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ǷҧԸջͧѹäҹԴ 2 㹻Ѩغѹ | ֡ҵͧ | 20 .. 2006

Է ¹è, .. ҹѪԹԡ ҹѪ çҺžطԹҪ ɳš

๵ آó, Pharm.D. , Ph.D. ҢѪԹԡ ҤԪѪ Ѫʵ ԷԴ

1-000-HPT-000-0504-01

ӹǹ 3 ˹¡Ե֡ҵͧ

ѹѺͧ : 11 ¹ 2548

ѹ : 10 ¹ 2550


äҹԴ 2 äѧѵ٧㹻Ѩغѹ СԴõ¢ͧ¨ҡá͹ʹʹᴧҴ ʹʹᴧҴ˭ á͹Դ鹡Ѻ¹ á͹ҧ (Retinopathy) (Nephropathy) кҷ (Neuropathy) äʹʹͧ ͡ҡ ˵õ·Ӥѭ㹼ҹԴ 2 ͨҡá͹ͧäʹʹ1

ͧ͹š (WHO) Ҵ๤ءͧҹ ¤ҴҨըӹǹ٧鹨ҡ 220 ҹ㹻 .. 2000 151 ҹ㹻 .. 2025 »ҳóһȡѧѲᶺջ¨ѵ٧ش2 㹨ӹǹͧҹ ҳ 90 繼ҹԴ 2 ҹԴ繻ѭӤѭҧҡ㹻ȡѧѲҫ觢ҴŹѾҡ÷ҧҹҸóآ 㹡ûͧѹä СѡҼҧ§3

ҧá Ҩҷѡäҹҡ 12 Դ㹻Ѩغѹ4 պؤҡ÷ҧᾷǪҭ мѺҺе˹ѡ֧çͧä §ҹԨ¶֧äǺäҹҧǴǡ عçҡá͹㹼ҹԴ 2 ѧФ繻ѭҵ ѧ ֧դԸա㹡ûͧѹդԴԷҧ metabolic ٧ԴäҹԴ 2 ͹Ҥ4-8

ҸҾѺäҹԴ 2

äҹԴ 2 ˵ҨҡԴԷҧ metabolic ͧ ÷ӧҹͧ b-cell 㹵Ѻ͹դͧ ͡д͵ insulin ÷¨äҹԴ 2 еͧТͧ͡ʷԴ (impaired glucose tolerance ,IGT) ҡ͹ Ǥ дѺӵʹ٧ insulin ж١觨ҡ b-cell ͧѺ͹ ҡաõ͵ҹ͡ķͧ insulin Ѻ͹о᷹ ¡ insulin ͡ʹѧ b-cell 㹵Ѻ͹ѧö insulin ᷹ ҡѺ͹ö insulin § 㹷ش觼дѺӵʹ٧9 ֧Դ IGT 繼ԴдѺӵѧѺзҹ٧ (postprandial hyperglycemia) Ҩäҹ㹷ش ͡ҡ ¡֡ҷʴ繶֧ѹҧдѺӵʹ٧鹡Ѻ§Դá͹ͧäҹ10-12

ҡ˵ؤԴԷҧ metabolic ͧ Դ IGT оѲäҹ ѧա˵ط繻Ѩ§͡ԴäҹԴ 2 ͪҵ äǹ ͨҡѨ§ͧä㨷 ͡ҡ IGT ѧ͡§͡Դäʹʹ ªԵäѧҡ10,12

Prediabetes СûͧѹäҹԴ 2

American Diabetes Association (ADA) Recommendation .. 2004 ˹դдѺӵẺ (fasting plasma glucose, FPG) ʹ٧дѺӵŻ ԹдѺӵŷѴäҹ ¡ impaired fasting glucose (IFG) /ͼ跴ͺ͡ʴ¡Ѻзҹӵš 75 дѺӵѧҡѺзҹ 2 (oral glucose tolerance test, OGTT) impaired glucose tolerance (IGT) ¡ҹ prediabetes1

ҧ 1 Categories of prediabetes1

1) FPG = 100-125 mg/dl (5.6-6.9 mmol/l)

= IFG (impaired fasting glucose)

and/or

2) 2-h postload 75 g oral glucose tolerance test

= 140-199 mg/dl (7.8-11.1 mmol/l)

= IGT (impaired glucose tolerance)

ҧ 2 Criteria for the diagnosis of diabetes1

Normoglycemia

Prediabetes (IFG and/or IGT)

Diabetes

FPG < 100 mg/dl

FPG³ 100 and <126 mg/ml (IFG)

FPG ³ 126 mg/dl

2-h OGTT PG < 140 mg/dl

2-h OGTT PG ³ 140 and < 200 mg/dl (IGT)

2-h OGTT PG³ 200 mg/dl

symptoms of diabetes and casual plasma glucose concentration ³ 200 mg/dl

ҡ Clinical Practice Recommendations 2004 Ҥäҹ觻Ѱԡ (ADA) Ƕ֧äѴͧ ҡջѨ§ҧҧ˹觵ҧ 3 þԨóҵǨäҹ13 觨ҡѨ§ѧ ;Ԩó¡ͧ͡ǹ ջѨ§ǹ˹觷ö䢻Ѩ§ ¡ modifiable risk factors 觶ҡöӡѴѨ§˹ҧ˹觷Ъ»ͧѹԴäҹԴ 2

prediabetes Ѵ繻Ѩ˹觷öѡ ֧§ҹԨ·ӡ prediabetes ੾м IFG ӡ֡ûѺ¹ԶաԹԵ (lifestyle modification) ͡ͻͧѹͪäҹԴ 2 ͡

ҧ 3 Ѩ§ѺõǨäҹԴ 213

Modifiable Risk Factors

Nonmodifiable Risk Factors

Overweight (body mass index ³ 25 kg/m2)

Age ³ 45 yrs

Habitual physical inactivity

First-degree relative with diabetes mellitus

Previously identified prediabetes (impaired glucose tolerance or impaired fasting glucose)

Ethnicity (African-American, Native American, Asian-American, or Pacific Islander)

Hypertension (blood pressure ³ 140/90 mmHg)

History of gestrational diabetes or delivery of a baby weight > 9 lbs

High-density lipoprotien chlolesterol level £ 35 mg/dl

Have polycystic ovary syndrome

Serum triglyceride level ³ 250 mg/dl

History of vascular disease

ŢͧѰԡ the third National Health and Nutrition Examination Survey (NHNESIII) ҧ ..1988-1994 NHNESIII .. 2000 §ҹҼչ˹ѡԹ ҧ 45-74 ҳ 12 ҹ prediabetes ա 5-6 բҧ˹ 㹨ӹǹ IGT IFG ҧҧ˹ ͡äҹԴ 2 20-34 мշ IGT IFG ͡äҹ֧ 38-65 ͡ҡѧҴóҼ·äҹԴ 2 prediabetes 5 ա͹ѺԹԨ12,14-15

ҹԨ·ǢͧѺûͧѹäҹԴ 2

ա÷ͧҧԹԡʴ繶֧Ţͧûͧѹ ҧª͡ԴäҹԴ 2 ͡ ¡ûѺ¹ԶաôԹԵ ͡ͻͧѹ3-4 ֡ǹ˭仡 IGT ͼ IGT IFG ա֡§ǹ·㹡 IFG §ҧ4 ͧҡ֡Ҷ֧غѵԡó (cumulative incidence) ͧþѲäҹԴ 2 ѧҡԴҡ 5-6 ҡչӵʹẺ зӡ÷ͺ OGTT ǻ § 4-5 Ѳäҹ ǹ㹡 IFG 跴ͺ OGTT ǻԾ 20-34 㹡շ IFG IGT ֧ 38-65 ͡ҡѧդᵡҧҧѴਹͧѵҡþѲäҹ㹡 IFG IGT ҧҧ˹4

ûѺ¹ԶաôԹԵ

¹ŧĵԡ㹼§äҹԴ 2 ¶֧ ¹ĵԡ㹪ԵШѹ ¡äǺ С͡ѧ

Da Quing study16 (China) Malmo study17 (Sweden) 2 ҹԨá ֡Ҷ֧ŢͧûѺ¹ôԹԶժԵ · IGT ҧá 2 ֡ҹѧբӡѴͧӹǹ subject ѧҡѡ ҡš֡Ңͧ Da Quing study Դ subject (n=577) 6 ԨóغѵԡóԴäҹԴ 2 (cumulative incidence) դᵡҧҧչӤѭºѺǺ ¾ҡǺ (ҳ calories ҳѹ 25-30 kcal/kg body wt ǹ BMI > 25 kg/m2 Ŵ˹ѡŧ 0.5-1 kg ͹ BMI й¡ 23 kg/m2 ) Դغѵԡó 43.8 ͡ѧ ( ѡҹ ෹ 5-30 ҷ ¨лѺ¹仵 äШӵ ) Դغѵԡó 41.1 СǺС͡ѧ Դغѵԡó 46 㹢зǺԴغѵԡó 67.7 ҡ֡ҹ ͡ѧ¨غѵԡóͧԴäҹ·ش Ѻ Malmo study (n=250 ੾Ȫ) ºº IGT ͡ѧ/ͤǺºѺ IGT intervention ѧҡԴ 6 㹡áԴäҹ 10.6 ǹ㹡ͧԴäҹ 28.6 ºº relative risk ͧԴäҹ = 0.37 (95% CI = 0.20-0.68, p<0.003)

The finnish diabetes prevention study18 (Finland) ա֡˹觷ûѺ¹ԶôԹԵ ֡ subject ӹǹ 522 IGT 55 BMI 31 kg/m2 ¡Ǻ (n=257) Ѻ͡ ͤйӻФ ͧͧС͡ѧ ǹա (n=265) ѺйͧäǺ С͡ѧ ҧ subject йŴ˹ѡ (Ŵŧҡ 5 ͧ˹ѡ) Ŵ (¡ 30 ͧҳ calories Ѻѹ) ͡ѧ (ҡ 150 ҷ/ѻ) աõԴҧǴ ѴǹͧѺй੾ҧǴöŴԴäҹͻ 3.2 ºѺ 7.8 㹡Ǻ ͡ҡ㹡ѺйŴ˹ѡҧǴ öŴ˹ѡŧ 3.5 š ºѺǺŴ 0.8 š ѧҡԴ 3.2 غѵԡóԴäҹẺ (cumulative incidence) 58 㹡ѺûѺ¹ԶժԵҧǴԴӡҡǺ ͡ ѺûѺ¹ԶժԵҧǴԴäҹ 0.4 ºѺǺ (Hazard ratio, HR = 0.4, 95% CI = 0.3-0.7, p<0.001)

The diabetes prevention program (DPP) study19 繡֡㹡 subject Ҵ˭ subject (n=3,234) ǹ (BMI 34 kg/m2) 51 IGT IFG 45 subject ҡͪҵ Caucasian, American Indian, Hispanic Asian American subject 3 ͡ǺѺ placebo (n=1,082) Ѻ metformin Ҵ 850 mg ѹ 2 (n=1,073) СѺûѺ¹ԶաôԹԵҧǴ Ǻ ˹ѡŴ 7 ͧ˹ѡ ͡ѧҧ 150 ҷյѻ (n=1,079) ҡõԴ 2.8 ҡѺûѺ¹ԶաôԹԵöŴغѵԡóԴäҹԴ 2 58 (95% CI = 48-66%, p< 0.001) ºѺǺ ѧöŴغѵԡó 39 (95% CI = 24-51%, p< 0.001) ºѺѺ metformin Шҡ֡ҹ 50 ͧѺûѺ¹ԶժԵöŴ˹ѡ öŴҡҡѺ 7 74 ö͡ѧѻ 150 ҷ

й ҡ֡ҷ駢ͧ the finnish study DPP study ֧׹ѹ繶֧ŢͧûѺ¹ԶôԹԵ㹡 subject IGT ö͡äҹԴ 2 ҡ 50

Ŵ˹ѡѺûͧѹäҹԴ 2

ADA Сȶ֧ѡСطͧäǺ˹ѡ ¨شʧͧûСȹ繡÷ǹҷ㹡ûͧѹ ѡäҹԴ 2 äǺ˹ѡӤѭ㹡ûѺ¹ԶժԵ ͤǺ˹ѡ֧ǹ㹡Ŵ˹ѡ20-21 ADA ˹բͨӡѴͧ੾㹼·äǹ 㹼·դ BMI ³ 30 mg/m2 BMI ³ 27 mg/m2 Ѻ§ͧäǹ 觨СǵǢ ADA Recommendations

Ŵ˹ѡ Ӥѭ㹼չ˹ѡԹ ͼ·äǹ ੾мäҹԴ 2 СŴ˹ѡЪäǺдѺӵբ4 ͡ҡªͧŴ˹ѡ 5 ͧ˹ѡ Ъ·͡ķͧ insulin բ20-21 ŴдѺ fasting blood glucose ŴѨ§㹡Դá͹ʹʹͧ зӤѭѧªäҹԴ 2prediabetes ա20-21

orlistat һ lipase inhibitor ҡԵѳҵԨҡ Streptomyces toxytricini ١͡Ŵ˹ѡ ͡ķѺ͹ pancreatic gastric lipase ҧШ ö͹Ѻ (irreversesible) Ҩҧ covalent bond Ѻ active serine site ͹ pancreatic gastric lipase 觶١ҨҡҧԹ ͹ö hydrolyze ÷ѹٻ triglyceride fatty acids monoglycerols ѧ triglyceride ж١Ѻҹҧب͡١ٴ㹷ҧԹ شҧ¡Ѻ calories ҡ triglyceride ѹͶ١ҧѧҹ22 Ѩغѹҹբ·仵ͧҴᶺջû ᶺԡ Ѻâ鹷¹Ѱԡ͹Ȩԡ¹ ..199723 բ㹻´

ͧҢͧѰԡ (USFDA) Сͺͧ orlistat (XenicalÒ)23-24 㹡Ŵ˹ѡͪª͡ԴäҹԴ 2 㹼ǹԹ prediabetes ŧ͡áӡѺѹ 9 Ҥ .. 2004 ¨ҡš֡Ңͧ Xenical in the prevention of diabetes in obese subjects (XENDOS) study25 ֡㹡 subject ǹçҺҧ .. 1997-2002 ӹǹ 3,304 (BMI ³ 30 mg/m2) 繡Ǻ 2,643 С IGT ӹǹ 661 Դ 4 ҡ IGT orlistat öŴ˹ѡЪ͡äҹԴ 2 relative risk reduction 42 (p < 0.01) ºѺ placebo 㹢з orlistat öŴ§㹡äҹԴ 2 㹡ǹդ͡ʻ ҡš÷ͧ й orlistat 繡á㹡Ŵ˹ѡͧǹ prediabetes ͡ҡҡ orlistat ͼ㹡Ŵ˹ѡ ռŵдѺӵ дѺ insulin ҧ

͡ҡ ѧ ա֡Ҷ֧ԷҾ㹡Ŵ˹ѡ㹼ǹäҹ ҡ֡Ẻ meta-analysis26 ҡҹŷҧ硷͹Ԥ Ԫҡ÷ѺѺҧ٧ ҧ ..1966-2002 ͧ 3 Դ fluoxitine, orlistat sibutramine ¾ 14 randomized control trials ըӹǹ subject 2,231 ҷ 3 ԴöŴ˹ѡѧ

  • fluoxitine Ŵ 3.4 š (95% CI, 1.7-5.2 kg) ѧõԴѻ 8-16 ͧҹ Ŵ 5.1 š (95% CI, 3.3-6.9 kg) ѻ 24-30 ͧҹ Ŵ 5.8 š (95% CI, 0.8-10.8 kg) ѻ 52 ͧҹ
  • orlistat Ŵ 2.6 š (95% CI, 2.1-3.2 kg) ѻ 52 subject ҴõԴ 2.6
  • sibutramine Ŵ 4.5 kg (95% CI, 1.8-7.2 kg) ѻ 26 subject ҴõԴ 3.3

͡ҡѧöŴдѺ HbA1c ´ѧҧ 4 ҡš֡ fluoxitine, orlistat sibutramine öŴ˹ѡҧչӤѭѻ 26-52 ͧ ҧá ˹ѡŴ§ 3-5 ͧ˹ѡ ǹҹǤա֡Ҷ֧ʹµ26

ҧ 4 Ţͧ fluoxitine, orlistat sibutramine 㹡ŴдѺ HbA1c26

ҷ

ѻ 8-16

ѻ 24-30

ѻ 50

Fluoxitine

1.0% (95% CI, 0.4-1.5%)

1.0 (95% CI, 0.6-1.4%)

1.8% (95%CI, -0.2-3.8%)

Orlistat

-

-

0.4% (95% CI, 0.3-0.5%)

Sibutramine

-

-

0.7% (95% CI, -0.5-1.9%)

Pharmacological treatments

ա֡Ҷ֧ ͹һͧѹ ͪ͡äҹ ੾ҷ㹡ѡäҹ metformin, acarbose thiazolidinediones

1. Metformin

Hess Ф27 鷺ǹó ¡׺鹨ҡҹŨҡ Medline .. 1966-2003 metformin ա֡ҧ 3 ֡ҷ׹ѹ֧öͧ㹡ûͧѹäҹԴ 2 prediabetes 㹨ӹǹ§˹觡֡ҷӡԨ㹻ЪҡâҴ˭觡 the Diabetes Prevention Program

ҡ仢ҧͧͧҹԨ·ûѺ¹ԶաôԹԵ ֡ DPP study28-29 繡֡㹡 prediabetes ӹǹҡش㹢й (n=3,234) ֡㹡 metformin Ҵ 850 mg ѹ 2 ººѺѺйͧäǺ ͡ѧҧǴ СǺ placebo ѧԴһҳ 3 ŢͧԴغѵԡóþѲäҹԴ 2 (cumulative incidence) ҡѺ 21.7, 14.4 28.9 ӴѺ ͡ҡѧöŴ˹ѡ㹼 2.1, 5.6 0.1 šӴѺ (p< 0.001) ºº washout data ͧ metformin ҹöŴ§㹡ԴäҹԴ 2 25 ºѺ placebo (risk ratio 0.75, 95% CI 0.62-0.92, p=0.005) شç ºº overall rate ͧþѲäҹԴ 2 йӡûѺ¹ԶաôԹԵҧǴ ѺѺ metformin ͧººѺѺ placebo 羺ҡйӡûѺ¹ԶաôԹԵҧǴ ö͡äҹ 58 ҡҡ metformin ( 31) ҡйӡûѺ¹ԶաôԹԵдա 㹡֡ҹ ʴ metformin ջª㹡ûͧѹͪ͡äҹ ҧá ͵Դš֡ DPP study 3 §ҹ˹觷ʴ֧·ҧç (direct medical costs)30 ʹ㹡Ѻ metformin 2,542 US dollar ͤ 觵ӡºѺйӡûѺ¹ԶաôԹԵҧǴ 2,780 US dollar ͤ 㹪ǧõԴáͧûѺ¹ԶաôԹԵ դͧͧؤҡ÷ͧԴйӡäǺС͡ѧ ֧·ͧԴ դҡҡ metformin ҳ 37 ;Ԩó subject ͧ㹻շͧ ѺҤ㹡ûѺ¹ԶժԵŴŧ 12 7 ӴѺ ͧҡ㹡õԴйŴŧ ͧؤҡŴŧ 㹢С metformin лѴ§ѭ (generic name) ҨѺ٧ ͧҡ֧ʧҡҫ觨繵ͧ֡ҵ

2. Acarbose

ҡ Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) study31-32 繡֡㹢й֡һԷҾͧ acarbose 㹡êª͡ԴäҹԴ 2 㹤ӹǹҡ ·㹡 IGT ӹǹ 714 ҧ 40-70 BMI ҡѺ 25-40 kg/m2 ººѺ acarbose Ҵ 50 mg ѹ öѺҴء 2 ѻ٧شԹ 300 mg ѹ Ѻ placebo ͡ҡ subject ءѺй㹡äǺ й˹ѡ¡͡ѧҧ ¨վҺŤйеԴŷء 6 ͹ ѧ֡ 3.3 վҡ acarbose оѲäҹԴ 2 ҡѺ 32 ºѺ placebo 42 (relative risk = 25%, hazard ratio = 0.75, 95% CI 0.63-0.90, p=0.0015) Ҽš֡ҹʴ繶֧Ŵբͧûͧѹäҹ acarbose ش Ţͧûͧѹ仴

3. Thiazolidinediones (TZDs)

ҡѭҢͧǹԹ оĵԡ͡ѧ㹻Ѩغѹ 觼Դд͵ insulin §Ѻ prediabetes äҹԴ 2 ҡ ҡ¡֡ ʴ繶֧˵آͧԴ endothelial dysfunction ҡŢͧд͵ insulin öԴäʹʹͧ͹Ҥ ҧ atherosclerosis9,33

դ֡ҷöѡ endothelial dysfunction Ѻ׹Ҿ ҡ peroxisome proliferators-activated receptor g ligands, angiotensin-converting enzyme inhibitors С angiotensin receptor blockers ͡ҡҹѧö»ͧѹäҹԴ 2 Ф§㹡Դäա

Thiazolidinediones 繡ѡäҹԴ 2 ռŵ͡ÿ鹿 b-cell 㹵Ѻ͹ ǵ insulin Ѻǹ prediabetes33 ҡ Troglitazone in the prevention of diabetes mellitus (TRIPOD) study34 ӡ֡ 㹡 subject ˭ԧҵԹԡäҹ ջѵ gestrational diabetes ҡ͹ 觡ººҧ troglitazone 400 mg ѹ (n=114) Ѻ placebo (n=122) subject ءѺй㹡͡ѧ¤ 30 ҷ 3 ѹѻ ֧äǺô ֡ҹͧشŧ troglitazone ١͹͡ҡҴ㹻 .. 2000 羺ѧҡԴ subject 30 ͹ Ѻ troglitazone Դغѵԡóͧäҹ§ 5.4 ºѺ placebo Դغѵԡó 12.1 (p<0.01) · risk reduction ͧ troglitazone ҡѺ 56

Bannett Ф35 ӡ֡ subject ӹǹ 18 IGT 繡Ѻ rosiglitazone 4 mg ѹ 2 ººѺ placebo Դ 12 ѻ 㹡 rosiglitazone öǵ insulin ͡Ѻ IGT Durbin36 ӡ֡ subject ӹǹ 172 (ҧ 29-86 ) IGT placebo ºѺ troglitazone ҡ͹ 10 ͹ (n=101) switch rosiglitazone 4 mg ѹ pioglitazone 30 mg ѹ ѧҡԴ 3 § 3 㹡Ѻ thiazolidinediones (TZDs) (2 pioglitazone 1 rosiglitazone) Ѳäҹ 㹡Ǻ 19 ·Ѳäҹ ѧա֡ҼŢͧŴдѺͧ HbA1c㹡Ѻ TZDs · baseline ͧ HbA1c ͹ѡդҡѺ 6.12 ± 0.60%, 6.23±0.74% 6.18 ± 0.20% rosiglitazone, piogltazone СǺӴѺ ش֡Ҿ HbA1c դҡѺ 5.57 ±0.37%, 5.65±0.48% 6.68±0.19% (p<0.001) rosiglitazone, piogltazone СǺӴѺ š֡ʴҶҡ TZDs ҵá㹡ѡ㹡 IGT ҷͧԴöŴдѺ HbA1c Ъª͡ԴäҹԴ 2 ҧչӤѭҧʶԵ

4. Angiotensin converting enzyme inhibitors Angiotensin receptor blockers

The heart outcome prevention evaluation (HOPE) study37-38 繧ҹԨ·֡㹡 4.5 ջѨ§٧͡Դäҧʹʹ stroke, peripheral vascular disease, diabetes 繵 觡 ramipril 10 mg ѹ 1 ºѺ placebo ҡ subgroup subject ӹǹ 5,270 äҹ ҡ ramipril Դغѵԡóͧäҹ 3.6 ºѺ placebo 5.4 С ramipril ѧŴ§㹡Դ macroalbuminuria ŴдѺͧ HbA1c 㹼äҹա ͡ҡѧա֡ ʹ the captopril primary prevention program (CPPP)39 ֡ҡ captopril ѡ㹼·դѹԵ٧ Դ 6 ҪŴѨ§㹡Դäҹ 14 ºѺ beta-blocker thiazide The antihypertensive and lipid lowering treatment to prevent heart attack (ALLHAT) trial40 ֡㹡 ACE inhibitors աԴ lisinopril 㹤ӹǹ 14,816 äѹԵ٧ ջѵäҹ (Ѵҡ FPG < 126 mg/dl) 觡ѡҴ lisinopril 10-40 mg ѹ amlodipine 2.5-10 mg ѹ chlortalidone 12.5-25 mg ѹ ѧõԴ 4 վغѵԡó㹡Դäҹ ҡѺ 8.1, 9.8 11.6 ӴѺ (p < 0.001 ºѺ lisinopril С chlortalidone) ֡ҹѧʴ ·äѹԵ٧ѡҴ lisinopril Ъª͡ԴäҹԴ 2 Ŵ relative risk 30 (95% CI = 23-37%, p< 0.001) ºѺҢѺ chlortalidone Ŵ relative risk 17 (95% CI = 7-26%, p< 0.001) ºѺ amlodipine

The losartan intervention for endpoint reduction in hypertension (LIFE) trial41 ա˹觧ҹԨ ֡ losartan Angiotensin receptor blockers subject ֡Ҩ繼äѹԵ٧ ѺѡҴ losartan غѵԡóԴäҹ㹼§ 25 ºѺѡҴ atenolol : 241 cases (6% or 13.0 per 1000 patient-years of follow up) Ѻ 319 cases (8% or 17.5 per 1000 patient-years of follow up) (RR = 0.75, 95% CI 0.63-0.88, p<0.001) Valsartan antihypertensive long-term use evaluation (VALUE) trial42 ֡㹡·äѹԵ٧ ջѨ§٧㹡ä ѵäҹ ѡҴ valsartan amlodipine غѵԡóԴäҹ㹡 valsartan §硹ºѺ amlodipine (690 ºѺ 845 ӴѺ) hazard ratio = 0.77 (95% CI 0.69-0.86, p<0.0001)

5. HMG Co-A reductase inhibitors

Фҹҹ insulin պҷӤѭ㹡ԴäѹԵ٧ äѹʹԴ äҹԴ 2 HMG Co-A reductase inhibitors statin öŴдѧ͡˹ͨҡŴдѺѹʹ ա֡ҷǶ֧ inflammation ռŵ͡Դҹҹ insulin 觼žѲäҹԴ 2 ѧ ҡҷŴ inflammation Ҩ觼Ŵҹҹ insulin Ŵ§㹡ԴäҹԴ 243

աù㹡 statins ֡ͪ͡ԴäҹԴ 2 оդسѵ 㹡Ŵ inflammation ҡҹԨ west of scotland coronary prevention study (WOSCOPS)44 ֡ subject Ȫҧ 45-65 myocardial infarction ҡ͹ (n=5,974) pravastatin 40 mg ѹФ ººѺ placebo (n=82 ҡ 2,975) С subject Ѻ pravastatin (n=57 ҡ 2,999) ҡѺ pravastatin öäҹŧ 30 㹡֡Ẻ retrospective cohort study Yee Ф43 ͻԹ㹡 statin ͪª㹡¹ҩմ insulin 㹡ҹԴ 2 ҧ ..1991-1996 ҡ֡Ҿ ¨ӹǹ 10,966 Ѻзҹѡäҹ ա statin 484 㹨ӹǹö͡¹ҡѺзҹ ҩմ insulin 10 ͹ ºѺѺ statin (hazard ratio = 0.74; 95% CI 0.56,0.97 p=0.028) ҧáҹԨ¹§֡ͧ鹢ͧҡ statin 㹡êªҹ еͧա÷ӡ֡ҵ

ҹԨ45-50

ҹԨ ѧҧ֡ ա֡Ҷ֧ intervention ҧ 㹡ê»ͧѹ ͪ͡ԴäҹԴ 2 ѧʴ㹵ҧ 5

American Diabetes Association Recommendations4,13,20

Ҥäҹ觻Ѱԡ йѺäѴͧ͵Ǩäҹ㹡Ҩ prediabetes 㹼·ҡҡѺ 45 ء੾м BMI ³ 25 kg/m2 ѺõǨ prediabetes ҨдԸ IGT IFG testing ǹ㹡صӡ 45 չ˹ѡԹ BMI ³ 25 kg/m2 ջѨ§㹡äҹ (ҧ 3) èѺõǨѴͧäҹ ͡ҡ㹡·ջѨ§٧ 㹼ٺ ѹʹԴ ͼդѹԵ٧ йԡ ͡ѧ Ŵ˹ѡ ͧҡҹ͡§͡Դäʹʹ٧

Ѻҧ͡㹡ѡѺ prediabetes ADA йѺ¹ԶաôԹԵ 觻Сͺ¡Ŵ˹ѡ 5-10 ͧ˹ѡ ͡ѧ 30 ҷյѹ ҧáѧաйͧͧ ͧҡš֡ҷҹ ѧաҪ»ͧѹäҹ㹼 prediabetes աҡûѺ¹ĵԡ ͡ҡҡ§ҹԨ ʴҡѧҨԴҡ֧ʧ ТѧҴ˹ѡͧͧŴá͹㹼 ʹѧҴŷҧҹ cost-effectiveness

ҧ 5 ҹԨ·ҧ֡ /ҧõվ

Trials

Study design

Intervention

Results

The early diabetes intervention (EDIT) trial45

Prospective, double-blind, randomized controlled trial

n = 631 with IGT

acarbose 50 mg or

metformin 500 mg or

combine or placebo

After 3 yrs; the risk reduction of progress to DM compare placebo: acarbose 8% (p=0.80) and metformin 37% (p=0.17)

Diabetes reduction assessment with ramipril and rosiglitazone medication (DREAM)46-47

Prospective, double-blind, randomized controlled trial

n = 4,000 with IGT

ramipril 10 mg or

rosiglitazone 4 mg

or placebo

The primary outcome is new onset DM or all-cause mortality will be followed up for 3 yrs

Nateglinide and valsartan in impaired glucose tolerance outcome research (NAVIGATOR)48

Prospective, double-blind, randomized controlled trial

n = 7,500 with IGT

valsartan 160 mg

and/or nateglinide 60 mg

or placebo

New onset DM over a minimum of 3 yrs will be assessed by FPG levels every 6 mo. And will be followed up for 6 yrs

Ongoing telmisartan alone and incombination with ramipril global endpoint trial (ONTARGET/TRANCEND)49-50

Prospective, double-blind, parallel-group trial

n = 22,400 (40 countries)

telmisartan 80 mg or

ramipril 10 mg or

telmisartan+ ramipril

Secondary endpoints, the trial will investigate new hypothesis on the physiological consequence of angiotensin II such as the development of type 2 DM and will be followed up for 5.5 yrs

ػ

ûͧѹäҹԴ 2 Ӥѭҧ ҹһȡѧʹ ҡ֡ ҹԨ㹻Ѩغѹ ʴҼŢͧûѺ¹ĵԡ㹡 prediabetes ¡͡ѧ·ҡѡ СäǺ˹ѡЪ»ͧѹäҹҡ 50 ͡ҡ ҡҧ ¡֡ҷʴǹªäҹԴ 2 蹡ѹ ҧáҡѧͧա֡ҵ һԷҾ¨ Фʹ㹡ҹ

͡ҧԧ

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