Additive effects of blood glucose lowering drugs, statins and renin-angiotensin system blockers on all-site cancer risk in patients with type 2 diabetes

BMC Medicine

Juliana CN Chan⁴  Chun-Chung Chow¹  Gang Xu³  Linda Yu⁵  Heung-Man Lee⁴  Kitty KT Cheung¹  Risa Ozaki¹  Ronald CW Ma¹  Andrea Luk¹  Wing-Yee So¹  Xilin Yang²  Alice PS Kong¹ 

[1] Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, SAR, China;Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin 300070, China;Hong Kong Institute of Diabetes and Obesity, Shatin, Hong Kong, SAR, China;Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, SAR, China;Hong Kong Hospital Authority Headquarter, Hong Kong, SAR, China

关键词: Renin-angiotensin-system inhibitors;    Statins;    Glycemic control;    Type 2 diabetes;    Cancer risk;   

Others  :  854890
DOI  :  10.1186/1741-7015-12-76

 received in 2014-02-07, accepted in 2014-03-25,  发布年份 2014

【 摘 要 】

Background

Hyperglycemia is associated with increased risk of all-site cancer that may be mediated through activation of the renin-angiotensin-system (RAS) and 3-hydroxy-3-methyl-glutaryl-coenzyme-A-reductase (HMGCR) pathways. We examined the joint associations of optimal glycemic control (HbA_1c <7%), RAS inhibitors and HMGCR inhibitors on cancer incidence in patients with type 2 diabetes.

Methods

Patients with type 2 diabetes, with or without a history of cancer or prior exposure to RAS or HMGCR inhibitors at baseline were observed between 1996 and 2005. All patients underwent a comprehensive assessment at baseline and were followed until the censored date at 2005 or their death.

Results

After a median follow-up period of 4.91 years (interquartile range, 2.81 to 6.98), 271 out of 6,103 patients developed all-site cancer. At baseline, patients with incident cancers were older, had longer disease duration of diabetes, higher alcohol and tobacco use, and higher systolic blood pressure and albuminuria, but lower triglyceride levels and estimated glomerular filtration rate (P <0.05). Patients who developed cancers during follow-up were less likely to have started using statins (22.5% versus 38.6%, P <0.001), fibrates (5.9% versus 10.2%, P = 0.02), metformin (63.8% versus 74.5%, P <0.001) or thiazolidinedione (0.7% versus 6.8%, P <0.001) than those who remained cancer-free. After adjusting for co-variables, new treatment with metformin (hazard ratio: 0.39; 95% confidence interval: 0.25, 0.61; P <0.001), thiazolidinedione (0.18; 0.04, 0.72; P = 0.015), sulphonylurea (0.44; 0.27, 0.73; P = 0.014), insulin (0.58; 0.38, 0.89; P = 0.01), statins (0.47; 0.31, 0.70; P <0.001) and RAS inhibitors (0.55; 0.39, 0.78; P <0.001) were associated with reduced cancer risk. Patients with all three risk factors of HbA_1c ≥7%, non-use of RAS inhibitors and non-use of statins had four-fold adjusted higher risk of cancer than those without any risk factors (incidence per 1,000-person-years for no risk factors: 3.40 (0.07, 6.72); one risk factor: 6.34 (4.19, 8.50); two risk factors: 8.40 (6.60, 10.20); three risk factors: 13.08 (9.82, 16.34); P <0.001).

Conclusions

Hyperglycemia may promote cancer growth that can be attenuated by optimal glycemic control and inhibition of the RAS and HMGCR pathways.

【 授权许可】

   
2014 Kong et al.; licensee BioMed Central Ltd.

【 图 表 】

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