Diabetes and cancer: the mechanistic implications of epidemiological analyses from the Hong Kong Diabetes Registry.

Authors:
Address: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, SAR, China; Department of Epidemiology, Public Health College, Tianjin Medical University, Tianjin, China. yxl@hotmail.com.
Journal:

Publication:

abstract

Diabetes is a disorder of energy metabolism associated with increased cancer risk but the underlying mechanism is poorly understood. In a prospective cohort of patients enrolled in the Hong Kong Diabetes Registry, we explored risk factors for cancer including drug usage in Type 2 diabetes (T2D). In a series of published papers, we reported a linear risk association of cancer with HbA(1c) with a threshold at 6.0-6.5% and non-linear risk associations of body mass index, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride and white blood cell count (WBC) in V or A shaped manners. Detailed pharmacoepidemiological analysis revealed markedly attenuated cancer risk in patients treated with insulin and oral antidiabetic drugs compared to non-users of these drugs. We further observed significant drug-subphenotype interactions with attenuated cancer risk in metformin-users with low HDL-C, users of renin-angiotensin system (RAS) inhibitors with high WBC and statin-users with co-presence of low LDL-C plus albuminuria. These novel observations corroborate with experimental findings of possible consequences of hyperglycemia on dysregulation of cholesterol metabolism, RAS and AMP-activated protein kinase pathways, all of which may be implicated in carcinogenesis. Based on these epidemiological and experimental findings, we argue for the strong need to strengthen the health care system to ensure that T2D subjects receive appropriate drugs to optimize internal milieu to reduce all events including cancer. Apart from mechanistic studies, large scale randomized clinical trials using medications such as statin, RAS inhibitors and metformin in patients with risk-conferring subphenotypes are needed to confirm their anti-cancer effects. Copyright © 2012 John Wiley & Sons, Ltd.

Related Articles
Final Report on Carcinogens Background Document for Formaldehyde.
Rep Carcinog Backgr Doc. 2010
Final Report on Carcinogens Background Document for Formaldehyde.
National Toxicology Program. Rep Carcinog Backgr Doc. 2010 Jan; (10-5981):i-512.
Final Report on Carcinogens Background Document for Styrene.
Rep Carcinog Backgr Doc. 2008
Final Report on Carcinogens Background Document for Styrene.
National Toxicology Program. Rep Carcinog Backgr Doc. 2008 Sep; (8-5978):i-398.
Low LDL cholesterol, albuminuria, and statins for the risk of cancer in type 2 diabetes: the Hong Kong diabetes registry.
Diabetes Care. 2009
Low LDL cholesterol, albuminuria, and statins for the risk of cancer in type 2 diabetes: the Hong Kong diabetes registry.
Yang X, So WY, Ma RC, Ko GT, Kong AP, Zhao H, Luk AO, Lam CW, Ho CS, Tong PC, et al. Diabetes Care. 2009 Oct; 32(10):1826-32. Epub 2009 Jul 10.
Review Repaglinide : a pharmacoeconomic review of its use in type 2 diabetes mellitus.
Pharmacoeconomics. 2004
Review Repaglinide : a pharmacoeconomic review of its use in type 2 diabetes mellitus.
Plosker GL, Figgitt DP. Pharmacoeconomics. 2004; 22(6):389-411.
Review Targeting low HDL-cholesterol to decrease residual cardiovascular risk in the managed care setting.
J Manag Care Pharm. 2008
Review Targeting low HDL-cholesterol to decrease residual cardiovascular risk in the managed care setting.
Cziraky MJ, Watson KE, Talbert RL. J Manag Care Pharm. 2008 Oct; 14(8 Suppl):S3-28; quiz S30-1.

To top • Home

TraveldoctorOnline 2001 • Disclaimer • webmaster

The contents within traveldoctoronline are presented only for informational purposes and cannot substitute for professional health care or any other medical treatment.All users of this website with health problems should be oblige always to consult their medical doctor before starting any treatment.