DM and its reltion to cancer proff.pptx
- 1. الرحيم الرحمن هللا بسم الكلمة هذة فضل كما إال األكبر هللا اسم وبين بينه وما هللا أسماء من اسم هو سواد بين القرب من وبياضهما العينين ( صحيح حديث ) السالم علية عيسى قال : وهللا مملكته والميم سناؤه والسين هللا بهاء الباء واآلخرة الدنيا رحمن والرحمن اآللهة إله اآلخرة رحيم والرحيم « كثير ابن تفسير
- 2. Relationship Between Diabetes Mellitus and Cancers & Underlying Mechanisms. Abdelmoneim Ahmed Ass.prof of internal medicine banha university
- 3. Lecture outlines Relation between DM &cancer MECHANISMS UNDERLYING THE ASSOCIATION BETWEEN DIABETES MELLITUS AND CANCERS DM therapy &cancer Cancer chemotherapy &DM Summary
- 4. Introduction Diabetes and cancer are common diseases with tremendous impact on health worldwide. People with diabetes are at significantly higher risk for many forms of cancer and the link between diabetes and cancer has been proposed for more than 100 years The risk of cancers appears to be increased in both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) Cancer therapy may induce DM
- 5. INCIDENCE AND MORTALITY OF CANCERS IN PATIENTS WITH DIABETES MELLITUS T1DM A five-country study of cancers in patients with T1DM has reported that T1DM was correlated with the risk of several common cancers. Cancer incidence significantly increased for both sexes with T1DM - liver, pancreas, kidney, - esophagus, stomach, lung, thyroid, - squamous cell carcinoma, and leukaemia
- 7. INCIDENCE AND MORTALITY OF CANCERS IN PATIENTS WITH DIABETES MELLITUS T2DM A comprehensive meta-analysis :the presence of T2DM is associated with approximately 10% increase of the risk to develop cancer . A substantial evidence of associations between T2DM and risks of cancer in hepatocellular, biliary tract, gallbladder, pancreas, gastrointestinal, kidney, bladder, lung, thyroid, breast, ovarian, endometrial, oral, leukemia, glioma, and melanoma
- 8. Among them, the highest risks have been demonstrated for colorectal cancer , hepatocellular cancer or pancreatic cancer. On the contrary, some cancers showed decreased risk in diabetic patients including brain, buccal cavity, esophageal, lung, breast, urinary bladder, and laryngeal cancer Reduced risk of prostate cancer in patients with T2DM Indeed, (lower levels of testosterone & HNF1B gene variants protect them from prostate cancer)
- 9. MECHANISMS UNDERLYING THE ASSOCIATION BETWEEN DIABETES MELLITUS AND CANCERS
- 10. MECHANISMS UNDERLYING THE ASSOCIATION BETWEEN DIABETES MELLITUS AND CANCERS
- 11. Obesity A large cohort study which included 900,000 individuals reported that severe obesity was associated with a significantly increased mortality from cancers of the liver, pancreas, colon and rectum, kidney, non-Hodjkins lymphoma, esophagus, and multiple myeloma.
- 12. Obesity The greatest influences were observed in cancers of liver, colon and rectum, and pancreas . Obesity associated with increased risk of cancers probably by mechanisms that involve cellular proliferation, inflammation, and hormonal balance .
- 13. Inflammation and Oxidative Stress&hyperglycemia Inflammation is a key element in the link between diabetes mellitus and cancer T2DM is associated with insulin secretory defects related to inflammation advanced glycation end products (AGEs). Receptor AGEs, (RAGE)
- 14. Hyperinsulinemia Increased risk for several cancers, including cancers of the endometrium, ovarian, breast, colon, pancreas, and kidney . The hepatic IGF-1 production increased due to the upregulation of the growth hormone receptor (GHR) and augment of GHR signaling Insulin, IGF-1 and IGF-2 could activate the PI3K/Akt/ mammalian target of rapamycin signaling pathway,.
- 15. Hyperinsulinemia
- 16. DM therapy &cancer Drugs Effect on cancer Mechanism Insulin Increase incidence (CRC,BC,HCC) increased levels of IGF-1 Insulin analogue (long acting ) dose-dependent increased risk of cancer increased levels of IGF-1 large randomized controlled trial study cohort study , and systematic review concluded that insulin (analog) treatment does not impact the risk of cancer Metoformin Protective inhibits the mTOR in (AMP)- activated protein kinase (AMPK) (DPPIV) inhibitor and glucagon- like peptide-1(GLP-1) Increase incidence of pancreatic cancer replication and apoptosis of beta-cell, pancreatic ductal metaplasia, and a four-fold increase in duct cell proliferation GLP1 Thyroid c cancer meta-analysis suggested that there is no exact evidence that the risk of pancreatic cancer in patients on incretin-based therapies .
- 17. DM therapy & cancer Drugs Effect on cancer Mechanism (SGLT 2) Inhibitors useful for cancer therapy inhibit cancer growth by inhibiting the complex I of the mitochondrial respiratory chain SU Controversy Thiazolidinediones (TZDs) bladder cancer with pioglitazone (2005, false impression) Protective : lower risk of colorectal and breast cancer anti-proliferative effects, TZDs can also enhance cytotoxic effects of some anticancer therapies as cisplatin and oxaliplatin by increasing the expression of apoptosis-inducing factor (AIF) and suppressing survivin
- 18. CANCER TREATMENT AND DIABETES Chemotherapy Chemotherapy such as Tegafur-uracil (UFT) paclitaxel and interferon alpha developed fulminant T1DM or autoimmune-mediated T1DM Glucocorticoid Glucocorticoids are a commonly used treatment for cancers of blood system & used to treat cancer pain, chemotherapy-induced nausea and vomiting, and cancer-related cachexia. Steroid-induced diabetes mellitus is a complication of glucocorticoid use for over 50 years
- 19. Targeted Cancer Therapies Targeted cancer therapies attempt to treat cancer by targeting the changed cellular pathways that drive unregulated growth. This treatment can somehow impair insulin sensitivity Mammalian target of rapamycin (mTOR) inhibitors has been used for multiple types of cancer (RCC, BC). mTOR inhibitors is associated with a high incidence of hyperglycemia and new-onset diabetes, ranging from 13% to 50%
- 20. Cancer Immunotherapy Including immune checkpoint inhibitors, adoptive cell therapy, oncolytic viruses, and cancer vaccines, manipulate the immune system to recognize and attack cancer cells. lead to toxicity profiles for endocrine system. For instance, insulin-dependent diabetes has been reported in patients treated with antiprogrammed cell death protein 1 (PD-1) about 0.4%-0.9% in this population
- 21. Summary There is a link between DM &cancer Many mechanisms underlie this link( obesity , hyperinsulinemia, oxidative stress) Metformin &TDZ protective from cancer Insulin &insulin analogue & Incretin increase incidence of cancer Cancer therapy (steroids , M-TOR inhibitors , checkpoint inhibitors ) induce DM
- 22. العالمين رب هلل الحمد Thank you