Primary Prevention of T2DM. KW Chan Endocrine & Diabetes Team Department of M&G, PMH 22 March 2009

Transcription

1 Primary Prevention of T2DM KW Chan Endocrine & Diabetes Team Department of M&G, PMH 22 March 2009

2 Primary Prevention of T2DM Why to intervene? When to intervene? Lifestyle intervention Pharmacological intervention IDF: A consensus on type 2 diabetes prevention 2007

3 DM is a large and growing public health problem and has emerged as a major worldwide epidemic. Costing Diabetes IDF 1997

4 In 2007 the 5 countries with the largest numbers of people with diabetes are India 40.9 million China 39.8 million USA 19.2 million Russia 9.6 million Germany 7.4 million Diabetes Facts & Figures, IDF

5 Each 10 seconds 2 people develop diabetes Each year a further 7 million people develop diabetes Diabetes currently affects 246 million people worldwide and is expected to affect 380 million by By 2025 the largest increases in diabetes prevalence will take place in developing countries. Diabetes Facts & Figures, IDF

6 Elliot Joslin 1921 There are entirely too many diabetic patients in the country Therefore, it is proper at the present time to devote attention not alone to treatment, but still more, as in the campaign against the typhoid fever, to prevention. The results may not be quite so striking or as immediate, but they are sure to come and to be important.

7 Primary Prevention of T2DM Why to intervene? When to intervene? Lifestyle intervention Pharmacological intervention IDF: A consensus on type 2 diabetes prevention 2007

8 Diabetes and prediabetes Normoglycemia IGT / IFG Diabetes Insulin resistance and insulin deficiency

9 Incidence of diabetes in IGT patients without any intervention in the Da Qing DPS 20 year FU Study Ave ann incidence: 11% Cum incidence in 20 years: 93% The Lancet 371, 24 May 2008

10 When to intervene? DM Macrovascular & microvascular disease IGT 1. Cardiovascular events increase linearly with 2HPG at levels well below the levels diagnostic of DM % participants with IGT in the DPP had findings consistent with DR.

11 How to intervene? 1. Lifestyle intervention 2. pharmacological intervention

12 Primary Prevention of T2DM Why to intervene? When to intervene? Lifestyle intervention Pharmacological intervention IDF: A consensus on type 2 diabetes prevention 2007

13 Melmo study 1991 The first prospective intervention trial to test the effect of diet & exercise on IGT to T2DM 217 men with IGT were assigned to either a diet & exercise program ( intervention gp ) or to standard medical care ( control gp ), and followed for 5 years The intervention group achieved sig weight loss with a 63% reduction in the risk of advancing to diabetes Patients not randomly assigned to treatment groups Diabetologia 1991; 34:

14 The Da Qing IGT & Diabetes Study In 1986, 110,660 men and women in the city of Da Qing were screened for IGT and DM. 577 were classified as having IGT. Subjects were randomized to control, diet alone, exercise alone or diet + exercise groups. Diabetes Care 1997

15 Control Results at 6 years CI of DM 67.7% Risk reduction (adjusted BMI FBG) P-value Diet 43.8% 31% <0.03 Exercise 41.1% 46% < Diet + Exercise 46.0% 42% <0.005 Diabetes Care 1997

16 Results at 20 years Compared with control participants those in the combined lifestyle intervention groups had a 43% lower incidence (0.57; ) over the 20 year period, controlled for age and clustering by clinic. Participants in the intervention group spent an average of 3.6 fewer years with diabetes than those in the control group. Lancet 371 May 24,2008

17 The Da Qing DPS:20-year follow up study Diabetes Ave ann incidence 20 year cum incidence Intervention 7% 80% Control 11% 93% The Lancet Vol 371 May 24, 2008

18 LSC for PP of T2DM in subjects with IGT Study Cohort size Mean BMI Duration (years) RRR (%) ARR (%) NNT DQS (PRC) Diab Care 1997 DPS (FIN) NEJM 2001 DPP (USA) NEJM 2002

19 LSC for PP of T2DM in Asian subjects with IGT Studies No of subjects Duration of intervention (years) RRR The Chinese study [CJEM 2001] % The Japanese study [DRCP 2005] % The IDPP study [Diabetologia 2006] %

20 The evidence is overwhelming. Intensive lifestyle changes are very powerful tools for the prevention of diabetes in high risk populations. However, it is well known that the long term success of weight reducing programs is less than 10% Jean-Louis Chiasson, Expert Opin Pharmacother (2007) 8 (18)

21 Primary Prevention of T2DM Why to intervene? When to intervene? Lifestyle intervention Pharmacological intervention IDF: A consensus on type 2 diabetes prevention 2007

22 DPP ( USA ) persons with IGT were randomly assigned to placebo metformin 850 mg bd or LSC program; average FU was 2.8 years DM incidence Reduction 95%C1 (cases per 100 person- years) Placebo Metlformin % 17-43% LSC % 48-66% NEJM 2002; 346:

23 DREAM Trial Methods: 5269 adults aged 30 or above with IGT, IFG or both and no previous cardiovascular disease were recruited from 191 sites in 21 countries and randomly assigned to receive RGZ 8mg daily or placebo and followed up for a median of 3 years. The primary outcome was a composite of incidental diabetes or death. Lancet 2006

24 DREAM Trial Results: 11.6% individual given RGZ and 26.0% given placebo developed the composite primary outcome HR:0.40 ( ) ; p< % individuals in the RG2 group and 30.3% in the placebo group became normoglycemic HR:1.71 ( ) ; p< Cardiovascular event rates were much the same in both groups although 14(0.5%) participants in the rosiglitazone group and 2(0.1%) in the placebo group developed HF (p=0.01) Lancet 2006

25 STOP-NIDDM Trial Aim: To assess the effect of acarbose in preventing or delaying conversion to IGT to T2DM. Method: In a multicentre placebo-controlled randomised trial patients with IGT were randomised to 100mg acarbose or placebo thrice daily. Lancet 2002

26 STOP-NIDDM Trial Findings: 714 patients with IGT were randomised to acarbose and 715 to placebo. 221(32%) patients randomised to acarbose and 285(42%) randomized to placebo developed T2DM [RR 0.75 ( ); p=0.0015] Acarbose significantly increased reversion of IGT to NGT (p<0.0001) Lancet 2002

27 Pharmacological PP of T2DM Study Subjects Drug RRR(%) DPP IGT Metformin 31 DREAM IGT and/or IFG Rosiglitazone 57.6 STOP- NIDDM IGT Acarbose 25

28 STOP-NIDDM Acarbose was associated with a 49% RRR in the development of cardiovascular events HR: 0.51 ( ); p=0.03 Among the cardiovascular events, the major reduction was in the risk of myocardial infarction HR: 0.09 ( ); p=0.02

29 Meta-analysis of 7 longterm studies on patients with T2 DM Intervention with acarbose can prevent myocardial infarction and cardiovascular disease in T2DM patients while most of them are already on intensive concomitant cardiovascular medication. Hanefeld et al EHJ Vol 25 No 1 (2004)

30 Jean-Louis Chiasson Expert Opin. Pharmacother (2007)8(18) The evidence is overwhelming- T2 diabetes can be prevented or delayed through lifestyle modifications or pharmacologic interventions. Access to drugs is important as these have been shown to be effective in lowering the risk of diabetes in subjects with IGT and/or IFG. Their use as adjuncts to lifestyle modification programs should be helpful in curtailing the epidemic explosion of diabetes worldwhile

31 Primary Prevention of T2DM Why to intervene? When to intervene? Lifestyle intervention Pharmacological intervention IDF: A consensus on type 2 diabetes prevention 2007

32 International Diabetes Federation A consensus on Type 2 diabetes prevention 2007 High risk approach Population approach Diabetic Medicine 24: (2007)

33 High risk approach 1. Identification of those who may be at higher risk 2. Measurement of risk 3. Intervention to prevent the development of T2 diabetes Diabetic Medicine 24: (2007)

34 Identification of those at high risk Questionnaire Criteria included in the questionnaire Obesity Family history Age Cardiovascular history Gestational history Drug history Diabetic Medicine 24: ( 2007 )

35 Measurement of risk Measurement of PBG will detect cases of IFG or IGT as well as undiagnosed DM Other risk factors for diabetes should also be assessed In addition, there should be assessment of additional cardiovascular risk factors Diabetic Medicine 24: ( 2007 )

36 Intervention to lower the risk Lifestyle changes Pharmacological intervention: 1. When lifestyle intervention alone has not achieved the desired goals, metformin should be considered. 2. Acarbose is worthy of consideration for those who can tolerates it. 3. PPAR gamma agonists have shown promising results but concerns must remain about side-effects. 4. Long term safety and specific diabetes preventive efficacy data are lacking for the newer agents which are not currently recommended for diabetes prevention. Diabetic Medicine 24: ( 2007 )

37 The IDF population approach to diabetes prevention: recommendations Everyone is encouraged to engage in at least 30 minutes of moderately intense ( e.g. brisk walking ) most days of the week. Everyone should be encouraged to maintain a healthy weight. Adults with BMI > 25 kg/m2 in Europids and > 23 kg/m2 in Asians should be encouraged to attain and maintain a healthy weight and/or 5-10% weight reduction. Diabetic Medicine 24: ( 2007 )

38 The IDF population approach to diabetes prevention: recommendations Children should be encouraged to attain and maintain weight for height in the normal range Priorities: Approach needs to be culturally sensitive Cultural beliefs need to be understood and addressed Diabetic Medicine 24: ( 2007 )

39 National diabetes prevention plans Government initiatives: Advocacy Community support Fiscal and legislative Engagement of private sector Media communication Diabetic Medicine 24: ( 2007 )

40 Thank you!