Cancer, obesity, diabetes, and antidiabetic drugs: is the fog clearing?

Abstract

The prevalence of obesity, of type 2 diabetes mellitus (T2DM), and of cancer are all increasing globally. The relationships between these diseases are complex, and thus difficult to elucidate; nevertheless, evidence supports the hypothesis that obesity increases the risks of both T2DM and certain cancers. Further complexity arises from controversial evidence that specific drugs used in the treatment of T2DM increase or decrease cancer risk or influence cancer prognosis. Herein, we review the current evidence from studies that have addressed these relationships, and summarize the methodological challenges that are frequently encountered in such research. We also outline the physiology that links obesity, T2DM, and neoplasia. Finally, we outline the practical principles relevant to the increasingly common challenge of managing patients who have been diagnosed with both diabetes and cancer.

The effects of metformin on gut microbiota and the immune system as research frontiers

“…These gastrointestinal effects can have both local and systemic consequences, but certainly do not exclude any effects of absorbed metformin on classic target organs such as the liver, or on more recently proposed target cell lineages such as those of the immune system or neoplastic tissue. The effects of metformin on the microbiome and immune system may be relevant not only to diabetes treatment, but also to proposed novel indications, for example in oncology and ageing [51][52][53]. In future work, careful attention to whole organism and cellular pharmacokinetics [14] will be crucial to establishing the clinical relevance of laboratory studies.…”

Metabolic signaling functions of ER–mitochondria contact sites: role in metabolic diseases

“…This is the case of neurodegenerative diseases, such as Alzheimer's disease (AD) (Kandimalla et al 2016), viral infections (Kralj et al 2016), Wolfram syndrome (Boutzios et al 2011) or some cancers (Klil-Drori et al 2016). Interestingly, ERmitochondria miscommunication has recently been suggested or reported in these pathologies.…”

SGLT2 inhibitors and risk of cancer in type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials

“…Certain diabetes risk factors (e.g. obesity) play a significant role in increasing cancer risk [3]. Furthermore, several glucose-lowering drugs have the potential to affect cancer risk [1].…”