Clinical and molecular mechanisms favoring cancer initiation and progression in diabetic patients.

Abstract

Cancer incidence and mortality are higher among diabetic patients. This review examines the mechanisms, both general and site-specific, for this increase. Hyperglycemia and hyperinsulinemia, which are the major abnormalities that characterize diabetes, can promote cancer via both independent and synergic mechanisms. Insulin is both a metabolic hormone and a growth factor that promotes cell proliferation. When insulin levels are increased due to either insulin resistance or insulin treatment, their mitogenic effect is more marked in malignant cells that frequently overexpress the insulin receptor and, more specifically, its A isoform that has predominant mitogenic activity. Hyperglycemia provides energy for malignant cell proliferation and, via the peculiar energy utilization of cancer cells, favors cancer growth and neoangiogenesis. Additionally, diabetes-associated obesity has cancer-promoting effects due to mechanisms that are specific to excess fat cells (such as increased peripheral estrogens, increased pro-mitogen cytokines and growth factors). Also fat-associated chronic inflammation can favor cancer via the cell damage caused by reactive oxygen species (ROS) and via the production of inflammatory cytokines and transcription factors that stimulate cancer growth and invasiveness. Finally, the multiple drugs involved in the treatment of diabetes can also play a role. Diabetes-associated comorbidities, tissue-specific inflammation, and organ-specific dysfunctions can explain why the risk of cancer can differ by tissue type among diabetic patients. The increased risk of cancer-related mortality is moderate among individual patients with diabetes (RR = 1.25), but the pandemic nature of the disease means that a considerable number of lives could be spared through a better understanding of the factors associating diabetes and cancer.

• Authors: L Sciacca, R Vigneri, A Tumminia, F Frasca, S Squatrito, L Frittitta, P Vigneri
• Journal: Nutrition, metabolism, and cardiovascular diseases : NMCD (Nutr Metab Cardiovasc Dis) Vol. 23 Issue 9 Pg. 808-15 (Sep 2013) ISSN: 1590-3729 [Electronic] Netherlands
• PMID: 23932729 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Cytokines
• Hypoglycemic Agents
• Insulin

Topics

• Breast Neoplasms (etiology, physiopathology)
• Colorectal Neoplasms (etiology, physiopathology)
• Cytokines (blood)
• Diabetes Mellitus, Type 2 (complications, drug therapy)
• Endometrial Neoplasms (etiology, physiopathology)
• Female
• Humans
• Hyperglycemia (complications, drug therapy)
• Hyperinsulinism (complications, drug therapy)
• Hypoglycemic Agents (therapeutic use)
• Inflammation (complications, drug therapy)
• Insulin (blood, therapeutic use)
• Insulin Resistance
• Liver Neoplasms (etiology, physiopathology)
• Male
• Obesity (complications, drug therapy)
• Pancreas (drug effects, metabolism)
• Prostatic Neoplasms (etiology, physiopathology)
• Risk Factors