Part 5 of 6 The Aetiology of Obesity Hormonal Obesity Theory Fattening Carbohydrates Increased Insulin level Insulin Resistance Fibre Obesity High TG Low HDL Hypertension Diabetes Metabolic ID: 933707
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Slide1
Diet and Disease
The Phantom Menace
Part 5 of 6
The Aetiology of Obesity
Slide2Hormonal 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.intensivedietarymanagement.com
Slide3Diseases of Civilization
Coronary Artery Disease
Obesity
Diabetes
Colorectal 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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Slide4First 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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Slide5Inuit
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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Slide6Masai
Pastoralists – diet of milk, meat and blood
Rarely eat fresh vegetables
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Slide7Tukisenta
“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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Slide8The
Kitava
Study
1990s - Kitavan diet
69% carbohydrateFruit, vegetables, roots, fish and coconuts
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Slide9Low 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 SSwedish reference range 10-90%
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Slide10Okinawa
Life expectancy among the highest in the
world
85% Carbohydrate
BMI average of 20.4
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Slide11Conclusions
Populations could be healthy with diets of 95% carbohydrate or 95% meat
No refined/ processed foods
No flour
No sugar
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Slide12Populations in Transition
Slide13Tokelau Island Migration Study
“Their
populations are notable for their low levels of blood
pressure… coronary
heart disease, obesity and
diabetes”
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Slide14Tokelau Island Migration Study
Impact of trading posts established on atolls
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Slide15Sugar consumption
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Slide16Tokelau Migrants Study
Average weight increased by 20-30
pounds
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Slide17Diabetes
Graph: www.wholehealthsource.blogspot.com
Slide18Gout
Graph: www.wholehealthsource.blogspot.com
Slide19Tooth Decay
Graph: www.wholehealthsource.blogspot.com
Slide20New Zealand Maori 2006
High levels of physical activity
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Slide21Maori Obesity
Staples of Maori diet - bread, flour, biscuits, breakfast cereals, sugar, and potatoes
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Slide22Increasing cancer with Westernization
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Slide23Increasing Cancer with Westernization
Regions in order of Westernization
From: US Treasury Public Health Reports 1934
Graph: www.wholehealthsource.blogspot.com
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Slide24Increasing cancer with Westernization
Migration patterns and breast cancer risk in Asian-American women
J
Natl
Cancer Inst.
1993 Nov 17;85(22):1819-27.
Equal risk in 2 generations
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Slide25Increasing Cancer with Westernization
Hong Kong
The Breast
, Volume 17, Issue 1, February 2008, Pages 42–5
Breast Cancer Incidence per 100,000
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Slide26Geographic Risk of Heart Attack
Source: Wholehealthsource.blogspot.ca
Geographic Pathology of Myocardial Infarction
Dr
. Kyu Taik Lee (Am. J. Cardiol. 13:30. 1964)
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Slide27The Saccharine Disease
1966 ‘
R
efined-carbohydrate disease’
1.
Overconsumption
– evades satiety signals
2.
Removal of protein – speeds digestion
3. Removal of fibre – speeds digestion4. Removal of fat – speeds digestion
Refining of Carbohydrateswww.intensivedietarymanagement.com
Slide28Metabolic Syndrome
Abdominal obesity
High triglycerides, low HDL
Hypertension
DiabetesInsulin resistanceElevated uric acid levels Alzheimers
’ disease Gallstones Fatty liver
Gerald Reaven (Stanford)
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Slide29Hormonal 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.intensivedietarymanagement.com
Slide30High 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
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Slide31Complications of Diabetes
Type 1 and 2 Diabetes
High Blood Sugars
(Oxidative Stress)
(Advance
Glycation
End Products)
Complications of Diabetes
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Slide32The 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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Slide33What about hyperinsulinemia?
Type 2 Diabetes
High Blood
Sugars
Increased
Insulin
Complications of Diabetes
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Slide34Insulin treatment has toxicity
12,272 new diabetics 1991-1996 Saskatchewan
Insulin
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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Slide35Insulin 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
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Slide36Insulin 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.intensivedietarymanagement.com
Slide37Non-diabetics
11,092 patients in ARIC study
Glycated
Hemoglobin
, Diabetes, and Cardiovascular Risk in Nondiabetic AdultsN Engl J Med 2010;362:800-11, Selvin E
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Slide38Long acting insulin increases risk
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Slide39Metformin 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
CLwww.intensivedietarymanagement.com
Slide40Sulfonylurea 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
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Slide41Glucose Control without Hyperinsulinemia
Slide42Proportion 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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Slide43Lowering 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 patients
3.3 year follow upwww.intensivedietarymanagement.com
Slide44Hypertension
HR 0.66 P= 0.006
17%
11%
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Slide45Stratified 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; 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
1.8
0.1
1
10
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
Slide46Hormonal 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.intensivedietarymanagement.com
Slide47Diabetes
Slide48Nutrition 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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Slide49Nutrition 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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Slide50Overall 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/ weekEat less, move morewww.intensivedietarymanagement.com
Slide51Editorial 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”
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Slide52NIH 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
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Slide53Look-Ahead Trial
Cardiovascular Effects of Intensive Lifestyle Intervention in Type 2 Diabetes
N Engl J Med 2013 DOI: 10.1056/NEJMoa1212914
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Slide54LOOK AHEAD
No measurable benefit after 9.6 years!
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Slide55Eat Less, Move More
Low Fat, Low
Calorie:
DOES NOT
WORKHAS NEVER WORKEDWILL NEVER WORK
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Slide56www.intensivedietarymanagement.com
Slide57Carbohydrates 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
Slide58Low Carbohydrate Diets
Effects of a low-carbohydrate diet on glycemic control in outpatients with severe type 2 diabetes
Nutrition
& Metabolism
2009,
6
:21 Haimoto H10.9%
7.4%
30% CHO dietwww.intensivedietarymanagement.com
Slide59Low 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 JenkinsRandomized trial 210 patients
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Slide60Dietary 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.intensivedietarymanagement.com
Slide61Dietary Therapy of Diabetes
Mediterranean
AHA 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 DiabetesGiugliano et al, Ann Int Med, 1 Sep 2009, Vol 151, (5) 306-313Randomized Trial4 year follow upwww.intensivedietarymanagement.com
Slide62Wheat 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
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Slide63www.intensivedietarymanagement.com
Slide64Fibre increases insulin sensitivity
Cereal
Fiber
Improves Whole-Body Insulin Sensitivity in Overweight and
Obese WomenDiabetes Care 29:775–780, 2006 Weickert MO
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Slide65Heart Disease
Increased Dietary
Carbohydrates
Heart Disease
Slide66Howard, B. V. et al. JAMA 2006;295:655-666
.
Epic Fail
Womens
Health Initiative Randomized Controlled Dietary Modification Trial
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Slide67Epic Fail
Howard, B. V. et al. JAMA 2006;295:655-666
.
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Slide68Carbohydrates 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 al
Nurses Health Study 1984-1994
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Slide69Risk 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 al
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Slide70Glycemic 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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Slide71Plaque 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.intensivedietarymanagement.com
Slide72Hormonal 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.intensivedietarymanagement.com
Slide73Cancer
Slide74Diabetes and Cancer
Diabetes and cancer: evaluating the temporal
relationship between
type 2 diabetes and cancer
incidence Diabetologia (2012) 55:1607–1618
www.intensivedietarymanagement.com
Slide75Womens
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.intensivedietarymanagement.com
Slide76Metformin 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.intensivedietarymanagement.com
Slide77Metformin 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
www.intensivedietarymanagement.com
Slide78Insulin 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
SL
www.intensivedietarymanagement.com
Slide79Insulin 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.intensivedietarymanagement.com
Slide80Hormonal 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.intensivedietarymanagement.com
Slide81Gum 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 Diseasewww.intensivedietarymanagement.com
Slide82Periodontitis
Cavities are the chronic disease equivalent of the canary in the coal mine
Sugar
Increased
Insulin
Diabetes
ObesityHeart Disease
Cavities
Slide83Hormonal 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.intensivedietarymanagement.com
Slide84H
yperinsulinemia
Slide85Mortality 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 CJ84,622 incident Type 2 DM cases in UK
Survival compared
To insulin
monotherapy
Slide86SU is BAD for you
Slide87Carbohydrates 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
Slide88Dietary Therapy of Diabetes
Mediterranean
AHA 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 Meds44%
70%59% RRREffects 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
Slide89Low 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
Slide90A 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.
2000 Jun;71(6):1455-61 Liu et al
Slide91A 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
Risk mostly driven by
Sucrose and Fructose
Slide92Distributions 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
Slide93Mechanism
Hyperinsulinemia?
Hyperglycemia
?
Diabetes and cancer: evaluating the temporal relationship
between type 2 diabetes and cancer incidence
Diabetologia
(2012) 55:1607–1618
Slide94Metformin reduces risk of cancer
Metformin and reduced risk of cancer in diabetic patients
BMJ
VOLUME 330 4 JUNE 2005, 1304-5Case control trial Tayside Scotland 1993-2001
Metformin
reduces
risk of cancer
Slide95Population 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. 2006 Feb;29(2):254-8 Bowker SL
Slide96The 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
Slide97Insulin 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 DatabaseNested case control
Slide98Lung 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):125-36Relative 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
Slide99Conclusions
All studies remarkably consistent
A low fat diet
is not effective
forObesityDiabetesHeart diseaseCancer
Slide100Effect of a Low–Glycemic
Index or
a High–Cereal
Fiber Diet on Type 2 DiabetesJAMA
. 2008;300(23):2742-2753 JenkinsRandomized trial 210 patients
Slide101Effect 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
Slide102More 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
Slide103Slide104