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

2. Hormonal Obesity Theory
Vinegar
Fibre
Obesity
High Protein
High TG
Low HDL
Increased
Insulin level
Fattening
Carbohydrates
Hypertension
Cortisol
Diabetes
Wheat
Super-carbohydrate
Fasting
Fatty Liver
Key is INSULIN
How does it link to diseases, not just risk factors
Insulin Resistance
Metabolic Syndrome
Fructose

3. Diseases of Civilization
Coronary Artery Disease
Obesity
Diabetes
Colorectal cancer
Breast cancer
Tooth decay
Constipation
Western Diseases
Certain diseases are rare to non existent amongst isolated populations that lived traditional lifestyles and ate traditional diets
African missionaries Dr. Schweitzer
“On my arrival in Gabon, I was astonished to encounter no cases of cancer”
Over the ensuing decades he witnessed a steady increase in cancer
“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

4. 1908 Smithsonian Institution’s Bureau of American Ethnology report
First Nations
“Malignant disease, if they exist at all … must be extremely rare”
“Not one pronounced instance of advanced arterial sclerosis”
life expectancy was as long or longer than the local white population
1910 – Indian Affairs Bureau survey of physicians
115,000 Native Americans only 29 documented cases of malignant tumours
1908 Smithsonian Institution’s Bureau of American Ethnology report

5. Inuit 1952 Queen’s University 1950-1974 Upernavik 1 case of diabetes
“It is commonly stated that cancer does not occur in the Eskimos, and to our knowledge no case has so far been reported”
Upernavik
1 case of diabetes
1902 – Samuel Hutton
“The Eskimo is a meat eater, the vegetable part of his diet is a meager one”
Did not see or hear of a case of malignant growth in an Eskimo in 11 years
Town of Upernavik 1800 population

6. Masai www.kidneylifescience.ca
Kenya and Tanzania
Hypertension and obesity almost non-existent
Pastoralists – diet of milk, meat and blood Rarely eat fresh vegetables

7. Tukisenta www.kidneylifescience.ca
“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
New Guinea highland tribe studied extensively in the 1960s and 70s

8. The Kitava Study www.kidneylifescience.ca
No indications of stroke, diabetes, dementia or congestive heart failure
No obesity
(yam, sweet potato, taro, tapioca)
Excellent blood pressure
– Dr Lindeberg
1990s - Kitavan diet 69% carbohydrate
Fruit, vegetables, roots, fish and coconuts

9. Low Serum Insulin despite high carb intake
Swedish reference range 10-90%
Less than 0.2% of the caloric intake came from Western food, such as edible fats, dairy products, sugar, cereals, and alcohol
Despite high carbohydrate intake, serum insulin levels low
But all carbohydrates are unrefined
Low Serum Insulin in Traditional Pacific Islanders—The Kitava Study
Metabolism, Vol 48, No 10 (Oct), 1999: Lindeberg S

10. Okinawa Life expectancy among the highest in the world
85% Carbohydrate
BMI average of 20.4
Noted for their low mortality from cardiovascular disease
Traditional diet compared to Japanese average
20% less calories
300% of the green/yellow vegetables
Less Rice, the staple was the sweet potato
25% of the sugar

11. Conclusions www.kidneylifescience.ca
Populations could be healthy with diets of 95% carbohydrate or 95% meat No refined/ processed foods No flour No sugar
Rare to find “Western diseases” in peoples eating traditional diets
Low serum insulin levels

12. Populations in Transition

13. Tokelau Island Migration Study
1841 Dietary staples
coconuts, fish and breadfruit
70% of calories from coconut
1966 Threat of over-population due to cyclone
more than half of Tokelauans moved to mainland
(New Zealand)
“Their populations are notable for their low levels of blood pressure… coronary heart disease, obesity and diabetes”

14. Tokelau Island Migration Study
6x increase in flour consumed
Impact of trading posts established on atolls

15. Sugar consumption

16. Tokelau Migrants Study
Decreased fat
Increased refined carbohydrates
Average weight increased by pounds

17. Diabetes Graph: www.wholehealthsource.blogspot.com
lower saturated-fat consumption
increases in diabetes, hypertension, gout and cancer
Graph:

18. Gout
Graph:

19. Tooth Decay
Graph:

20. New Zealand Maori 2006 www.kidneylifescience.ca
Despite increased physical activity – very high prevalence of obesity
High levels of physical activity

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

22. Increasing cancer with Westernization
Nutritional transition – Westernization of diet, lifestyle, and health status
Eskimos living near European settlers ate a “settler’s dietary” mostly “tea, bread, ship’s biscuits, molasses, and salt fish or pork” – refined carbohydrates

23. Increasing Cancer with Westernization
Flour and sugar prominent changes
Not explained by increased life span
Regions in order of Westernization
From: US Treasury Public Health Reports 1934
Graph:

24. Increasing cancer with Westernization
Equal risk in 2 generations
Within 1 generation, risk of Japanese immigrants increased by 60%
Within 2 generations, risk is equal
Migration patterns and breast cancer risk in Asian-American women J Natl Cancer Inst Nov 17;85(22):

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

26. Geographic Risk of Heart Attack
Japanese in Japan have much lower risk of MI than Janpanese in USA
African in Africa has much lower risk of MI than African in USA
Geographic Pathology of Myocardial Infarction Dr. Kyu Taik Lee (Am. J. Cardiol. 13: )
Source: Wholehealthsource.blogspot.ca

27. The Saccharine Disease
Refining of Carbohydrates
1. Overconsumption – evades satiety signals
2. Removal of protein – speeds digestion
3. Removal of fibre – speeds digestion
4. Removal of fat – speeds digestion
George Campbell and Dr. Cleave – argued that Western diseases constituted the manifestations of a single primary disorder that could be called “refined carbohydrate disease”
Theory eventually replaced in 1977 by McGovern and Dietary Fat Hypothesis
1966 ‘Refined-carbohydrate disease’

28. Metabolic Syndrome www.kidneylifescience.ca Abdominal obesity
High triglycerides, low HDL
Hypertension
Diabetes
Insulin resistance
Elevated uric acid levels
Alzheimers’ disease
Gallstones
Fatty liver
1980’s - metabolic abnormalities common to obesity, diabetes, and heart disease
Clustering of risk factors suggests a common cause
Diseases identical to ‘diseases of civilization’
Gerald Reaven (Stanford)

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

30. High Insulin levels are a risk factor for heart disease
Blood samples from 2103 men without diabetes
Insulin more than risk factor – linked to heart disease
Hyperinsulinemia as an independent risk factor for ischemic heart disease NEJM 1996 Apr 11;334(15): Despres JP

31. Complications of Diabetes
Type 1 and 2 Diabetes
High Blood Sugars
(Oxidative Stress)
(Advance Glycation
End Products)
This is the way we think about diabetes and its complications
Complications of Diabetes

32. ACCORD www.kidneylifescience.ca Hazard Ratio 1.22
Randomized 10,251 diabetic patients to tight vs. less tight glycemic control
After 3.5 years, study stopped early due to increased deaths
27.8% of patients in aggressive group gained > 10 kg
The Action to Control Cardiovascular Risk in Diabetes Study Group. N Engl J Med 2008;358:

33. What about hyperinsulinemia?
Type 2 Diabetes
Increased
Insulin
High Blood Sugars
Are complications related to high insulin levels?
Complications of Diabetes

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

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

36. Insulin is BAD for you www.kidneylifescience.ca
Oral Combination
Insulin
27,965 patients intensified from oral monotherapy to combination therapy
20,005 patients changed regimens to include insulin
Mean follow up 4.5 years
Adjusted Hazard Ratios by A1c
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

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

38. Long acting insulin increases risk
FDA rejects new insulin based on increased risk of MACE

39. Metformin versus Sulfonylurea
Retrospective cohort study of 253,690 patients initiating treatment
(98,665 sulfonylurea and 155,025 with metformin)
Comparative Effectiveness of Sulfonylurea and Metformin Monotherapy on Cardiovascular Events in Type 2 Diabetes Mellitus Ann Intern Med. 2012;157: Roumie CL

40. Sulfonylurea versus Metformin
Multicenter, randomized, double-blind, placebo-controlled trial
304 DM2 with CAD
Mean age 63.3 years
3 year follow up
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

41. Glucose Control without Hyperinsulinemia

42. Proportion of Participants with Events over Time.
ORIGIN
Randomized 12,537 with CV risk factors and type 2 diabetes to tight control with insulin or less tight control
Proportion of Participants with Events over Time.
No measureable difference in outcomes
The ORIGIN Trial Investigators. N Engl J Med 2012;367:

43. Lowering glucose without raising insulin improves outcomes
Randomized 1,429 patients
3.3 year follow up
49% RRR
2.5% ARR
12 MI Acarbose 1 MI Placebo
32 events Acarbose 15 events Placebo
Acarbose Treatment and the Risk of Cardiovascular Disease and Hypertension in Patients with Impaired Glucose Tolerance JAMA 2003; 290:

44. Hypertension
17%
11%
HR 0.66 P= 0.006

45. Stratified Analyses of CV Events: Pooled Data from Registration Trials (DPP-4 Inhibitors)69
Risk ratio
95% CI
No.
Sitagliptin1
0.68a
[0.41–1.12] 64
Saxagliptin2
0.43b
[0.23–0.80]
40c
Linagliptin3*
0.34b
[0.16–0.70]
34d
This slide compares data from the cardiovascular meta-analyses at the time of registration for sitagliptin, saxagliptin and linagliptin.1-3
For sitagliptin (Januvia), the relative risk reduction of cardiovascular events was calculated to be 0.68 in a meta-analysis of over 10,246 patients, with confidence intervals of 0.41 and 1.12.
For saxagliptin (Onglyza), the relative risk reduction of cardiovascular events was calculated to be 0.43 in a meta-analysis of 4,607 patients, with confidence intervals of 0.23 and 0.80.
For linagliptin (Trajenta), the relative risk reduction was calculated to be 0.34 in a meta-analysis of 5,239 patients, with confidence intervals of 0.16 and It is important to note that the main contributor to the number of events was a head-to-head study of linagliptin vs. sulfonylureas. When linagliptin was compared to placebo, the comparison was not statistically significant (per Trajenta Canadian Product Monograph, July 2011).
Given the fact that the study program for each of the drugs varied considerably with regard to study population, comparator, duration of follow-up, etc., one should not compare the results of one drug vs. another.
References:
1. Williams-Herman D, Engel SS, Round E, et al. Safety and tolerability of sitagliptin in clinical studies: a pooled analysis of data from 10,246 patients with type 2 diabetes. BMC Endocr Disord 2010; 10:7.
2. Frederich R, Alexander JH, Fiedorek FT, et al. A systematic assessment of cardiovascular outcomes in the saxagliptin drug development program for type 2 diabetes. Postgrad Med 2010; 122(3):16-27.
Johansen OE, Neubacher D, von Eynatten M, et al. Cardiovascular safety with linagliptin in patients with type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a phase 3 programme. Cardiovasc Diabetol 2012; 11:3.
1.3
1.8
0.1 1 10
Risk ratio
DPP-4 inhibitor better
Comparator better
*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).
aCalculated using exact procedures for the Poisson processes; bCox hazard ratio; cPatients with events: n = 22, saxagliptin; n = 18, control; dPatients with events: n = 11, linagliptin; n = 23, comparator.
1. Williams-Herman D, et al. BMC Endocr Disord 2010; 10: Frederich R, et al. Postgrad Med 2010; 122: Johansen O-E, et al. Cardiovasc Diabetol 2012; 11:3.

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

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”
(it’s true – they really wrote this) Page S65
WTF??
Diabetes Care 1 Jan 2008 Vol 31 S61-81

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
A position statement of the American Diabetes Association
EAT LESS MOVE MORE

50. Overall Primary Outcome Results.
No Benefit to Low Calorie Low Fat!
kcal low fat diet
Exercise min/ week
Eat less, move more
Randomized trail
699 patients
A Clinical Trial to Maintain Glycemic Control in Youth with Type 2 Diabetes
N Engl J Med 2012; 366(24):

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”
Cannot believe their own advice is flawed and therefore blame must lie with patients
Advice that has never worked in the history of dieting

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
( kcal)
Meal replacement products,
Increased exercise (175 min/week)
Eat less, move more
“A low fat diet (<30% of kcal from fat with <10% saturated fat) and increased physical activity are key components of the intervention”
Maintained weight loss of 5% over 4 years compared to 1% in control group
randomized to lifestyle intervention or usual care
Advice to ‘eat less, move more’ DOES NOT WORK – key is not calories but insulin

53. Look-Ahead Trial www.kidneylifescience.ca
5,145 patients randomized – 9.6 year follow up
Cardiovascular Effects of Intensive Lifestyle Intervention in Type 2 Diabetes
N Engl J Med 2013 DOI: /NEJMoa

54. No measurable benefit after 9.6 years!
LOOK AHEAD
Low Fat, Low Calorie diet DOES NOT WORK, HAS NEVER WORKED
No measurable benefit after 9.6 years!

55. Eat Less, Move More Low Fat, Low Calorie: DOES NOT WORK
HAS NEVER WORKED
WILL NEVER WORK
Has been tried over and over again – no benefits
Target is not fat and calories and exercise – it is INSULIN

57. Carbohydrates and Diabetes
Cohort of 64,227 Chinese women
no history of diabetes or other chronic disease at baseline
Follow up for 4.6 years
Prospective study of dietary carbohydrates, glycemic index, glycemic load,
and incidence of type 2 diabetes mellitus in middle-aged Chinese women
Arch Intern Med. 2007 Nov 26;167(21):2310-6

58. Low Carbohydrate Diets
10.9%
30% CHO diet
7.4%
6 months
LDL decreased, HDL increased
33 patients with DM A1C 10.9%
Final A1C 7.4%
Effects of a low-carbohydrate diet on glycemic control in outpatients with severe type 2 diabetes
Nutrition & Metabolism 2009, 6:21 Haimoto H

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): Jenkins Randomized trial 210 patients

60. Dietary Therapy of Diabetes
Primary outcome - need for DM drugs if HgBA1C > 7%
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)

61. Dietary Therapy of Diabetes
Mediterranean
AHA Low Fat
Weight Lost
3.8 kg
3.2 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)
0.09
0.02 (p<0.05)
Triglycerides (mmol/L)
-0.28
-0.07 (p<0.05)
% requiring Diabetic Meds
44%
70%
215 patients
<50% carbs, >30% fats
Mostly olive oil
<30% fat
Randomized Trial
4 year follow up
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)

62. Wheat vs. Beans www.kidneylifescience.ca
Randomized controlled 121 pts wheat vs beans
1 cup/ day legumes or increase whole wheat products
3 month follow up
Glycemic index decreased from 80 – 66
Fibre increase 15.6 g to 25.6 g/day
More weight loss, more abdominal fat loss, lower BP, lower 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
Arch Intern Med Nov 26;172(21): , Jenkins D

63. www.kidneylifescience.ca Consensus diet: whole grains, low fat dairy
Paleo diet: avoid cereals, dairy, margarine, sugar and salt
29 DM with CAD patients randomized

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
17 overweight non diabetic women randomized to usual diet vs 31.2 g/day insoluble fiber over 3 days

65. Heart Disease
Increased Dietary
Carbohydrates
Heart Disease

66. Epic Fail www.kidneylifescience.ca
48, 835 patients
8.1 year average follow up
No difference in weight
Intervention - Low fat diet (20% of calories) with increased veg/fruit (5 servings/day) and grains (6 servings/day) vs usual diet
Womens Health Initiative Randomized Controlled Dietary Modification Trial
Howard, B. V. et al. JAMA 2006;295:

67. Epic Fail www.kidneylifescience.ca
No difference in stroke – no benefit to low fat diet
Howard, B. V. et al. JAMA 2006;295:

68. Carbohydrates and Heart Disease
women previously healthy
10 year follow up
Higher intake of carbs associated with increased risk of CHD
Nurses Health Study
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): Liu et al

69. Risk driven by Sugar www.kidneylifescience.ca
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): Liu et al

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

71. Plaque Progression www.kidneylifescience.ca
Higher carbohydrate intake = More progression CAD
235 women with heart disease
3.1 year follow up with coronary angiogram
As increase fat – tend to have less progression
As increase protein and carbohydrate – more progression
Dietary fats, carbohydrate, and progression of coronary atherosclerosis in postmenopausal women Am J Clin Nutr 2004;80:1175–84 Herrington et al

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

73. Cancer

74. Diabetes and Cancer www.kidneylifescience.ca
Diabetics at increased risk of cancer
Mechanism – high insulin or high glucose?
Diabetes and cancer: evaluating the temporal relationship between type 2 diabetes and cancer incidence Diabetologia (2012) 55:1607–1618

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

76. Metformin reduces Cancer Risk
Not likely that metformin reduces risk of cancer but more likely that insulin (SU) increases the risk
Metformin and reduced risk of cancer in diabetic patients
BMJ VOLUME JUNE 2005,
Case control trial Tayside Scotland

77. Metformin reduces Cancer Risk
Adjusted hazard ratio 0.63
Comparators
Proportion Cancer Free
Observational cohort study of 4,085 pt from UK
New users of Metformin
( )
New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes Diabetes Care Sep;32(9): Libby G

78. Insulin increases cancer risk
Average follow up 5.4 years
Average age 64.3 years
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 Feb;29(2):254-8 Bowker SL

79. Insulin increases cancer risk
2051 events noted
in UK newly started on diabetes medications since 2000
Retrospective cohort of patients
The influence of glucose-lowering therapies on cancer risk in type 2 diabetes
CJ Currie Diabetologia (2009) 52:

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

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
Type 2 DM patients have 3x risk of periodontal disease
Serious research performed to determine if brushing teeth can reduce heart disease
Periodontitis
Heart Disease
Periodontal Disease and risk of subsequent Cardiovascular Disease in US male physicians
Howell et al. JACC 2001; 37:

82. Periodontitis
Cavities are the chronic disease equivalent of the canary in the coal mine
Cavities caused primarily by eating sugar and white flour
Traditional societies did not brush their teeth!
Diabetes
Obesity
Heart Disease
Increased
Insulin
Sugar
Cavities

83. Hormonal Obesity Theory
Vinegar
Fibre
Obesity
High Protein
High TG
Low HDL
Increased
Insulin level
Fattening
Carbohydrates
Diseases Of
Civilization
Hypertension
Cortisol
Diabetes
Wheat
Super-carbohydrate
Fasting
Fatty Liver
All are diets that target increased insulin
Diet not only related to diabetes, but to entire metabolic syndrome and all the diseases of civilization
Diabetes
Heart Disease
Cancer
Periodontitis
Insulin Resistance
Metabolic Syndrome
Fructose

84. Hyperinsulinemia
Increased adhesion molecule expression on endothelial cells
Increased transendothelial migration of leukocytes
Stimulation of smooth muscle cell proliferation[3,4]
Pro-inflammatory effects (5)

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

86. SU is BAD for you

87. Carbohydrates and Diabetes
Cohort of 64,227 Chinese women
no history of diabetes or other chronic disease at baseline
Follow up for 4.6 years
Prospective study of dietary carbohydrates, glycemic index, glycemic load,
and incidence of type 2 diabetes mellitus in middle-aged Chinese women
Arch Intern Med. 2007 Nov 26;167(21):2310-6

88. Dietary Therapy of Diabetes
Mediterranean
AHA Low Fat
Weight Lost
3.8 kg
3.2 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)
0.09
0.02 (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%
215 patients
<50% carbs, >30% fats
Mostly olive oil
<30% fat
59% RRR
Randomized Trial
4 year follow up
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)

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

90. 75 521 women previously healthy 10 year follow up
A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women
women previously healthy
10 year follow up
Higher intake of carbs associated with increased risk of CHD
Am J Clin Nutr. 2000 Jun;71(6): 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 Jun;71(6): 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
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
Stampfer MJ et al. N Engl J Med 2000;343:16-22.

93. Mechanism Hyperinsulinemia? 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
Record linkage databases – Diabetes Clinical Information System and database of dispensed prescriptions
Metformin and reduced risk of cancer in diabetic patients
BMJ VOLUME JUNE 2005,
Case control trial Tayside Scotland

95. Population based cohort study from Saskatchewan 10,309 new users
Average follow up 5.4 years
Average age 64.3 years
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 Feb;29(2):254-8 Bowker SL

96. Relative risk compared to metformin mono-therapy
2051 events noted
The influence of glucose-lowering therapies on cancer risk in type 2 diabetes
CJ Currie Diabetologia (2009) 52:
Retrospective cohort of patients in UK newly started on diabetes medications since 2000

97. Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus patients
Gastroenterology Vol 127, #4 Oct
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
Relative risk 1.17 (95% CI: )
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): Jenkins Randomized trial 210 patients

101. Randomized controlled 121 pts wheat vs beans
1 cup/ day legumes or increase whole wheat products
3 month follow up
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 Nov 26;172(21): , Jenkins D

102. 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
More weight loss
Lower blood pressure, heart rate
Reduced absolute CHD risk score