Diabetes, obesity and cancer: risk and anti-risk factors

Abstract

Observable diabetes and obesity epidemics may result in alteration of cancer morbidity and mortality. This increasingly recognized problem is reviewed here from the perspective of interplay between factors that differently modify association of diabetes mellitus with malignant neoplasms. Heterogeneity and familial aspects of diabetes and obesity, genomic traits, anti-diabetic medications and weight-reducing treatment are important examples of such factors. Addressing them might promote development of efficient preventive measures.

Genetic polymorphisms potentially associated with response to metformin in postmenopausal diabetics suffering and not suffering with cancer

“…Although DM is considered to be associated with higher cancer incidence this association greatly varies based on tumor localization, DM type, patient age, gender, and several other factors. 5-7 Some DM-associated factors may have independent effects on cancer risk and disease course, [6][7][8] and, understandably, antidiabetic treatment is also brought to notice in this regard.…”

Hormonal, metabolic and genetic predictors of metformin efficacy in patients with diabetes mellitus and cancer

“…Особенностью метформина в случае при-менения как у больных сахарным диабетом 2 типа (СД2), так и по другим показаниям у людей, не страдающих диа-бетом, является вариабельность выраженности его эф-фектов. Среди иных причин [4,5] эта вариабельность может быть объяснена и различиями в индивидуаль-ной чувствительности к данному препарату. Известны две основные группы маркеров, на основании которых делаются попытки предсказания того, насколько эф-фективным может оказаться использование метформина при лечении эндокринных заболеваний (прежде всего, СД2, а также поликистоза яичников и ожирения).…”

“…Выбор последних определялся тем, что применительно к потребностям онкологии обычно принимается во внимание не только так называемое непря-мое действие метформина, реализуемое путем устранения или ослабления гиперинсулинемии/инсулинорезистентно-сти, но и его прямое действие, опосредуемое на клеточном уровне через AMPK-зависимое или AMPK-независимое угнетение mTOR-сигналинга и приводящее, в частности, к угнетению пролиферации [3,5,10].…”

Cancer Endocrinology Through own Experience: Areas for Further Thought and Development

“…In systematic experimental and clinical studies we were able to show that processes resulting in responses to tamoxifen as an agonist and the development of estrogen hypersensitivity of breast cancer cells could potentially be mechanistically linked and involve activation of MAPK signaling and the aromatase system [3]. As to science sensu stricto, my interests were focused (and I believe resulted in the most significant advances) on endocrine-genotoxic switching as a factor that increases the risk of tumor development through the predominant usage of a genotoxic type of hormonal carcinogenesis [4], on the association of different types of macrosomia (including newborn macrosomy) with cancer risk [5,6], on the heterogeneity of obesity and diabetes as a factor that at times may modify predisposition to cancer in an opposing way [7,8], and on the controversial role of antidiabetic biguanides as potential and, in a sense, selective means for cancer prevention and treatment [9,10]. The differences between these duties are significant.…”