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PROF. DR. I. DASKALOVAMilitary Medical Academy, Sofia          BULGARIA
Link between diabetes and cancer have beenan interesting question for clinical communitysince last century. But the result...
   Aging   Sex   Obesity   Physical activity   Diet   Alcohol   Smoking
   Age – 78% of all newly diagnosed cancer > – 55    years and older   Diabetes Type 2- increasingly common with    age...
   Overweigh - (BMI >25 and <30kg/m2)   Obesity – BMI > 30 kg/m2   Weight change
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   Breast (postmenopausal women)   Colon/rectum   Endometrial   Pancreas   Adenocarcinoma of the esophagus   Kidney...
   Increase in adipose tissue rather than lean    mass   Total body fat a better measure of the risk    than BMI   Obes...
   Low in red and processed meats   Higher in vegetables, fruits   Whole grains cereals   Monounsaturated fatty acid ...
   Lowers disease risk   Decreases diabetes incidence   DCCT       Intensive lifestyle intervention of diet (5-7%     ...
   Obese women who underwent bariatric    surgery were at lower risk of cancer    (relative risks ranging from 0.58 to 0....
   Lower risk of colon   Postmenopausal breast   Endometrial cancer   Prevent other cancer including   Lung   Aggres...
   Diabetes may influence the neoplastic process    by several mechanisms:       Hyperinsulinemia (either endogenous due...
   Most cancer cells express insulin and IGF-I    receptors   The A receptor isoform can stimulate insulin-    mediated ...
   Reduction in the hepatic synthesis   Sex hormone binding globulin, leading to     increases in bioavailable estrogen...
   Higher risk of postmenopausal women     Breast     Endometrial     Other cancers
   Diabetes   Diabetes treatment   Cancer   Insulin receptor activation may be a more    important variable than hyper...
   Direct effects of insulin; type 2 DM   Adipose tissue - active endocrine organ    producing:     Free fatty acids   ...
   Each of these factors might play an etiologic    role in regulating malignant transformation    or cancer progression...
35                                                                                                               *        ...
Insulin       Vascularresistans      inflamation            C-RPType 2 DM          CVD
   Metformin   Thiazolidinediones   Insulin secretagogues   Incretin - based therapies   Insulin and insulin analogs
   Furthermore, the cancer risk may be    modified by treatment choices. In this    respect, metformin may be protective,...
   Endogenous or exogenous    hyperinsulinemia /insulins or    sulfanilureas/ causing inappropriate    prolonged stimulat...
   The potential mechanisms to explain this    higher risk are:   mitogenic effect of insulin /endogenous or    exogenou...
   The results from the latest epidemiological    studies are amazing. Several studies have    shown metformin to be asso...
   The results from the well controlled and    randomized studies with intensive    glycaemic control, have showed that t...
   A case-controlled study in Scotland with    newly diagnosed diabetes mellitus, the    therapy with metformin reduces c...
   A study of human prostate cancer cells    demonstrated a strong anti-proliferative    effect of metformin. This effect...
   Diabetes (primarily type 2) is associated    with increased risk for some cancers:       Liver       Pancreas      ...
   Risk factors between the two diseases     Aging     Obesity     Diet     Physical inactivity     Hyperinsulinemia...
   Healthy diets   Physical activity   Weight management   Appropriate cancer screenings for patients    with diabetes...
Ivon daskalova.diabetes and cancer
Ivon daskalova.diabetes and cancer
Ivon daskalova.diabetes and cancer
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Ivon daskalova.diabetes and cancer

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Transcript of "Ivon daskalova.diabetes and cancer"

  1. 1. PROF. DR. I. DASKALOVAMilitary Medical Academy, Sofia BULGARIA
  2. 2. Link between diabetes and cancer have beenan interesting question for clinical communitysince last century. But the results were notsimilar. The observations and investigationscontinue. Several meta-analyses indicate thestrongest association between diabetes mellitusand increased cancer risk(metaanalyses of Vinery et all.)
  3. 3.  Aging Sex Obesity Physical activity Diet Alcohol Smoking
  4. 4.  Age – 78% of all newly diagnosed cancer > – 55 years and older Diabetes Type 2- increasingly common with age Sex – sexspecific (cervix,uterine,testicular,prostate), breast Men have slightly higher age–adjusted risk of diabetes than women Race/ethnicity
  5. 5.  Overweigh - (BMI >25 and <30kg/m2) Obesity – BMI > 30 kg/m2 Weight change
  6. 6. 6
  7. 7.  Breast (postmenopausal women) Colon/rectum Endometrial Pancreas Adenocarcinoma of the esophagus Kidney Gallbladder liver
  8. 8.  Increase in adipose tissue rather than lean mass Total body fat a better measure of the risk than BMI Obesity Insulin resistance Type 2 diabetes Waist circumference Waist-to-hip ratio Measures of visceral adiposity
  9. 9.  Low in red and processed meats Higher in vegetables, fruits Whole grains cereals Monounsaturated fatty acid Dietary fiber Low-carbohydrate diets
  10. 10.  Lowers disease risk Decreases diabetes incidence DCCT  Intensive lifestyle intervention of diet (5-7% weight loss)  Physical activity  58% reduction in diabetes incidence  Limit risk of gestational diabetes
  11. 11.  Obese women who underwent bariatric surgery were at lower risk of cancer (relative risks ranging from 0.58 to 0.62) compared with untreated obese women. Protective effect on breast and endometrial cancer Very effective treatment for Type 2 DM
  12. 12.  Lower risk of colon Postmenopausal breast Endometrial cancer Prevent other cancer including Lung Aggressive prostate cancer
  13. 13.  Diabetes may influence the neoplastic process by several mechanisms:  Hyperinsulinemia (either endogenous due to insulin resistance or exogenous due to administered insulin or secretogogues)  Hyperglycemia  Chronic inflammation
  14. 14.  Most cancer cells express insulin and IGF-I receptors The A receptor isoform can stimulate insulin- mediated mitogenesis, even in cells deficient in IGF-I receptors The insulin receptor is also capable of stimulating cancer cell proliferation and metastasis.
  15. 15.  Reduction in the hepatic synthesis Sex hormone binding globulin, leading to  increases in bioavailable estrogen in men and women  Increased levels of bioavailable testosterone in women but not in men  Androgen synthesis in the ovaries and adrenals is increased
  16. 16.  Higher risk of postmenopausal women  Breast  Endometrial  Other cancers
  17. 17.  Diabetes Diabetes treatment Cancer Insulin receptor activation may be a more important variable than hyperglycemia in determining tumor growth
  18. 18.  Direct effects of insulin; type 2 DM Adipose tissue - active endocrine organ producing:  Free fatty acids  Interleukin - 6 (IL – 6)  Monocyte chemoatractant protein  Plasminogen activator inhibitor-1 (PAI-1)  Adiponectin  Leptin  Tumor necrosis factor – α (TNF–α)
  19. 19.  Each of these factors might play an etiologic role in regulating malignant transformation or cancer progression Plasminogen system→expression of PAI- 1→poor outcome in breast cancer IL-6→enhance cancer cell proliferation, survival and invasion Suppressing host anti-tumor immunity
  20. 20. 35 * 30 * PAI-1 антиген (ng/ml) 25 20 * 15 10 5 0 Normal GTT IGTT Type 2 DMn = 1551*P < 0.001 Festa A, et al. Insulin Resistance Atherosclerosis Study Arterioscler Thromb Vasc Biol 1999;
  21. 21. Insulin Vascularresistans inflamation C-RPType 2 DM CVD
  22. 22.  Metformin Thiazolidinediones Insulin secretagogues Incretin - based therapies Insulin and insulin analogs
  23. 23.  Furthermore, the cancer risk may be modified by treatment choices. In this respect, metformin may be protective, whereas insulin, insulin analogues and some oral hypoglycaemic agents can function as growth factors and therefore have theoretical potential to promote tumour proliferation.
  24. 24.  Endogenous or exogenous hyperinsulinemia /insulins or sulfanilureas/ causing inappropriate prolonged stimulation of the insulin receptor, or excess stimulation of the IGF-1 receptor, are the most likely to show mitogenic properties in laboratory studies. Some recent epidemiological studies appear to be consistent with these experimental findings, suggesting that there could be different relative risks for cancer associated with different therapy, although these studies have attracted some methodological criticism.
  25. 25.  The potential mechanisms to explain this higher risk are: mitogenic effect of insulin /endogenous or exogenous hyperinsulinemia/ metabolic disorders like oxidative stress, hyperlypidemia, overweight, hyperglycemia
  26. 26.  The results from the latest epidemiological studies are amazing. Several studies have shown metformin to be associated with a lower risk of cancer than insulin or sulfonylureas. Bowker and colleagues examined the relationship between diabetes treatment and mortality in a health database from Saskatchewan, and found that cancer mortality was almost doubled among insulin users (HR 1.9, 95% CI 1.5–2.4, p<0.0001) relative to metformin users, and that sulfonylureas were also associated with increased mortality (HR 1.3, 95% CI 1.1–1.6, p=0.012).
  27. 27.  The results from the well controlled and randomized studies with intensive glycaemic control, have showed that the improvement of the glycaemic control do not decrease the cancer risk. UKPDS in the group with metformin have shown 29 % decreased cancer mortality in overweight patients with intensive glycaemic control with metformin v.s group that have been controlled with diet. This results are similar to results from another, that investigated the relation metformin and cancer and shows that the cancer risk is decreased of therapy with metformin.
  28. 28.  A case-controlled study in Scotland with newly diagnosed diabetes mellitus, the therapy with metformin reduces cancer risk at all. Observation data shows, that antitumor effect of metformin seems to be mediated via post-receptors changes and its ability to increase the AMP-activated protein kinase (AMPK) signalling pathway.
  29. 29.  A study of human prostate cancer cells demonstrated a strong anti-proliferative effect of metformin. This effect was unaffected by inhibition of the AMPK pathway, but was associated with cell cycle arrest in G0/G1 phase, together with a major reduction in cyclin D1 levels. Laboratory findings show that metformin inhibits cells proliferation and cells arrest in carcinomas calls lines. It may selectively kills carcinomas steams cells and increases the cytostatic treatment.
  30. 30.  Diabetes (primarily type 2) is associated with increased risk for some cancers:  Liver  Pancreas  Endometrium  Colon and rectum  Breast  Bladder  Reduced risk of prostate cancer
  31. 31.  Risk factors between the two diseases  Aging  Obesity  Diet  Physical inactivity  Hyperinsulinemia  Hyperglycemia  Inflammation
  32. 32.  Healthy diets Physical activity Weight management Appropriate cancer screenings for patients with diabetes Pharmacotherapy effects on cancer risk factors such as body weight, hyperinsulinemia, hyperglicemia
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