Type-2 diabetes mellitus-associated cancer risk: In pursuit of understanding the possible link

Srinivasa Rao Vulichi; Ashish Runthala; Nagaraju Begari; Kumar Rupak; Venkata Rao Chunduri; Suman Kapur; Appa Rao Chippada; Durga Srinivasa Murthy Sistla

doi:10.1016/j.dsx.2022.102591

Type-2 diabetes mellitus-associated cancer risk: In pursuit of understanding the possible link

Diabetes Metab Syndr. 2022 Sep;16(9):102591. doi: 10.1016/j.dsx.2022.102591. Epub 2022 Aug 10.

Authors

Srinivasa Rao Vulichi¹, Ashish Runthala², Nagaraju Begari³, Kumar Rupak⁴, Venkata Rao Chunduri³, Suman Kapur⁵, Appa Rao Chippada⁶, Durga Srinivasa Murthy Sistla⁷

Affiliations

¹ S V University College of Pharmaceutical Sciences, S V University, Tirupati, India; Department of Biological Sciences, BITS-Pilani, Hyderabad Campus, Hyderabad, India. Electronic address: nivschem@gmail.com.
² Department of Biotechnology, Koneru Lakshmaiah Education Foundation, Vijayawada, India. Electronic address: ashish.runthala@gmail.com.
³ Department of Chemistry, S V University, Tirupati, India.
⁴ CDSCO, FDA Bhawan, New Delhi, India.
⁵ Department of Biological Sciences, BITS-Pilani, Hyderabad Campus, Hyderabad, India. Electronic address: skapur@hyderabad.bits-pilani.ac.in.
⁶ S V University College of Pharmaceutical Sciences, S V University, Tirupati, India; Department of Biochemistry, S V University, Tirupati, India.
⁷ Department of Biochemistry, S V University, Tirupati, India.

PMID: 35995030
DOI: 10.1016/j.dsx.2022.102591

Abstract

Background and aim: The insulin resistance-mediated abnormal gluconeogenesis when exceeds a given threshold culminates in type 2 diabetes mellitus (T2DM). This induces severe cellular oxidative stress that may eventually facilitate typical neoplastic transformations. This narrative review aims to portray some of the plausible key mechanistic links bridging T2DM and specific cancers.

Methods: A thorough literature search was conducted in the PubMedCentral database to retrieve information from various reputed biomedical reports/articles published from the year 2000. The information regarding the key biochemical signaling pathways mediating the carcinogenic transformation, especially in T2DM patients, was extensively excavated to systematically compile and present a narrative review.

Results: T2DM-associated insulin resistance is known to negatively influence certain crucial genetic and metabolic components (such as insulin/IGFs, PI-3K/Akt, AMPK, and AGEs/RAGE) that may eventually lead to neoplastic transformation. In particular, the risk of developing cancers like pancreatic, colorectal, breast, liver, endometrial, and bladder seems to be more significant in T2DM patients.

Conclusion: Despite the fact that several studies have suggested a possible correlation between T2DM and cancer mortality, a more detailed research at both pre-clinical and clinical levels is still required so as to fully understand the intricate relationship and make a precise conclusion.

Keywords: Cancer; Hyperglycemia; Insulin resistance; Type 2 diabetes mellitus.

Publication types

Review

MeSH terms

AMP-Activated Protein Kinases / metabolism
Diabetes Mellitus, Type 2* / metabolism
Humans
Insulin / metabolism
Insulin Resistance* / genetics
Neoplasms* / etiology
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-akt / metabolism

Substances

Proto-Oncogene Proteins c-akt
AMP-Activated Protein Kinases
Insulin
Phosphatidylinositol 3-Kinases