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Latest experiences fromcoffee intervention trials          Jaakko Tuomilehto      Department of Public Health     Universi...
Epidemiological dataPossible mechanism MEDIACENTER                  THE
Coffee consumption and      the development of Type 2 diabetes           among the Finns who havethe highest coffee consum...
Incidence of type 2 diabetes by volume        of coffee consumption                   among menCoffee            Age and e...
Incidence of type 2 diabetes by volume        of coffee consumption            among womenCoffee            Age and exam  ...
Incidence of type 2 diabetes by volume of    coffee consumption among subjects                by age group      1.0      0...
Incidence of type 2 diabetes by volume of           coffee consumption   among obese and non-obese subjects      1.0      ...
Coffee consumption is associated with reduced diabetes risk       Summary estimate derived from 25 epidemiological studies...
Coffee consumption is associated with reduced diabetes risk        Is it a cause-effect relationship?   ? YES: Drinking co...
Coffee consumption tested in intervention trials   Single dose: effect on glucose metaboIism?    No beneficial effects in ...
Possible mechanismsChlorogenic acid is found in green coffee:- An inhibitor of glucose-6- phosphatasethat catalyzes the te...
Coffee consumption tested in intervention trials4-8 weeks coffee: effect on glucose metaboIism?                           ...
Coffee consumption tested in intervention trials4-8 weeks coffee: effect on glucose metaboIism? Kempf, Herder, Erlund, Kol...
Coffee consumption tested in intervention trials   4-8 weeks of coffee: adiponectin increased! Trial                      ...
PROTECTIVE MECHANISMS                       Caffeine                                          Magnesium Thermogenesis ↑   ...
Nfr2 =nuclear factor (erythroi
Integr Comp Biol. 2010 Nov;50(5):829-43.Nrf2, a guardian of healthspan and gatekeeper of species longevity.Lewis KN, Mele ...
Integr Comp Biol. 2010 Nov;50(5):829-43.Nrf2, a guardian of healthspan and gatekeeper of species longevity.Lewis KN, Mele ...
IIS: insulin and IGF signalling pathwaysThe role of the antioxidant and longevity-promoting Nrf2pathway in metabolic regul...
WCPD 2012:Jaakko Tuomilehto
WCPD 2012:Jaakko Tuomilehto
WCPD 2012:Jaakko Tuomilehto
WCPD 2012:Jaakko Tuomilehto
WCPD 2012:Jaakko Tuomilehto
WCPD 2012:Jaakko Tuomilehto
WCPD 2012:Jaakko Tuomilehto
WCPD 2012:Jaakko Tuomilehto
WCPD 2012:Jaakko Tuomilehto
WCPD 2012:Jaakko Tuomilehto
WCPD 2012:Jaakko Tuomilehto
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WCPD 2012:Jaakko Tuomilehto

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Transcript of "WCPD 2012:Jaakko Tuomilehto"

  1. 1. Latest experiences fromcoffee intervention trials Jaakko Tuomilehto Department of Public Health University of Helsinki, Finland Hubert Kolb Institute of Molecular Medicine University of Düsseldorf, Germany
  2. 2. Epidemiological dataPossible mechanism MEDIACENTER THE
  3. 3. Coffee consumption and the development of Type 2 diabetes among the Finns who havethe highest coffee consumption rate in the world - 11.3 kg/year per capita THE MEDIACENTER
  4. 4. Incidence of type 2 diabetes by volume of coffee consumption among menCoffee Age and exam Multivariateconsumption year adjustment adjustment<=2 cups 1.00 1.003-4 cups 0.83 (0.54-1.25) 0.74 (0.48-1.14)5-6 cups 0.88 (0.60-1.30) 0.71 (0.47-1.10)7-9 cups 0.86 (0.53-1.39) 0.67 (0.40-1.14)>=10 cups 0.69 (0.40-1.19) 0.45 (0.25-0.81)P for trend 0.735 0.121Adjusted for age, exam year, BMI, SBP, smoking,education, physical activity, alcohol and teaconsumption
  5. 5. Incidence of type 2 diabetes by volume of coffee consumption among womenCoffee Age and exam Multivariateconsumption year adjustment adjustment<=2 cups 1.00 1.003-4 cups 0.72 (0.49-1.04) 0.73 (0.50-1.08)5-6 cups 0.49 (0.32-0.73) 0.40 (0.26-0.63)7-9 cups 0.47 (0.25-0.87) 0.42 (0.22-0.79)>=10 cups 0.26 (0.08-0.85) 0.21 (0.06-0.70)P for trend 0.002 <0.001Adjusted for age, exam year, BMI, SBP, smoking,education, physical activity, alcohol and teaconsumption
  6. 6. Incidence of type 2 diabetes by volume of coffee consumption among subjects by age group 1.0 0.8 0.6 0.4 0.2 Age >50 0.0 Age <50Coffee (cups) <=2 3-4 5-6 7-9 >=10Adjusted for sex, exam year, BMI, SBP, smoking,education, physical activity, alcohol and tea consumption.
  7. 7. Incidence of type 2 diabetes by volume of coffee consumption among obese and non-obese subjects 1.0 0.8 0.6 0.4 0.2 BMI >=30 0.0 BMI <30Coffee (cups) <=2 3-4 5-6 7-9 >=10Adjusted for age, sex, exam year, SBP, education,smoking, physical activity, alcohol and tea consumption.
  8. 8. Coffee consumption is associated with reduced diabetes risk Summary estimate derived from 25 epidemiological studies: 1-2 cups per day: rel. risk approx. 0.9 3-4 cups per day: rel. risk approx. 0.8 ≥ 5 cups per day: rel. risk approx. 0.6van Dam 2002 Lancet 360:1477, Saremi 2003 Diabetes Care 26:2211, Reunanen 2003 Lancet 361:702,Rosengren 2004 J Intern Med 255:89, Salazar-Martinez 2004 Ann Intern Med 140:1, Tuomilehto 2004JAMA 291:1213, Carlsson 2004 Int J Epidemiol 33:616, van Dam 2004 Diabetologia 47:2152, Greenberg2005 AJCN 84:682, van Dam 2006 Diabetes Care 29:398, Iso 2006 Ann Intern Med 144:554, Pereira 2006Arch Intern Med 166:1311, Smith 2006 Diabetes Care 29:2385, Paynter 2006 Am J Epidemiol 164:1075,Schulze 2007 Diabetes Care 30:510, Hamer 2008 Brit J Nutr 100:1046, Odegaard 2008 AJCN 88:979, vanDieren 2009 Diabetologia 62:2561, Sartorelli 2010 AJCN 91:1002, Boggs 2010 AJCN 92:960, Oba 2010Br J Nutr 103:453, Goto 2011 Diabetes 60:269, Zhang 2011 Nutr Metab Cardiovasc Dis 21:418, Lin 2011Eur J Clin Invest 41:659, Hjellvik 2011 22:418.
  9. 9. Coffee consumption is associated with reduced diabetes risk Is it a cause-effect relationship? ? YES: Drinking coffee protects from diabetes ? NO: Coffee-associated lifestyle is protective, people drinking coffee are “different”
  10. 10. Coffee consumption tested in intervention trials Single dose: effect on glucose metaboIism? No beneficial effects in OGTT: Modestly increased insulin resistance (caffeine!)Graham 2001 Can J Physiol Pharmacol 79:559, Keijzers 2002 Diabetes Care 25:364, Johnston 2003 Am J Clin Nutr 78:728, Robinson 2004 J Nutr 134:2528, Petrie 2004 Am J Clin Nutr 80:22, Battram2006 J Nutr 136:1276, Moisey 2008 Am J Clin Nutr 87:1254, van Dijk 2009 Diabetes Care 32:1023,Moisey 2010 Br J Nutr 103:833, Greenberg 2010 Diabetes Care 33:278, Beaudoin 2011 Crit RevFood
  11. 11. Possible mechanismsChlorogenic acid is found in green coffee:- An inhibitor of glucose-6- phosphatasethat catalyzes the terminal reaction ofglycogenolysis and gluconeogenesis, thetwo glucose-producing pathways in humanliver.- It also inhibits glucose transporters (Na+-dependent glucose transporter) at theintestinal stage and may also inhibit theaction of the α-Glucosidase enzyme.
  12. 12. Coffee consumption tested in intervention trials4-8 weeks coffee: effect on glucose metaboIism? No ! Kempf, Herder, Erlund, Kolb, Martin, Carstensen, Koenig, Sundvall, Bidel, Kuha, Tuomilehto 2010 Am J Clin Nutr 91: 950-957 Wedick, Brennan, Sun, Hu, Mantzoros, van Dam 2011 Nutrition Journal 10: 93
  13. 13. Coffee consumption tested in intervention trials4-8 weeks coffee: effect on glucose metaboIism? Kempf, Herder, Erlund, Kolb, Martin, Carstensen, Koenig, Sundvall, Bidel, Kuha, Tuomilehto 2010 Am J Clin Nutr 91: 950-957
  14. 14. Coffee consumption tested in intervention trials 4-8 weeks of coffee: adiponectin increased! Trial Adiponectin (µg/ml serum) at baseline after 4-8 w coffeeKempf 2010 (n=47) 7.96 8.42 (p<0.05)Wedick 2011 (n=45) 7.80 8.24 (p<0.05) Epidemiological studies also find higher adiponectin levels with coffee drinking (Adiponectin is a diabetes-protective factor) Wiiliams 2008 Diabetes Care 31:504, Imatoh 2011 Eur J Nutr 50:279 (Li 2009 JAMA 302:179)
  15. 15. PROTECTIVE MECHANISMS Caffeine Magnesium Thermogenesis ↑ Glucose metabolism Satiety ↑Insulin secretion ↑ Glucose absorption ↓ Iron absorption ↓ Chlorogenic acid N-Methylpyridinium (et al.) Nrf2 ? Fat: adiponectin ↑ Gut: GLP-1 ↑ Hypothalamus: anorexic peptides ↑ General: anti-oxidant defence ↑ Body weight ↓ Insulin sensitivity ↑ Diabetes risk↓ Westererp-Platenga 2005 Obes Res 13:1195, Kovacs 2004 Br J Nutr:431, Pimentel 2009 Diabetol Metab Syndr 1:6, Boettler 2011 Mol Nutr Food Res 55:798, Bakuradze 2011 Mol Nutr Food Res 55:793, Paur 2010 Free Radic Biol Med 48:1218
  16. 16. Nfr2 =nuclear factor (erythroi
  17. 17. Integr Comp Biol. 2010 Nov;50(5):829-43.Nrf2, a guardian of healthspan and gatekeeper of species longevity.Lewis KN, Mele J, Hayes JD, Buffenstein R.AbstractAlthough aging is a ubiquitous process that prevails in all organisms, the mechanisms governingboth the rate of decline in functionality and the age of onset remain elusive. A profoundconstitutively upregulated cytoprotective response is commonly observed in naturally long-livedspecies and experimental models of extensions to lifespan (e.g., genetically-altered and/orexperimentally manipulated organisms), as indicated by enhanced resistance to stress andupregulated downstream components of the cytoprotective nuclear factor erythroid 2-related factor2 (Nrf2)-signaling pathway. The transcription factor Nrf2 is constitutively expressed in alltissues, although levels may vary among organs, with the key detoxification organs(kidney and liver) exhibiting highest levels. Nrf2 may be further induced by cellularstressors including endogenous reactive-oxygen species or exogenous electrophiles.The Nrf2-signaling pathway mediates multiple avenues of cytoprotection by activatingthe transcription of more than 200 genes that are crucial in the metabolism of drugs andtoxins, protection against oxidative stress and inflammation, as well as playing anintegral role in stability of proteins and in the removal of damaged proteins viaproteasomal degradation or autophagy. Nrf2 interacts with other important cell regulatorssuch as tumor suppressor protein 53 (p53) and nuclear factor-kappa beta (NF-κB) andthrough their combined interactions is the guardian of healthspan, protecting againstmany age-related diseases including cancer and neurodegeneration. We hypothesizethat this signaling pathway plays a critical role in the determination of species longevityand that this pathway may indeed be the master regulator of the aging process.
  18. 18. Integr Comp Biol. 2010 Nov;50(5):829-43.Nrf2, a guardian of healthspan and gatekeeper of species longevity.Lewis KN, Mele J, Hayes JD, Buffenstein R.AbstractNrf2 interacts with other important cell regulatorsAlthough aging is a ubiquitous process that prevails in all organisms, the mechanisms governingboth the rate of decline in functionality and the age of onset remain elusive. A profoundsuch as tumor suppressor protein 53 (p53) andconstitutively upregulated cytoprotective response is commonly observed in naturally long-livedspecies and experimental models of extensions to lifespan (e.g., genetically-altered and/ornuclear factor-kappa beta (NF-κB) and through theirexperimentally manipulated organisms), as indicated by enhanced resistance to stress andupregulated downstream components of the cytoprotective nuclear factor erythroid 2-related factorcombined interactions is the guardian of healthspan,2 (Nrf2)-signaling pathway. The transcription factor Nrf2 is constitutively expressed in alltissues, although levels may vary among organs, with the keydiseasesprotecting against many age-related detoxification organs(kidney and liver) exhibiting highest levels. Nrf2 may be further induced by cellularincluding cancer and neurodegeneration. electrophiles.stressors including endogenous reactive-oxygen species or exogenousThe Nrf2-signaling pathway mediates multiple avenues of cytoprotection by activatingthe transcription of more than 200 genes that are crucial in the metabolism of drugs andWe hypothesize that this and inflammation, as well as playing an atoxins, protection against oxidative stress signaling pathway playsintegral role role inof proteins and in the removal of damaged proteins viacritical in stability the determination of species longevityproteasomal degradation or autophagy. Nrf2 interacts with other important cell regulatorsand that this pathway may indeedfactor-kappa master andsuch as tumor suppressor protein 53 (p53) and nuclear be the beta (NF-κB)through their combined interactions is the guardian of healthspan, protecting againstregulator of the aging process.many age-related diseases including cancer and neurodegeneration. We hypothesizethat this signaling pathway plays a critical role in the determination of species longevityand that this pathway may indeed be the master regulator of the aging process.
  19. 19. IIS: insulin and IGF signalling pathwaysThe role of the antioxidant and longevity-promoting Nrf2pathway in metabolic regulationGerasimos P. Sykiotis2, Ioannis G. Habeos2, Andrew V. Samuelson1, and Dirk Bohmann1
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