PCOS & Diet Therapy. Dr. Ladan Giahi Immunonutritionist Avicenna Research Institute October 2015

Transcription

1 PCOS & Diet Therapy Dr. Ladan Giahi Immunonutritionist Avicenna Research Institute October 2015

2 Questions to be discussed: 1) Why dietary modification is considered as first line of treatment? 2) What is the first step for dietary modification? 3) What are the main dietary concerns? 4) What is the best practical diet? 5) How the diet must be prescribed to increase compliance? 6) How long the diet needs to be followed? 2

3 PCOS Relates to : Metabolic Risks Pregnancy Complications Antioxidants Fatty acids Vitamin D 3

4 Pathophysiology of PCOS Neuroendocrine Menstrual Irregularity + Hyperandrogenism Androgens Insulin 4

5 Hyperandrogenemia Liogenesis Lipolysis in Subcutaneous AT Influence adipocyte function Influence adipocyte distribution Inibition of adipocyte differentiation 5 Diabetes 2012; 61:

6 Hyperandrogenemia Low grade inflammation Induced oxidative stress, Activation of reactive oxygen species (ROS) Sensitivity to glucose TNF α and IL 6 gene transcription TNF α.. Reduce expression of GLUT4 6 Steroids 2012; 77:

7 Insulin Resistance and PCOS Insulin resistance is a very common feature of women with PCOS (60-75%) Insulin resistance occurs in both obese and nonobese women with PCOS Obesity has a synergystic effect on glucose metabolism and IR Palomba S, Endocrine Review,

8 IR is present in both lean and obese PCOS compared to their BMI and age matched counterpart Insulin Sensitivity 8 Nl Lean Nl Obese PCOS Lean PCOS Obese Dunaif A et al, 1987

9 Prevalence of Glucose intolerance and Diabetes in PCOS Evidence of Decades 9

10 PCOS: IGT & Type II diabetes 35 to 50% of obese women with PCOS develop either impaired glucose tolerance or type 2 diabetes by the age of 30! Legro RS 1999; Dahlgren E 1992; Dunaif A1995;Ehrmann DA, PCOS women are at risk for IGT and DM II at all weights 10

11 PCOS and Type II diabetes Nurses Health Study II (NHSII): women Women followed for 8 years 3-7x increase as compared to the general population Conversion rate to DMII was 2-fold higher in oligomenorrheic women, independent of weight Legro et al, JCEM,

12 Mechanisms of Predisposition to the development Type II DM in PCOS Defects in insulin receptor or post-receptor signal transduction (50%) Altered adipocyte lipolysis Decrease GLUT-4 expression in the adipocytes Many PCOS women exhibit β-cell dysfunction Ek I et al JCEM 1997 Ek I et al, Diabetes 2002 Kelsey ES, JCEM

13 Insulin Signaling Pathways in PCOS Differential Effects 13 IRS1/2 mediation of PI3 kinase glucose transport & carbohydrate metabolism MAP kinase mitogenesis

14 Detection is markedly improved by the use of post-challenge glucose values Position of the Androgen Excess Society (2008): Women with PCOS regardless of their weight should be Screened for IGT and DMII by an OGTT at 14 presentation And every 2 yrs.

15 Development of Gestational DM in PCOS Meta-analysis 720 women with PCOS and 4505 controls RR 2.94 (CI ) of developing GDM than control women Besides converting to IGT or type 2 DM, women with PCOS are also at high risk for developing gestational DM Boomsma et al, Hum Reprod Update,

16 Pregnancy Complications Spontaneous Abortions Increased in high BMI/PCOS patients Impaired Glucose Tolerance Gestational Diabetes Wang JX et al, Human Reproduction, Turhan NO et al, International Journal of Gynecology & Obstetrics, Hypertension Bjercke S et al, Gynecologic and Obstetric Investigation, Small for Gestational Age Weerakiet S et al, Gynecological Endocrinology, Sir-Petermann T et al, Human Reproduction, 2005.

17 PCOS and Metabolic Syndrome > 3 of the following for women: Triglycerides >150 mg/dl HDL Cholesterol (F) < 50 mg/dl Blood Pressure >130/85 mm/hg Waist > 88 cm Glucose (fasting) > 100 mg/dl 17

18 Prevalence of Metabolic syndrome in PCOS compared to NHANES women Age Group BMI (kg/m 2 ) < > yr (n = 29) PCOS (%) U.S. females (%) yr (n = 49) PCOS (%) U.S. females (%) Apridonidze T eta al JCEM 2005

19 Evaluation of metabolic anomalies In PCOS patients is crucial 19

20 Evaluation of Women with PCOS: Metabolic issues Screen for : GLUCOSE INTOLERANCE HYPERTENSION DYSLIPIDEMIA 20 RISK FACTORS FOR HEART DISEASE

21 PCOS and Obesity Majority of PCOS BMI> 27 Obesity among adult PCOS..42 to 58% Obesity in women with anovulation and PCO. 30%-75% Android obesity. ~52% 70% Abdominal adiposity in particular is present in ~30% of normal weight women with PCOS. Is obesity an intrinsic clinical sign of PCOS or promoting environmental factor? 21 Nelson SM, 2007

22 Common report in obese individuals: I don't feel hungry when I get up in the morning often skip breakfast (number one risk factor for obesity, Insulin resistancy ) The brain interprets this as more starvation signals and further shuts down the metabolism 22

23 Most insulin resistant obese individuals with PCOS start eating at noon This exacerbate insulin sensitivity Definitely affect Ovulation Cycle cancelation + Depression Higher prevalence in PCOS patients, associated with higher body mass index (BMI, P=0.05) and greater insulin resistance (P=0.02) 23 Rasgon NL et al, Journal of Affective Disorders, 2003

24 PCOS: Weight Loss 12 to 24 weeks Loss an average of 1-3kg / month Decreased fasting insulin Decrease testosterone Increases in SHBG 5% reduction in body mass.. restore ovulation ovulation (92%) 5% reduction in body mass.. became pregnant (85%) Infertile women are usually highly motivated Clark AM et al, Human Reproduction,

25 Obesity results in decreased serum LH LH LH 25

26 Preventive Value for PCOS in next generation Three distinct groups of patients with polycystic ovaries: Those who had above average birth weight Those born to overweight mothers HORMONES 2006, 5(1): LBW girls (experience spontaneous catch up growth develop higher dehydro epiandrosterone and lower SHBG together with increased visceral adiposity between 6 and 8 years of age PCOS by 24 year ) 26

27 No ONE SIZE FITS ALL Individualized approach to achieving appropriate BMI THE IDEAL FOOD FOR YOU is what you are capable to: Prepare Digest Feel good 27

28 Dietitian Approach Meal timing (Circadian rhythm is critical to consider) Quantity of food intake during 24hrs Low glycemic load : minimize changes in post prandial glucose levels Antioxidant intake Quality of fat intake Dietary pattern.. Personalized modification 28

29 Effects of caloric intake timing on insulin resistance and hyperandrogenism in lean women with polycystic ovary syndrome. Clinical Science, 2013; 125 (9): 423 N= 60 Duration: 90 days Calorie 1800 A) 983 calorie breakfast, a 645 calorie lunch, and a 190 calorie dinner. B) 190 calorie breakfast, a 645 calorie lunch, and 983 calorie dinner. Result: (Without change in BMI) 56 % Decrease in insulin resistance 50% decrease in testosterone 50 % ovulation rate Rise in progesterone 29

30 Factors Influencing Gycemic Index Ranking Type of starch Physical entrapment Viscosity of fiber Sugar content Fat and protein content Acid content Food processing Cooking 30

31 Glycemic Load (GL): What does it mean? Glycemic load measures the degree of glycemic response and insulin demand produced by a specific amount of a specific food.. GL = GI/100 x CHO (grams) per serving Example: GL of an apple = 40/100 x 15g = 6g 31

32 Glycemic Index and Load Standards for Foods GI (based on glucose reference) Low GI 0 to 55 Intermediate GI 56 to 69 High GI 70 GL (based on glucose reference) Low GL 0 to 10 Intermediate GL 11 to 19 High GL 20 Brand-Miller J, et al. The New Glucose Revolution: The Authoritative Guide to the Glycemic Index-The Dietary Solution for Lifelong Health. 3rd ed. New York, NY: Marlowe and Co.; Brand-Miller JC, et al. Am J Clin Nutr. 2003;77(4):

33 33

34 Blood Glucose Response to High vs Low Glycemic Index Foods 34 Blood Glucose, mmol/l Wolever TM, et al. Am J Clin Nutr. 1991;54(5): Lentils Bread Time, minutes

35 Benefits of Low GI Diet Are there any documented benefits to lowering the GI of one s diet? YES! BG levels cholesterol levels type 2 DM risk heart disease risk weight 35

36 Caution! Do not focus exclusively on achieving a low glycemic load diet with all low glycemic index food choices. Result could be: high fat low carbohydrate low fiber calorically dense Instead 36

37 A Better Idea Aim for a well-balanced diet Hint: Low GI CHOs allow for larger portions, while regulating the GL. High GI CHOs require smaller portions to regulate the GL. 37

38 Pictures of Low/High GI Meals & Snacks GI = 60 GL = 48 GI = 42 GL = 31 38

39 Pictures of Low/High GI Meals & Snacks GI = 85 GL = 48 GI = 39 GL = 22 39

40 Pictures of Low/High GI Meals & Snacks GI = 83 GL = 19 GI = 14 GL = 1 40

41 Pictures of Low/High GI Meals & Snacks GI = 80 GL = 32 GI = 61 GL = 12 41

42 Pictures of Low/High GI Meals & Snacks GI = 57 GL = 31 GI = 32 GL = 16 42

43 Fatty Acids Change in plasma EPA, DHA, or total PUFA concentrations were strongly associated with androgen concentration reduction. Rice bran oil Flax sees oil Grapeseed oil Extra virgin olive oil Canola oil 43

44 HOW to BALANCE Start the day with protein based smoothie of high quality. Don t exercise in the morning without some caloric imput to stabilize sugars. High in phytonutrients and soluble fiber (Legumes) Eating smaller amounts at REGULAR intervals (every 4 hrs) Finish eating at least 2 to 3 hours before bed. If you have a snack earlier in the day, you won t be as hungry, even if you eat a little later. CINNAMON on fruits will decrease sugar spikes. Cinnamon has an insulin-modulating affect. 44

45 Circulating markers of oxidative stress and polycystic ovary syndrome (PCOS): a systematic review and meta-analysis Hum. Reprod. Update (2013) Circulating markers of oxidative stress are abnormal in women with PCOS independent of weight excess 45

46 Schematic representation of mechanisms and pathways that may contribute to oxidative stress in polycystic ovary syndrome (PCOS). 46 Murri M et al. Hum. Reprod. Update 2013;humupd.dms059

47 47

48 48

49 Mechanism relate Vitamin D & PCOS VDR-related polymorphisms (Cdx2, Bsm-I, Fok-I, Apa-I, and Taq-I) contribute to PCOS susceptibility VDR regulates more than 3% of the human genome. genes that are crucial for glucose metabolism Stimulating the expression of insulin receptors: Enhancing insulin responsiveness for glucose transport Regulates extracellular and intracellular calcium Insulin-responsive tissues such as skeletal muscle and adipose tissue Effect on the immune system hypovitaminosis D might induce a higher inflammatory response associated with 49 insulin resistance

50 1. Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome Experimental and Clinical Endocrinology and Diabetes Serum 25-hydroxyvitamin D concentrations in obese and non-obese women with polycystic ovary syndrome Archives of Gynecology and Obstetrics Association of hypovitaminosis D with metabolic disturbances in polycystic ovary syndrome European Journal of Endocrinology Calciotropic hormones, insulin resistance, and the polycystic ovary syndrome Fertility and Sterility Vitamin D deficiency is common and associated with metabolic risk factors in patients with polycystic ovary syndrome 50 Metabolism

51 vitamin D supplementation resulted in a higher number of dominant follicles when compared with metformin alone and placebo, which might indicate a beneficial effect on fertility Taiwanese Journal of Obstetrics and Gynecology Hypovitaminosis D should be kept in mind while managing obese women with PCOS 51

52 CONCLUSION: Metabolic risks (IR, MS) Low glycemic diet Antioxidants Fatty acids Vitamin D Pregnancy complications 52

53 Thank you