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Metabolic Syndrome

Part 2: Diabetes & Cancer

Rachele Pojednic, EdM PhD

• Quiz Due: Tuesday 10/24 11:59pm

• Critical Review of Popular Press Nutrition

Project Due: Friday 10/20 11:59pm
• Introduce Diabetes (Type 1, Type 2,
• Understand how diet and lifestyle affect
development of T2D
• Introduce American Cancer Society (ACS) Diet
• Discuss Meat Consumption and Cancer Risk
Metabolic Syndrome
• Cluster of metabolic risk factors that increases
the chance of cardiovascular disease or
• Combination effect – The chances of
developing disease are greater when a patient
has more than one risk factor
• 34% of the US population has metabolic
Diagnosing Metabolic Syndrome
• Three or more of the following:
– Abdominal Obesity
• Waist circumference >40in for men and >35inches for
– Triglyceride Level
• 140mg/dL or greater
– HDL cholesterol
• <40mg/dL (men) or <50mg/dL (women)
– Systolic Blood pressure (top number) of 130mmHg or
greater OR diastolic pressure of 85mmHg or greater
– Fasting glucose of 100mg/dL or greater
• Currently 29.1 million individuals (>age20)
have diabetes in the United States (9.3%)
– 37% have prediabetes
• Diagnosis will increase to 48.3 million by 2050
• Total estimated cost of diagnosed diabetes in
the US is $245 billion per year
– People with diagnosed diabetes have medical
expenditures 2.3x higher than healthy individuals
– 41% increase in $$ from 2007
Diabetes Complications
• Hypoglycemia
• Hyperglycemia
• Hypertension
• Increased LDL Cholesterol
• Heart Disease/Stroke
• Blindness Eye Problems
• Kidney Disease
• Amputations
• Death (7th leading cause in US)
Metabolic Syndrome and Diabetes
• Manufactured in islet-cells in pancreas
• Released from β-cells in the pancreas in response to serum
• Activates glucose uptake, metabolism and storage in muscles
and fat cells
Insulin Resistance
• Response to insulin is deficient
• Body can produce insulin, but does not use it
• Glucose builds up in blood instead of being
absorbed by cells
– Muscle, Fat, and Liver cells do not respond properly to
insulin (results in increased insulin production)
– Leads to prediabetes or Type 2 Diabetes when β-cells
can no longer produce enough insulin
Insulin Resistance
Causes of Insulin Resistance
• Overweight (too much glucose)
• Physical Inactivity (not burning enough glucose)
• Ethnicity
• Hormone/steroid use
• Age
• Sleep problems
• Cigarette Smoking
Three classifications
– Type 1 Diabetes: Due to β-cell destruction in
– Type 2 Diabetes: Due to progressive insulin
secretory defect on the background of insulin
– Gestational Diabetes Mellitus: Due to pregnancy
Diagnosis of Type 2 Diabetes
• HbA1C ≥ 6.5%
• Fasting Plasma Glucose ≥ 126mg/dL
• Two-hour Plasma Glucose ≥ 200mg/dL after
Oral Glucose Tolerance Test (OGTT)
Hemoglobin A1C
• Blood test that provides information about a
patient’s concentration of blood glucose (“blood
• Based on the attachment of glucose to
– Percentage of red blood cell glycation
• Average glucose of the past 3 months
– Normal < 5.7%
– PreDiabetes 5.7-6.4%
– Diabetes ≥ 6.4%
Fasting Plasma Glucose
• Amount of glucose present in the blood after
12+ hours of not eating
– Normal <100mg/dL
– PreDiabetes 100-125mg/dL
– Diabetes >125mg/dL
Oral Glucose Tolerance Test
• Measures the body’s ability to manage
glucose (via insulin action)
• Fasting Blood Glucose taken
• Glucose drink with measured glucose ingested
• Blood Samples taken at 1, 2, and 3 hours after
– Normal 2hr PG: <140mg/dL
– Diabetes 2hr PG: ≥ 200mg/dL
Oral Glucose Tolerance Test
Prevention/Delay of Type 2 Diabetes
• Weight loss (up to 7% of body weight)
• Increase Physical Activity to ≥ 150min/wk
• Metformin Therapy
• Screening for and treatment of modifiable risk
factors for CVD
• Follow-up Counseling
Treatment of Type 2 Diabetes
Pharmacologic Therapy
– Metformin
• Suppresses Liver glucose production “gluconeogenesis” and induces GLUT4 for glucose
uptake into tissue
– Insulin
• Increases glucose uptake into tissue
– GLP-1 receptor agonist
• Increases insulin secretion while inhibiting glucagon
– DPP-4 Inhibitor
• Blocks the breakdown of GLP-1 (DPP-4 signals degradation of GLP-1)

Lifestyle Therapy
– Physical Activity ≥ 150min/wk
– Medical Nutritional Therapy
– Weight Control
– Follow-up Counseling

Garber, 2011, Diabetes Care

Diabetes Prevention Program Results

Risk reduction:
• 33% by metformin
• 58% by lifestyle

(Knowler et al, 2002, NEJM)

Medical Nutrition Therapy
• Recommended as part of overall treatment
• Reduce energy intake while maintaining
healthful eating pattern
• Modest weight loss with MNT may provide
clinical benefits (improved glycemia, blood
pressure and lipids/cholesterol)
Eating Patterns
Macronutrient Distribution
• No ideal percentage of calories
• Should be from vegetables, fruits, whole
grains, legumes and dairy products
• Consume at least the amount of fiber and
whole grains recommended for general public
• Avoid sugar sweetened beverages
Eating Patterns
Macronutrient Distribution

Maki & Phillips, 2015, J Nutr

Eating Patterns
Macronutrient Distribution
• Evidence is inconclusive
• Quality appears to be more important than
• Increased MUFA (mono-unsaturated fat) may
benefit glycemic control
• Increased PUFA (polyunsaturated fat) is
• Saturated fat, trans fat and cholesterol is the
same as recommended for general public
Eating Patterns
Macronutrient Distribution
• No Ideal Percentage from Protein
• Reduction below usual intake not
• Be careful with diabetic kidney
disease, because high intake may be
detrimental (Weickert et al, 2011, AJCN)
• Choose lean protein and meat alternatives
ADA Recommended Eating Patterns
No standard meal plan or eating pattern works
universally for all persons with diabetes

– Nutrition therapy should be individualized and based on:

• Health Goals
• Personal & Cultural Preferences
• Health Literacy
• Access to Healthful Choices
• Readiness, willingness, and ability to change
– Nutrition Interventions should:
• Emphasize variety of minimally processed, nutrient dense foods in
appropriate portions
• Provide person with diabetes with tools for day-to-day food plan
and behavior change that can be maintained for the long-term
ADA Recommended Eating Patterns
Dietary Pattern Main Food Components
DASH High in fruits, vegetables, low-fat dairy, whole
grains, poultry, fish, nuts. Low in saturated fat,
red meat, sweets, sugar-containing beverages,
Low Carbohydrate Foods high in protein, fat; veggies low in carbs.
Avoid sugar-containing foods, and grains.
Low Fat High in veggies, fruits, starches, lean protein,
low-fat dairy. Total fat intake <30% total energy
intake, sat fat intake <10%.
Mediterranean Abundant plant food, minimally processed,
seasonal, fresh foods. Fruit as dessert;
sugar/honey infrequently. Olive oil primary fat.
Low to moderate dairy, eggs, red meat, wine
(with meals)
Vegan No flesh foods or animal products.
Vegetarian No flesh foods; includes eggs and/or dairy.
Comparing Dietary Eating Patterns

Forest plots that show

differences in Hb A1c

(A) Low-carbohydrate
and other diets
(B) Low-GI and other
(C) Mediterranean and
other diets
(D) High-protein and
other diets

Olubukola Ajala et al. Am J Clin Nutr 2013;97:505-516


Tai Le & Sabate, 2014, Nutrients

Nutrition & Cancer
• 572,000 Cancer Deaths per year
• 1/3 attributed to diet and physical activity
– Overweight/Obesity
• 1/3 attributed to tobacco products
• Some genetic susceptibility, most risk due to
factors that are not inherited
Lifestyle & Cancer
• Maintaining a healthy weight, staying
physically active throughout the lifetime and
consuming a healthy diet can substantially
reduce one’s lifetime risk of developing or
dying from cancer
Lifestyle and Mortality
• Maintaining a healthy weight, staying
physically active throughout the lifetime and
consuming a healthy diet can reduce risk of
early death by 80% (Ford et al, 2012)
American Cancer Society Guidelines
• Nutrition and Physical Activity Guidelines
• Advise health care professionals, policy
makers, and general public
• Based on consensus of scientific evidence on
diet and physical activity and cancer risk
– Reviewed publications since 2006
ACS Guidelines Evidence
• Randomized Controlled Trials
• Prospective Cohort Studies
• Case Control Studies (Larger > Smaller)
– Most credible: Adjusted for total caloric intake,
considered other dietary factors, and controlled
for known risk factors
ACS Guidelines Challenges
• “…the evidence is not definitive because the
published results are inconsistent, or because
the methods of studying nutrition and chronic
disease in human populations continue to
evolve” (Kushi et al, 2012)

– Studies focus on specific nutrients

– Dose, timing, duration of exposure not considered
– Large variations of nutritional status among
human populations
ACS Guidelines Challenges
• Randomized Controlled Trials
– Considered gold standard
– May fail to find effect if:
• Intervention begins to late in life
• Sample size is too small
• Follow-up is too short
– Not feasible in many lifestyle interventions
• Ex. Long term consequences of interventions that begin
in infancy and extend for many years
ACS Guidelines Challenges
• “No set of nutrition and physical activity
guidelines can offer 100% protection against
any disease; the potential health benefit
represents a decreased likelihood that a
disease will occur, but is not a guarantee of
total protection.”(Kushi et al, 2012)
ACS Guidelines
• Consistent with:
– American Heart Association
– American Diabetes Association
– 2010 Dietary Guidelines for Americans
– 2008 Physical Activity Guidelines for Americans
ACS Recommendations
• Achieve and Maintain a Healthy
Weight over the lifetime
– Be as lean as possible without being
– Avoid Excess weight gain at all ages.
For those who are currently
overweight/obese, losing even a
small amount of weight has health
– Engage in regular physical activity
– Limit consumption of high-calorie
foods and beverages
ACS Recommendations
• Adopt a Physical Active Lifestyle
– Adults should engage in at least
150 minutes of moderate
physical activity each week OR 75
minutes of vigorous activity
– Children/Adolescents should
engage in 1hr of moderate to
vigorous activity every day
– Limit sedentary behavior
– Doing some physical activity, no
matter what, can have health
ACS Recommendations
• Consume a Healthy Diet, with
an emphasis on plant foods
– Choose foods and beverages in
amounts that help achieve a
healthy weight
– Limit consumption of
processed meat and red meat
– Eat at least 2.5 cups of
fruits/vegetables each day
– Choose whole grains instead of
refined grains
ACS Recommendations
• Community Action
– Public, private, and community organizations should
work collaboratively at national, state and local levels
to implement policy and environmental change that:
• Increase access to affordable, healthy foods in communities,
worksites and schools and decrease access to and marketing
of foods and beverages of low nutritional quality, especially
to youth
• Provide safe, enjoyable and accessible environments for
physical activity in schools and worksites, and for
transportation and recreation in communities
ACS Recommendations
• Community Action
– Institute of Medicine: “It is unreasonable to
expect that people will change either behavior
easily when so many forces in the social, cultural,
and physical environment conspire against such
ACS Recommendations
• Community Action
– Combats:
• Increasing Portion Sizes
• Consumption of high-calorie convenience food
• Sugar-sweetened beverages
• Reduced Food Preparation at Home
• Declining Physical Activity
– Sitting at desks, in cars, on trains
– Standing on Escalators or in Elevators
– Unsafe neighborhoods (or perception)
– Poorly designed built environment
ACS Nutrition Guidelines
1. Achieve and Maintain a Healthy
Weight Throughout the Lifetime
• Overweight and Obesity contribute to 14-20%
of all cancer-related mortality
– Breast
– Colon & Rectal (particularly abdominal fatness)
– Endometrial
– Kidney
– Esophagus
– Pancreas
1. Achieve and Maintain a Healthy
Weight Throughout the Lifetime
• Mechanisms:
– Reduce immune function & inflammation
– Alters metabolism of several hormones
• Insulin
• Estradiol
– Alters factors that regulate cell proliferation/growth
• Insulin-like growth factor (IGF-1)
– Alters proteins that make hormones more or less
available to tissue
• Sex hormone binding globulin
• IGF-binding proteins
2. Adopt a Physically Active Lifestyle
• Reduces the risk of:
– Breast
– Colon
– Endometrial
– Prostate
– Pancreatic
– Associations are less strongly linked to other
cancers, but evidence is mounting
2. Adopt a Physically Active Lifestyle
• Mechanisms:
– Balance caloric intake with energy expenditure
– Regulates:
• Sex hormones
• Insulin
• Prostaglandins
• Immune system
• Inflammation

McTiernan, 2008)
2. Adopt a Physically Active Lifestyle
• 150min of moderate OR 75min of vigorous
each week
– Optimal intensity, duration, and frequency to
reduce cancer risk is unknown
– Approaching and exceeding 300min of moderate
or 150min of vigorous activity is likely to provide
additional protection
– Limited evidence to show whether one long bout
of exercise or several smaller bouts is more
2. Adopt a Physically Active Lifestyle
• Limit time spent sitting
– Limit TV & Screen time
– Use stationary bike/treadmill when in front of screen
– Use stairs
– Walk or bike to your destination
– Exercise at lunch
– Take an exercise break at work
– Walk to visit instead of sending text/email
– Plan active vacations
– Wear a Pedometer
3. Consume a Healthy Diet, with an
emphasis on plant foods
• Choose foods and beverages in amounts that
help achieve and maintain a healthy weight
– Read Labels
– Eat smaller portions
– Choose vegetables, whole fruits and other low calorie
– Limit consumption of sugar sweetened beverages
(soft drinks, sports drinks, and fruit drinks)
– When eating away from home, be mindful to choose
low fat/sugar/calorie foods and avoid large portions
3. Consume a Healthy Diet, with an
emphasis on plant foods
• Limit consumption of processed
meats and red meat (beef, pork,
– Minimize consumption of processed
meats such as bacon, sausage,
luncheon meat and hot dogs
– Choose fish, poultry, or beans as a
protein alternative
– If you eat red meat, select lean cuts
and small portions
– Prepare meat, poultry and fish by
baking, broiling or poaching rather
than frying or grilling (charring)
3. Consume a Healthy Diet, with an
emphasis on plant foods
• Limit consumption of processed meats and
red meat (beef, pork, lamb)
– 15-20% increased risk of colorectal cancer per
100g of red meat or 50g of processed meat per
3. Consume a Healthy Diet, with an
emphasis on plant foods
• Eat at least 2.5cups of vegetables
and fruit each day
– Include vegetables and fruit at
every meal and for snacks
– Eat a variety of vegetables and fruit
– Emphasize whole vegetables and
fruit; choose 100% juice
– Limit consumption of creamy
sauces, dressings, and dips with
vegetables and fruit
3. Consume a Healthy Diet, with an
emphasis on plant foods
• Dark Green Vegetables (Kale)
• Orange Vegetables (Pepper, Butternut Squash)
• Cruciferous Vegetables (Cabbage, Broccoli,
Cauliflower, Brussels Sprouts)
• Soy Products (Edamame, Tofu)
• Allium Vegetables (Onions & Garlic)
• Legumes
• Tomato Products
3. Consume a Healthy Diet, with an
emphasis on plant foods
• Choose Whole Grains instead of refined grain
– Choose whole-grain foods such as whole grain
bread, pasta, and cereal
– Choose brown rice instead of white
– Limit consumption of other refined carbohydrate
foods, including pastries, candy, sugar sweetened
breakfast cereal and other high-sugar foods.
Do the ACS Guidelines work?
• 65,838 Post Menopausal Women in Women's Health
Initiative Study
• After 12.6 years, 8632 incidents of Cancer and 2356 Cancer
Deaths identified
• Highest ACS guidelines scores compared with the lowest
– 17% lower risk of any CA [0.75-0.92]
– 22% lower risk of breast CA [0.67-0.92]
– 52% lower risk of colorectal [0.32-0.73]
– 20% lower risk CA mortality [0.71-0.90]

(Thomsen et al, Cancer Prev Res, 2014)

Food Patterns and Cancer
• The Human Diet is highly complex, so studying
food patterns over time is most beneficial for
determining cancer risk

Pradhan P, 2013
Dietary Patterns and Cancer Risk
• Adventist Health Study 2 of 77,659
• 380 colon and 110 rectal CA at 7.3 yrs
• Adjusted HR in vegetarians vs non
– All CRC 0.78 [0.64-0.95]
• Vegans 0.84 [0.59-1.19]
• Lacto-Ovo 0.82 [0.65-1.02]
• Pescoveg 0.57 [0.40-0.82]
• Semiveg 0.92 [0.62-1.37]
– Colon CA 0.81 [0.65-1.00]
– Rectal CA 0.71 [0.46-1.06]

(Orlich et al; JAMA Intern Med 2015)

Food Patterns and Cancer
• Individuals who eat less red and processed
meat also tend to eat fewer refined grain
products and consume more vegetables and
fruit and have lower risk of developing or
dying from certain cancers.
Food Patterns and Cancer
• Individuals who eat more processed and red
meat, potatoes, refined grains, and sugar
sweetened beverages/foods are at higher risk
of developing or dying from cancer
Why is Red/Processed Meat Bad?
Heterocyclic amines (HCAs) are
mutagenic agents found in meat
products that are cooked at
high temperatures (>500F).

HCAs are formed in meat products

most often when they are grilled,
baked, or pan fried. When the meat is
exposed to heat that is > 300 degrees
F, mutations
in the creatine/creatinine-proteins in
the muscle, amino acids, and sugars
may cause formation of HCAs.
Why is Red/Processed Meat Bad?
WHO estimates that 50g of
processed meat or 100g of
red meat increase the risk
of colorectal cancer by 18%
and 17%, respectively​

133,000 patients will be

diagnosed with colorectal
cancer, the third most
common cancer in the US​

The lifetime risk of

developing colorectal
cancer is 5% - so this
equates to only an
increased risk factor of 1.2
or 1.1 for ever serving of
processed/red meat
Overall Risk
Reduced Risk Increased Risk
Fruits Red Meat
Vegetables Processed Meat
Nuts &Seeds Sugar Sweetened Beverages
Milk (?) Trans Fatty Acids
Fiber Sodium

Lim et al, Lancet, 2012

Nutrients in Isolation and Cancer
• Evidence that vegetable and fruit
consumption reduces cancer risk has led to
attempts to isolate specific nutrients from
these foods and study their effects as
supplements, sometimes in very high doses
– Many RCT’s fail to confirm promising leads and
some even suggest harm!
Nutrients in Isolation and Cancer
Nutrients in Isolation and Cancer
• No benefit of antioxidant supplementation
and reduced cancer risk
Nutrients in Isolation and Cancer
• Beta-Carotene
– In 2 trials of individuals at high risk for lung cancer
(heavy smokers, former heavy smokers, exposure
to asbestos) high dose beat-carotene supplements
developed lung cancer at higher rates than

NEJM, 1994
Nutrients in Isolation and Cancer
• SELECT: Selenium and Vitamin E Cancer
Prevention Trial
– Failed to demonstrate benefit for prostate cancer
– Increased risk in high dose Vitamin E

Nicastro &
Dunn, 2013
Nutrients in Isolation and Cancer

Le Gal et al, 2015, Science Translational Medicine

Nutrients in Isolation and Cancer
Food Additives And Contaminants
– Food Quality Protection Act of 1996 created
uniform health-based standards for labeling raw
and processed food
– USDA must clear any additives that must
demonstrate rigorous testing in animals
Food Additives And Contaminants
• Food Additives and Contaminants
– Growth Hormones
– Antibiotics
– Pesticide
– Herbicide
– BPA (Bisphenol A)
• Some are not carcinogenic, but
others may alter metabolic
pathways that influence cancer
risk (i.e. act as disruptors or
modifiers of hormone
Food Additives And Contaminants
– Unintentional Contamination

• Aflotoxin: Fungal contamination of grains/legumes

– Potent carcinogen in animals and liver cancer in humans
• Heavy Metals: Cadmium or Mercury
– Accumulation in the food chain: Fish
– Transfer from environment: Shellfish
Food Processing
• Food Processing
– Detrimental:
• Hydrogenated Vegetable Oils (CVD)
• Sodium or Sodium Nitrite to meat (Cancer)
– Beneficial:
• Freezing Vegetables may preserve nutrients
• Heating may release nutrients more readily
Book Club Book

Today, buffeted by one food fad after

another, America is suffering from what can
only be described as a national eating
disorder. Will it be fast food tonight, or
something organic? Or perhaps something
we grew ourselves? The question of what to
have for dinner has confronted us since man
discovered fire. But as Michael Pollan
explains in this revolutionary book, how we
answer it now, as the dawn of the twenty-
first century, may determine our survival as
a species. Packed with profound surprises,
The Omnivore's Dilemma is changing the
way Americans thing about the politics,
perils, and pleasures of eating.