Design of and rationale for the Japan Diabetes Optimal Integrated Treatment study for 3 major risk factors of cardiovascular diseases (J-DOIT3): a multicenter, open-label, randomized, parallel-group trial

Kohjiro Ueki, Takayoshi Sasako, Masayuki Kato, Yukiko Okazaki, Sumie Okahata, Hisayuki Katsuyama, Mikiko Haraguchi, Ai Morita, Ken Ohashi, Kazuo Hara, Atsushi Morise, Kazuo Izumi, Yasuo Ohashi, Mitsuhiko Noda, Takashi Kadowaki, J-DOIT3 Study Group, Kohjiro Ueki, Takayoshi Sasako, Masayuki Kato, Yukiko Okazaki, Sumie Okahata, Hisayuki Katsuyama, Mikiko Haraguchi, Ai Morita, Ken Ohashi, Kazuo Hara, Atsushi Morise, Kazuo Izumi, Yasuo Ohashi, Mitsuhiko Noda, Takashi Kadowaki, J-DOIT3 Study Group

Abstract

Objective: Multifactorial intervention including the management of levels of blood glucose (BG), blood pressure (BP), and lipids has been suggested to decrease cardiovascular disease (CVD) risk. However, the target ideal and feasible levels for these individual parameters have not been fully evaluated. In this study, we examine the hypothesis that stricter control compared with the current targets in the Japanese guideline for BG, BP, and lipids could efficiently and safely reduce CVD risk.

Research design and methods: We screened patients with type 2 diabetes and hypertension and/or dyslipidemia among 81 hospitals in Japan and allocated them into 2 groups: the intensive therapy group (ITG) and the conventional therapy group (CTG). For the 2 respective groups, the target for glycated hemoglobin (HbA1c) is <6.2% (44 mmol/mol) and <6.9% (52 mmol/mol), for BP it is <120/75 mm Hg and <130/80 mm Hg, and for low-density lipoprotein cholesterol it is <80 mg/dL (<70 mg/dL in the presence of CVD history) and <120 mg/dL (<100 mg/dL in the presence of CVD history). The primary end point is the occurrence of CVD events or death by any cause. These patients are scheduled for stepwise intensifications of medication for BG, BP, and lipid control in the ITG, until the number of primary end point events reaches 250.

Results: We recruited 2542 patients and randomly allocated 1271 into the ITG and 1271 into the CTG between June 2006 and March 2009. The mean HbA1c was 8.0% (64 mmol/mol) and the mean duration of diabetes was 8.3 years.

Conclusions: This randomized controlled study will test the hypothesis that strict multifactorial intervention therapy is effective for the prevention of CVDs in patients with type 2 diabetes who are at high CVD risk.

Trial registration number: NCT00300976.

Keywords: Intensified Therapy; Lifestyle Modification; Multifactorial Interventions; Weight Control.

Figures

Figure 1
Figure 1
Screening, enrollment, and randomization of study participants (BMI, body mass index; CTG, conventional therapy group; HbA1c, glycated hemoglobin; HDL-C, high-density lipoprotein cholesterol; IHD, ischemic heart disease; ITG, intensive therapy group; LDL-C, low-density lipoprotein cholesterol).

References

    1. Fujishima M, Kiyohara Y, Kato I et al. . Diabetes and cardiovascular disease in a prospective population survey in Japan: the Hisayama study. Diabetes 1996;45(Suppl 3):S14–16. 10.2337/diab.45.3.S14
    1. Sone H, Tanaka S, Tanaka S et al. , Japan Diabetes Complications Study Group. Serum level of triglycerides is a potent risk factor comparable to LDL cholesterol for coronary heart disease in Japanese patients with type 2 diabetes: subanalysis of the Japan Diabetes Complications Study (JDCS). J Clin Endocrinol Metab 2011;96:3448–56. 10.1210/jc.2011-0622
    1. Ohkubo Y, Kishikawa H, Araki E et al. . Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract 1995;28:103–17. 10.1016/0168-8227(95)01064-K
    1. [No authors listed] Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837–53. 10.1016/S0140-6736(98)07019-6
    1. Stratton IM, Adler AI, Neil HA et al. . Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000;321:405–12. 10.1136/bmj.321.7258.405
    1. Holman RR, Paul SK, Bethel MA et al. . Long-term follow-up after tight control of blood pressure in type 2 diabetes. N Engl J Med 2008;359:1565–76. 10.1056/NEJMoa0806359
    1. Dormandy JA, Charbonnel B, Eckland DJ et al. . Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005;366:1279–89. 10.1016/S0140-6736(05)67528-9
    1. Gerstein HC, Miller ME, Byington RP et al. , Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545–59. 10.1056/NEJMoa0802743
    1. Patel A, Macmahon S, Chalmers J et al. , ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008;358:2560–72. 10.1056/NEJMoa0802987
    1. Duckworth W, Abraira C, Moritz T et al. . Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009;360:129–39. 10.1056/NEJMoa0808431
    1. Gaede P, Vedel P, Larsen N et al. . Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003;348:383–93. 10.1056/NEJMoa021778
    1. Gaede P, Lund-Andersen H, Parving HH et al. . Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med 2008;358:580–91. 10.1056/NEJMoa0706245
    1. Griffin SJ, Borch-Johnsen K, Davies MJ et al. . Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITION-Europe): a cluster-randomised trial. Lancet 2011;378:156–67. 10.1016/S0140-6736(11)60698-3
    1. Zinman B, Wanner C, Lachin JM et al. , EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117–28. 10.1056/NEJMoa1504720
    1. Yazaki Y, Kadowaki T. Combating diabetes and obesity in Japan. Nat Med 2006;12:73–4. 10.1038/nm0106-73
    1. Sakane N, Kotani K, Takahashi K et al. . Japan Diabetes Outcome Intervention Trial-1 (J-DOIT1), a nationwide cluster randomized trial of type 2 diabetes prevention by telephone-delivered lifestyle support for high-risk subjects detected at health checkups: rationale, design, and recruitment. BMC Public Health 2013;13:81 10.1186/1471-2458-13-81
    1. Izumi K, Hayashino Y, Yamazaki K et al. . Multifaceted intervention to promote the regular visiting of patients with diabetes to primary care physicians: rationale, design and conduct of a cluster-randomized controlled trial. The Japan Diabetes Outcome Intervention Trial-2 study protocol. Diabetol Int 2010;1:83–9. 10.1007/s13340-010-0015-6
    1. The J-DOIT3 Study Group. What is J-DOIT3?
    1. The Japan Diabetes Society. Treatment guide for diabetes.
    1. Lewington S, Clarke R, Qizilbash N et al. , Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002;360:1903–13. 10.1016/S0140-6736(02)11911-8
    1. Colhoun HM, Betteridge DJ, Durrington PN et al. , CARDS investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004;364:685–96. 10.1016/S0140-6736(04)16895-5
    1. The Japan Diabetes Society. Food exchange lists—dietary guidance for persons with diabetes (in Japanese).
    1. The Ministry of Health, Labor and Welfare and the Ministry of Education, Culture, Sports, Science and Technology Ethical guidelines for medical and health research involving human subjects.
    1. Japan Diabetes Optimal Integrated Treatment study for 3 major risk factors of cardiovascular diseases (J-DOIT3). .

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren