The Data-Driven Fasting (DDF) app implements glucose-guided eating (GGE), an innovative dietary intervention that encourages individuals to eat when their glucose level, measured via glucometer or continuous glucose monitor, falls below a personalized threshold to improve metabolic health. Clinical trials using GGE, facilitated by paper logging of glucose and hunger symptoms, have shown promising results.

This study aimed to describe user demographics, app engagement, adherence to glucose monitoring, and the resulting impact on weight and glucose levels.

Data from 6197 users who logged at least 2 days of preprandial glucose readings were analyzed over their first 30 days of app use. App engagement and changes in body weight and fasting glucose levels by baseline weight and diabetes status were examined. Users rated their preprandial hunger on a 5-point scale.

Participants used the app for a median of 19 (IQR 9-28) days, with a median of 7 (IQR 3-13) weight entries and 52 (IQR 25-82) glucose entries. On days when the app was used, it was used a median of 1.8 (IQR 1.4-2.1) times. A significant inverse association was observed between perceived hunger and preprandial glucose concentrations, with hunger decreasing by 0.22 units for every 1 mmol/L increase in glucose (95% CI -0.23 to -0.21; P<.001). Last observation carried forward analysis resulted in weight loss of 0.7 (95% CI -0.8 to -0.6) kg in the normal weight category, 1 (95% CI -1.1 to -0.9) kg in the overweight category, and 1.2 (95% CI -1.3 to -1.1) kg in the obese category. All weight changes nearly doubled when analyzed using a per-protocol (completers) analysis. Fasting glucose levels increased by 0.11 (95% CI 0.09-0.12) mmol/L in the normal range and decreased by 0.14 (95% CI -0.16 to -0.12) mmol/L in the prediabetes range and by 0.5 (95% CI -0.58 to -0.42) mmol/L in the diabetes range. Per-protocol analysis showed fasting glucose reductions of 0.26 (SD 4.7) mg/dL in the prediabetes range and 0.94 (16.9) mg/dL in the diabetes range.

The implementation of GGE through the DDF app in a real-world setting led to consistent weight loss across all weight categories and significant improvements in fasting glucose levels for users with prediabetes and diabetes. This study underscores the potential of the GGE to facilitate improved metabolic health.

Insulin resistance and prostate cancer (PCa) association results remain controversial. However, few studies have compared the role of various non-insulin-based insulin resistance (NI-IR) indices and mean platelet volume (MPV) in PCa.

We conducted a cross-sectional study, the case group included 354 patients with PCa, and the control group included 1,498 non-PCa participants. We performed inverse probability weighting to reduce the impact of differences in baseline information between the case and control groups on results. Weighted logistic regression analysis for assessing the relationship between NI-IR indices and PCa risk. Fitting 4-point restricted cubic spline (RCS) plots to show the trend of NI-IR indices with PCa risk. The interaction between insulin resistance and platelet volume based on generalized additive model (GAM) to reveal the impact of the interaction between insulin resistance and cardiovascular risk on PCa. In the end, we performed three sensitivity analyses to verify the stability of results.

Weighted logistic regression analysis revealed that all NI-IR indices were associated with PCa. When NI-IR indices were evaluated as continuous variables, in the all variables adjusted model (model 3), the adjusted OR of ZJU index was 1.337 (95%CI: 1.296-1.379), the adjusted OR of TyG index was 5.300 (95%CI:4.208-6.675), the adjusted OR of TG/HDL-c was 1.431 (95%CI:1.335-1.534), and the adjusted OR of METS-IR was 1.129 (95%CI:1.110-1.149). When NI-IR indices were analyzed as categorical variables, also in model 3, using Q1 as reference, the adjusted OR of ZJU index in Q5 was 15.592 (95%CI:10.809-22.492), the adjusted OR of TyG index in Q5 was 7.306 (95%CI:5.182-10.301), the adjusted OR of TG/HDL-c in Q5 was 4.790 (95%CI:3.459-6.632), and the adjusted OR of METS-IR in Q5 was 9.844 (95%CI:6.862-14.121). RCS displayed that PCa risk tended to increase as the ZJU index, TyG index, TG/HDL-c, and METS-IR increased. The interaction test based on the GAM indicated that the value of the interaction between TG/HDL-c and MPV on the PCa risk was χ2 = 6.924(P = 0.009). With the increase in TG/HDL-c and the decrease in MPV, the PCa risk progressively increases. The sensitivity analysis further confirmed the robustness of the results.

NI-IR indices were associated with an increased PCa risk. The interaction between MPV and insulin resistance may further contribute to the PCa risk.

Diabetes and cancer are two of the most common public health concerns worldwide. The complex interplay of these two conditions is a growing area of research, as patients with diabetes are at increased risk for developing cancer, and vice versa. Furthermore, both patient populations show increased risk of many communicable infectious diseases and their adverse consequences, while vaccination can play a crucial role in their prevention, improving patient outcomes. Vaccination should represent a standard part of care for patients with cancer, diabetes, and both the diseases simultaneously, including people undergoing cancer treatment or in remission. Several international guidelines provide recommendations for vaccinating people with cancer or diabetes, but the two conditions have not been specifically evaluated together. Here we present a multidisciplinary consensus position paper on vaccination in patients with cancer and diabetes. The position paper is the result of a collaborative effort between experts from the Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE), and Italian Society of Pharmacology (SIF). The paper provides a comprehensive overview of the current state-of-the-art knowledge on vaccination in patients with cancer and diabetes. It discusses the importance of vaccination in preventing infections, focuses attention on the need to consider the unique challenges faced by patients with cancer and diabetes when it comes to vaccine administration, and highlights the need for coordinated care to optimize treatment outcomes. Overall, the consensus position paper provides healthcare professionals caring for patients with cancer and diabetes recommendations on the use of various vaccines, including influenza, COVID-19, HZV, and HPV vaccines, as well as guidance on how to address common concerns and challenges related to vaccine administration.

Alzheimer's disease is linked with diabetes and cancer, emphasising the need for effective treatments. Plantago lanceolata, recognised as safe by various pharmacopeias, was investigated in this study for therapeutic potential. We examined the effects of its leaf extracts and sub-extracts (methanol, hexane, dichloromethane, ethyl acetate, butanol, aqueous) on AChE, BChE, α-amylase, α-glucosidase enzymes, as well as their impact on HDF-a and U87-MG cancer cells. The phytochemical characterisation was performed using ICP-MS and LC-MS/MS. Cytotoxic effects were evaluated on HDF-a and U87-MG cell lines, along with assessments for nuclear abnormalities. Na and K were detected in extracts, with isoleucine and cyanidin-3-O-glucoside being the most concentrated compounds. Extracts at concentrations exceeding 25 µg/mL significantly increased cytotoxicity in HDF-a cell lines compared to the control group, without inducing nuclear abnormalities. Methanol extract demonstrated moderate inhibition against AChE and BChE at concentrations of 100 µg/mL and 500 µg/mL, respectively. These findings suggest that extracts exhibit potential therapeutic effects.

Diabetes and Cancer are the most complex chronic diseases, accounting for significant global mortality and morbidity. The association between Type 2 DM (T2DM) and endometrial cancer (EC) is multifaced, sharing numerous risk factors, including insulin resistance, obesity, hypoxia, and oxidative stress. Hypoxia plays a vital role in T2DM pathogenesis by altering the insulin level and pancreatic β-cell failure through an imbalance between antioxidant enzymes and cellular oxidative levels, while chronic inflammation contributes to EC malignancy. HIF-1α is a potent transcription factor involved in modulating cellular responses to hypoxia within the disease environment. Targeting the HIF-1α signaling cascade, a major metabolic regulator may contribute to advanced therapeutic advances. This review focuses on the association between T2DM and EC, especially focusing on hypoxia and HIF signaling pathways. These intersect with key pathways involved in T2DM and EC pathology, such as insulin signaling, PI3K/AKT, mTOR pathway, MUC1/HIF-1α pathway, and hormonal imbalance. Understanding this complex relationship paves the way for future researchers to develop HIF-1α-targeted therapies that could lead to novel combination therapies to treat these comorbid conditions.

High fasting plasma glucose (HFPG) has been indicated as one of the important risk factors for cancers. This study aimed to estimate the disease burden of cancers attributable to HFPG in China from 1990 to 2021 and predict the burden until 2031.

The data of cancers attributable to HFPG were extracted from Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 project. A joinpoint regression model was conducted to estimate the temporal trends from 1990 to 2021. The effects of age, period, and cohort were estimated by an age-period-cohort (APC) model. Lastly, a Bayesian APC model was employed to predict the disease burden for the next decade.

From 1990-2021, cancer deaths attributable to HFPG in China increased by 232 % (95 % uncertainty interval [UI]: 156-330.77 %), and disability-adjusted life-years (DALYs) increased by 195.4 % (95 % UI: 127.38-289.7 %). In addition, the average annual percentage change (AAPC) for the age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR) were 0.6364 % (95 % confidence interval [CI]: 0.4234-0.8498 %) and 0.6263 % (95 % CI: 0.3024-0.9512 %), respectively. Among all cancer types, pancreatic cancer had the largest increase in disease burden. The risks of mortality and DALYs increased with age, while showing initial rapid increase with period growth followed by relative stabilization. The cohort effect indicates that males born later had higher risks of mortality and DALYs. Finally, despite a continuous decline in both ASMR and ASDR, the numbers of deaths and DALYs were projected to continue increasing in the next decade.

The disease burden of cancers attributable to HFPG significantly increased from 1990 to 2021 in China, and the numbers of deaths and DALYs would continuously increase in the next decade. Therefore, it is necessary to introduce targeted policies controlling the disease burden.

Diabetes mellitus (DM) and neurodegenerative diseases/disturbances are worldwide health problems. The most common chronic conditions diagnosed in persons 60 years and older are type 2 diabetes mellitus (T2DM) and cognitive impairment. It was found that diabetes mellitus is a major risk for cognitive decline, dementia, Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. Different mechanisms of associations between these diseases and diabetes mellitus have been suggested. For example, it is postulated that an impaired intracellular insulin signaling pathway, together with hyperglycemia and hyperinsulinemia, may cause pathological changes, such as dysfunction of the mitochondria, oxidative stress inflammatory responses, etc. The association between diabetes mellitus and neurodegenerative diseases, as well as the mechanisms of these associations, needs further investigation. The aim of this review is to describe the associations between diabetes mellitus, especially type 1 (T1DM) and type 2 diabetes mellitus, and selected neurodegenerative diseases, i.e., Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. Suggested mechanisms of these associations are also described.

Pancreatic cancer poses a significant challenge in individuals with diabetes, prompting a reevaluation of established risk factors beyond conventional glycemic control measures.

To explore the complex interplay of metabolic and psychosocial determinants in pancreatic cancer risk among individuals with diabetes, challenging prevailing perspectives and advocating for a comprehensive approach.

A total of 21,945 UK Biobank participants with baseline diabetes diagnosis were analyzed. Social isolation was assessed through a questionnaire capturing five factors: household size, social activities, friend/family visits, loneliness, and confiding in others. Incident pancreatic cancer was identified using ICD codes. Baseline characteristics, insulin use, and other relevant factors were analyzed. Hazard ratios and mediation analyses were conducted to determine the relationship between social isolation, inflammation, and pancreatic cancer risk.

Individuals with high social isolation were more likely to be male, smokers, non-drinkers, and have shorter sleep duration. They also had an increased risk of pancreatic cancer (HR = 2.65, 95% CI = 1.12-6.24) compared to those with low social isolation. Mediation analyses highlighted inflammation as a crucial mediator, with the proportion mediated by inflammation being 19.44% for insulin use, 10.34% for smoking, and 8.33% for social isolation.

Our findings highlight the importance of psychosocial factors in pancreatic cancer risk and underscore the need for further research to elucidate the underlying mechanisms.

In the curative treatment of cancer with adjuvant chemotherapy, antineoplastic drugs, along with glucocorticoids, can induce hyperglycemia. The objective of this study was to assess the utility of the Indian Diabetes Risk Score (IDRS) in predicting treatment-induced hyperglycemia in women who were nondiabetic and normoglycemic at the start of chemotherapy. This prospective study was conducted with nondiabetic women who required adjuvant chemotherapy. Participants voluntarily completed the IDRS, providing information on age, waist circumference, family history of diabetes, and physical activity. Chemotherapy-induced hyperglycemia was defined as fasting blood glucose levels ≥100 mg/dL or random blood glucose levels ≥140 mg/dL during treatment. Data were categorized into women who developed hyperglycemia and those who remained normoglycemic during treatment and were analyzed using Fisher's exact test. A significance level of p  < 0.05 was applied. Receiver operating characteristic (ROC) curves were constructed to validate the IDRS for predicting hyperglycemia. A total of 208 women met the inclusion criteria and participated in the study. The results revealed that 38.93% (81/208) developed hyperglycemia by the end of chemotherapy, as observed during their first follow-up after treatment. Fisher's exact test demonstrated a significant difference in the total IDRS score and its domains, including family history, physical activity, and waist circumference ( p  = 0.017-< 0.001), but not age. ROC analysis indicated that an IDRS score above 60 increased the likelihood of developing hyperglycemia, with a sensitivity of 81.3%, specificity of 54.7%, and an area under the curve of 0.727. These findings suggest that the IDRS is a sensitive tool for predicting adjuvant chemotherapy-induced hyperglycemia in breast cancer patients without diabetes. To the best of the authors' knowledge, this is the first study to evaluate the utility of the IDRS in predicting treatment-induced hyperglycemia in women undergoing adjuvant chemotherapy for breast cancer. Ongoing efforts are focused on understanding the underlying mechanisms and strategies for mitigation.

The objective of our study was to evaluate bladder cancer risk among Lithuanian type 2 diabetes mellitus (T2DM) patients and the effect of antihyperglycemic therapy on bladder cancer risk.

We analyzed bladder cancer risk in a cohort of patients who were diagnosed with T2DM between 2001 and 2012 in Lithuania. Bladder cancer risk in four groups of antihyperglycemic medication users (insulin-only, metformin-only, sulfonylurea-only, and pioglitazone ± any other drug) was also assessed. Standardized incidence ratios for bladder cancer were calculated.

A total of 76,818 patients (28,762 males and 48,056 females) with T2DM were included in the final cohort. In the whole cohort of diabetic patients, 277 bladder cancer cases were observed, compared to 232.75 expected cases, according to bladder cancer rates in the general population (Standardized Incidence Ratio 1.19; 95% Confidence Interval: 1.06-1.34). Higher risk of bladder cancer was found in both men and women; however, in women the risk increase was not statistically significant. We found higher risk of bladder cancer in patients of both sexes diagnosed with T2DM at the age of 50-79 years and also in all groups of different antihyperglycemic medication users.

T2DM was associated with increased risk of bladder cancer.

The inhibition of dipeptidyl- peptidase 4 (DPP-4) is an essential therapy for controlling hyperglycemia in patients with type 2 diabetes (T2DM). However, the role of DPP-4 in cancer is not yet clear, with some studies suggesting that it may either promote or suppress tumors. This makes it crucial to have personalized treatment for diabetic women with cancer to effectively manage their diabetes whilst and preventing cancer mortality. To address this issue, we conducted an integrative in-silico analysis and systematic review of the literature to comprehensively examine the relationship between DPP-4 expression and the effects of its inhibitors on prevalent female malignancies. We specifically chose studies that examined the effects of DPP-4 expression and DPP-4 inhibition (DPP-4i) on prevalent cancers in women, such as breast cancer (BC), ovarian cancer (OV), cervical cancer (CC), and endometrial cancer (EC). These studies comprised those conducted both in vivo and in vitro. The review of the literature indicated that DPP-4i may worsen aggressive traits such as metastasis, Epithelial-to-mesenchymal transition (EMT), and chemotherapy resistance in BC cells. However, cohort studies on diabetic and BC patients did not confirm these findings. In vitro studies indicate that on OV, DPP-4 upregulation has been shown to prevent metastasis, while CCappears to be influenced by DPP-4 expression in terms of cell migration. sitagliptin, a pharmaceutical inhibitor of DPP-4, had a significant impact on reducing adhesion in CC cells in vitro. Overexpression of DPP-4 increased cell migration and proliferation in CC and EC cells, and hence the application of sitagliptin is expected to prevent this effect. On the other hand, the result of in-silico data confirmed that a significant correlation exists between DPP-4 expression and immune cell infiltration in breast, ovarian, cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) as well as downregulated in these cancers compared to their normal tissue samples. Furthermore, a significant (p < 0.05) effect on OS of BC and CESC patients has been reported due to the elevation of DPP-4 methylation on a specific CPG Island. These findings could aid in creating specialized treatments for diabetic women with specific malignancies, but caution should be exercised when considering the patient's medical history and cancer type.

Drug repurposing in cancer taps into the capabilities of existing drugs, initially designed for other ailments, as potential cancer treatments. It offers several advantages over traditional drug discovery, including reduced costs, reduced development timelines, and a lower risk of adverse effects. However, not all drug classes align seamlessly with a patient's condition or long-term usage. Hence, repurposing of chronically used drugs presents a more attractive option. On the other hand, metabolic reprogramming being an important hallmark of cancer paves the metabolic regulators as possible cancer therapeutics. This review emphasizes the importance and offers current insights into the repurposing of antidiabetic drugs, including metformin, sulfonylureas, sodium-glucose cotransporter 2 (SGLT2) inhibitors, dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), thiazolidinediones (TZD), and α-glucosidase inhibitors, against various types of cancers. Antidiabetic drugs, regulating metabolic pathways have gained considerable attention in cancer research. The literature reveals a complex relationship between antidiabetic drugs and cancer risk. Among the antidiabetic drugs, metformin may possess anti-cancer properties, potentially reducing cancer cell proliferation, inducing apoptosis, and enhancing cancer cell sensitivity to chemotherapy. However, other antidiabetic drugs have revealed heterogeneous responses. Sulfonylureas and TZDs have not demonstrated consistent anti-cancer activity, while SGLT2 inhibitors and DPP-4 inhibitors have shown some potential benefits. GLP-1RAs have raised concerns due to possible associations with an increased risk of certain cancers. This review highlights that further research is warranted to elucidate the mechanisms underlying the potential anti-cancer effects of these drugs and to establish their efficacy and safety in clinical settings.

The development of agents for cancer prevention is a lengthy process requiring a delicate balance between the safety and tolerability of potential interventions and effectiveness in preventing future cancer. Individuals at risk for a specific cancer are frequently at risk for multiple types of cancer as well as other chronic diseases, especially ones associated with aging. Shared environmental exposures, genetic predisposition, metabolic factors, and commonalities in pathogenesis suggest opportunities for combined targeting of cancer and other chronic diseases. Examples discussed here include mechanisms shared between various cancers and obesity, diabetes, and cardiovascular disease.

Observational studies have shown that the correlation between neurodegenerative diseases and colorectal cancer (CRC) remains controversial. Therefore, this study aimed to verify the causal association between these two diseases.

Mendelian randomization (MR) analysis was used to assess the causal relationships between five major neurodegenerative diseases and CRC. Multivariable MR (MVMR) analysis was conducted to assess the direct causal effect of neurodegenerative diseases on CRC. Colocalization and pathway enrichment analyses were conducted to further elucidate our results. Sensitivity analysis was conducted to assess the robustness of the results.

Genetically predicted Alzheimer's disease (AD) nominally increased CRC risk (OR = 1.0620, 95%CI = 1.0127-1.1136, P = 0.013). There was no causal effect of genetically predicted CRC on neurodegenerative diseases. Furthermore, we demonstrated that genetically predicted AD marginally increased colon cancer risk (OR = 1.1621, 95%CI = 1.0267-1.3153, P = 0.017). Genetically predicted Lewy body dementia (LBD) had a significant causal effect on the increasing risk of colon cancer (IVW OR = 1.1779, 95%CI = 1.0694-1.2975, P = 0.001). MVMR indicated that effect of AD on colon cancer was driven by LBD, type 2 diabetes, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, total cholesterol (TC), processed meat consumption, smoking, alcohol consumption, and educational attainment, whereas the effect of LBD on colon cancer was only influenced by TC. Colocalization and pathway enrichment analysis suggested that LBD and colon cancer possibly shared causal variants (nearby gene APOE), and ERBB4 signaling and lipid metabolism may mediate the causal association between LBD and colon cancer. Sensitivity analysis confirmed the reliability of our findings.

Our study demonstrated that genetic vulnerabilities to AD nominally increased the overall risk of CRC and colon cancer. Genetically predicted LBD indicated an elevated risk of colon cancer, potentially linked to ERBB4 signaling and lipid metabolism.

Insulin resistance is associated with the development and progression of various cancers. However, the epidemiological evidence for the association between insulin resistance and prostate cancer is still limited.

To investigate the associations between insulin resistance and prostate cancer prevalence.

A total of 451 patients who were pathologically diagnosed with prostate cancer in the First Affiliated Hospital of Xinjiang Medical University were selected as the case population; 1,863 participants who conducted physical examinations during the same period were selected as the control population. The metabolic score for insulin resistance (METS-IR) was calculated as a substitute indicator for evaluating insulin resistance. The Chi-square test and Mann-Whitney U test were performed to compare the basic information of the case population and control population. Univariate and multivariate logistic regression analyses to define factors that may influence prostate cancer prevalence. The generalized additive model (GAM) was applied to fit the relationship between METS-IR and prostate cancer. Interaction tests based on generalized additive model (GAM) and contour plots were also carried out to analyze the interaction effect of each factor with METS-IR on prostate cancer.

METS-IR as both a continuous and categorical variable suggested that METS-IR was negatively associated with prostate cancer prevalence. Smoothed curves fitted by generalized additive model (GAM) displayed a nonlinear correlation between METS-IR and prostate cancer prevalence (P < 0.001), and presented that METS-IR was negatively associated with the odds ratio (OR) of prostate cancer. The interaction based on the generalized additive model (GAM) revealed that METS-IR interacted with low-density lipoprotein cholesterol (LDL-c) to influence the prostate cancer prevalence (P = 0.004). Contour plots showed that the highest prevalence probability of prostate cancer was achieved when METS-IR was minimal and low-density lipoprotein cholesterol (LDL-c) or total cholesterol (TC) was maximal.

METS-IR is nonlinearly and negatively associated with the prevalence of prostate cancer. The interaction between METS-IR and low-density lipoprotein cholesterol (LDL-c) has an impact on the prevalence of prostate cancer. The study suggests that the causal relationship between insulin resistance and prostate cancer still needs more research to confirm.

In this study, the antidiabetic activities of Lepionurus sylvestris Blume extract (LSB) in rats was investigated. The in vitro antidiabetic properties of LSB was evaluated using α-amylase, α-glucosidase and DPP-IV inhibitory assays, while the antioxidant assay was analysed using DPPH, ABTS and FRAP assays. Type 2 diabetes was with high-fructose/streptozotocin, and the diabetic animals were treated with LSB for 5 weeks. At the end of the experiment, the effects of LSB were evaluated via insulin level, lipid profile and hepatorenal function biomarkers. The level of oxido-inflammatory parameters, histopathology and insulin immunohistochemical staining in the pancreas was evaluated. Diabetic rats manifested significant increases in the blood glucose level, food/water intake, lipid profiles, hepatorenal function biomarkers, as well as a marked decreases in the body weight and serum insulin levels. Histopathological and insulin immunohistochemical examination also revealed decreased pancreatic beta cells and insulin positive cells, respectively. These alterations were associated with significant increases in malondialdehyde, TNF-α and IL-1β, in addition to significant declines in GSH, SOD and CAT activities. LSB significantly reduced blood glucose level, glucose intolerance, serum lipids, restored altered hepatorenal and pancreatic functions in the treated diabetic rats. Further, LSB showed antioxidant and anti-inflammatory activities by reducing malondialdehyde, TNF-α, IL-1β, and increasing antioxidant enzymes activities in the pancreatic tissues. A total of 77 secondary metabolites were tentatively identified in the UPLC-Q-TOF-MS analysis of LSB. Overall, these findings provides insight into the potentials of LSB as an antidiabetic agent which may be associated to the plethora bioactive compounds in the plant.

Drug resistance is currently one of the biggest challenges in cancer treatment. With the deepening understanding of drug resistance, various mechanisms have been revealed, including metabolic reprogramming and alterations of redox balance. Notably, metabolic reprogramming mediates the survival of tumor cells in harsh environments, thereby promoting the development of drug resistance. In addition, the changes during metabolic pattern shift trigger reactive oxygen species (ROS) production, which in turn regulates cellular metabolism, DNA repair, cell death, and drug metabolism in direct or indirect ways to influence the sensitivity of tumors to therapies. Therefore, the intersection of metabolism and ROS profoundly affects tumor drug resistance, and clarifying the entangled mechanisms may be beneficial for developing drugs and treatment methods to thwart drug resistance. In this review, we will summarize the regulatory mechanism of redox and metabolism on tumor drug resistance and highlight recent therapeutic strategies targeting metabolic-redox circuits, including dietary interventions, novel chemosynthetic drugs, drug combination regimens, and novel drug delivery systems.

Cancer is one of the major causes of mortality and is the second leading cause of death. Diabetes mellitus is a serious and growing problem worldwide, and its prevalence continues to grow; it is the 12th leading cause of death. An association between diabetes mellitus and cancer has been suggested for more than 100 years. Diabetes is a common disease diagnosed among patients with cancer, and evidence indicates that approximately 8-18% of patients with cancer have diabetes, with investigations suggesting an association between diabetes and some particular cancers, increasing the risk for developing cancers such as pancreatic, liver, colon, breast, stomach, and a few others. Breast and colorectal cancers have increased from 20% to 30% and there is a 97% increased risk of intrahepatic cholangiocarcinoma or endometrial cancer. On the other hand, a number of cancers and cancer therapies increase the risk of diabetes mellitus. Complications due to diabetes in patients with cancer may influence the choice of cancer therapy. Unfortunately, the mechanisms of the associations between diabetes mellitus and cancer are still unknown. The aim of this review is to summarize the association of diabetes mellitus with selected cancers and update the evidence on the underlying mechanisms of this association.

Despite advances in primary and secondary prevention of cardiovascular disease, excess mortality persists within the diabetes population. This study explores the components of this excess mortality and their interaction with sex.

Using Danish registries (2002-2019), we identified residents aged 18-99 years, their diabetes status, and recorded causes of death. Applying Lexis-based methods, we computed age-standardized mortality rates (asMRs), mortality relative risks (asMRRs), and log-linear trends for cause-specific mortality.

From 2002 to 2019, 958,278 individuals died in Denmark (T2D: 148,620; T1D: 7830) during 84.4 M person-years. During the study period, overall asMRs declined, driven by reducing cardiovascular mortality, notably in men with T2D. Conversely, cancer mortality remained high, making cancer the leading cause of death in individuals with T2D. Individuals with T2D faced an elevated mortality risk from nearly all cancer types, ranging from 9% to 257% compared to their non-diabetic counterparts. Notably, obesity-related cancers exhibited the highest relative risks: liver cancer (Men: asMRR 3.58 (3.28; 3.91); Women: asMRR 2.49 (2.14; 2.89)), pancreatic cancer (Men: asMRR 3.50 (3.25; 3.77); Women: asMRR 3.57 (3.31; 3.85)), and kidney cancer (Men: asMRR 2.10 (1.84; 2.40); Women: asMRR 2.31 (1.92; 2.79)). In men with type 2 diabetes, excess mortality remained stable, except for dementia. In women, diabetes-related excess mortality increased by 6-17% per decade across all causes of death, except cardiovascular disease.

In the last decade, cancer has emerged as the leading cause of death among individuals with T2D in Denmark, emphasizing the need for diabetes management strategies incorporating cancer prevention. A sex-specific approach is crucial to address persistently higher relative mortality in women with diabetes.

Supported by Steno Diabetes Center Aarhus, which is partially funded by an unrestricted donation from the Novo Nordisk Foundation, and by The Danish Diabetes Academy.

There are 1·3 billion people with disabilities globally. On average, they have poorer health than their non-disabled peers, but the extent of increased risk of premature mortality is unknown. We aimed to systematically review the association between disability and mortality in low-income and middle-income countries (LMICs).

We searched MEDLINE, Global Health, PsycINFO, and EMBASE from Jan 1, 1990 to Nov 14, 2022. Longitudinal epidemiological studies in any language with a comparator group that measured the association between disability and all-cause mortality in people of any age were eligible for inclusion. Two reviewers independently assessed study eligibility, extracted data, and assessed risk of bias. We used a random-effects meta-analysis to calculate the pooled hazard ratio (HR) for all-cause mortality by disability status. We then conducted meta-analyses separately for different impairment and age groups.

We identified 6146 unique articles, of which 70 studies (81 cohorts) were included in the systematic review, from 22 countries. There was variability in the methods used to assess and report disability and mortality. The meta-analysis included 54 studies, representing 62 cohorts (comprising 270 571 people with disabilities). Pooled HRs for all-cause mortality were 2·02 (95% CI 1·77-2·30) for people with disabilities versus those without disabilities, with high heterogeneity between studies (τ2=0·23, I2=98%). This association varied by impairment type: from 1·36 (1·17-1·57) for visual impairment to 3·95 (1·60-9·74) for multiple impairments. The association was highest for children younger than 18 years (4·46, [3·01-6·59]) and lower in people aged 15-49 years (2·45 [1·21-4·97]) and people older than 60 years (1·97 [1·65-2·36]).

People with disabilities had a two-fold higher mortality rate than people without disabilities in LMICs. Interventions are needed to improve the health of people with disabilities and reduce their higher mortality rate.

UK National Institute for Health and Care Research; and UK Foreign, Commonwealth and Development Office.

To investigate the risk of cancer in people with diabetes compared to the population without diabetes and to gain insight into the timely association between diabetes and cancer at national level.

A retrospective cohort study was conducted to analyse the role of diabetes in the development of cancer, based on service utilisation and antidiabetic dispensing data of the population between 2010 and 2021. Univariate and multivariate Cox regression were used to examine how diabetes status, in relationship with age and sex are related to the time to cancer diagnosis.

Examining a population of 3 681 774 individuals, people with diabetes have a consistently higher risk for cancer diagnosis for each cancer site studied. Diabetes adds the highest risk for pancreatic cancer (HR = 2.294, 99 % CI: 2.099; 2.507) and for liver cancer (HR = 1.830, 99 % CI: 1.631; 2.054); it adds the lowest - but still significant - risk for breast cancer (HR = 1.137, 99 % CI: 1.055; 1.227) and prostate cancer (HR = 1.171, 99 % CI: 1.071; 1.280).The difference in cancer rate is driven by the younger age group (40-54 years: for patients with diabetes 5.4 % vs. controls 4.4 %; 70-89 years: for patients with diabetes 12.7 % vs. controls 12.4 %). There are no consistent results whether the presence of diabetes increases the risk of cancer diagnosis differently in males and females. The cancer incidence starts to increase before the diagnosis of diabetes and peaks in the year after. By the year after the start of the inclusion date, the incidence is 114/10,000 population in the control group, vs 195/10,000 population in the group with diabetes. Following this, the incidence drops close to the control group.

Screening activities should be revised and the guidelines on diabetes should be complemented with recommendations on cancer prevention also considering that the cancer incidence is highest around the time of the diagnosis of diabetes. For prostate cancer, our results contradict many previous studies, and further research is recommended to clarify this.

Meta-analyses have shown modest positive associations between diabetes mellitus (DM) and bladder cancer risk, but results are heterogeneous. This might be due to lack of distinction between bladder cancer subtypes, between sexes, and possibly between Type 2 and Type 1 DM (T2DM and T1DM). The relationship of T2DM (and secondarily T1DM) characteristics with risk of bladder cancer subtypes (invasive versus noninvasive) was investigated in the Netherlands Cohort Study. In 1986, 120,852 men and women aged 55-69 years provided information on DM and lifestyle data. After 20.3 years of follow-up, multivariable case-cohort analyses were based on 1020 invasive and 1088 noninvasive bladder cancer cases, and 4267 subcohort members with complete data on DM and confounders. While T2DM was not associated with noninvasive bladder cancer, it was statistically significantly associated with invasive bladder cancer risk: the multivariable-adjusted was HR = 1.57 (95% CI 1.04-2.37), comparing participants with T2DM versus without DM. The association was only significant in women, and women showed a stronger association [HR = 2.19 (95% CI 1.10-4.34)] between T2DM and invasive bladder cancer than men [HR = 1.42 (95% CI 0.88-2.30)]; interaction by sex was nonsignificant. Associations were stronger positive in those whose age at diagnosis of T2DM was 55+ years, and in those diagnosed with T2DM less than five years before baseline. T2DM participants using antidiabetic medication had higher invasive bladder cancer risk than those without DM. Exploratory age-sex-adjusted analyses suggested a positive association between T1DM and invasive bladder cancer, but this was based on few cases. These findings suggest that T2DM and possibly T1DM are positively associated with invasive bladder cancer risk.

The potential involvement of type 2 diabetes mellitus (T2DM) as a risk factor for colon cancer (CC) has been previously reported. Epigenetic changes, such as deregulation of long non-coding RNA (lncRNA) and microRNA (miR), have been linked to the advancement of CC; however, the effects of high glucose levels on their deregulation and, in turn, colon cancer remain unexplored.

Fifty patients had a dual diagnosis of CC and T2DM, and 60 patients with CC without diabetes mellitus were included in the study. qRT-PCR was used to examine the expression of lncRNA ANRIL and miR-186-5p in tissue samples. ANRIL, miR-186-5p, and their downstream target genes HIF-1α, PFK, HK, Bcl-2, and Bax were also determined in CC cell lines under various glucose conditions. Glucose uptake, lactate production and cells proliferation were estimated in CC cell lines.

A significant upregulation of ANRIL expression levels (p<0.001) and a significant downregulation of miR-186-5p expression (p<0.001) in diabetic colon cancer specimens compared to those in non-diabetic colon cancer group were observed. MiR-186-5p expression levels were inversely correlated with ANRIL expression levels, blood glucose levels and HbA1c%. Concerning in vitro model, a significant upregulation of ANRIL, downregulation of miR-186-5p, upregulation of HIF-1α, glycolytic enzymes and activation of antiapoptotic pathway was detected in higher glucose concentrations than lower one. There was a significant increase of glucose uptake, lactate accumulation and proliferation of the Caco2 and SW620 cell lines in a dose dependent manner of glucose concentrations. Moreover, a significant positive correlation between glucose uptake and ANRIL expression was shown.

A high-glucose environment can increase the tumor-promoting effect of ANRIL. ANRIL can promote glucose metabolism and colon cancer proliferation by downregulating miR-186-5p with subsequent upregulation of glycolysis enzymes expression and inhibition of apoptosis.

Breast cancer increases the risk of type 2 diabetes 1.07- to 4.27-fold, depending on patient and treatment characteristics, such as postmenopausal status, hormone therapy, and treatment with adjuvant chemotherapy. We evaluated the current evidence and considered the role of increased screening for type 2 diabetes in this at-risk population. This narrative review was conducted using Embase and MEDLINE databases. Keywords including diabetes and breast cancer were used. Articles were limited to those published in English between 2000 and 2022. It appears that the increased risk of diabetes begins at or just after breast cancer diagnosis, and remains elevated for at least 10 to 15 years, with greatest risk in the first 2 years after diagnosis. Subsets of patients with breast cancer appear to be at higher risk of developing type 2 diabetes, including those who were treated with adjuvant chemotherapy or hormone therapy. Further investigation is needed to develop specific screening recommendations for this population. If screening is performed with a glycated hemoglobin test during breast cancer treatment, then hemoglobin should be measured at the same time given the association of breast cancer therapy with anemia. Presence of breast cancer should not be a major factor when choosing among available antihyperglycemic agents. Overall, patients with breast cancer appear to be at an increased risk of developing type 2 diabetes. This increased risk suggests the need for further investigation to develop specific screening recommendations for this at-risk population.

Bladder cancer is 1 of the 10 most common cancers in the world. However, the relationship between diabetes, hypertension and bladder cancer are still controversial, limited study used machine learning models to predict the development of bladder cancer. This study aimed to explore the association between diabetes, hypertension and bladder cancer, and build predictive models of bladder cancer. A total of 1789 patients from the National Health and Nutrition Examination Survey were enrolled in this study. We examined the association between diabetes, hypertension and bladder cancer using multivariate logistic regression model, after adjusting for confounding factors. Four machine learning models, including extreme gradient boosting (XGBoost), Artificial Neural Networks, Random Forest and Support Vector Machine were compared to predict for bladder cancer. Model performance was assessed by examining the area under the subject operating characteristic curve, accuracy, recall, specificity, precision, and F1 score. The mean age of bladder cancer group was older than that of the non-bladder cancer (74.4 years vs 65.6 years, P < .001), and men were more likely to have bladder cancer. Diabetes was associated with increased risk of bladder cancer (odds ratio = 1.24, 95%confidence interval [95%CI]: 1.17-3.02). The XGBoost model was the best algorithm for predicting bladder cancer; an accuracy and kappa value was 0.978 with 95%CI:0.976 to 0.986 and 0.01 with 95%CI:0.01 to 0.52, respectively. The sensitivity was 0.90 (95%CI:0.74-0.97) and the area under the curve was 0.78. These results suggested that diabetes is associated with risk of bladder cancer, and XGBoost model was the best algorithm to predict bladder cancer.

The full text of this preprint has been withdrawn by the authors due to author disagreement with the posting of the preprint. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author.

Finding patterns among risk factors and chronic illness can suggest similar causes, provide guidance to improve healthy lifestyles, and give clues for possible treatments for outliers. Prior studies have typically isolated data challenges from single-disease datasets. However, the predictive power of multiple diseases is more helpful in establishing a healthy lifestyle than investigating one disease. Most studies typically focus on single-disease datasets; however, to ensure that health advice is generalized and contemporary, the features that predict the likelihood of many diseases can improve health advice effectiveness when considering the patient's point of view. We construct and present a novel knowledge-based qualitative method to remove redundant features from a dataset and redefine the outliers. The results of our trials upon five annual chronic disease health surveys demonstrate that our Knowledge Graph-based feature selection, when applied to many machine learning and deep learning multi-label classifiers, can improve classification performance. Our methodology is compatible with future directions, such as graph neural networks. It provides clinicians with an efficient process to select the most relevant health survey questions and responses regarding single or many human organ systems.

Cancer management has significantly evolved in recent years, focusing on a multidisciplinary team approach to provide the best possible patient care and address the various comorbidities, toxicities, and complications that may arise during the patient's treatment journey. The co-occurrence of diabetes and cancer presents a significant challenge for health care professionals worldwide. Management of these conditions requires a holistic approach to improve patients' overall health, treatment outcomes, and quality of life, preventing diabetes complications and cancer treatment side-effects. In this article, a multidisciplinary panel of experts from different Italian scientific societies provide a critical overview of the co-management of cancer and diabetes, with an increasing focus on identifying a novel specialty field, 'diabeto-oncology', and suggest new co-management models of cancer patients with diabetes to improve their care. To better support cancer patients with diabetes and ensure high levels of coordinated care between oncologists and diabetologists, 'diabeto-oncology' could represent a new specialized field that combines specific expertise, skills, and training.

The systemic immune-inflammation index (SII) is a novel and integrated marker that has not been studied with prostate cancer. We aimed to ascertain the association between SII levels and prostate cancer. We utilized data from the 1999-2010 cycles of the National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression analyses were conducted to evaluate the relationship between SII and prostate cancer. Additionally, subgroup analyses stratified by age, BMI, history of hypertension and diabetes were performed. A total of 8,020 participants were included in our analysis. After full adjustment, SII was associated with a 7% increased risk of prostate cancer (OR 1.07, 95% CI 0.99-1.15, p = 0.094). We further categorized SII values into three segments and found that individuals in the highest SII group had a 33% increased risk of prostate cancer than those in the tertile 1 group (OR 1.33; 95% CI 1.01-1.81; p = 0.044; P for trend = 0.046). In addition, a higher SII level was associated with a 137% increased risk of prostate cancer in the diabetes subgroup (OR 2.37; 95% CI 1.08-5.21; p = 0.031). The current study suggested that SII was positively associated with increased risks of prostate cancer. The SII might be an easily accessible indicator for identifying prostate cancer.

Type 2 diabetes and colorectal cancer (CRC) disproportionately burden indviduals of low socioeconomic status and African American race. Although diabetes is an emerging CRC risk factor, associations between diabetes and CRC in these populations are understudied.

To determine if diabetes is associated with CRC risk in a cohort representing understudied populations.

This cohort study uses data from the prospective Southern Community Cohort Study in the US, which recruited from 2002 to 2009 and completed 3 follow-up surveys by 2018. Of about 85 000 participants, 86% enrolled at community health centers, while 14% were enrolled via mail or telephone from the same 12 recruitment states. Participants with less than 2 years of follow-up, previous cancer diagnosis (excluding nonmelanoma skin cancer) at enrollment, missing enrollment diabetes status, diabetes diagnosis before age 30, and without diabetes at enrollment with no follow-up participation were excluded. Data were analyzed from January to September 2023.

Physician-diagnosed diabetes and age at diabetes diagnosis were self-reported via survey at enrollment and 3 follow-ups.

Diabetes diagnosis was hypothesized to be positively associated with CRC risk before analysis. Incident CRC was assessed via state cancer registry and National Death Index linkage. Hazard ratios and 95% CIs were obtained via Cox proportional hazard models, using time-varying diabetes exposure.

Among 54 597 participants, the median (IQR) enrollment age was 51 (46-58) years, 34 786 (64%) were female, 36 170 (66%) were African American, and 28 792 (53%) had income less than $15 000 per year. In total, 289 of 25 992 participants with diabetes developed CRC, vs 197 of 28 605 participants without diabetes. Diabetes was associated with increased CRC risk (hazard ratio [HR], 1.47; 95% CI, 1.21-1.79). Greater associations were observed among participants without colonoscopy screening (HR, 2.07; 95% CI, 1.16-3.67) and with smoking history (HR, 1.62; 95% CI, 1.14-2.31), potentially due to cancer screening differences. Greater associations were also observed for participants with recent diabetes diagnoses (diabetes duration <5 years compared with 5-10 years; HR, 2.55; 95% CI, 1.77-3.67), possibly due to recent screening.

In this study where the majority of participants were African American with low socioeconomic status, diabetes was associated with elevated CRC risk, suggesting that diabetes prevention and control may reduce CRC disparities. The association was attenuated for those who completed colonoscopies, highlighting how adverse effects of diabetes-related metabolic dysregulation may be disrupted by preventative screening.

Brain metastases (BM) cause relevant morbidity and mortality in cancer patients. The presence of cerebrovascular diseases can alter the tumor microenvironment, cellular proliferation and treatment resistance. However, it is largely unknown if the presence of distinct cerebrovascular risk factors may alter the prognosis of patients with BM.

Patients admitted for the radiotherapy of BM at a large tertiary cancer center were included. Patient and survival data, including cerebrovascular risk factors (diabetes mellitus (DM), smoking, arterial hypertension, peripheral arterial occlusive disease, hypercholesterolemia and smoking) were recorded.

203 patients were included. Patients with DM (n = 39) had significantly shorter overall survival (OS) (HR 1.75 (1.20-2.56), p = 0.003, log-rank). Other vascular comorbidities were not associated with differences in OS. DM remained prognostically significant in the multivariate Cox regression including established prognostic factors (HR 1.92 (1.20-3.06), p = 0.006). Furthermore, subgroup analyses revealed a prognostic role of DM in patients with non-small cell lung cancer, both in univariate (HR 1.68 (0.97-2.93), p = 0.066) and multivariate analysis (HR 2.73 (1.33-5.63), p = 0.006), and a trend in melanoma patients.

DM is associated with reduced survival in patients with BM. Further research is necessary to better understand the molecular mechanisms and therapeutic implications of this important interaction.

The co-occurrence of depression and diabetes mellitus has been linked to an increased risk of developing cancer. This study aimed to investigate whether depression further amplifies the risk of cancer among individuals with diabetes.

This population-based matched cohort study utilized Taiwan's National Health Insurance claims database. A total of 85,489 newly diagnosed diabetic patients with depressive disorders were selected, along with 427,445 comparison subjects. The matching process involved age, sex, and the calendar year of diabetes onset. The average follow-up duration for the two cohorts was 6.4 and 6.5 years, respectively. The primary outcome of interest was the occurrence of overall cancer or cancer at specific anatomical sites.

The adjusted hazard ratios for overall cancer incidence were 1.08 (95% CI, 1.05-1.11). For site-specific cancers, depression exhibited significant associations with oropharyngeal, esophageal, liver, gynecological, prostate, kidney, and hematologic malignancies among patients with diabetes. Notably, a severity-response relationship was observed, indicating that patients with recurrent episodes of major depressive disorders exhibited a higher incidence of cancer compared to those diagnosed with dysthymia or depressive disorder not otherwise specified. Furthermore, the strength of the association between depression and cancer risk was more pronounced among younger patients with diabetes as opposed to older adults. However, no significant relationship was observed between adherence to antidepressant treatment and cancer risk.

The findings of this study indicate a significant association between depression and an elevated risk of cancer among individuals diagnosed with diabetes. Future investigations should replicate our findings, explore the effects of pharmacological and non-pharmacological treatments on cancer risk, and identify the underlying mechanisms.

Diabetes mellitus (DM) is a highly prevalent chronic metabolic disorder. Although DM has been associated with immune dysfunction, the effect of DM on the efficacy of immunotherapy is unknown. This study aimed to evaluate the impact of DM on the efficacy of pembrolizumab in metastatic non-small cell lung cancer (NSCLC).

The authors reviewed the medical records of consecutive metastatic NSCLC patients treated with first-line pembrolizumab either alone or in combination with chemotherapy at a single tertiary center. For validation, a computerized data from Maccabi Healthcare Services, a 2.5-million-member state health service was used.

Of the 203 eligible patients, 51 (25%) had DM. Patients with DM had a significantly shorter median progression-free survival (PFS) (5.9 vs. 7.1 months, p = .004) and overall survival (OS) (12 vs. 21 months, p = .006). The shorter OS in diabetic patients was more pronounced when pembrolizumab was given alone (12 vs. 27 months, p = .03) than when combined with chemotherapy (14.3 vs. 19.4 months, p = .06). Multivariate analysis confirmed DM as an independent risk factor for shorter PFS (hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.11-2.50, p = .01) and OS (HR, 1.73; 95% CI, 1.09-2.76, p = .02). In a validation cohort of 452 metastatic NSCLC patients, the time on pembrolizumab treatment was shorter in diabetic patients (p = .025), with only 19.6% of patients remaining on treatment at 12 months compared to 31.7% of the nondiabetic patients.

This study suggests immunotherapy is less beneficial in diabetic NSCLC patients. More work is needed to verify our findings and explore similar effects in other cancer entities.

Coronavirus disease 2019 (COVID-19) has been associated with various liver injury cases worldwide. To date, the prevalence, mechanism, clinical manifestations, diagnosis, and outcomes of COVID-19-induced liver injury in various at-risk groups are not well defined. Liver injury may arise in the prevention and treatment of COVID-19 from direct causes such as viral infection and indirect causes such as systemic inflammation, hypoxic changes, and drugs that exacerbate any pre-existing liver disease. Studies have found that patients with underlying liver disease are at higher risk of COVID-19-induced liver injury. Certain condition of cardiopulmonary and metabolic diseases and vulnerable stages in lifespan may also involve in the development of COVID-19-induced liver injury. This review summarized studies of COVID-19-induced liver injury in different at-risk groups regarding their clinical characteristics, parameters, and correlations of the severity with these indicators and signs as well as potential treatment suggestions, to increase attention to physiological and pathological conditions and continue liver function monitoring as they can help in strengthening early supportive treatment and reducing the incidence of adverse outcomes.

Hurdles in the identification of new drugs for cancer treatment have made drug repurposing an increasingly appealing alternative. The approach involves the use of old drugs for new therapeutic purposes. It is cost-effective and facilitates rapid clinical translation. Given that cancer is also considered a metabolic disease, drugs for metabolic disorders are being actively repurposed for cancer therapeutics. In this review, we discuss the repurposing of such drugs approved for two major metabolic diseases, diabetes and cardiovascular disease (CVD), which have shown potential as anti-cancer treatment. We also highlight the current understanding of the cancer signaling pathways that these drugs target.

Messenger ribonucleic acid (mRNA) vaccines are a relatively new class of vaccines that have shown great promise in the immunotherapy of a wide variety of infectious diseases and cancer. In the past 2 years, SARS-CoV-2 mRNA vaccines have contributed tremendously against SARS-CoV2, which has prompted the arrival of the mRNA vaccine research boom, especially in the research of cancer vaccines. Compared with conventional cancer vaccines, mRNA vaccines have significant advantages, including efficient production of protective immune responses, relatively low side effects and lower cost of acquisition. In this review, we elaborated on the development of cancer vaccines and mRNA cancer vaccines, as well as the potential biological mechanisms of mRNA cancer vaccines and the latest progress in various tumour treatments, and discussed the challenges and future directions for the field.

Compelling pieces of epidemiological, clinical, and experimental research have demonstrated that Diabetes mellitus (DM) is a major risk factor associated with increased cancer incidence and mortality in many human neoplasms. In the pathophysiology context of DM, many of the main classical actors are relevant elements that can fuel the different steps of the carcinogenesis process. Hyperglycemia, hyperinsulinemia, metabolic inflammation, and dyslipidemia are among the classic contributors to this association. Furthermore, new emerging actors have received particular attention in the last few years, and compelling data support that the microbiome, the epigenetic changes, the reticulum endoplasmic stress, and the increased glycolytic influx also play important roles in promoting the development of many cancer types. The arsenal of glucose-lowering therapeutic agents used for treating diabetes is wide and diverse, and a growing body of data raised during the last two decades has tried to clarify the contribution of therapeutic agents to this association. However, this research area remains controversial, because some anti-diabetic drugs are now considered as either promotors or protecting elements. In the present review, we intend to highlight the compelling epidemiological shreds of evidence that support this association, as well as the mechanistic contributions of many of these potential pathological mechanisms, some controversial points as well as future challenges.

This study aims to investigate the influence of type 2 diabetes mellitus (T2DM) on stage IV colorectal cancer (CRC) patients performed primary surgery in terms of short-term and long-term outcomes.

Patients diagnosed with stage IV CRC and received primary CRC surgery at a single clinical center from Jan, 2013 to Jan, 2020 were included in this study. Baseline characteristics, short-term and long-term outcomes were compared between the T2DM group and the Non-T2DM group. Univariate and multivariate analysis were used to find risk factors for overall survival (OS). Propensity score matching (PSM) using a 1:1 ratio was used to minimize selective bias between the two groups. Statistical analysis was performed using SPSS (version 22.0) software.

A total of 302 eligible patients were enrolled, and there were 54 (17.9%) patients with T2DM, and 248 (82.1%) patients without T2DM. The T2DM group had more older patients (P < 0.01), higher body mass index (BMI) (P < 0.01), and a higher proportion of hypertension (P < 0.01) than the Non-T2DM group. After PSM, there were 48 patients in each group. There were no significant differences in short-term outcomes or OS between the two groups, either before or after PSM (P > 0.05). In multivariate analysis, older age (P < 0.01, HR = 1.032, 95% CI = 1.014-1.051) and larger tumor size (P < 0.01, HR = 1.760, 95% CI = 1.179-2.626) were independent factors for OS.

Although T2DM did not influence short-term outcomes or OS in stage IV CRC patients after primary surgery, age and tumor size might have predictive value for OS.

Krishna PrasadBackground  Development of treatment-induced hyperglycemia/diabetes is a considerable problem in women undergoing chemotherapy for breast cancer. In this study, baseline levels of blood cell-associated inflammatory indices (BCAII) were analyzed to understand their role in the development of treatment-induced hyperglycemia and diabetogenesis. Materials and Methods  This was a retrospective study, and information on women who were normoglycemic and nondiabetic and of women who were diabetic at the beginning of the treatment were collected from files. Demographic, pathology-related details, and complete blood profile were noted. Neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammatory index (SII) which indicate BCAII were calculated. Demographic details were subjected to frequency and percentage, while blood parameters were subjected to one-way analysis of variance followed by post hoc Bonferroni's multiple comparison tests. A p -value of <0.05 was considered significant. Results  The results indicated that a significant difference in levels of total count ( p  < 0.035), neutrophil, lymphocyte, and platelets ( p  < 0.001) were observed. Regarding BCAII, when compared with women who were normoglycemic at the end of treatment, NLR, dNLR, PLR, and SII were significantly high for people who were known diabetics at the beginning of treatment ( p  < 0.001). The dNLR ( p  = 0.0008), PLR ( p  < 0.001), and SII ( p  < 0.001) were significant for people who developed secondary hyperglycemia/diabetes, while only dNLR was significant for people who progressed from normal to prediabetes stage ( p  = 0.049) Conclusion  To the best of the authors' knowledge, this is the first study that indicates difference in baseline BCAII and development of treatment-induced hyperglycemia/diabetes indicating that underlying low levels of inflammation may contribute to diabetogenesis in women affected with breast cancer.

Urologic cancers (UC) account for 13.1% of all new cancer cases and 7.9% of all cancer-related deaths. A growing body of evidence has indicated a potential causal link between obesity and UC. The aim of the present review is to appraise in a critical and integrative manner evidence from meta-analyses and mechanistic studies on the role of obesity in four prevalent UC (kidney-KC, prostate-PC, urinary bladder-UBC, and testicular cancer-TC). Special emphasis is given on Mendelian Randomization Studies (MRS) corroborating a genetic causal association between obesity and UC, as well as on the role of classical and novel adipocytokines. Furthermore, the molecular pathways that link obesity to the development and progression of these cancers are reviewed. Available evidence indicates that obesity confers increased risk for KC, UBC, and advanced PC (20-82%, 10-19%, and 6-14%, respectively), whereas for TC adult height (5-cm increase) may increase the risk by 13%. Obese females tend to be more susceptible to UBC and KC than obese males. MRS have shown that a higher genetic-predicted BMI may be causally linked to KC and UBC but not PC and TC. Biological mechanisms that are involved in the association between excess body weight and UC include the Insulin-like Growth Factor axis, altered availability of sex hormones, chronic inflammation and oxidative stress, abnormal secretion of adipocytokines, ectopic fat deposition, dysbiosis of the gastrointestinal and urinary tract microbiomes and circadian rhythm dysregulation. Anti-hyperglycemic and non-steroidal anti-inflammatory drugs, statins, and adipokine receptor agonists/antagonists show potential as adjuvant cancer therapies. Identifying obesity as a modifiable risk factor for UC may have significant public health implications, allowing clinicians to tailor individualized prevention strategies for patients with excess body weight.