Metabolic Consequences of Polycystic Ovary Syndrome

1,195 views

Published on

Presentation at the 2013 meeting of the Philippine Society for Reproductive Endocrin

Published in: Health & Medicine
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
1,195
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
58
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide

Metabolic Consequences of Polycystic Ovary Syndrome

  1. 1. Metabolic Consequences of PCOSIris Thiele Isip Tan MD, MSc, FPCP, FPSEMChief, UP Medical Informatics UnitAssociate Professor, UP College of Medicine“Eggs” by John Loohttp://www.flickr.com/photos/johnloo/5483256997/27 May 2013Monday, May 27, 13
  2. 2. A Baranova et al. Aliment Pharmacol Ther 2011; 33:801-804Monday, May 27, 13
  3. 3. In 25 minutes?!Me and my boys 2 days ago ...Monday, May 27, 13
  4. 4. A Baranova et al. Aliment Pharmacol Ther 2011; 33:801-804Monday, May 27, 13
  5. 5. A Baranova et al. Aliment Pharmacol Ther 2011; 33:801-804Monday, May 27, 13
  6. 6. A Baranova et al. Aliment Pharmacol Ther 2011; 33:801-804Insulin resistance,obesity and diabetesImplicationsfor practiceMetabolicSyn!ome& PCOSMonday, May 27, 13
  7. 7. Diamanti-Kandarakis E & Dunaif A.Endocrine Reviews 2012; 33:981-1030Monday, May 27, 13
  8. 8. Insulinresistancedecreased ability ofinsulin to mediatemetabolic actionsrequirement forincreased amounts ofinsulin to achieve a givenmetabolic action“Push” by Adam Bakerhttp://www.flickr.com/photos/atbaker/5125230312/Monday, May 27, 13
  9. 9. Insulin responsesbasally and after a 40 g/m2 oral glucose loadobese & lean PCOS women ●ovulatory hyperandrogenic women ●age- & weight-comparable ovulatory control women ○Adapted from A Dunaif et al. Aliment J Clin Endocrinol Metab 1987 (34)PCOSHAcontrolObese LeanPCOSHAcontrolMonday, May 27, 13
  10. 10. Hyperinsulinemia is a unique featureof PCOS and not hyperandrogenicstates in generalAdapted from A Dunaif et al. Aliment J Clin Endocrinol Metab 1987 (34)PCOSHAcontrolPCOSHAcontrolObese LeanMonday, May 27, 13
  11. 11. Diamanti-Kandarakis E & Dunaif A. Endocrine Reviews 2012; 33:981-1030Monday, May 27, 13
  12. 12. NICHD PCOSNICHD PCOSObese LeanHAcontrolHAcontrolHA & PCO(ovulatory PCOS)leaner with mildermetabolic abn/normalAnov & PCOnormal insulin sensitivityMonday, May 27, 13
  13. 13. Do non-NIH PCOS phenotypes present with similarmetabolic risk as the NIH PCOS phenotype?NIH PCOSgreater obesity, abdominalobesity, insulin resistance& risk factors for T2Dnon-NIH PCOSgreater metabolic abn thancontrols but primarilylinked to abdominalobesityMoran L & Teede H. Human Reprod Update 2009; 4:477-88Monday, May 27, 13
  14. 14. Increasedprevalence ofobesity in PCOSIncreased frequency ofhyperandrogenism inwomen with upper (vslower body) obesityAndrogens can increasevisceral fat in womenAndrogens can increasemuscle mass“Malaga - July 2012” by Evo Flashhttp://www.flickr.com/photos/evoflash/7663963294/Monday, May 27, 13
  15. 15. Insulin-mediated glucose disposal(IMGD) in PCOS by euglycemic clampObese LeanDiamanti-Kandarakis E & Dunaif A. Endocrine Reviews 2012; 33:981-1030Monday, May 27, 13
  16. 16. Insulin-mediated glucose disposalwas significantly decreased (~35-40%) in PCOS womenDecrease in IMGD in PCOS similar to that seen in T2DDecreased IMGD in lean women with normal glucose toleranceObese LeanDiamanti-Kandarakis E & Dunaif A. Endocrine Reviews 2012; 33:981-1030PCOSPCOSMonday, May 27, 13
  17. 17. “Push” by Adam Bakerhttp://www.flickr.com/photos/atbaker/5125230312/Dysglycemia developswhen the β-cell is nolonger able to secretesufficient amounts ofinsulin to meet theincreased requirements.Monday, May 27, 13
  18. 18. Hyperbolic relationship: Compensatory increase ininsulin secretion when insulin sensitivity declinesβ-cell dysfunction in PCOSAdapted from A. Dunaif & D.T. Finegood J Clin Endocrinol Metab 1996; (81):942-947Obese PCOS ●Lean PCOS ▲AIRg = acute insulin response to glucoseMonday, May 27, 13
  19. 19. Obese PCOS ●Lean PCOS ▲Adapted from A. Dunaif & D.T. FinegoodJ Clin Endocrinol Metab 1996; (81):942-947DI significantlydecreasedin both lean & obesePCOS womenDisposition index (DI)product of insulin sensitivity and insulin secretionhighly heritable, associated with specific genetic locimost powerful predictor of diabetes riskMonday, May 27, 13
  20. 20. Defect in glucose-stimulated insulin secretion in PCOSindependent of obesityAbnormality is found as early as adolescence in girlswith PCOS & IGTObese PCOS ●Lean PCOS ▲Adapted from A. Dunaif & D.T. FinegoodJ Clin Endocrinol Metab 1996; (81):942-947Defectmore pronouncedin women withfirst-degree relativewith T2DMonday, May 27, 13
  21. 21. PCOS & (+) FH of DM ●PCOS & (-) FH of DM ○75-g OGTTEhrmann DA et al. J Clin Endocrinol Metab 2005; (90):66-71Monday, May 27, 13
  22. 22. Other genes evidentlyparticipating in PCOSpathogenesisSteroid biosynthesis pathwayCYP11A, CYP17, SRD5AAndrogen signaling pathwaySHBG, SGTAObesity-associated gene FTOLeukotriene metabolismrelated genes ALOX15, FEM1A,FEM1BAdipokines & cytokines IL-6,IL-18, hs-CRP, TNFα, TNFR2A Baranova et al. Aliment Pharmacol Ther 2011; 33:801-804“A Sister’s Love” by Carmella Fernandohttp://www.flickr.com/photos/13923263@N07/1471151698/Monday, May 27, 13
  23. 23. Insulin receptor signaling pathwayDiamanti-Kandarakis E & Dunaif A. Endocrine Reviews 2012; 33:981-1030Monday, May 27, 13
  24. 24. Insulin signaling defects in PCOSSerine phosphorylation of the insulin receptor and IRS-1secondary to intracellular serine kinases resulting inresistance to metabolic actions of insulinDiamanti-Kandarakis E & Dunaif A. Endocrine Reviews 2012; 33:981-1030Monday, May 27, 13
  25. 25. Fasting and post-challengedysglycemia in PCOSAdapted from RS Legro et al. J Clin Endocrinol Metab 1999; (84):165-169Monday, May 27, 13
  26. 26. Fasting hyperglycemiaIFG: FBS 100-125 mg/dL OR T2D: FBS > 126 mg/dLAdapted from RS Legro et al. J Clin Endocrinol Metab 1999; (84):165-169Monday, May 27, 13
  27. 27. Post-challenge hyperglycemiaIGT: 2h >140 mg/dL OR T2D: 2h > 200 mg/dLAdapted from RS Legro et al. J Clin Endocrinol Metab 1999; (84):165-169Monday, May 27, 13
  28. 28. Postprandialdysglycemiaperipheral (primarilyskeletal muscle) insulinresistanceMost women with PCOShave post-challengerather than fastingdysglycemiaFasting dysglycemiaincreased endogenous(liver and kidney) glucoseproductionAdapted from RS Legro et al.J Clin Endocrinol Metab 1999; (84):165-169Monday, May 27, 13
  29. 29. Diamanti-Kandarakis E & Dunaif A. Endocrine Reviews 2012; 33:981-1030Prevalence of glucose intoleranceand T2D in PCOS (US data)Monday, May 27, 13
  30. 30. Prevalence of IGT& T2D in US PCOSwomenIGT: 25-35%3-fold higher than inwomen of similar age inNHANES IIT2D: 4-10%7.5- to 10-fold higherthan in women of similarage in NHANES IIPrevalence of T2D likelyunderestimatedbecause diagnosedT1D or T2D excludedin cohortsDiamanti-Kandarakis E & Dunaif A.Endocrine Reviews 2012; 33:981-1030Monday, May 27, 13
  31. 31. A Baranova et al. Aliment Pharmacol Ther 2011; 33:801-804Insulin resistance,obesity and diabetesImplicationsfor practiceMetabolicSyn!ome& PCOSMonday, May 27, 13
  32. 32. Screening for glucose intoleranceA Consensus Statement by the AE-PCOS SocietyWild et al. J Clin Endocrinol Metab 2010;95:2038-4975-g OGTT for PCOS women with BMI>30 kg/m2Lean PCOS women >40 yPersonal history of gestational diabetesFamily history of type 2 diabetesMonday, May 27, 13
  33. 33. Screening for glucose intoleranceA Consensus Statement by the AE-PCOS SocietyWild et al. J Clin Endocrinol Metab 2010;95:2038-49Those with IGT should be screened ANNUALLY fordeveloping T2DM, acknowledging efficacy of treatingIGT, but not necessarily IFG, to prevent T2DM.Monday, May 27, 13
  34. 34. Screening for glucose intoleranceA Consensus Statement by the AE-PCOS SocietyWild et al. J Clin Endocrinol Metab 2010;95:2038-49Suggest re-screening if normal glucose toleranceevery TWO years or soonerif additional risks are identifiedMonday, May 27, 13
  35. 35. Screening for glucose intoleranceA Consensus Statement by the AE-PCOS SocietyWild et al. J Clin Endocrinol Metab 2010;95:2038-49HbA1c above 6.5% has been proposed as the definingcriterion for diabetes. We endorse this criterion for riskassessment, but further studies are needed.Monday, May 27, 13
  36. 36. Lifestyle Modification in PCOSA Consensus Statement by the AE-PCOS SocietyWild et al. J Clin Endocrinol Metab 2010;95:2038-49Overweight/obese PCOS womenshould initially attempt 5-10% weight loss.Monday, May 27, 13
  37. 37. Metformin for PCOSA Consensus Statement by the AE-PCOS SocietyWild et al. J Clin Endocrinol Metab 2010;95:2038-49Women on lifestyle modification withno improvement in IGTWomen with IGT of normal weightMonday, May 27, 13
  38. 38. Anti-obesity drugs for PCOSA Consensus Statement by the AE-PCOS SocietyWild et al. J Clin Endocrinol Metab 2010;95:2038-49The use of weight loss medicationsis not recommended.Orlistat induces small weight reduction without changingglucose-insulin homeostasis or lipid patterns.Monday, May 27, 13
  39. 39. Bariatric surgery for PCOSA Consensus Statement by the AE-PCOS SocietyWild et al. J Clin Endocrinol Metab 2010;95:2038-49Option for severely obese women with PCOS, in whomlong-term diet-based strategies are seldom successfulBMI >40 kg/m2 or >35 kg/m2with a high-risk obesity-related conditionMonday, May 27, 13
  40. 40. Insulin resistance,obesity and diabetesImplicationsfor practiceMetabolicSyn!ome& PCOSThank Youwww.slideshare.net/isiptanMonday, May 27, 13

×