diet and disease the phantom menace part 5 of 6 the aetiology of obesity
TRANSCRIPT
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Diet and Disease
The Phantom Menace
Part 5 of 6The Aetiology of Obesity
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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
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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
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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
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Gout
Graph: www.wholehealthsource.blogspot.com
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Tooth Decay
Graph: www.wholehealthsource.blogspot.com
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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
www.kidneylifescience.ca
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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
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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
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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
www.kidneylifescience.ca
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Diabetes
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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
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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
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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
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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
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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
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Cancer
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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
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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 DiseaseCancerPeriodontitis
www.kidneylifescience.ca