scholarly journals Type 2 Diabetes and Breast Cancer: The Interplay between Impaired Glucose Metabolism and Oxidant Stress

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Patrizia Ferroni ◽  
Silvia Riondino ◽  
Oreste Buonomo ◽  
Raffaele Palmirotta ◽  
Fiorella Guadagni ◽  
...  

Metabolic disorders, especially type 2 diabetes and its associated complications, represent a growing public health problem. Epidemiological findings indicate a close relationship between diabetes and many types of cancer (including breast cancer risk), which regards not only the dysmetabolic condition, but also its underlying risk factors and therapeutic interventions. This review discusses the advances in understanding of the mechanisms linking metabolic disorders and breast cancer. Among the proposed mechanisms to explain such an association, a major role is played by the dysregulated glucose metabolism, which concurs with a chronic proinflammatory condition and an associated oxidative stress to promote tumour initiation and progression. As regards the altered glucose metabolism, hyperinsulinaemia, both endogenous due to insulin-resistance and drug-induced, appears to promote tumour cell growth through the involvement of innate immune activation, platelet activation, increased reactive oxygen species, exposure to protumorigenic and proangiogenic cytokines, and increased substrate availability to neoplastic cells. In this context, understanding the relationship between metabolic disorders and cancer is becoming imperative, and an accurate analysis of these associations could be used to identify biomarkers able to predict disease risk and/or prognosis and to help in the choice of proper evidence-based diagnostic and therapeutic protocols.

2021 ◽  
Vol 22 (7) ◽  
pp. 3566
Author(s):  
Chae Bin Lee ◽  
Soon Uk Chae ◽  
Seong Jun Jo ◽  
Ui Min Jerng ◽  
Soo Kyung Bae

Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.


2021 ◽  
pp. 509-522
Author(s):  
Tomas Grega ◽  
Gabriela Vojtechova ◽  
Monika Gregova ◽  
Miroslav Zavoral ◽  
Stepan Suchanek

A substantial body of literature has provided evidence that type 2 diabetes mellitus (T2DM) and colorectal neoplasia share several common factors. Both diseases are among the leading causes of death worldwide and have an increasing incidence. In addition to usual risk factors such as sedentary lifestyle, obesity, and family history, common pathophysiological mechanisms involved in the development of these diseases have been identified. These include changes in glucose metabolism associated with adipose tissue dysfunction including insulin resistance resulting to hyperinsulinemia and chronic hyperglycemia. In addition to altered glucose metabolism, abdominal obesity has been associated with accented carcinogenesis with chronic subclinical inflammation. An increasing number of studies have recently described the role of the gut microbiota in metabolic diseases including T2DM and the development of colorectal cancer (CRC). Due to the interconnectedness of different pathophysiological processes, it is not entirely clear which factor is crucial in the development of carcinogenesis in patients with T2DM. The aim of this work is to review the current knowledge on the pathophysiological mechanisms of colorectal neoplasia development in individuals with T2DM. Here, we review the potential pathophysiological processes involved in the onset and progression of colorectal neoplasia in patients with T2DM. Uncovering common pathophysiological characteristics is essential for understanding the nature of these diseases and may lead to effective treatment and prevention.


2019 ◽  
Author(s):  
Yasmine Kemkem ◽  
Daniela Nasteska ◽  
Anne De Bray ◽  
Paula Bargi-Souza ◽  
Rodrigo A. Peliciari-Garcia ◽  
...  

ABSTRACTDuring pregnancy, maternal metabolic diseases and hormonal imbalance may alter fetal beta cell development and/or proliferation, thus leading to an increased risk for developing type 2 diabetes in adulthood. Although thyroid hormones play an important role in fetal endocrine pancreas development, the impact of maternal hypothyroidism on glucose homeostasis in adult offsprings remains poorly understood. Here, we show that when fed normal chow, adult mice born to hypothyroid mothers were more glucose-tolerant due to beta cell hyperproliferation and increased insulin sensitivity. However, following high fat feeding, these offsprings became profoundly hyperinsulinemic, insulin-resistant and glucose-intolerant compared to controls from euthyroid mothers. Suggesting presence of epigenetic changes, altered glucose metabolism was maintained in a second generation of animals. As such, gestational hypothyroidism induces long-term and persistent alterations in endocrine pancreas function, which may have important implications for type 2 diabetes prevention in affected individuals.SIGNIFICANCEDiabetes and hypothyroidism are two major public health issues, affecting ∼ 9 and 2 % of the population worldwide, respectively. As master metabolic gatekeepers, the thyroid hormones play an essential role in metabolism and fetal development. However, gestation increases demand on the thyroid axis in the mother, leading to hypothyroidism in 0.5 % of pregnancies. Maternal hypothyroidism is associated with deficits in fetal growth that may lead to long-term alterations in metabolism in the offspring. We therefore sought to investigate the effects of gestational hypothyroidism on glucose metabolism in adult offspring and their descendants, and how this may predispose to diabetes development.


2020 ◽  
pp. 48-52
Author(s):  
I. M. Dolgov ◽  
M. G. Volovik

Aim. To evaluate the temperature proximal-to-distal dorsalhand gradient (PDG) in patients with altered glucose metabolism.Methods. Analyzed 120 patients with altered glucose metabolism, divided to three groups: group 1 — abnormal glucose tolerance test (R73) and type 2 diabetes mellitus without complications (E11.9) — 50 pts, 30 m/20 f, mean age 61,5 ± 11,1), group 2 — Type 1 diabetes mellitus [Е10] — 25 pts, 7 m/18 f, mean age 44,4 ± 13,1); group 3 — type 2 diabetes mellitus with multiple complications [Е11.7] and type 2 diabetes mellitus with unspecified complications [Е11.8] — 45 pts, 14 m /31 f., mean age 62,2 ± 10,8). Thermal images were shoot by Russian made thermography camera TVS–300med, 388 x 360 pix, sensitivity 0,03℃. PDG calculated as a difference between mean temp of proximal and distal phalanges of 2–5 fingers and estimated for right or left hand separately.Results. Two thermography signs were observed: «inverted» PDG, when temperature of distal phalanges is higher than proximal and founded more often in group 1 and «false normal», when temperature of proximal phalanges is higher than distal, and name in this manner, because founded more often in «complicated» groups 2 and 3. Analysis confirmed that group 1 and group 3 pts significantly differed in mean PDG value (p<0,05).Conclusion. Our results show that thermography examination pointed out variety of dorsal hand signs for altered glucose metabolism and significant difference in mean PDG value for group 1 and 3. Therefore infrared thermography could be suggested as an objective tool for screening and monitoring of disease.


2005 ◽  
Vol 99 (5) ◽  
pp. 1998-2007 ◽  
Author(s):  
Naresh M. Punjabi ◽  
Vsevolod Y. Polotsky

Sleep is a complex behavioral state that occupies one-third of the human life span. Although viewed as a passive condition, sleep is a highly active and dynamic process. The sleep-related decrease in muscle tone is associated with an increase in resistance to airflow through the upper airway. Partial or complete collapse of the airway during sleep can lead to the occurrence of apneas and hypopneas during sleep that define the syndrome of sleep apnea. Sleep apnea has become pervasive in Western society, affecting ∼5% of adults in industrialized countries. Given the pandemic of obesity, the prevalence of Type 2 diabetes mellitus and metabolic syndrome has also increased dramatically over the last decade. Although the role of sleep apnea in cardiovascular disease is uncertain, there is a growing body of literature that implicates sleep apnea in the pathogenesis of altered glucose metabolism. Intermittent hypoxemia and sleep fragmentation in sleep apnea can trigger a cascade of pathophysiological events, including autonomic activation, alterations in neuroendocrine function, and release of potent proinflammatory mediators such as tumor necrosis factor-α and interleukin-6. Epidemiologic and experimental evidence linking sleep apnea and disorders of glucose metabolism is reviewed and discussed here. Although the cause-and-effect relationship remains to be determined, the available data suggest that sleep apnea is independently associated with altered glucose metabolism and may predispose to the eventual development of Type 2 diabetes mellitus.


Diabetologia ◽  
2020 ◽  
Vol 63 (9) ◽  
pp. 1822-1835 ◽  
Author(s):  
Yasmine Kemkem ◽  
Daniela Nasteska ◽  
Anne de Bray ◽  
Paula Bargi-Souza ◽  
Rodrigo A. Peliciari-Garcia ◽  
...  

Abstract Aims/hypothesis During pregnancy, maternal metabolic disease and hormonal imbalance may alter fetal beta cell development and/or proliferation, thus leading to an increased risk for developing type 2 diabetes in adulthood. Although thyroid hormones play an important role in fetal endocrine pancreas development, the impact of maternal hypothyroidism on glucose homeostasis in adult offspring remains poorly understood. Methods We investigated this using a mouse model of hypothyroidism, induced by administration of an iodine-deficient diet supplemented with propylthiouracil during gestation. Results Here, we show that, when fed normal chow, adult mice born to hypothyroid mothers were more glucose-tolerant due to beta cell hyperproliferation (two- to threefold increase in Ki67-positive beta cells) and increased insulin sensitivity. However, following 8 weeks of high-fat feeding, these offspring gained 20% more body weight, became profoundly hyperinsulinaemic (with a 50% increase in fasting insulin concentration), insulin-resistant and glucose-intolerant compared with controls from euthyroid mothers. Furthermore, altered glucose metabolism was maintained in a second generation of animals. Conclusions/interpretation Therefore, gestational hypothyroidism induces long-term alterations in endocrine pancreas function, which may have implications for type 2 diabetes prevention in affected individuals.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Lihong Yang ◽  
Anne F. Fish ◽  
Yuanyuan Zhu ◽  
Xiaodan Yuan ◽  
Jianing Li ◽  
...  

Abstract Background Cardiovascular disease has become a serious public health problem in recent years in China. The aim of the study was to examine sex differences in cardiovascular risk factors and 10-year ischemic cardiovascular disease (ICVD) risk in Chinese patients with prediabetes (PreDM) and type 2 diabetes mellitus (T2DM). Methods This was a multi-site retrospective case-control study conducted from April–November 2016 using an electronic medical record database, involving 217 PreDM and 900 T2DM patients admitted to endocrinology units in four hospitals in China. CVD risk was estimated using the Chinese 10-year ICVD risk model. The differences in 10-year absolute ICVD risk according to PreDM, T2DM < 1 year, T2DM 1–5 years or T2DM ≥5 years and sex were analyzed using ANOVA. Results When compared to PreDM females, males with PreDM had significantly higher 10-year ICVD risk In contrast, the opposite pattern of 10-year ICVD risk was observed in T2DM; males had significantly lower 10-year ICVD risk. Moreover, compared to T2DM females, males with T2DM had a lower proportion s with moderate or greater ICVD risk (p < 0.001). When compared to PreDM males, males with T2DM < 1 year, and with T2DM 1–5 years had no difference in 10-year ICVD risk, but had higher ICVD risk with T2DM ≥5 years (p < 0.05). Compared to PreDM females, females with T2DM in all subgroups had higher ICVD risk (p < 0.05). Among those with T2DM, hypertension rates of awareness, treatment and control were 78.60%, 65.38% and 31.10%, respectively; hyperlipidemia rates of awareness, treatment and control were lower (29.15%, 8.30% and 3.47%, respectively). Females with T2DM had higher prevalence, awareness and treatment of hypertension and hyperlipidemia than males with T2DM (p < 0.001). Conclusions There is a greater need for cardiovascular risk reduction programs for females with T2DM at diagnosis. Given the low numbers for awareness, treatment and control of hypertension and hyperlipidemia in both males and females, significant resources focused on them must be expended, specifically improving regular assessment of blood pressure and blood lipids. Strengthening the management of chronic diseases through adherence to evidence-based guidelines to enhance clinical treatment may reduce 10-year ICVD in patients with T2DM in China.


2014 ◽  
Vol 13 (1) ◽  
pp. 57 ◽  
Author(s):  
Mattia Bellan ◽  
Gabriele Guzzaloni ◽  
Maura Rinaldi ◽  
Elena Merlotti ◽  
Carlotta Ferrari ◽  
...  

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