Diet and Disease

The Phantom Menace

Part 5 of 6The Aetiology of Obesity

Hormonal Obesity Theory

FatteningCarbohydrates

Increased Insulin level

Insulin Resistance

Fibre Obesity

High TGLow HDL

Hypertension

Diabetes

Metabolic Syndrome

Fatty Liver

High Protein

Cortisol

Vinegar

Fructose

WheatSuper-carbohydrate Fasting

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Diseases of Civilization

Coronary Artery DiseaseObesityDiabetesColorectal cancerBreast cancerTooth decayConstipation “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

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First Nations

1908 Smithsonian Institution’s Bureau

of American Ethnology report

“Not one pronounced instance of advanced arterial sclerosis”

“Malignant disease, if they exist at all … must be extremely rare”

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Inuit

1952 Queen’s 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

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Masai

Pastoralists – diet of milk, meat and bloodRarely eat fresh vegetables

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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

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The Kitava Study

1990s - Kitavan diet 69% carbohydrateFruit, vegetables, roots, fish and coconuts

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Low Serum Insulin despite high carb intake

Low Serum Insulin in Traditional Pacific Islanders—The Kitava Study

Metabolism, Vol 48, No 10 (Oct), 1999:1216-1219 Lindeberg S

Swedish reference range 10-90%

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Okinawa

Life expectancy among the highest in the world85% CarbohydrateBMI average of 20.4

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Conclusions

Populations could be healthy with diets of 95% carbohydrate or 95% meat

No refined/ processed foodsNo flourNo sugar

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Populations in Transition

Tokelau Island Migration Study

“Their populations are notable for their low levels of blood pressure… coronary heart disease, obesity and diabetes”

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Tokelau Island Migration Study

Impact of trading posts established on atolls

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Sugar consumption

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Tokelau Migrants Study

Average weight increased by 20-30 pounds

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Diabetes

Graph: www.wholehealthsource.blogspot.com

Gout

Graph: www.wholehealthsource.blogspot.com

Tooth Decay

Graph: www.wholehealthsource.blogspot.com

New Zealand Maori 2006

High levels of physical activity

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Maori Obesity

Staples of Maori diet - bread, flour, biscuits, breakfast cereals, sugar, and potatoes

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Increasing cancer with Westernization

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Increasing Cancer with Westernization

Regions in order of WesternizationFrom: US Treasury Public Health Reports 1934

Graph: www.wholehealthsource.blogspot.com

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Increasing cancer with Westernization

Migration patterns and breast cancer risk in Asian-American womenJ Natl Cancer Inst. 1993 Nov 17;85(22):1819-27.

Equal risk in 2 generations

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Increasing Cancer with Westernization

Hong KongThe Breast, Volume 17, Issue 1, February 2008, Pages 42–5

Breast Cancer Incidence per 100,000

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Geographic Risk of Heart Attack

Source: Wholehealthsource.blogspot.ca

Geographic Pathology of Myocardial InfarctionDr. Kyu Taik Lee (Am. J. Cardiol. 13:30. 1964)

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The Saccharine Disease

1966 ‘Refined-carbohydrate disease’

1. Overconsumption – evades satiety signals2. Removal of protein – speeds digestion3. Removal of fibre – speeds digestion4. Removal of fat – speeds digestion

Refining of Carbohydrates

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Metabolic Syndrome

Abdominal obesityHigh triglycerides, low HDLHypertensionDiabetesInsulin resistanceElevated uric acid levels

Alzheimers’ disease Gallstones Fatty liver

Gerald Reaven (Stanford)

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Hormonal Obesity Theory

FatteningCarbohydrates

Increased Insulin level

Insulin Resistance

Fibre Obesity

High TGLow HDL

Hypertension

Diabetes

Metabolic Syndrome

Fatty Liver

High Protein

Cortisol

Vinegar

Fructose

WheatSuper-carbohydrate Fasting

DiseasesOf Civilization

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High Insulin levels are a risk factor for heart disease

Hyperinsulinemia as an independent risk factor for ischemic heart diseaseNEJM 1996 Apr 11;334(15): 952-7 Despres JP

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Complications of DiabetesType 1 and 2 Diabetes

High Blood Sugars (Oxidative Stress) (Advance Glycation End Products)

Complications of Diabetes

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The Action to Control Cardiovascular Risk in Diabetes Study Group. N Engl J Med 2008;358:2545-2559

ACCORD

Hazard Ratio 1.22

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What about hyperinsulinemia?

Type 2 Diabetes

High Blood SugarsIncreasedInsulin

Complications of Diabetes

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Insulin treatment has toxicity

12,272 new diabetics 1991-1996 SaskatchewanInsulin use and increased risk of mortality in type 2 diabetesDiabetes, Obesity and Metabolism 12: 47–53, 2010 Gamble JM

“significant and graded association between mortality risk and insulin exposure level”

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Insulin treatment has toxicity

Metform Sulfonylurea Insulin0.8

1

1.2

1.4

1.6

1.8

2

1 1.436 1.808

Adjusted Hazard RatioFor Mortality

84,622 incident Type 2 DM cases

Mortality and Other Important Diabetes-Related Outcomes With Insulin vs Other Antihyperglycemic Therapies in Type 2 DiabetesJ Clin Endocrinol Metab 98: 668–677, 2013 Currie CJ

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Insulin is BAD for you

1986-2008 UK General Practice Research DatabaseSurvival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort studyLancet 2010; 375:481-89, Currie CJ

Oral CombinationInsulin

Adjusted Hazard Ratios by A1c

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Non-diabetics

11,092 patients in ARIC studyGlycated Hemoglobin, Diabetes, and Cardiovascular Risk in Nondiabetic AdultsN Engl J Med 2010;362:800-11, Selvin E

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Long acting insulin increases risk

Tresiba

Comparato

r0

0.050.1

0.150.2

0.25

350% increase rate of MI

STEMI rate

Tresiba

Comparato

r0

0.4

0.8

1.2

1.61.614

1

MACE

MACE

Odd

s Ra

tio

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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

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Sulfonylurea versus Metformin

Multicenter, randomized, double-blind, placebo-controlled trial

Deaths M

I

Stroke

s

Revasc

Total0

10

20

30

40

50

60

70

GlipizideMetformin

35.1%

25%

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

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Glucose Control without Hyperinsulinemia

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

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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% RRR2.5% ARR

Randomized 1,429 patients3.3 year follow up

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Hypertension

HR 0.66 P= 0.006

17%

11%

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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).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; 10:7. 2. Frederich R, et al. Postgrad Med 2010; 122:16-27. 3. Johansen O-E, et al. Cardiovasc Diabetol 2012; 11:3.

Risk ratio 95% CI No.

DPP-4 inhibitor better

Risk ratio

1.3 1.80.1 1 10

Sitagliptin1 0.68a [0.41–1.12] 64

Saxagliptin2 0.43b [0.23–0.80] 40c

Linagliptin3* 0.34b 34d[0.16–0.70]

Comparator better

69

Hormonal Obesity Theory

FatteningCarbohydrates

Increased Insulin level

Insulin Resistance

Fibre Obesity

High TGLow HDL

Hypertension

Diabetes

Metabolic Syndrome

Fatty Liver

High Protein

Cortisol

Vinegar

Fructose

WheatSuper-carbohydrate Fasting

DiseasesOf Civilization

www.kidneylifescience.ca

Diabetes

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 S65WTF??

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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

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Overall Primary Outcome Results.

A Clinical Trial to Maintain Glycemic Control in Youth with Type 2 DiabetesN 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/ weekEat less, move more

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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

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 patientsLow Fat, Low Calorie diet

(1200-1800 kcal)Meal replacement products, Increased exercise (175 min/week)

Eat less, move more

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Look-Ahead Trial

Cardiovascular Effects of Intensive Lifestyle Intervention in Type 2 DiabetesN Engl J Med 2013 DOI: 10.1056/NEJMoa1212914

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LOOK AHEAD

No measurable benefit after 9.6 years!www.kidneylifescience.ca

Eat Less, Move More

Low Fat, Low Calorie:

DOES NOT WORKHAS NEVER WORKEDWILL NEVER WORK

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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 womenArch Intern Med. 2007 Nov 26;167(21):2310-6

Q1 Q2 Q3 Q4 Q50.8

0.850.9

0.951

1.051.1

1.151.2

1.251.3

Relative Risk of Diabetes

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

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Low Glycemic Index Diet

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

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Dietary Therapy of Diabetes

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

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Dietary Therapy of DiabetesMediterranean 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%

59% RRR

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

Randomized Trial4 year follow up

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Wheat vs. BeansWgt Loss (kg) Waist (cm) sBP dBP

-4.5

-4

-3.5

-3

-2.5

-2

-1.5

-1

-0.5

0

-2

-1.3

0 0

-2.6-2.4

-4

-3

WheatBeans

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

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Fibre increases insulin sensitivityCereal Fiber Improves Whole-Body Insulin Sensitivity in Overweight and Obese WomenDiabetes Care 29:775–780, 2006 Weickert MO

Usual Fibre5.6

5.8

6

6.2

6.4

6.6

6.8

76.85

6.06

M value

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Heart Disease

Increased DietaryCarbohydrates

Heart Disease

Howard, B. V. et al. JAMA 2006;295:655-666.

Epic Fail

Womens Health Initiative Randomized Controlled Dietary Modification Trial

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Epic Fail

Howard, B. V. et al. JAMA 2006;295:655-666.

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Carbohydrates and Heart Disease

Q1 Q2 Q3 Q4 Q50.8

1

1.2

1.4

1.6

1.8

2

1 1.01

1.25

1.51

1.98Quintiles of Glycemic Load

Adj

uste

d Re

lativ

e Ri

sk

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 al

Nurses Health Study 1984-1994

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Risk driven by Sugar

Starch Sucrose Fructose Lactose0.9

0.951

1.051.1

1.151.2

1.251.3

0.94

1.22

1.07

0.94

Adjusted Relative Risk of CAD

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 al

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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

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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

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Hormonal Obesity Theory

FatteningCarbohydrates

Increased Insulin level

Insulin Resistance

Fibre Obesity

High TGLow HDL

Hypertension

Diabetes

Metabolic Syndrome

Fatty Liver

High Protein

Cortisol

Vinegar

Fructose

WheatSuper-carbohydrate Fasting

DiseasesOf Civilization

DiabetesHeart Disease

www.kidneylifescience.ca

Cancer

Diabetes and Cancer

Breast

Colorectal

Endometrial

Kidney

Lymphoma

Pancre

asLiv

er0

0.5

1

1.5

2

2.5

3

1.21.3

2.3

1.421.19

2.5 2.5

Risk Estimate

Diabetes and cancer: evaluating the temporal relationship between type 2 diabetes and cancer incidence Diabetologia (2012) 55:1607–1618

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Womens Health Initiative Randomized Controlled Dietary Modification TrialPrentice, R. L. et al. JAMA 2006;295:629-642.

Epic Fail

Low Fat Diet does not reduce Cancer

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No Yes0

0.2

0.4

0.6

0.8

1

1.21

0.77

Any exposure to Metformin

Adj

uste

d O

dds

Ratio

Metformin and reduced risk of cancer in diabetic patientsBMJ VOLUME 330 4 JUNE 2005, 1304-5

Case control trial Tayside Scotland 1993-2001

Metformin reduces Cancer Risk

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Metformin reduces Cancer Risk

Adjusted hazard ratio 0.63

Pro

po

rtio

n C

ance

r F

ree

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

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Insulin increases cancer risk

Metformin Sulphonylurea0

0.20.40.60.8

11.21.4

1

1.3

Adjusted Hazard Ratio

Insulin - No Insulin - Yes0

0.4

0.8

1.2

1.6

2

1

1.9Adjusted Hazard Ratio

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

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Insulin increases cancer risk

Metformin Met + SU Sulphonylurea Insulin0.6

0.7

0.8

0.9

1

1.1

1.2

1.3

1.4

1.5

11.08

1.36 1.42Re

lativ

e Ri

sk

Retrospective cohort of 62 809 patients The influence of glucose-lowering therapies on cancer risk in type 2 diabetesCJ Currie Diabetologia (2009) 52:1766-1777

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Hormonal Obesity Theory

FatteningCarbohydrates

Increased Insulin level

Insulin Resistance

Fibre Obesity

High TGLow HDL

Hypertension

Diabetes

Metabolic Syndrome

Fatty Liver

High Protein

Cortisol

Vinegar

Fructose

WheatSuper-carbohydrate Fasting

DiseasesOf Civilization

DiabetesHeart DiseaseCancer

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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 physiciansHowell et al. JACC 2001; 37: 445-50

Periodontitis Heart Disease

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Periodontitis

Cavities are the chronic disease equivalent of the canary in the coal mine

Sugar

IncreasedInsulin

DiabetesObesityHeart Disease

Cavitieswww.kidneylifescience.ca

Hormonal Obesity Theory

FatteningCarbohydrates

Increased Insulin level

Insulin Resistance

Fibre Obesity

High TGLow HDL

Hypertension

Diabetes

Metabolic Syndrome

Fatty Liver

High Protein

Cortisol

Vinegar

Fructose

WheatSuper-carbohydrate Fasting

DiseasesOf Civilization

DiabetesHeart DiseaseCancerPeriodontitis

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