prevalence will occur in low- and middle-income
  countries
• Each year an additional 7 million people
  worldwide develop diabetes

Diabetes Atlas, 3rd edition, International
Diabetes Federation, 2006
51
??IGT????????????
??11?(?)?????????(IGT)?????
?????()
????????, 1998, 19(5)282-285.
52
?????????? CHD???????
Factors ? CHD deaths include ? smoking,
cholesterol, and BP and changes in treatments
Factors ? CHD deaths include diabetes and obesity
???????
20,000
(? 2,0003,000)
0
-20,000
Deaths prevented or postponed in 2000
-40,000
-60,000
-80,000
? 68,230
-100,000
Data from England and Wales between 1981 and 2000
in men and women aged 3584 years There were
68,230 fewer CHD deaths than expected from
baseline mortality rates in 1981
Unal B, et al. Circulation 2004 10911011107.