Diabetes mellitus, hyperglycaemia and cancer

Abstract

Epidemiology of diabetes, obesity and chronic kidney disease over the lifecourse. SummaryA moderate increase of cancer risk has been shown in diabetic patients and in subjects with abnormal glucose tolerance, mainly in digestive sites, independently of obesity, with on the contrary a protective effect for prostate cancer. Insulin-resistance with compensatory hyperinsulinemia, and elevated levels of circulating growth factors are usually considered as the link between cancer and hyperglycaemia, through activated cell proliferation. Antidiabetic treatments inducing elevated plasma insulin seem to increase cancer risk and, on the opposite, insulin-sensitizers antidiabetic drugs (metformine, thiazolidinediones) seem to reduce cancer risk. In 2009, a big fuss has been raised concerning a specific action of glargine insulin to increase cancer risk from an observational study in Germany accumulating methodological pitfalls, without any clear confirmation from other studies.Unexplained poor glycaemic control in known diabetic patients should lead to screen for a cancer, and diagnosis of cancer should not distract from appropriate management of diabetes care.Greater public awareness about healthy lifestyles (diet, physical activity) is needed to prevent these two major increasing Public Health issues, and in the meanwhile should reduce the frequency of obesity and cardiovascular diseases in the whole population.Keywords : type 2 diabetes, cancer, hyperinsulinemia, growth factors, epidemiology -3 - RésuméSauf pour la prostate, il existe un risque modérément accru de cancer, en particulier digestif,

Inflammation, Aging and Cancer: Friend or Foe?

“…The influence of these hormones and growth factors on multiple organs and sub-cellular systems (e.g., CNS and brain cognition, stem cells, mitochondrial function, neurogenesis and myelination, traumatic injury, wound healing responses) in reproductive and non-reproductive, immune and non-immune systems and their association in the development of chronic diseases or cancer have been the topic of extensive studies (Davis et al, 2011, Deng et al, 2008, Khatami 2009, Mikkola and Clakson 2002, Pisani 2008, Piatkliewicz and Czech 2011, Poulsen and Kruger 2006, Rauvala and Rouhianen 2001, Ren et al, 2009, Schwarts and Pashko 2004. For example, steroids or insulin play important roles not only in the function of reproductive organs and regulation of fluid homeostasis and/or metabolic pathways and immune responses to stress, but they are also involved in physiology, function and remodeling of bone, neuronal function, myelination and neurogeneration of brain and CNS and/or membrane-associated fatty acid metabolism (Bosch et al, 2002, Brunello et al, 2011, Campisi 2011, Chung et al, 2011, Goronzy and Wavand 2005, Hotamisisligil 2006, Khatami 1990, Li et al, 1986, Mikkola and Clarkson 2002, Sansoni et al, 2008, Simon and Balkau 2010, van Kruijsdijk et al, 2009). Insulin deficiency, insulin-resistance or hyper-insulinimia, or glucose toxicity and hyperglycemia of diabetes-induced increased glycosylation of proteins (advanced glycation end-products-AGE and their receptors RAGE) are associated with disturbances in transport and metabolism of important nutrients (e.g., ascorbic acid, pyridoxal phosphate, myo-inositol, etc), increased oxidative stress, accumulation of ROS, and co-expression of pro-and anti-inflammatory mediators such as NF-kB, VEGF, TNF-, IL1a, IL-6, IL-8, IL-12, and Ikappa B kinase (IKK-), platelets' CD40L, VCAM-1, in endothelial, hepatocytes or myeloid cells and/or tissues that are insulin-dependent (e.g., muscle, liver, adipocytes) or insulin-independent (e.g., vasculature, kidney, nerves, retina, RPE, lens) for glucose transport or metabolism , 1990, Li et al, 1986, Park et al, 2005…”

“…For example, steroids or insulin play important roles not only in the function of reproductive organs and regulation of fluid homeostasis and/or metabolic pathways and immune responses to stress, but they are also involved in physiology, function and remodeling of bone, neuronal function, myelination and neurogeneration of brain and CNS and/or membrane-associated fatty acid metabolism (Bosch et al, 2002, Brunello et al, 2011, Campisi 2011, Chung et al, 2011, Goronzy and Wavand 2005, Hotamisisligil 2006, Khatami 1990, Li et al, 1986, Mikkola and Clarkson 2002, Sansoni et al, 2008, Simon and Balkau 2010, van Kruijsdijk et al, 2009). Insulin deficiency, insulin-resistance or hyper-insulinimia, or glucose toxicity and hyperglycemia of diabetes-induced increased glycosylation of proteins (advanced glycation end-products-AGE and their receptors RAGE) are associated with disturbances in transport and metabolism of important nutrients (e.g., ascorbic acid, pyridoxal phosphate, myo-inositol, etc), increased oxidative stress, accumulation of ROS, and co-expression of pro-and anti-inflammatory mediators such as NF-kB, VEGF, TNF-, IL1a, IL-6, IL-8, IL-12, and Ikappa B kinase (IKK-), platelets' CD40L, VCAM-1, in endothelial, hepatocytes or myeloid cells and/or tissues that are insulin-dependent (e.g., muscle, liver, adipocytes) or insulin-independent (e.g., vasculature, kidney, nerves, retina, RPE, lens) for glucose transport or metabolism , 1990, Li et al, 1986, Park et al, 2005, Pisan 2008, Piatkiewicz and Czech 2011, Simon and Balkau 2010, Stern et al, 2002. The relationship between diabetes, inflammation and production of AGE/RAGE and the increased risk of certain cancers has been the topic of many recent studies (Piatkiewicz and Czech 2011, Simon and Balkau 2010, Simon et al, 2010, Zhang and Hu 2010.…”

“…Insulin deficiency, insulin-resistance or hyper-insulinimia, or glucose toxicity and hyperglycemia of diabetes-induced increased glycosylation of proteins (advanced glycation end-products-AGE and their receptors RAGE) are associated with disturbances in transport and metabolism of important nutrients (e.g., ascorbic acid, pyridoxal phosphate, myo-inositol, etc), increased oxidative stress, accumulation of ROS, and co-expression of pro-and anti-inflammatory mediators such as NF-kB, VEGF, TNF-, IL1a, IL-6, IL-8, IL-12, and Ikappa B kinase (IKK-), platelets' CD40L, VCAM-1, in endothelial, hepatocytes or myeloid cells and/or tissues that are insulin-dependent (e.g., muscle, liver, adipocytes) or insulin-independent (e.g., vasculature, kidney, nerves, retina, RPE, lens) for glucose transport or metabolism , 1990, Li et al, 1986, Park et al, 2005, Pisan 2008, Piatkiewicz and Czech 2011, Simon and Balkau 2010, Stern et al, 2002. The relationship between diabetes, inflammation and production of AGE/RAGE and the increased risk of certain cancers has been the topic of many recent studies (Piatkiewicz and Czech 2011, Simon and Balkau 2010, Simon et al, 2010, Zhang and Hu 2010. It should also be noted that chronic inflammation in patients with neurodegenerative diseases, asthma or diabetes are reported to increase the risks for certain site-specific cancers (e.g., lung cancer in asthmatic patients, or liver and pancreas in diabetics) and decreased risk for certain other cancers (e.g., prostate in diabetics) (Brunello and Kappor 2011b, Piatkkiewicz and Czech 2011, Stern et al, 2002, Vena et al, 1985, Vesterinen et al, 1993, Vingeri et al 2009, Zhang and Hu 2010.…”

What are the health benefits of physical activity in type 1 diabetes mellitus? A literature review

“…Cancer is a recognised complication of type 2 diabetes and obesity [62]. The data for type 1 diabetes is less clear [63].…”

Incidence of diabetes among postmenopausal breast cancer survivors

“…This association is hypothesised to be due in part to the effects of insulin resistance and hyperinsulinaemia, which are known risk factors for both type 2 diabetes [5] and cancer [6]. Other common risk factors, such as obesity and sedentary lifestyle [7], may also contribute to this association.…”