ReviewDiabetes mellitus, hyperglycaemia and cancerDiabète sucré, hyperglycémie et cancer
Section snippets
Epidemiological data on the association between diabetes or hyperglycaemia and cancer
Although there are many publications on this topic, only the more recent and the most informative studies are discussed, all on large populations. They all adjust for age and most of them adjust also for body mass index (BMI), the main confounder in the association between type 2 diabetes and cancer; the impact of BMI on mortality from cancer was documented in a large prospective study on more than 900,000 adults in the US [5].
Speculative mechanisms for the link between glycaemic level and cancer
Several hypotheses have been proposed to explain the link between glycaemic level and cancer (Fig. 1).
A common mechanism could induce both type 2 diabetes and cancer: type 2 diabetes and cancer would be just associated, without any direct link, and no causal relationship. For example, environmental or lifestyle factors could contribute at the same time to type 2 diabetes and to cancer. It could be diet – around 35% of cancers in the US are attributable to dietary habits [22], and populations
Treatment of type 2 diabetes and cancer
Before the “glargine controversy”, a potential role for pharmacological treatments of type 2 diabetes in cancer had been suggested from pharmaco-epidemiological studies. The largest, population-based and prospective study is from the Saskatchewan province in Canada [37]. The database covers 90% of the residents of the province, with 900,000 individuals; it includes information on drug prescriptions. In this region, a cancer registry, hospital charts and vital statistics are well validated.
Conclusion
An association between type 2 diabetes or hyperglycaemia and the risk of cancer appears to exist, with a gradually increased risk of cancer, in particular for cancers of the digestive tract, with increasing glycaemic levels. In contrast, for prostate cancer, hyperglycaemia appears to carry a lower risk. A causal relationship is probable, with a key role played by hyperinsulinaemia and growth factors, independently of (and in addition to) the risk of cancer linked with obesity. In addition to
Conflict of interest
Dominique Simon has served as a speaker for Glaxo-Smith Kline, sanofi-aventis, and Servier; and on advisory panels for Astra-Zeneca, Bristol Myers Squibb, Glaxo-Smith Kline and Novartis. Beverley Balkau has served as a speaker for sanofi-aventis, and on advisory panels for Astra Zeneca, Bristol Myers Squibb, and sanofi-aventis, and has research funding from Abbott.
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Metformin and risk of cancer among patients with type 2 diabetes mellitus: A systematic review and meta-analysis
2021, Primary Care DiabetesCitation Excerpt :There is strong evidence to suggest that cancer incidence is increased in patients with DM [4]. The pathophysiological hypotheses to explain the link between diabetes or hyperglycaemia and cancer rely on biological, particularly hormonal, mechanisms involving insulin-resistance [5]. Indeed, in the genesis of type 2 diabetes, reduced insulin sensitivity plays a key role, inducing compensatory hyperinsulinaemia with an increased level of circulating Insulin-like Growth Factors (IGF), well-known to stimulate cell proliferation in many organs, including the liver, pancreas, colon, ovary, breast, the most frequent sites with an increased risk of cancer in type 2 diabetic patients [6].
Imbalance in the antioxidant defence system and pro-genotoxic status induced by high glucose concentrations: In vitro testing in human liver cells
2020, Toxicology in VitroCitation Excerpt :According to the common soil hypothesis, type 2 diabetes mellitus and cancer would be just casually associated, without any direct link. Common risk factors (e.g., environmental or lifestyle factors) could contribute at the same time to type 2 diabetes mellitus and to cancer (Simon and Balkau, 2010). Mechanisms postulated by the pathophysiological hypotheses for increased cancer risk in diabetes mellitus include hyperglycaemia, hyperinsulinemia with stimulation of insulin-like growth factors (IGF), and oxidative stress.
Regulation of pancreatic cancer TRAIL resistance by protein O-GlcNAcylation
2020, Laboratory InvestigationAn overview on insulin preparations during the last past decade. Towards endless improvements
2018, Medecine des Maladies MetaboliquesEpidemiological bases and molecular mechanisms linking obesity, diabetes, and cancer
2017, Endocrinologia, Diabetes y NutricionDiabetes and cancer mortality: A multifaceted association
2014, Diabetes Research and Clinical PracticeCitation Excerpt :The present data confirm increased mortality in diabetic patients from multiple cancer sites: liver, pancreas, colon-rectum, breast, and uterus. Different possible biologic pathways leading to cancer risk in diabetes have been proposed: hyperinsulinemia, which promotes cancer growth directly [12] or through the effect of insulin-like growth factor-1 [13]; hyperglycemia, reported to promote tumor cell proliferation and metastasis in type 2 diabetes [14–16]; the permanent pro-inflammatory condition that characterize diabetes especially under poor metabolic control [17]. The report has both limits and strengths to explore different mechanisms underlying the association between diabetes and cancer.