Metabolic Syndrome, Exercise & Carbs

1. Indigenous Diet Project Part 2: Metabolic Syndrome, Exercise & Carbs UBC January 23, 2008 Jay Wortman MD

2. Review of Part 1 Diseases of Civilization Metabolic Syndrome Exercise Calls for Change

7. Obesity, MetS and Type 2 Diabetes among Canadian First Nations • 73% of First Nations are overweight vs 51% for other Canadians • First Nations obesity rate is double • 42% of First Nations have metabolic syndrome vs 25% of other Canadians • First Nations diabetes rates are 3 to 5 times greater than the Canadian rate

8. Worldwide Epidemic of Obesity and Related Conditions

9. Obesity Trends* Among U.S. AdultsBRFSS*, 1985 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) * Behavioral Risk Factor Surveillance System No Data <10% 10%–14%

10. Obesity Trends* Among U.S. AdultsBRFSS, 2005 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person) No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

11. Comparing Two Hypotheses • 1. The Positive Caloric Balance Hypothesis Obesity is a disorder of energy balance. Defect is in the brain • “in the regulation of ingestive behaviors • particularly at the cognitive level” • Defect causes us to eat too much Causative agents: • Overeating and sedentary behaviour (gluttony and sloth) Excess calories accumulate and are “pushed” into fat cells • Fat cells play passive role. • Ein and Eout are independent variables “The vast majority of the notoriously unsuccessful weight control programs are predicated on this assumption.”

12. First Law of Thermodynamics ∆E = Ein - Eout

13. Comparing Two Hypotheses • 2. The Alternate Hypothesis: Obesity is a disorder of excess fat accumulation. Primary defect is in the body, not the brain: • hormonal or metabolic defect • disorder of fat storage and/or fat oxidation Defect causes excessive accumulation of fat • Overeating and inactivity are side effects, not causes • Calories are “pulled” into fat cells, not pushed • Fat cells play an active role, not a passive one • Energy intake and expenditure are dependent variables • Body adjusts intake to expenditure, and vice versa • Explains why eating less or exercising more doesn’t work The only effective treatment - remedy the defect.

14. Macronutrient Intake and Obesity Obesity (BMI>30) Carbohydrate Fat Protein Based on NHANES data. Int J Obes 1998;22:39-47. JAMA 2002;288:1723. MMWR 2004;53:80-82.

15. Adiposity 101 • 1920s - 1960s: a forty-year revolution in the science of fat metabolism 1920s: Fat is metabolically active -- not an inert garbage can 1930s - 1940s: Fat in the fat cells is in a continual state of flux • Fatty acids and triglycerides cycling within cell • 1948: Ernst Wertheimer, Physiological Reviews: • “Mobilization and deposition of fat go on continuously, without regard to the nutritional state of the animal.” • “Lowering of the fat content of the tissue… is the result of mobilization exceeding deposition.” • Raising of the fat content of the tissue is the result of deposition exceeding mobilization. • “The `classical theory’ that fat is deposited in the adipose tissue only when given in excess of the caloric requirement has been finally disproved.”

16. FFA insulin glucose LPL TAG glycerol phosphate TAG Adipocyte

17. starch sugar blood sugar cells have plenty of energy insulin resistance improves FFA released from adipocytes lipogenesis slows insulin

18. at 2 weeks • weight loss of 17 lbs (8 kg) • blood glucose normalizes • discontinues insulin • at 4 weeks • weight loss of 31 lbs (14 kg) • blood pressure normalizes • discontinues ACE inhibitor • at 9 weeks • weight loss of 37 lbs (17 kg) • BP 118/72 • fasting glucose 5.0 – 6.0 mmol • at 18 weeks • weight loss of 46 lbs (21 kg) • normal glucose • normal BP • normal cholesterol • no meds

20. Namgis Preliminary Data n from 24 to 29 (based on complete data over 3 months)

21. Diseases of Civilization

22. Diseases of Civilization • Concept common mid-19th to mid-20th century • Based on extensive reports of no cancer, diabetes, stroke and heart disease in native populations not exposed to western foods • Absence of cavities, gum disease, ulcers, appendicitis, diverticulitis, gall bladder disease, hemorrhoids, varicose veins and constipation • This changed with increasing exposure to refined CHO: sugar, flour, polished rice

23. Physiological and Medical Observations among the Indians of Southwestern United States and Northern MexicoAles Hrdicka, 1908 • Virtual absence of chronic diseases including diabetes, cancer and heart disease • Not attributable to shorter life expectancy

24. “Not by Bread Alone” Vilhjalmur Stefansson, 1946 • Inuit diet was protein and fat, no carbohydrates • caribou, fish, seal, polar bear, rabbit, birds and eggs • They chose the fattiest foods and dipped everything in whale fat • They avoided plant foods • They ate plants only when starving, as a last resort before eating their dogs and resorting to cannibalism

25. “The Chinese noted with surprise and disgust the ability of the Mongol warriors to survive on little food and water for long periods; according to one, the entire army could camp without a single puff of smoke since they needed no fires to cook. Compared to the Jurched soldiers, the Mongols were much healthier and stronger. The Mongols consumed a steady diet of meat, milk, yogurt, and other diary products, and they fought men who lived on gruel made from various grains. The grain diet of the peasant warriors stunted their bones, rotted their teeth, and left them weak and prone to disease. In contrast, the poorest Mongol soldier ate mostly protein, thereby giving him strong teeth and bones. Unlike the Jurched soldiers, who were dependent on a heavy carbohydrate diet, the Mongols could more easily go a day or two without food.” Jack Weatherford, Genghis Khan and the Making of the Modern World

26. The Worst Mistake in the History of the Human Race • recent discoveries suggest that the adoption of agriculture was a catastrophe from which we have never recovered • farmers grow high-carbohydrate crops like rice and potatoes • hunter-gatherer diets of wild plants and animals provide more protein and a better balance of other nutrients • skeletons from Greece and Turkey show that the average height of hunter-gatherers toward the end of the ice ages was 5'9" for men and 5'5" for women • with the adoption of agriculture, height decreased to a low of 5'3" for men and 5’0” for women by 3000 BC Jared Diamond, May 1987, Discover

27. The Worst Mistake in the History of the Human Race 800 skeletons excavated at Dickson Mounds, near the confluence of the Spoon and lllinois rivers, demonstrate health changes as hunter-gatherer culture gave way to intensive maize farming around 1150 AD • 50% increase in enamel defects indicative of malnutrition • 4 X increase in iron-deficiency anemia (porotic hyperostosis) • 3 X rise in infectious bone lesions • increase in degenerative conditions of the spine • 7 year drop in life expectancy at birth Jared Diamond, May 1987, Discover

28. The Worst Mistake in the History of the Human Race “Hunter-gatherers practiced the most successful and longest lasting lifestyle in human history. In contrast, we're still struggling with the mess into which agriculture has tumbled us, and it's unclear whether we can solve it” Jared Diamond, May 1987, Discover

29. Metabolic Syndrome

30. Metabolic Syndrome • described by Reaven in 1980’s • metabolic abnormalities associated with obesity, heart disease and T2DM • elevated TAG, low HDL, hypertension, hyperinsulinemia, insulin resistance, glucose intolerance. Additional factors: • small dense LDL, fibrinogen, uric acid, chronic inflammation, elevated C-reactive protein • NAFLD, PCOS

31. Metabolic Syndrome a cluster of the most dangerous heart attack risk factors: diabetes and pre-diabetes, abdominal obesity, high cholesterol and high blood pressure • 25% of adults world-wide have metabolic syndrome • 2X risk of death from heart attack or stroke • 5X risk of developing type 2 diabetes • 200 million people with diabetes globally • up to 80% will die of cardiovascular disease International Diabetes Federation

32. The underlying cause of the metabolic syndrome continues to challenge the experts but both insulin resistance and central obesity are considered significant factors. Genetics, physical inactivity, ageing, a pro-inflammatory state and hormonal changes may also have a causal effect, but the role of these may vary depending on ethnic group. International Diabetes Federation

33. Type 2 Diabetes is the Tip of the Iceberg of Metabolic Syndrome The Metabolic Syndrome is synonymous to an iceberg with glucose intolerance above the surface but a group of other key cardiovascular disease risk factors lurking below Zimmet, Journal of Internal Medicine 2000

34. diabetes metabolic syndrome weight gain • abdominal fat • high cholesterol • blood pressure • insulin resistance • hyperinsulinemia CVD

35. increased calories + decreased activity FAT

36. ? disorder of fat metabolism High Carb Diet increased calories + decreased activity FAT

37. Type 2 Diabetes is the Tip of the Iceberg of Metabolic Syndrome The Metabolic Syndrome is synonymous to an iceberg with glucose intolerance above the surface but a group of other key cardiovascular disease risk factors lurking below Zimmet, Journal of Internal Medicine 2000

38. A Single Factor Underlies the Metabolic SyndromeA Confirmatory Factor Analysis “These analyses support the current clinical definition of metabolic syndrome, as well as the existence of a single factor that links all of the core components.” Pladeval et al, Diabetes Care 2006

39. Five symptoms common to most definitions of MetS are those that are reliably improved by CHO restriction. Carbohydrate restriction is one strategy for weight loss but, in addition, improves glycemic control, insulin levels, TAG and HDL levels even in the absence of weight loss. We suggest that response to CHO restriction may, in fact, be an operational definition of MetS. Its underlying basis would rest on the idea that the features of MetS are associated with a disruption in insulin metabolism which is strongly influenced by dietary CHO. Volek and Feinman, Nutrition and Metabolism 2005

40. Type 2 Diabetes is the Tip of the Iceberg of CHO Intolerance Syndrome The Metabolic Syndrome is synonymous to an iceberg with glucose intolerance above the surface but a group of other key cardiovascular disease risk factors lurking below Zimmet, Journal of Internal Medicine 2000

41. How do we manage intolerances? • Gluten intolerance • Lactose intolerance • Carbohydrate intolerance … avoid wheat products ... avoid dairy products … eat lots of carbohydrates!!!

42. Inflammation and MetS

43. Comparison of Low Carb and Low Fat Diets New features that appear to be associated with metabolic syndrome include disturbed circulating fatty acid composition, perturbed lipid metabolism and increased oxidative stress and inflammation. Forsythe et al, Lipids 2007

44. Comparison of Low Carb and Low Fat Diets Total saturated fatty acids and 16:1n-7 were consistently decreased following the VLCKD [low carb diet]. Both diets significantly decreased the concentration of several serum inflammatory markers, but there was an overall greater anti-inflammatory effect associated with the VLCKD, as evidenced by greater decreases in TNF-a, IL-6, IL-8, MCP-1, E-selectin, I-CAM, and PAI-1. In summary, a very low carbohydrate diet resulted in profound alterations in fatty acid composition and reduced inflammation compared to a low fat diet. Forsythe et al, Lipids 2007

45. Exercise

47. Dependent vs Independent Variables “When a person consumes a surplus of 3,500 kcal above his or her requirements, this extra amount will usually produce a weight gain of about 0.45 kilogram. Researchers estimate that putting sweeteners into beverages added about 137 kcal to the average American's daily diet between 1977 and 2006. Over a year this surplus can cause a weight gain of about 6.4 kilograms.” Popkin, B. “The World is Fat” Sci Am 2007

48. Dependent vs Independent Variables “If an animal has been at a stable weight… significantly altering its energy intake will produce physical and behavioral changes that appear to be geared toward restoring weight to the previous level. An animal whose food is suddenly restricted tends to reduce its energy expenditure both by being less active and by slowing energy use in cells, thereby limiting weight loss. It also experiences increased hunger so that once the restriction ends, it will eat more than its prior norm until the earlier weight is attained. Likewise, after intentional overfeeding, an animal will start to expend more energy and exhibit reduced appetite, with both states persisting until weight falls to the previous level.” Flier J and Maratos-Flier T “What Fuels Fat” Sci Am 2007

49. “…whether increasing energy expenditure or reducing energy intake by 100 kcal/day would prevent weight gain remains to be empirically tested.” Hill et al “Obesity and the Environment: Where Do We Go From Here?” Science 2002

50. Efficacy of Exercise for Weight Loss “It is reasonable to assume that persons with relatively high daily energy expenditures would be less likely to gain weight over time, compared with those who have low energy expenditures. So far, data to support this hypothesis are not particularly compelling.” AHA/ACSM, Physical Activity Guidelines, 2007