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Diet and Disease The Phantom Menace Part 5 of 6 The Aetiology of Obesity.

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Presentation on theme: "Diet and Disease The Phantom Menace Part 5 of 6 The Aetiology of Obesity."— Presentation transcript:

1 Diet and Disease The Phantom Menace Part 5 of 6 The Aetiology of Obesity

2 Hormonal Obesity Theory Fattening Carbohydrates Increased Insulin level Insulin Resistance Fibre Obesity High TG Low HDL Hypertension Diabetes Metabolic Syndrome Fatty Liver High Protein Cortisol Vinegar Fructose Wheat Super-carbohydrate Fasting www.kidneylifescience.ca

3 Diseases of Civilization Coronary Artery Disease Obesity Diabetes Colorectal cancer Breast cancer Tooth decay Constipation My observations inclined me to attribute this to the fact that the native were living more and more after the manner of the whites Dr. Schweitzer West Africa 1913 www.kidneylifescience.ca

4 First Nations 1908 Smithsonian Institutions Bureau of American Ethnology report Not one pronounced instance of advanced arterial sclerosis Malignant disease, if they exist at all … must be extremely rare www.kidneylifescience.ca

5 Inuit 1952 Queens University It is commonly stated that cancer does not occur in the Eskimos, and to our knowledge no case has so far been reported 1950-1974 Upernavik 1 case of diabetes www.kidneylifescience.ca

6 Masai Pastoralists – diet of milk, meat and blood Rarely eat fresh vegetables www.kidneylifescience.ca

7 Tukisenta Investigators found them to be fit, lean and muscular, with no sign of protein deficiency (Trowell and Burkitt. Western Diseases. 1981) 94.6% of their energy intake as carbohydrate www.kidneylifescience.ca

8 The Kitava Study 1990s - Kitavan diet 69% carbohydrate Fruit, vegetables, roots, fish and coconuts www.kidneylifescience.ca

9 Low Serum Insulin despite high carb intake Low Serum Insulin in Traditional Pacific IslandersThe Kitava Study Metabolism, Vol 48, No 10 (Oct), 1999:1216-1219 Lindeberg S Swedish reference range 10-90% www.kidneylifescience.ca

10 Okinawa Life expectancy among the highest in the world 85% Carbohydrate BMIBMI average of 20.4 www.kidneylifescience.ca

11 Conclusions Populations could be healthy with diets of 95% carbohydrate or 95% meat No refined/ processed foods No flour No sugar www.kidneylifescience.ca

12 Populations in Transition

13 Tokelau Island Migration Study Their populations are notable for their low levels of blood pressure… coronary heart disease, obesity and diabetes www.kidneylifescience.ca

14 Tokelau Island Migration Study Impact of trading posts established on atolls www.kidneylifescience.ca

15 Sugar consumption www.kidneylifescience.ca

16 Tokelau Migrants Study Average weight increased by 20-30 pounds www.kidneylifescience.ca

17 Diabetes Graph: www.wholehealthsource.blogspot.com

18 Gout Graph: www.wholehealthsource.blogspot.com

19 Tooth Decay Graph: www.wholehealthsource.blogspot.com

20 New Zealand Maori 2006 High levels of physical activity www.kidneylifescience.ca

21 Maori Obesity Staples of Maori diet - bread, flour, biscuits, breakfast cereals, sugar, and potatoes www.kidneylifescience.ca

22 Increasing cancer with Westernization www.kidneylifescience.ca

23 Increasing Cancer with Westernization Regions in order of Westernization From: US Treasury Public Health Reports 1934 Graph: www.wholehealthsource.blogspot.com www.kidneylifescience.ca

24 Increasing cancer with Westernization Migration patterns and breast cancer risk in Asian-American women J Natl Cancer Inst.J Natl Cancer Inst. 1993 Nov 17;85(22):1819-27. Equal risk in 2 generations www.kidneylifescience.ca

25 Increasing Cancer with Westernization Hong Kong The BreastThe Breast, Volume 17, Issue 1, February 2008, Pages 42–5Volume 17, Issue 1 Breast Cancer Incidence per 100,000 www.kidneylifescience.ca

26 Geographic Risk of Heart Attack Source: Wholehealthsource.blogspot.ca Geographic Pathology of Myocardial Infarction Dr. Kyu Taik Lee (Am. J. Cardiol. 13:30. 1964) www.kidneylifescience.ca

27 The Saccharine Disease 1966 Refined-carbohydrate disease 1. Overconsumption – evades satiety signals 2. Removal of protein – speeds digestion 3. Removal of fibre – speeds digestion 4. Removal of fat – speeds digestion Refining of Carbohydrates www.kidneylifescience.ca

28 Metabolic Syndrome Abdominal obesity High triglycerides, low HDL Hypertension Diabetes Insulin resistance Elevated uric acid levels Alzheimers disease Gallstones Fatty liver Gerald Reaven (Stanford) www.kidneylifescience.ca

29 Hormonal Obesity Theory Fattening Carbohydrates Increased Insulin level Insulin Resistance Fibre Obesity High TG Low HDL Hypertension Diabetes Metabolic Syndrome Fatty Liver High Protein Cortisol Vinegar Fructose Wheat Super-carbohydrate Fasting Diseases Of Civilization www.kidneylifescience.ca

30 High Insulin levels are a risk factor for heart disease Hyperinsulinemia as an independent risk factor for ischemic heart disease NEJM 1996 Apr 11;334(15): 952-7 Despres JP www.kidneylifescience.ca

31 Complications of Diabetes Type 1 and 2 Diabetes High Blood Sugars (Oxidative Stress) (Advance Glycation End Products) Complications of Diabetes www.kidneylifescience.ca

32 The Action to Control Cardiovascular Risk in Diabetes Study Group. N Engl J Med 2008;358:2545-2559 ACCORD Hazard Ratio 1.22 www.kidneylifescience.ca

33 What about hyperinsulinemia? Type 2 Diabetes High Blood Sugars Increased Insulin Complications of Diabetes www.kidneylifescience.ca

34 Insulin treatment has toxicity 12,272 new diabetics 1991-1996 Saskatchewan Insulin use and increased risk of mortality in type 2 diabetes Diabetes, Obesity and Metabolism 12: 47–53, 2010 Gamble JM significant and graded association between mortality risk and insulin exposure level www.kidneylifescience.ca

35 Insulin treatment has toxicity 84,622 incident Type 2 DM cases Mortality and Other Important Diabetes-Related Outcomes With Insulin vs Other Antihyperglycemic Therapies in Type 2 Diabetes J Clin Endocrinol Metab 98: 668–677, 2013 Currie CJ www.kidneylifescience.ca

36 Insulin is BAD for you 1986-2008 UK General Practice Research Database Survival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study Lancet 2010; 375:481-89, Currie CJ Oral Combination Insulin Adjusted Hazard Ratios by A1c www.kidneylifescience.ca

37 Non-diabetics 11,092 patients in ARIC study Glycated Hemoglobin, Diabetes, and Cardiovascular Risk in Nondiabetic Adults N Engl J Med 2010;362:800-11, Selvin E www.kidneylifescience.ca

38 Long acting insulin increases risk www.kidneylifescience.ca

39 Metformin versus Sulfonylurea Retrospective cohort study of 253,690 patients initiating treatment Comparative Effectiveness of Sulfonylurea and Metformin Monotherapy on Cardiovascular Events in Type 2 Diabetes Mellitus Ann Intern Med. 2012;157:601-610 Roumie CL www.kidneylifescience.ca

40 Sulfonylurea versus Metformin Multicenter, randomized, double-blind, placebo- controlled trial Effects of Metformin Versus Glipizide on Cardiovascular Outcomes in Patients With Type 2 Diabetes and Coronary Artery Disease Diabetes Care, epub Dec 10, 2012 Hong Jie www.kidneylifescience.ca

41 Glucose Control without Hyperinsulinemia

42 Proportion of Participants with Events over Time. The ORIGIN Trial Investigators. N Engl J Med 2012;367:319-328 ORIGIN No measureable difference in outcomes www.kidneylifescience.ca

43 Lowering glucose without raising insulin improves outcomes Acarbose Treatment and the Risk of Cardiovascular Disease and Hypertension in Patients with Impaired Glucose Tolerance JAMA 2003; 290: 486-494 49% RRR 2.5% ARR Randomized 1,429 patients 3.3 year follow up www.kidneylifescience.ca

44 Hypertension HR 0.66 P= 0.006 17% 11% www.kidneylifescience.ca

45 Stratified Analyses of CV Events: Pooled Data from Registration Trials (DPP-4 Inhibitors) *The main contributor to the overall differences in the primary endpoint was the events in the head-to-head study of linagliptin vs. glimepiride. Comparisons with placebo were not statistically significant (Johansen et al 2012; Trajenta Canadian Product Monograph July 2011). a Calculated using exact procedures for the Poisson processes; b Cox hazard ratio; c Patients with events: n = 22, saxagliptin; n = 18, control; d Patients with events: n = 11, linagliptin; n = 23, comparator. 1. Williams-Herman D, et al. BMC Endocr Disord 2010; 10:7. 2. Frederich R, et al. Postgrad Med 2010; 122:16-27. 3. Johansen O-E, et al. Cardiovasc Diabetol 2012; 11:3. Risk ratio95% CINo. DPP-4 inhibitor better Risk ratio 1.31.8 0.1110 Sitagliptin 1 0.68 a [0.41–1.12]64 Saxagliptin 2 0.43 b [0.23–0.80]40 c Linagliptin 3 * 0.34 b 34 d [0.16–0.70] Comparator better 69

46 Hormonal Obesity Theory Fattening Carbohydrates Increased Insulin level Insulin Resistance Fibre Obesity High TG Low HDL Hypertension Diabetes Metabolic Syndrome Fatty Liver High Protein Cortisol Vinegar Fructose Wheat Super-carbohydrate Fasting Diseases Of Civilization www.kidneylifescience.ca

47 Diabetes

48 Nutrition Recommendations 2008 Intake of sucrose and sucrose-containing foods by people with diabetes does not need to be restricted because of concern about aggravating hyperglycemia (its true – they really wrote this) Page S65 WTF?? www.kidneylifescience.ca

49 Nutrition Recommendations 2008 Dietary strategies including reduced calories and reduced intake of dietary fat, can reduce the risk for developing diabetes and are therefore recommended. Diabetes Care 1 Jan 2008 Vol 31 S61-81 www.kidneylifescience.ca

50 Overall Primary Outcome Results. A Clinical Trial to Maintain Glycemic Control in Youth with Type 2 Diabetes N Engl J Med 2012; 366(24):2247-2256 No Benefit to Low Calorie Low Fat! 1200-1500 kcal low fat diet Exercise 200-300 min/ week Eat less, move more www.kidneylifescience.ca

51 Editorial Dr. David Allen Chronic caloric surplus is a central cause of epidemic type 2 diabetes (so, so wrong) Because changes in eating and activity habits were calculated to decrease baseline weight by 7 to 10%, most participants clearly did not adopt these habits (blame the victim) Lifestyle change by definition works and that any lack of effect is therefore due to poor adherence (blame the victim) Eat Less, Move More Flawed advice 40 year perfect record - unblemished by success www.kidneylifescience.ca

52 NIH Trial Of Lifestyle Intervention For Type 2 Diabetes Stopped For Futility After 11 Years Forbes October 19, 2012 LOOK-AHEAD trial – 5,145 overweight diabetic patients Low Fat, Low Calorie diet (1200-1800 kcal) Meal replacement products, Increased exercise (175 min/week) Eat less, move more www.kidneylifescience.ca

53 Look-Ahead Trial Cardiovascular Effects of Intensive Lifestyle Intervention in Type 2 Diabetes N Engl J Med 2013 DOI: 10.1056/NEJMoa1212914 www.kidneylifescience.ca

54 LOOK AHEAD No measurable benefit after 9.6 years! www.kidneylifescience.ca

55 Eat Less, Move More Low Fat, Low Calorie: DOES NOT WORK HAS NEVER WORKED WILL NEVER WORK www.kidneylifescience.ca

56

57 Carbohydrates and Diabetes Cohort of 64,227 Chinese women Prospective study of dietary carbohydrates, glycemic index, glycemic load, and incidence of type 2 diabetes mellitus in middle-aged Chinese women Arch Intern Med.Arch Intern Med. 2007 Nov 26;167(21):2310-6

58 Low Carbohydrate Diets Effects of a low-carbohydrate diet on glycemic control in outpatients with severe type 2 diabetes Nutrition & Metabolism 2009, 6:21 Haimoto H 10.9% 7.4% 30% CHO diet www.kidneylifescience.ca

59 Low Glycemic Index Diet Effect of a Low–Glycemic Index or a High–Cereal Fiber Diet on Type 2 Diabetes JAMA. 2008;300(23):2742-2753 Jenkins Randomized trial 210 patients www.kidneylifescience.ca

60 Dietary Therapy of Diabetes Effects of a Mediterranean-Style Diet on the Need for Antihyperglycemic Drug Therapy in Patients with Newly Diagnosed Type 2 Diabetes Giugliano et al, Ann Int Med, 1 Sep 2009, Vol 151, (5) 306-313 www.kidneylifescience.ca

61 Dietary Therapy of Diabetes MediterraneanAHA Low Fat Weight Lost3.8 kg3.2 kg HgB A1C-0.9%-0.5% (p<0.05) HOMA-1.5-0.9 (p<0.05) Serum Insulin (pmol/L)-9.8-5.6 (p<0.05) HDL (mmol/L)0.090.02 (p<0.05) Triglycerides (mmol/L)-0.28-0.07 (p<0.05) % requiring Diabetic Meds 44%70% 59% RRR Effects of a Mediterranean-Style Diet on the Need for Antihyperglycemic Drug Therapy in Patients with Newly Diagnosed Type 2 Diabetes Giugliano et al, Ann Int Med, 1 Sep 2009, Vol 151, (5) 306-313 Randomized Trial 4 year follow up www.kidneylifescience.ca

62 Wheat vs. Beans Effect of Legumes as Part of a Low Glycemic Index Diet on Glycemic Control and Cardiovascular Risk Factors in Type 2 Diabetes Mellitus Arch Intern Med. 2012 Nov 26;172(21):1653-60, Jenkins D www.kidneylifescience.ca

63

64 Fibre increases insulin sensitivity Cereal Fiber Improves Whole- Body Insulin Sensitivity in Overweight and Obese Women Diabetes Care 29:775–780, 2006 Weickert MO www.kidneylifescience.ca

65 Heart Disease Increased Dietary Carbohydrates Heart Disease

66 Howard, B. V. et al. JAMA 2006;295:655-666. Epic Fail Womens Health Initiative Randomized Controlled Dietary Modification Trial www.kidneylifescience.ca

67 Epic Fail Howard, B. V. et al. JAMA 2006;295:655-666. www.kidneylifescience.ca

68 Carbohydrates and Heart Disease A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women Am J Clin Nutr. 2000 Jun;71(6):1455-61 Liu et alAm J Clin Nutr. Nurses Health Study 1984-1994 www.kidneylifescience.ca

69 Risk driven by Sugar A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women Am J Clin Nutr. 2000 Jun;71(6):1455-61 Liu et alAm J Clin Nutr. www.kidneylifescience.ca

70 Glycemic Load and Heart Disease Am J Clin Nutr June 2000 vol. 71 no. 6 1455-1461 Manson et al Relative Risk for Coronary Heart Disease www.kidneylifescience.ca

71 Plaque Progression Dietary fats, carbohydrate, and progression of coronary atherosclerosis in postmenopausal women Am J Clin Nutr 2004;80:1175–84 Herrington et al Higher carbohydrate intake = More progression CAD www.kidneylifescience.ca

72 Hormonal Obesity Theory Fattening Carbohydrates Increased Insulin level Insulin Resistance Fibre Obesity High TG Low HDL Hypertension Diabetes Metabolic Syndrome Fatty Liver High Protein Cortisol Vinegar Fructose Wheat Super-carbohydrate Fasting Diseases Of Civilization Diabetes Heart Disease www.kidneylifescience.ca

73 Cancer

74 Diabetes and Cancer Diabetes and cancer: evaluating the temporal relationship between type 2 diabetes and cancer incidence Diabetologia (2012) 55:1607–1618 www.kidneylifescience.ca

75 Womens Health Initiative Randomized Controlled Dietary Modification Trial Prentice, R. L. et al. JAMA 2006;295:629-642. Epic Fail Low Fat Diet does not reduce Cancer www.kidneylifescience.ca

76 Metformin and reduced risk of cancer in diabetic patients BMJ VOLUME 330 4 JUNE 2005, 1304-5 Case control trial Tayside Scotland 1993-2001 Metformin reduces Cancer Risk www.kidneylifescience.ca

77 Metformin reduces Cancer Risk Adjusted hazard ratio 0.63 Proportion Cancer Free Comparators Metformin New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes Diabetes Care. 2009 Sep;32(9):1620-5 Libby G Diabetes Care. www.kidneylifescience.ca

78 Insulin increases cancer risk Population based cohort study from Saskatchewan 10,309 incident patients Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin Diabetes Care. 2006 Feb;29(2):254-8 Bowker SLDiabetes Care. www.kidneylifescience.ca

79 Insulin increases cancer risk Retrospective cohort of 62 809 patients The influence of glucose-lowering therapies on cancer risk in type 2 diabetes CJ Currie Diabetologia (2009) 52:1766-1777 www.kidneylifescience.ca

80 Hormonal Obesity Theory Fattening Carbohydrates Increased Insulin level Insulin Resistance Fibre Obesity High TG Low HDL Hypertension Diabetes Metabolic Syndrome Fatty Liver High Protein Cortisol Vinegar Fructose Wheat Super-carbohydrate Fasting Diseases Of Civilization Diabetes Heart Disease Cancer www.kidneylifescience.ca

81 Gum disease and Heart Attacks There are a lot of studies that suggest that oral health, and gum disease in particular, are related to serious conditions like heart disease, American Dental Association Periodontal Disease and risk of subsequent Cardiovascular Disease in US male physicians Howell et al. JACC 2001; 37: 445-50 Periodontitis Heart Disease www.kidneylifescience.ca

82 Periodontitis Cavities are the chronic disease equivalent of the canary in the coal mine Sugar Increased Insulin Diabetes Obesity Heart Disease Cavities www.kidneylifescience.ca

83 Hormonal Obesity Theory Fattening Carbohydrates Increased Insulin level Insulin Resistance Fibre Obesity High TG Low HDL Hypertension Diabetes Metabolic Syndrome Fatty Liver High Protein Cortisol Vinegar Fructose Wheat Super-carbohydrate Fasting Diseases Of Civilization Diabetes Heart Disease Cancer Periodontitis www.kidneylifescience.ca

84 Hyperinsulinemia

85 Mortality and Other Important Diabetes-Related Outcomes With Insulin vs Other Antihyperglycemic Therapies in Type 2 Diabetes J Clin Endocrinol Metab 98: 668–677, 2013 Currie CJ 84,622 incident Type 2 DM cases in UK Survival compared To insulin monotherapy

86 SU is BAD for you

87 Carbohydrates and Diabetes Cohort of 64,227 Chinese women Prospective study of dietary carbohydrates, glycemic index, glycemic load, and incidence of type 2 diabetes mellitus in middle-aged Chinese women Arch Intern Med.Arch Intern Med. 2007 Nov 26;167(21):2310-6

88 Dietary Therapy of Diabetes MediterraneanAHA Low Fat Weight Lost3.8 kg3.2 kg HgB A1C-0.9%-0.5% (p<0.05) Plasma Glucose (mmol/L) -1.7-0.8 (p<0.05) HOMA-1.5-0.9 (p<0.05) Serum Insulin (pmol/L)-9.8-5.6 (p<0.05) HDL (mmol/L)0.090.02 (p<0.05) Triglycerides (mmol/L)-0.28-0.07 (p<0.05) Total Cholesterol-0.25-0.1 (p<0.05) % requiring Diabetic Meds 44%70% 59% RRR Effects of a Mediterranean-Style Diet on the Need for Antihyperglycemic Drug Therapy in Patients with Newly Diagnosed Type 2 Diabetes Giugliano et al, Ann Int Med, 1 Sep 2009, Vol 151, (5) 306-313 Randomized Trial 4 year follow up

89 Low HgbA1c is BAD 11,157 cases of DM2 A1C and Cardiovascular Outcomes in Type 2 Diabetes Diabetes Care 34:77–83, 2011, Colacayo et al

90 A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women 75 521 women previously healthy 10 year follow up Higher intake of carbs associated with increased risk of CHD Am J Clin Nutr.Am J Clin Nutr. 2000 Jun;71(6):1455-61 Liu et al

91 A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women Am J Clin Nutr.Am J Clin Nutr. 2000 Jun;71(6):1455-61 Liu et al Risk mostly driven by Sucrose and Fructose

92 Distributions of Individual Modifiable Risk Factors and Relative Risk of Coronary Events in the Nurses' Health Study, 1980 to 1994 Stampfer MJ et al. N Engl J Med 2000;343:16-22. 84,129 women 14 years of follow up Diet composite measure based on a diet low in trans fat and glycemic load, high in cereal fiber, marine n–3 fatty acids, and folate, and with a high ratio of polyunsaturated to saturated fat

93 Mechanism – Hyperinsulinemi a? – Hyperglycemia? Diabetes and cancer: evaluating the temporal relationship between type 2 diabetes and cancer incidence Diabetologia (2012) 55:1607–1618

94 Metformin reduces risk of cancer Metformin and reduced risk of cancer in diabetic patients BMJ VOLUME 330 4 JUNE 2005, 1304-5 Case control trial Tayside Scotland 1993-2001 Metformin reduces risk of cancer

95 Population based cohort study from Saskatchewan 10,309 new users Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin Diabetes Care.Diabetes Care. 2006 Feb;29(2):254-8 Bowker SL

96 The influence of glucose-lowering therapies on cancer risk in type 2 diabetes CJ Currie Diabetologia (2009) 52:1766-1777 Retrospective cohort of 62 809 patients in UK newly started on diabetes medications since 2000 Relative risk compared to metformin mono-therapy

97 Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus patients Gastroenterology Vol 127, #4 Oct 2004 1044-1050 Retrospective cohort of UK General Practice Research Database Nested case control

98 Lung Cancer Lung cancer mortality after 16 years in MRFIT participants in intervention and usual-care groups. Multiple Risk Factor Intervention Trial Ann Epidemiol. 1997 Feb;7(2):125-36 Ann Epidemiol. Relative risk 1.17 (95% CI:0.92- 1.51) DESPITE the fact that 21% in intervention group quit smoking compared to 6% in usual care

99 Conclusions All studies remarkably consistent A low fat diet is not effective for – Obesity – Diabetes – Heart disease – Cancer

100 Effect of a Low–Glycemic Index or a High–Cereal Fiber Diet on Type 2 Diabetes JAMA. 2008;300(23):2742-2753 Jenkins Randomized trial 210 patients

101 Effect of Legumes as Part of a Low Glycemic Index Diet on Glycemic Control and Cardiovascular Risk Factors in Type 2 Diabetes Mellitus Arch Intern Med. 2012 Nov 26;172(21):1653-60, Jenkins D

102 More weight loss Lower blood pressure, heart rate Reduced absolute CHD risk score Effect of Legumes as Part of a Low Glycemic Index Diet on Glycemic Control and Cardiovascular Risk Factors in Type 2 Diabetes Mellitus

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