Insulin Resistance: The Increased Risk of Cancers

Abstract

Insulin resistance, also known as impaired insulin sensitivity, is the result of a decreased reaction of insulin signaling to blood glucose levels. This state is observed when muscle cells, adipose tissue, and liver cells, improperly respond to a particular concentration of insulin. Insulin resistance and related increased plasma insulin levels (hyperinsulinemia) may cause metabolic impairments, which are pathological states observed in obesity and type 2 diabetes mellitus. Observations of cancer patients confirm that hyperinsulinemia is a major factor influencing obesity, type 2 diabetes, and cancer. Obesity and diabetes have been reported as risks of the initiation, progression, and metastasis of several cancers. However, both of the aforementioned pathologies may independently and additionally increase the cancer risk. The state of metabolic disorders observed in cancer patients is associated with poor outcomes of cancer treatment. For example, patients suffering from metabolic disorders have higher cancer recurrence rates and their overall survival is reduced. In these associations between insulin resistance and cancer risk, an overview of the various pathogenic mechanisms that play a role in the development of cancer is discussed.

View on Metformin: Antidiabetic and Pleiotropic Effects, Pharmacokinetics, Side Effects, and Sex-Related Differences

“…A meta-analysis based on 37 studies for a total of more than 1.5 million subjects showed that metformin reduces the incidence of cancer in the liver (−78%), pancreas (−46%), colon (−23%), and breast (−6%), as well as mortality from liver and breast cancer [ 159 ]. The marked reduction in the incidence of certain types of cancer, such as those of the liver and pancreas, may be explained by the known fact that insulin resistance plays a pivotal role in their growth [ 160 ]. Of interest, a large meta-analysis of 121 cohorts, including more than 19 million individuals with about one million all-site cancer events, showed that T2DM is associated with an additional risk of all-site cancer of 6% higher in women than in men [ 161 ].…”

“…Diabetes mellitus Higher all-cause mortality [122,123] Higher risk PAD [115][116][117] Higher RR for oral, stomach, and kidney cancers, and leukemia [160] Met: antihyperglycemic effect No difference [31] Met: pharmacokinetics No difference, considering weight difference and monitoring eGFR. [76] Met: ADRs Higher [23,24] Met: CRC-specific mortality * Lower […”

Insulin Resistance/Hyperinsulinemia as an Independent Risk Factor That Has Been Overlooked for Too Long

“…It is supposed that hyperinsulinemia may play a role in tumorigenesis [4] even if the intimate mechanisms have not been completely elucidated. Recent observations in cancer patients have shown how Hypein may be a determining factor in influencing the development of obesity, diabetes, and cancer [34]. Both the insulin A receptor and the IGF-2 receptor mediate their effects through common oncogenic signaling pathways such as Ras/MAPK and β-catenin, which explains at least in part their involvement in carcinogenesis and the possibility that a chronic increase in circulating insulin levels leads to an increased risk of cancer in insulin-resistant subjects [35].…”