title: Drug-subphenotype interactions for cancer in type 2 diabetes mellitus.
abstract: On the basis of data obtained from a prospective cohort of Chinese patients with type 2 diabetes mellitus (T2DM), we discuss cancer subphenotypes (risk factors) in patients with T2DM, which can lead to drug-cancer subphenotype interactions. These subphenotypes include HDL cholesterol levels <1.0 mmol/l, co-occurrence of LDL cholesterol levels <2.8 mmol/l and triglyceride levels <1.7 mmol/l, and co-occurrence of LDL cholesterol levels <2.8 mmol/l and albuminuria. The increased risk of cancer associated with low levels of HDL cholesterol, low LDL cholesterol levels plus low triglyceride levels, and low levels of LDL cholesterol plus albuminuria can be reduced by treatment with metformin, renin-angiotensin system (RAS) inhibitors and statins, respectively. Mechanistic studies support the hypothesis that dysregulation of the 5'-AMP-activated protein kinase pathway and crosstalk between the RAS and insulin-like growth factor 1-cholesterol pathways create a cancer-promoting milieu in patients with T2DM. These findings highlight that in Chinese individuals, multiple pathways are implicated in the link between T2DM and cancer, which can generate multiple subphenotypes as well as drug-subphenotype interactions.
authors: Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China.
authors: Xilin
authors: X
authors: Yang
authors: Department of Medicine and Therapeutics, Hong Kong Institute of Diabetes and Obesity, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, New Territories, Hong Kong SAR, China.
authors: Heung M
authors: HM
authors: Lee
authors: Department of Medicine and Therapeutics, Hong Kong Institute of Diabetes and Obesity, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, New Territories, Hong Kong SAR, China.
authors: Juliana C N
authors: JC
authors: Chan
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000453:epidemiology* / Q000378:metabolism; D050171:Dyslipidemias / Q000453:epidemiology* / Q000378:metabolism; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D009369:Neoplasms / Q000453:epidemiology*; D010641:Phenotype; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D012084:Renin-Angiotensin System; D012307:Risk Factors; D015398:Signal Transduction; D051779:Sterol Regulatory Element Binding Proteins / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007004:Hypoglycemic Agents; D051779:Sterol Regulatory Element Binding Proteins; D014280:Triglycerides; D007334:Insulin-Like Growth Factor I; D002784:Cholesterol; D055372:AMP-Activated Protein Kinases