scholarly journals Diabetes, Antidiabetic Medications and Cancer Risk in Type 2 Diabetes: Focus on SGLT-2 Inhibitors

2021 ◽  
Vol 22 (4) ◽  
pp. 1680
Author(s):  
Mariusz Dąbrowski
Keyword(s):  
Type 2 Diabetes ◽  
Cancer Risk ◽  
The European Union ◽  
Sodium Glucose Cotransporter ◽  
Incidence And Mortality ◽  
Increasing Risk ◽  
Risk Of Cancer ◽  
Diabetes And Obesity ◽  
Increased Activity

In the last decade, cancer became the leading cause of death in the population under 65 in the European Union. Diabetes is also considered as a factor increasing risk of cancer incidence and mortality. Type 2 diabetes is frequently associated with being overweight and obese, which also plays a role in malignancy. Among biological mechanisms linking diabetes and obesity with cancer hyperglycemia, hyperinsulinemia, insulin resistance, increased levels of growth factors, steroid and peptide hormones, oxidative stress and increased activity of pro-inflammatory cytokines are listed. Antidiabetic medications can modulate cancer risk through directly impacting metabolism of cancer cells as well as indirectly through impact on risk factors of malignancy. Some of them are considered beneficial (metformin and thiazolidinedions—with the exception of bladder cancer); on the other hand, excess of exogenous insulin may be potentially harmful, while other medications seem to have neutral impact on cancer risk. Inhibitors of the sodium-glucose cotransporter-2 (SGLT-2) are increasingly used in the treatment of type 2 diabetes. However, their association with cancer risk is unclear. The aim of this review was to analyze the anticancer potential of this class of drugs, as well as risks of site-specific malignancies associated with their use.

scholarly journals Obesity and Diabetes: The Increased Risk of Cancer and Cancer-Related Mortality

2015 ◽  
Vol 95 (3) ◽  
pp. 727-748 ◽  
Author(s):  
Emily Jane Gallagher ◽  
Derek LeRoith
Keyword(s):  
Type 2 Diabetes ◽  
Cancer Risk ◽  
Cancer Progression ◽  
Intentional Weight Loss ◽  
Obesity And Diabetes ◽  
Increased Risk ◽  
Incidence And Mortality ◽  
Onset Of Diabetes ◽  
Risk Of Cancer

Obesity and type 2 diabetes are becoming increasingly prevalent worldwide, and both are associated with an increased incidence and mortality from many cancers. The metabolic abnormalities associated with type 2 diabetes develop many years before the onset of diabetes and, therefore, may be contributing to cancer risk before individuals are aware that they are at risk. Multiple factors potentially contribute to the progression of cancer in obesity and type 2 diabetes, including hyperinsulinemia and insulin-like growth factor I, hyperglycemia, dyslipidemia, adipokines and cytokines, and the gut microbiome. These metabolic changes may contribute directly or indirectly to cancer progression. Intentional weight loss may protect against cancer development, and therapies for diabetes may prove to be effective adjuvant agents in reducing cancer progression. In this review we discuss the current epidemiology, basic science, and clinical data that link obesity, diabetes, and cancer and how treating obesity and type 2 diabetes could also reduce cancer risk and improve outcomes.

scholarly journals ADRB2 G–G haplotype associated with breast cancer risk among Hispanic and non-Hispanic white women: interaction with type 2 diabetes and obesity

2012 ◽  
Vol 23 (10) ◽  
pp. 1653-1663 ◽  
Author(s):  
Avonne Connor ◽  
Richard N. Baumgartner ◽  
Richard A. Kerber ◽  
Elizabeth O’Brien ◽  
Shesh N. Rai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Type 2 Diabetes ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
White Women ◽  
Diabetes And Obesity ◽  
Hispanic White

scholarly journals Type 2 diabetes and obesity in midlife and breast cancer risk in the Reykjavik cohort

2019 ◽  
Vol 30 (10) ◽  
pp. 1057-1065
Author(s):  
Gertraud Maskarinec ◽  
Álfheiður Haraldsdóttir ◽  
Kristjana Einarsdóttir ◽  
Thor Aspelund ◽  
Laufey Tryggvadóttir ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Type 2 Diabetes ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Diabetes And Obesity

scholarly journals Metformin use and risk of cancer in patients with type 2 diabetes: a cohort study of primary care records using inverse probability weighting of marginal structural models

2019 ◽  
Vol 48 (2) ◽  
pp. 527-537 ◽  
Author(s):  
Ruth E Farmer ◽  
Deborah Ford ◽  
Rohini Mathur ◽  
Nish Chaturvedi ◽  
Rick Kaplan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Primary Care ◽  
Cancer Risk ◽  
Structural Models ◽  
Marginal Structural Models ◽  
Diabetes Diagnosis ◽  
Inverse Probability ◽  
Risk Of Cancer

Abstract Background Previous studies provide conflicting evidence on whether metformin is protective against cancer. When studying time-varying exposure to metformin, covariates such as body mass index (BMI) and glycated haemoglobin (HbA1c) may act as both confounders and causal pathway variables, and so cannot be handled adequately by standard regression methods. Marginal structural models (MSMs) with inverse probability of treatment weights (IPTW) can correctly adjust for such confounders. Using this approach, the main objective of this study was to estimate the effect of metformin on cancer risk compared with risk in patients with T2DM taking no medication. Methods Patients with incident type 2 diabetes (T2DM) were identified in the Clinical Practice Research Datalink (CPRD), a database of electronic health records derived from primary care in the UK. Patients entered the study at diabetes diagnosis or the first point after this when they had valid HbA1c and BMI measurements, and follow-up was split into 1-month intervals. Logistic regression was used to calculate IPTW; then the effect of metformin on all cancers (including and excluding non-melanoma skin cancer) and breast, prostate, lung, colorectal and pancreatic cancers was estimated in the weighted population. Results A total of 55 629 T2DM patients were alive and cancer-free at their study entry; 2530 people had incident cancer during a median follow-up time of 2.9 years [interquartile range (IQR) 1.3–5.4 years]. Using the MSM approach, the hazard ratio (HR) for all cancers, comparing treatment with metformin with no glucose-lowering treatment, was 1.02 (0.88–1.18). Results were robust to a range of sensitivity analyses and remained consistent when estimating the treatment effect by length of exposure. We also found no evidence of a protective effect of metformin on individual cancer outcomes. Conclusions We find no evidence that metformin has a causal association with cancer risk.

scholarly journals Dexamethasone Sensitizes the Neonatal Intestine to Fructose Induction of Intestinal Fructose Transporter (Slc2A5) Function

Endocrinology ◽  
2007 ◽  
Vol 149 (1) ◽  
pp. 409-423 ◽  
Author(s):  
Veronique Douard ◽  
Xue-Lin Cui ◽  
Patricia Soteropoulos ◽  
Ronaldo P. Ferraris
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Transporter ◽  
Microarray Hybridization ◽  
Transporter Family ◽  
Sodium Glucose Cotransporter ◽  
Timing Mechanisms ◽  
Dietary Fructose ◽  
Diabetes And Obesity ◽  
Effect Of Age

The recent dramatic increase in fructose consumption is tightly correlated with an equally dramatic surge in the incidence of type 2 diabetes and obesity in children, but little is known about dietary fructose metabolism and absorption in neonates. The expression of the rat intestinal fructose transporter GLUT5 [Slc2A5, a member of the glucose transporter family (GLUT)] can be specifically induced by its substrate fructose, but only after weaning begins at 14 d of age. In suckling rats younger than 14 d old, dietary fructose cannot enhance GLUT5 expression. The aim of this study was to identify the mechanisms allowing fructose to stimulate GLUT5 during weaning. After intestines were perfused with fructose or glucose (control), using microarray hybridization we showed that of 5K genes analyzed in 10-d-old pups, only 13 were fructose responsive. Previous work found approximately 50 fructose-responsive genes in 20-d-old pups. To identify fructose-responsive genes whose expression also changed with age, intestines of 10- and 20-d-old littermate pups perfused with fructose were compared by microarray. Intestines of 10- and 20-d-old pups perfused with glucose were used to segregate age- but not fructose-responsive genes. About 28 genes were up- and 22 down-regulated in 20- relative to 10-d-old pups, under conditions of fructose perfusion, and many were found, by cluster analysis, to be regulated by corticosterone. When dexamethasone was injected into suckling pups before fructose perfusion, the expression of GLUT5 but not that of the sodium glucose cotransporter (SGLT) 1 and of GLUT2, as well as the uptake of fructose but not of glucose increased dramatically. Thus, dexamethasone, which allows dietary fructose to precociously stimulate intestinal fructose absorption, can mimic the effect of age and modify developmental timing mechanisms regulating GLUT5.

scholarly journals Assessment of the prognostic cancer risk in patients with type 2 diabetes mellitus

2021 ◽  
Vol 17 (1) ◽  
pp. 86-91
Author(s):  
T.S. Vatseba ◽  
L.K. Sokolova ◽  
N.M. Koshel
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cancer Risk ◽  
Malignant Neoplasms ◽  
Increased Risk ◽  
Risk Of Cancer ◽  
Prognostic Power ◽  
Uterine Body

Background. The epidemiological analysis has shown an increased risk of cancer of the mammalian gland (MG), ute­rine body, and pancreas in patients with type 2 diabetes mellitus (T2DM). The different clinical characteristics and features of the course of DM, and schemes of treatment of patients with these types of oncological diseases (OD) were identified. The purpose of the study was to create a model of mathematical calculation and assessment of the predicted risk of cancer of MG, uterine body, pancreatic and colorectal cancer (CRC) in patients with T2DM, given the importance of diabetes-associated factors of oncogenesis. Materials and methods. The study included an analysis of medical records of patients with T2DM with first diagnosed OD during 2012–2016. The statistical analysis of the results was performed in the program Statistica 12.0 (StatSoft Inc., USA). The differences between indicators were determined by Student’s t-test, considered significant at p < 0.05. The method of multi-factor analysis and the logistic regression equation was used to calculate the coefficient of prognostic risk of the OD. Results. It was found that cancer of MG and the uterine body was most often diagnosed in people at the age of 60–70 years, with obesity, duration of DM more than 5 years, with HbA1c level > 7.5 %, on combination therapy with drugs without influence on the insulin synthesis with stimulators of insulin production. Patients with CRC had the same characteristics, without gender diffe­rences. Pancreatic cancer was most often diagnosed in patients aged 60–70 years, without obesity, with a duration of DM up to 5 years, with HbA1c > 7.5 %, on monotherapy with insulin or sulfonylureas, without gender differences. The created model for calculating the coefficient of the prognostic risk of MG and uterine body cancer is characterized by high prognostic power (accuracy 76.24 %), good prognostic power for cancer of the pancreas (accuracy 75.0 %), and CRC (accuracy 72.2 %). Conclusions. Correction of dysmetabolic disorders is a method of prevention of OD in patients with T2DM. The calculation of the predicted cancer risk will contribute to the prevention of malignant neoplasms in patients with T2DM.

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