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Nutrition Study Guide
1A. Nutrition and Primary Prevention of CVD:
Prevention of CHD in Women Through Diet and Lifestyle
Things that increase risk of CHD
-Diet high in transfat
->15 cigarettes / day
-BMI > 25 kg/m2
-Low level of physical activity
-Low level of EtOH consumption
-High dietary glycemic load (low fat diet)
Things that lower risk of CHD
-Diet high in mono/poly unsat. fats
-Not smoking
-BMI < 25 kg/m2
-Physical activity > ½ hr / day
-*Consuming > 1 drink / day
-Consuming 1 serving of fish / week
-Diet high in cereal fiber
-Diet high in folate
*Consuming EtOH increases risk of breast cancer
Be careful with the “low-fat diet”: the current low-fat, high-carbohydrate diet recommended in the US may not be
optimal for prevention of CHD and may increase risk in those with high degrees of insulin resistance or glucose
intolerance.
Take home message:
To prevent CHD, avoid transfat, don’t smoke, watch your weight, exercise when you can, have a drink a day, and
eat some fish.
2A. Salt/Cholesterol and CVD Prevention
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Characteristics of populations with low BP: (1) low salt, (2) high veggies, (3) low meat, (4) little obesity
DASH (Dietary Approaches to Stop Hypertension) Study
 Purpose: to identify a diet that lowers BP and is acceptable to general population
 3 diets: Control (normal US diet), Fruit/Veg diet, DASH diet (high in fruits, vegs, nuts, fish, and dairy; low
in fats, red meat, and sweets)
 DASH diet most effective at reducing BP if you are hypertensive, but can also slightly decrease BP even if
you are normotensive.
 DASH diet was equal to or better than most antihypertensive meds.
 Study did NOT alter sald intake, so…
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DASH-Sodium Trial
 6 diets: low, intermediate, and high-sodium with either normal US diet or DASH diet.
 Found ADDITIVE effect: DASH diet was even better at low-sodium intake at reducing BP, both for
hypertensive and normotensive individuals.
 Enhanced effect in African-Americans. Role of polymorphism in AT II receptor that contributed to saltsensitivity??? More prevalent in Blacks???
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Obesity further increased risk for CVD in those who consumed high-salt diets.
Replacement of saturated fat by unsaturated fat improves lipid profile more than consuming a low-fat diet,
where carbohydrates replace fat. Carbs LOWER HDL and RAISE TG. Unsaturated fat lowers LDL more than
carbs.
Mediterrranean-style diet REDUCES risk of MI. Includes: abundant plant foods, fresh fruit, olive oil, low
cheese, low yogurt, low fish/poultry, low red meat, and don’t forget the wine!
High glycemic index foods increase TG (white bread, potatoes, cakes, cookies, etc.)
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2B. Nutrition and CVD Prevention (Ruth Adams)
ATP III Guidlines
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Major Risk Factors (Exclusive of LDL) that modify LDL goals:
o Cigarette smoking
o HTN (BP≥140/90, or on anti-hypertensive meds)
o Low HDL (≤40mg/dl)
o Family history of CHD (first degree rel. male≤55, female ≤65)
o Age (male≥45, female≥55)
LDL Goals based on risk category:
o CHD and CHD risk equivalents – LDL<100
o 2+ risk factors – LDL<130
o 0-1 risk factor – LDL<160
- CHD risk equivalents = other clinical forms of atherosclerotic disease, diabetes, multiple risk factors that
confer a 10-year risk for CHD >20%
- 10-year risk calculated using Framingham Risk Assessment System. Calculations based on age, total
cholesterol, smoking status, HDL, and systolic BP (treated vs. untreated)
LDL-lowering therapy initiation:
o CHD or CHD risk equivalents – LDL≥130
o 2+ risk factors – 10yr risk 10-20% - LDL≥130; 10yr risk <10% - LDL≥160
o 0-1 risk factor – LDL≥190
- Possible drug therapies include statins (↓↓LDL, ↓TG, ↑HDL), bile acid sequestrants (↓LDL, ↑HDL),
Nicotinic acid (↓LDL, ↓TG, ↑HDL), Fibric Acids (↓LDL, ↓↓TG, ↑HDL)
- Lifestyle changes should be initiated at LDL levels ~30 mg/dL lower than the above.
Therapeutic lifestyle changes include diet and exercise:
o Recommended intake of:
 Saturated Fat <7% of total calories
 Polyunsaturated fat up to 10% of total calories
 Monounsaturated Fat up to 20 % of total calories
 Total Fat 25-35% of total calories
 Carbs 50-60% of total calories
 Protein ~15% of total calories
 Fiber 20-30 g/day
o Total Fat intake dependent on keeping saturated fats and trans fats low. Higher intake of unsat.
fats can help lower triglycerides and raise HDL.
Metabolic Syndrome = constellation of lipid and non-lipid risk factors of metabolic origin. Closely linked
to insulin resistance. Enhances risk of CHD at any LDL level. Exists when 3 or more of the following are
present:
o Abdominal obesity (based on waist circumference >102 cm in men, >88cm in women)
o Triglycerides ≥ 150 mg/dl
o HDL <40 mg/dl in men, <50 mg/dl in women
o Blood Pressure ≥135/85
o Fasting glucose ≥110 mg/dl
3A. Nutrition and Cancer Prevention
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Scope
o 1/3 US Dx of cancer in lifetime, 1/3 cancer deaths due to diet
o Affluent countries: lung, colon, breast, prostate
o Developing countries: stomach, liver, oral, esoph, cervix
o Difference b/c inherited DNA, lifestyle
Carcinogenesis via food:
o Initiation
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 Bind to DNA  misreading
 Phase I, II enzymes, free radicals
o Promotion/Progression
 Interact w/ tumor suppressor genes/oncogenes
 Hormonal
 Malnutrition  low immunosurveillance
o Metastasis: Angiogenesis modulated by nutrition
>> Total Energy 
 Insulin/insulin growth Fx dysregulation
 Earlier menarche  breast, ovarian
 > height  breast, prostate, colorectal
 obesity  ovarian
Fat: inconclusive
 Animal fat  tumor promoter? Breast, colon, prostate
 High fat (vs high energy?) = high cancer
Meat: colon strong correlation
Fruits/veg: suggestive ↓ oropharynx, esoph, lung, stomach, colon
Folate: ↓ adenoma, ↓colorectal, ↓breast?
Alcohol: ↑ breast, colon, oral, larynx, esoph, liver
Others:
o Retinol: ↑ immunity, ↓ breast, lung?
o Carotenoids: ↑ or ↓ lung, breast, prostate, ovary?
o Vit E: no clear breast, lung, colon, some prostate?
o Phytoestrogens: ↑ breast, endometrial
3B. Dietary Fiber and Colon Cancer
Objectives:
 Differences between case-control, cohort, randomized trials, meta-analysis
o Case-control: get cases, then controls. OR = ad/bc, AR%, PAR%, recall past
o Cohort: follow baseline population RR from today to see AR, AR%, PAR, time, incidence
o Randomized: get subjects, randomly assign to treatments
o Meta-analysis: statistically analyze aggregate data from several studies
 Key studies fiber/colorectal CA, state of the science:
1st Author
Ghadirian
Study Design
Case control
Fuchs
Cohort
Schatzkin
RCT
Howe
Meta-analysis
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Patient Population
1070 ♀ 35-79 y.o.
French Canadians
88,757 ♀ 34-59 y.o. no
colon cancer Hx
1905 35+ y.o., + colon
cancer Hx
5,287 w/ cancer
10,470 w/o
Diet Assessment
12 mo. intake
questionairre every
2 yrs for 6 yrs
Assigned diets
Various
Results
↑ fiber  ↓ cancer,
OR = 0.5
No assoc w/
development
No assoc w/
recurrence
↑ fiber  ↓ cancer
Followup
N/a
16 yrs
4 yrs
N/a
Advice to patient: unclear how to interpret variable data, but fiber can’t hurt (in moderation)
4A. Vitamin Deficiency & Methods of Dietary Assessment
Who is susceptible: elderly, alcoholics, patients with malabsorption, inborn errors of metabolism, those undergoing
hemodialysis or receiving parenteral nutrition, and people using fad diets.
FOLIC ACID
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neural tube deficits; colorectal cancer; macrocytic anemia; Cardiovascular Dz: needed for the metabolism of
homocystine. High homocystine predisposes to venous thromboembolism and atherosclerosis.
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Sources: Leafy veggies (folate), Fruits (folate), Supplements (folic acid--more bioavailable)
VITAMIN D (elderly susceptible)
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Rickets; Ostiomalacia; Hypovitaminosis D-- high bone turnover, low bone mineralization, high risk fractures,
high PTH
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Sources: Cod liver oil, oily fish, Fortified dairy products, Sun exposure, Supplement
VITAMIN B12 (elderly susceptible)
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dementia, neurologic deficits, anemia
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Causes: poor intake, absorption
ANTIOXIDANTS
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Vit C, E, A
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Originally thought to prevent cancer, don’t know if it really works.
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TOXICITY of vitamins
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In pregnancy, very high Vit A increases risk for congenital malformation
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No HRT + Retinol = increased relative risk for bone fractures
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Too much Vit D causes Vit D intoxication calcemia
Other noteworthy points:
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B3--High doeses improve migranes
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Fat-soluble vitamins (ADEK) stay in body longer, therefore toxicity greater
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Some more deficiencies
VITAMIN B1--Beriberi: neropathy, cardiomyopathy, encephalopathy
VITAMIN B2: angular stomatitis, dermatitis
VITAMIN B3--Pellagra: dermatitis, dementia, diarrhea
VITAMIN C--scurvy: capillary fragility, bleeding
VITAMIN E--anemia
4B. Mary Morris (Nutritional deficiency)
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Mary Morris is an 84yo woman with a non-healing wound. She also has poor dentition and bleeding gums,
ecchymoses, and hemorrhages around hair follicles. She is a "light eater" and drinks one glass of wine each
night.
She has pancytopenia, macrocytosis, multi-lobed PMNs, normal coags, normal serum protein.
Patient has many symptoms of scurvy (vitamin C deficiency): impaired connective tissue formation, bleeding
into skin (ecchymoses, petechiae, perifollicular hemorrhages), inflamed and bleeding gums, and other
manifestations of bleeding into joints and body cavities/organs. Also, weakness, fatigue, and depression.
Folate deficiency is also consistent with this patient's presentation. It causes megaloblastic anemia similar to
B12 deficiency, but without the neurolgic abnormalities. The most common cause is nutritional due to poor diet
and/or alcoholism. Megablastosis can develop within four to five months of a folate-deficient diet because
body stores are small and even earlier in alcoholics.
It would be helpful to measure folate and B12 levels in the patient's serum and to get a blood smear and bone
marrow aspirate.
Scurvy is rare in the U.S., but more common in the elderly. The elderly commonly have B12 deficiency
because of gastric atrophy and lack of gastric-produced intrinsic factor, but this is accompanied by neurologic
signs.
Treat her with replacement therapy: 200 mg/d Vitamin C, 1 mg/d folate by mouth.
5A. Vitamins for Chronic Disease Prevention
In this lecture, Dr. Fletcher talked about taking vitamins to 1. prevent deficiency 2. optimize normal health and 3.
prevent or treat chronic disease. The major topic of discussion was 3. prevention and treatment of chronic disease.
The take home points are the following:
1.
The major water soluble and fat soluble vitamins are: water soluble--B1(thiamin),2(riboflavin),3(niacin),6,
folate, B12, C, biotin, panthothenic acid. Fat soluble: ADEK. The ones focused on in lecture were folic
acid, D, B12, and antioxidants.
2. The major topic of discussion was about vitamins being used to prevent or treat chronic disease. Namely
folic acid preventing BIRTH DEFECTS, CVD, and CANCER.
3. Prior to discussing prevention and treatment of chronic diseases, severe deficiencies were briefly
mentioned. The big ones mentioned, which are relatively rare now a days, were: C—scurvy, niacin(B3)—
pellagra, thiamine(B1)—beriberi, D—rickets, folate—macrocytic anemia, B12—macrocytic anemia and
neuro disorders.
4. In terms of prevention and treatment of chronic disease, the idea conveyed was to treat suboptimal levels of
vitamins, such as B12, folate, and D, to prevent the chronic problems that arise from those lower levels.
5. Mechanistic basis for suboptimal levels leading to chronic disease—e.g. low folate, B12, B6 can lead to
high homocysteine, which can lead to CVD; also low D raises PTH which increases bone turnover and
fractures.
6. Folic Acid is a hot topic of interest because of its ability to decrease the risk of neural tube defects (75%
reduction), cardiovascular disease (RCTs are in the works, but proven to lower homocysteine levels, which
are clearly associated with CVD), and colorectal cancer (multivitamins showed a 25% reduction).
7. Vitamin D has been shown in RCTs to prevent fractures. B12 benefits mainly elderly with anemia,
dementia, neuro deficits.
8. Antioxidants have also been implicated in prevention and treatment of chronic disease, but evidence is not
consistent. Namely with beta carotene and E. Beta carotene proven to increase risk of lung and prostate
cancer in ATBC and CARET study. E shown to have no effect on CAD in recent RCT.
9. Beyond prevention…niacin (pharmacologic doses--200x RDA) has been shown to reduce migraines by
50%.
Final recommendations from Dr. Fletcher: 1 multivitamin/d for adults, 2 for elderly, avoid beta-carotene, consider E
in CAD, Ca supplement separately, and do lab tests to diagnose disease, not to determine what vitamins to use to
prevent disease
5B. Dietary Assessment (Dietitians visit tutorials)
Quick Review1) Flip through “Rate your Plate” (2pgs) realizing that it’s a quick (under 5 minutes) screen for heart
unhealthy eating habits. Column A =Bad, Column C=Good.
2) Think back to your Dietician Visit for a few minutes—24hr diet Hx. What questions did he/she ask?
3) Think about your own 24 hour diet and what surprised you about NAT
4) Move on…
Dietician Visit:
-How to take a 24 hour diet history
1)Ask about everything (ex. # of pats of butter on muffins.)
2)Use standards of size and volume for servings (ex. your fist)
3)People forget about snack foods
4)Diet diaries more accurate than diet recall
-General Principles of Counseling:
1)Try to make small, achievable changes. (People won’t cut out McD’s, but they might cut down slowly or
change to the McChicken and a small fries…)
2)People have to want to change their diet. Scare tactics rarely work.
3)Fruit Juice-not good. High glycemic index and often “empty”
NAT (http://www.nat.uiuc.edu/):
-Comprehensive Tool for dietary intake analysis
-Calculation of Dietary intake requirements (Estimate). http://www.nat.uiuc.edu/energy/daily.html
Total daily Requirement = Basal Metabolic Rate + Energy Expenditure of Activity (+ Specific dynamic
action of food + Energy Expenditure of Stress.)
BMR calculated using weight, age, and sex—WHO table.
6A. Nutrition needs for Growth & Development
Goals of this lecture: Review what growth curve looks like, know how to plot and interpret,
understand falling off the curve and failure to thrive
Why is growth important?
- Child's protein and energy intake important; deficiency => predisposed to childhood illness
and child at increased risk morbidity and mortality
- Study in Philippines demonstrated that children with a WAZ score of -3 (indicative of severe
malnutrition) had a higher attributable risk of diarrheal mortality
Normal growth patterns imply health
Abnormal patterns imply disease or altered intake of nutrients
Growth Assessment in Pediatrics (incorrect measurements can make a big difference)
Weight:
Length: Child <2 should be measured lying down, child >2 should stand, should measure in triplicate
Head Circumference: Indicative of normal brain development
Body Mass Index: Since can't use weight for length measurements (length off chart after ~ 8 years old),
BMI great way to follow. Does NOT directly measure body fat, but correlates reasonably well.
Also correlates with risk factors CV disease.
Arm anthropometerics: Good approximation of peripheral lean body mass/fat. Done by measuring tricep
skin fold (TSF), calculations based on estimated mid upper arm circumference (MUAC). This
estimate has some errors, arm not perfect circle, and in the mid arm muscle area (MAMA) bone
also present
Reference populations and growth curves: Children all shapes and sizes
 Z score preferred measure, uses standard deviations from median on bell curve (e.g., Z score 1 is1 std
deviation to the right. Z score of -3 is 3 std deviations to the left)
 Gomez Classification: Used weight for age, Normal (>90% median), Mild (89-75%), Moderate (74-60%),
Severe (<60%). Problem => didn't account for difference of chronic vs. acute
 Waterlow Criteria uses weight for length (good to assess wasting) and height for age (good to assess
stunting or chronic problem).
 Pediatric nutrition problems: Undernutrition => Wasting (Wt for ht <5 th %), Stunting (Ht for age <5th%),
Underweight (Wt for age < 5th %). Must measure, can't assess visually
 Previous problem with ref data = not nationally representative, largely formula fed, not ethnically diverse.
New CDC growth charts 2000- improved and accounts former problems
 Interpretation chart: Child can follow at 3% or even below and be normal. Problem when child grows at
higher level and then drops off -> failure to thrive. Big problem US, overweight (BMI >95 th%)
6B. Isabelle Bede (Nutrition in childhood / Chronic Disease)
1) How can a child’s progress in weight and height be assessed?
[Be able to Weight-for-age and Weight-for-Stature Growth Curves.]
2) How can a child’s caloric requirements be estimated?
Caloric requirements can be estimated using the WHO BEE formula/ Harris Benedict Equation
For men, the B.E.E. =
66.5 + (13.75 x weight in kg) + (5.003 x height in cm) - (6.775 x age)
For women, the B.E.E. =
655.1 + (9.563 x weight in kg) + (1.850 x height in cm) - (4.676 x age)
Total Caloric Requirements equal the B.E.E. multiplied by the sum of the stress and activity factors. Stress plus
activity factors range from 1.2 to over 2.
3) What potential nutritional complications are associated with chronic disease?
From Dr. Christopher Duggan’s Lecture Notes:
a) Undernutrition 
wasting (weight for height < 5th %),
stunting (height for age < 5th %),
underweight status (weight for age < 5th %)
b) Deficiency of protein and micronutrients 
From Robbins, p.438
[PROTEIN MALNUTRITION IN CHRONIC DISEASE]
Syndrome
Marasmus-like
protein-energy
malnutrition
Clinical Setting
Time
Course
Chronic illness (e.g., chronic Months
lung disease, cancer)
Laboratory
Findings
Clinical Features
History of weight
loss Muscle
wastingAbsent
subcutaneous fat
Normal or
mildly reduced
serum proteins
Prognosis
Variable;
depends on
underlying
disease
From Robbins, p.452
FUNCTIONS OF TRACE METALS AND DEFICIENCY SYNDROMES
Nutrient
Functions
Deficiency Syndromes
Iron
Essential component of hemoglobin as well as a number
of iron-containing metalloenzymes
Hypochromic microcytic
anemia
Zin c
Component of enzymes, principally oxidases
Acrodermatitis
enteropathica, growth
retardation, infertility
Iodine
Component of thyroid hormone
Goiter and hypothyroidism
Selenium
Component of glutathione peroxidase
Myopathy, rarely
cardiomyopathy
Copper
Component of cytochrome c oxidase, dopamine betahydroxylase, tyrosinase, lysyl oxidase, and unknown
enzyme involved in cross-linking keratin
Muscle weakness,
neurologic defects,
hypopigmentation,
abnormal collagen crosslinking
Manganese
Component of metalloenzymes, including
No well-defined deficiency
FUNCTIONS OF TRACE METALS AND DEFICIENCY SYNDROMES
Nutrient
Fluoride
Functions
Deficiency Syndromes
oxidoreductases, hydrolases, and lipases
syndrome
Mechanism unknown
Dental caries
From “Calcium Requirements of Infants, Children, and Adolescents” published by the American Academy of
Pediatrics in Pediatrics, Volume 104, November 1999 p. 1152-1157 [required reading for the week of 3.12]: “In
children with chronic illnesses, fractures may occur during childhood secondary to mineral deficiency associated
with the disease process or the effects of therapeutic interventions (i.e. corticosteriods) on calcium metabolism.
However, minimal data generally are not available on the risks and benefits of increasing calcium intake in children
with chronic illnesses above current dietary recommendations. Supplementation of vitamin D along with calcium
may be necessary for a maximal response.”
Deficiencies of vitamins  [see lectures/tutorials on vitamins]
4) What potential chronic diseases influence growth?
Prominent chronic illnesses with early onset (i.e. in childhood) include: * diabetes * chron’s * cystic fibrosis and *
various cancers (leukemias/lymphomas, neuroblastoma and ganglioneuroma, wilm’s tumor) etc. … These and
others may influence growth.
7A. Nutrition Debates : Alcohol
Alcohol consumption and CVD
Thun et al 1997.
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490,000 men and women ages 30 to 104 (mean 56) who reported their alcohol and tobacco use
were followed up over 9 years
the rate of death from all CVD was 30 to 40 percent lower among men (RR=0.7) and women
(RR=0.6) reporting at least one drink daily compared to non-drinkers
Benefits for CVD were greatest for those over 60 years of age with increased risk. (Potter 1997)
Bovet and Paccaud 2001
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reviews the literature on alcohol and CVD
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evidence from many ecological, case-control and prospective studies as well as a plausible
biological mechanism (alcohol increases HDL levels) suggest a cardioprotective effect of
moderate alcohol consumption
However there are many negatives to alcohol use
Alcohol has negative effects such as increase risk of:
1) hepatic cirrhosis
2) injury from external causes
3) hemorrhagic stroke (Mazzaglia, Britton et al. 2001)
4) upper digestive tract cancers (Tuyns 2001)
5) breast cancer (Gapstur, Potter et al. 1992)
6) large bowel cancer (Thun, Peto et al. 1997; Bovet and Paccaud 2001)
7) hypertension (with heavy consumption of alcohol)
People should abstain from drinking if
1) have personal or family history of alcoholism or any other risk for misuse
2) when taking medications that interacts with alcohol or when planning to drive or engage in other
activities that require one to be alert
3) pregnant
7B. Nutrition Debates : Vitamin E
Vitamin E
1. Antioxidant
2. Carried on LDL and blocks oxidation of LDL cholesterol
3. Atherogenesis/Cardiovascular Disease
4. Inhibits intima-media (smooth muscle) proliferation
5. Reduce platelet adhesion
DATA:
Prospective observational studies followed subjects with known CVD who took
400IU Vit E /day, 2+ years: Results: 20-40% decr. Risk of CVD
Nurses Health Study – prospective cohort study began in 1980 of 87,245 US
female nurses aged 34-59 years: Results: women who were in the top fifth of vit E supplement use had lowest RR for
non-fatal MI. Use was for 2+ years, 41% reduction in risk of coronary heart disease
Health Professionals Follow-up Study – Results: Reduction in risk of coronary heart
disease with vit E supplementation
 if use of Vit E based on self-selection, is this group already a healthier population? confounding
effect
Published RCT – focused on subjects with known CAD: Results: inconsistent evidence for short-term benefit of
supplementation in addition to medication already taking for diagnosed CAD, long term benefits inconclusive
Meir and Stampfer: "What vitamins should I be taking, doctor?" NEJM Dec 2001. Vit E supplements 200-800IU
much greater than 40IU RDA and that which obtained from diet alone
CURRENT RECOMMENDATIONS: Vit E at 400IU/day reasonable for middle aged to
older Americans at reasonable risk of CAD (Review annually as more data collected
Possible concern that more than 800 IU/d adversely affect platelet function,
more than 1200 IU with Vit K function
8A. Obesity
Stats – prevalence & costs
 52% of US adults are overweight (BMI>25)
 23% US adults are obese (BMI>30)
 22% US children are “at risk” for obesity/ 11% are obese (BMI>95%ile)
 costs of obesity are high – 300,000 premature deaths/yr in US, $100 bill. US healthcare expenditures
Complications of Obesity
(1) Metabolic (DM II, HTN, dyslipidemia, platelet dysfx)
(2) Anatomic (obst sleep apnea, venous insuff, GERD, GERD-assoc asthma, gallstones, skinfold infections,
injuries, orthopedic probs, steatohepatitis)
(3) Degenerative (atherosclerosis, diabetic complic, axial arthritis, disc disease, LV hypertrophy, pulm HTN,
infertility)
(4) Neoplastic (reproductive sx – endometriosis, breast/ovarian/prostate CA; GI sx)
(5) Psychological (depression, anxiety, panic a, bulimia/binge eating)
Causes of Obesity – linear model: genetics  environment psychology
(1) Psychology (exacerbates obesity)
(2) Environment – (via inactivity facilitates obesity))
(3) Genetrics – (critical determinant) –
 body tends to return to set point weight from over/underweight once allowed to feed freely;
 obesity can be intractable (weight loss/gain hard to sustain);
 increased weight concordance between monozygotic >dizygotic twins;
 leptin (increases food intake, decreases energy expenditure) not the whole answer but plays a role (most
human obesity assoc w/leptin excess; most obese pts are leptin resistant).
 Genetic approach to tx involves identifying:
- metabolic pathways
- neural pathways underlying eating behavior
- therapy targets and determinants of therapeutic response
- obesity subgroups
Treatment of obesity – multi-dimensional
(1) Behavioral programs – diet, behavior, exercise interventions; success
w/intense, longterm, multimodal treatments; espec good if intervention
starts in childhood, includes whole family.
(2) Surgery – approp to severely obese adults (most successful interven -5070% - at 5 yrs)
(3) Pharmacological therapies – current drugs only limited efficacy (leptin
def v. rare, serotongergic agents, intest lipase inhibitors); potential targets
(food intake, thermogenesis, fat metab & absorption)
(4) Prevention – identify children/adults at risk, family based behavior
modification, treat often/early).
8B. Dana Termin (Weight Loss diets)
Dana’s Atkins Diet
 Does not illicit calorie vigilance
 High protein, high fat, very low carbohydrates
 Positives: lose some weight very quickly
 Negatives: weight loss most likely due to natriuresis from decreased insulin and glycogenolysis
o Metabolic acidosis
o Decreased muscle synthesis from decreased insulin
o Hyperuricemia, fatigue, orthostatic hypotension, possible hyperlipidemia from high fat
Dana’s Low Fat Diet
 risk of high in calories because decrease in satiety from low fat
 Insufficiency of vitamins A, D, E, K
 Decrease in unsaturated fats in diet
Dana’s Zone diet
 Allows her to adjust her calorie intake by requiring calorie counting for adequate ratios
 Her diet is very low in calories, possibly decreasing her glycogen stores and limiting her performance
ability as a distance runner
9A. Lecture: Smoking Cessation
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Epidemiology: Smoking kills >400,000 Americans each year, both by directly killing the smoker and through
second-hand smoke (children, spouses of smokers).
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What kills smokers: 1) CVD/MI 2) Lung cancer (squamous and small cell)
Why don’t smokers quit? Both a pharmacological/physiological addiction (it is a stimulant) and a
psychological (smoke when stressed or after meals).
How can doctors help patients quit? Both counseling and pharmacological methods, but for these to work,
patient must want to quit (contemplation stage or greater).
Pharmacological methods:
1)
Bupriopion SR: a heterocyclic antidepressant (weak NE, 5-HT and DA reuptake inhibitor) found to aid in
smoking cessation. More effective in patients w/o active depression. Bupropion is safe seizures occur in
less than 1/1000 patients.
2)
Nicotine replacement: Gum, patch, nasal spray, inhaler
3)
Bottom line: nicotine replacement work best if combined with counseling. Recall that these
pharmacological treatments only aid in dampening nicotine withdrawal symptoms. Moreover, the nicotine
from these drugs rarely achieves the same rapid surge that cigarettes deliver. The nasal spray is most
similar, but inhaler mimics the feel of smoking most closely (nicotine is absorbed through the mouth, not
lungs).
Counseling methods
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Ask Advise Assess Assist Arrange
1) Ask if they smoke
2) Advise that “quitting smoking is the most important action you can take to stay healthy.”
3) Assess if the patient is ready to quit. Four progressive stages: precontemplation (35% of smokers) 
contemplation preparation action
4) Assist the patient whether they are willing to quit or not. If they are, set a quit date (so that they have enough
time to formulate a treatment plan), and assist in a treatment plan with booklets, pharmacotherapy or social
referral.
5) For those patients not yet ready to quit, ask “ Why is it not an option for you now?” or “Has smoking ever
harmed someone in your family?” or “What would it take to get you to quite smoking?” Remind them of the
harms of smoking: CVD, cancer, wrinkles, upper respiratory tract infections, infertility, impotence,
osteoporosis, blindness, hearing loss. Be sure to address the barriers to smoking (fear of failure, weight gain—
avg. gain=10 pounds).
6) Arrange for follow-up soon after quit date, and keep pressing the issue with patient.
For a nice summary flow chart: Rigotti, N. NEJM, 2002 346(7): 508.
9B. Counseling Practice
2 patient cases: counseling about tobacco use (role play 1 pt, 1 dr.)
3 discussion points: 1. readiness to quit, 2. barriers/strengths, 3. many “right” approaches
Patient A
Mr. A – 56 yo man with a recent MI
(72 pack yr history)
--scared enough to quit
--wife and daughter do not smoke
--workplace can’t smoke
--quits for a few months cold turkey because of booklet medical student gave him follow-up recurrence – Tx: try
more gradual approach with Nicotine patch, repeated counseling sessions.
Patient B
Mrs. B – 29 yo woman asking for refill on OCPs
(13 pack yr history)
 no smoking at work
 husband – non smoker with asthma
 next yr having a baby, “readiness to quit then” + buying a house
 claims to smoke “light” cigarettes
 Tx: talk about saving $ by not buying cigarettes, low birthweight of baby, misconception of “light”
cigarettes
 OCP + smoking  approx 30% increase in clot formation
3 articles:
1st 2 articles (Rigotti JAMA): 36 yo woman, repeat upper respiratory infections, tried to quit (talked about in lecture.
See 9A)
3rd article: Tobacco Use – US 1900-1999, Morb Mort Weekly Rep
Summary:
 PRIMARY preventable cause of death
 1/5 deaths per year are from Tobacco use
 Tobacco use: heart disease, cancer (LUNG, esophageal, laryngeal), COPD/chronic bronchitis, low
birthweight
 2nd hand smoke: LUNG cancer, asthma, respiratory infections, (increased “cotinine levels”)
 cigarette + cancer  1st = adenocarcinoma, 2nd = squamous cell carcinoma
 LUNG cancer among women increased trend!
 Smoking  highest among: 1. Native Americans, 2. Blacks, Southeast Asian men
 Smoking  lowest among: Hispanic, Asian American women
 Smoking in High School  high: whites, low: blacks (recent trend shift)
 New restrictions: no advertising, restrictions at workplace and at home
 Increase federal/state excise tax and increase price of cigarettes (decreases smoking in low income people)
 1998 Tobacco Company Settlement (not used for prevention though!! But scared people…)
 FDA recommendations for quitting smoking: 1. pharmacotherapy, 2. behavioral counseling
10A. Lecture: Childhood Immunization – A public success story
What is in a Vaccine?
1) active immunizing agents 2) suspending fluid 3) preservatives, stabilizers, antibiotics, 4) adjuvants
What Types of Vaccines are Commonly Available?
1) live attenuated 2) inactivated/killed 3) antigen or product (polysaccharides, toxoids, etc)
What Characterizes the Phases of Vaccine Development?
Phase I: safety and immunogenicity in low-risk population Phase II: safety and immunogenicity in target
population Phase IIIa: randomized clinical trials Phase IIIb: cost justified by vaccine’s effectiveness Phase IV:
suitable safe and protective in practice
Why Vaccinate Children?
1) protection of the individual child (Hib, PCV7) 2) future protection of the individual (Hep B)
3) protection of vulnerable populations (measles, rubella) 4) eradication of disease (polio? measles)
5) decrease in cost of illness to society
Why should Immunization be Compulsory?
The costs of not vaccinating are borne collectively by the community our government has vowed to protect. We, as
community members, have a right to be protected.
(Immunization recommendations from the CDC and the American Academies of Pediatrics and Family Medicine
are translated into school entrance requirements by State Departments of Public Health.)
What Vaccines are Currently Administered?
Hepatitis B (Hep B), Diptheria, Tetanus, Pertussis (DtaP), Haemophilus influenzae type (Hib), Inactivated Polio
(IPV), Penumococcal Conjugate (PCV), Measles, Mumps, Rubella (MMR), and Varicella (Var). 1 Hence, the “pincushion problem.” In the future, vaccines can hopefully be combined, sparing children, parents, and providers pain.
What Insights can be Gleaned from Efforts to Eradicate Specific Diseases?
Polio Vaccine: 1) Vaccines are effective (1952: >20,000 cases, 1955 w/ IPV licensed: 14,000 cases, 1963 w/ TOPV
licensed: 396 cases) 2) The safety of vaccine administration is monitored rigorously … Any morbidity secondary to
vaccine administration prompts changes in public policy (1990: 1/1 million cases of vaccine-associated paralytic
polio (VAPP)  1997-2000 transition from OPVto IPV. Incidentally, the advantages of OPV include cost, ease of
administration, gut immunity, and herd immunity.) 3) Parents have the right to complete, accurate information about
the benefits and risks of vaccines compared to the risks of vaccine-preventable disease.
Pneumococcal Conjugate Vaccine: 1) Irrespective of vaccine efficacy and safety, under-vaccination persists due to
* cost per dose * parental misconceptions * failure to track children’s progress in a decentralized medical system
Rotavirus Vaccine: see Polio 2) The safety of vaccine administration is monitored rigorously (Rotashield approved
by FDS in 1999  made part of 1999 schedule  shown to have caused rare cases of intusssusception 
voluntarily withdrawn by manufacturer the same year.)
Measles Mumps Rubella Vaccine: 1) It is difficult to disprove definitively associations between widely
administered vaccines and particular outcomes (MMR and autism).
In Summary: Risks of immunization are far outweighed by their efficacy in preventing disease for children 
Immunizations are extremely safe thanks to advances in medical research and ongoing review by researchers and
public health officials  Information abounds but is not all credible  physicians must commit to educating
patients in balanced, credible way.
10B. Adult Vaccination Vignettes
Adult Vaccination Vignettes (Tutorial case)
Influenza Virus Vaccine Recommendations
 People at increased risk of complications
o Persons>65 y.o.
o Adults and children with chronic cardio/pulm diseases (e.g. asthma)
o Pregnant women or women who will be pregnant (esp. 2nd or 3rd trimester) during influenza season
 People who can transmit influenza to those at high risk
o Doctors, nurses, hospital employees, nursing home employees who are in contact with high risk
individuals
o Household members of people in high risk groups
 Influenza vaccine benefits young people (reduces lost work days and less disruption of daily life) but
should only be considered when there are adequate vaccine supplies for high risk individuals (esp. the
elderly), or when the young adult is also in a high risk group.
 Contraindications: acute febrile illness
Hepatitis A Vaccine Recommendations
 Persons traveling to countries with high Hep A infection endemicity.
 IV and non-IV drug users
 Persons with chronic liver disease
 Homosexual men
 Contraindications: acute febrile illness
Lyme Disease (Borrelia burgdorferi) Vaccine Recommendations
 Persons with regular and intense outdoor exposure in areas of high risk for tick infestation
 Long term residents of highly endemic areas (due to cumulative yearly risk)
1
Hepatitis A (Hep A) is administered to high risk groups only.
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Contraindications: acute febrile illness, persons <15 y.o. or >70 y.o.
11A & 11B. Lecture: Hormone Replacement Therapy + Ruth Adams, revisited
Benefits and Adverse Effects of HRT and Raloxifene on Several Outcomes
Outcome
HRT
Raloxifene
Hot flashes
Substantial decrease
No effect
Lipids
Pros:
Decreased total & LDL
Decreased total & LDL
cholesterol
cholesterol, increased HDL
Favorable effects on endothelial
function, prostacyclin production
and blood vessel tone.
Cons:
Increased triglycerides. Adverse
effects on hemostatic factors, Creactive protein, and other
inflammatory markers.
CHD
Venous Thromboembolism
Osteoporosis
Endometrial Cancer
Breast Cancer
Alzheimer’s
Gallstones
Statistically insignificant increase
in CHD in most studies of
primary and secondary
prevention!
Statistically insignificant increase
in venous thromboembolism in
one study of primary prevention
Decreased fractures
8-10 fold increase with estrogen
alone. No effect with estrogen +
progesterone
30-50% increase when therapy
continued for > 5 yrs
??
1.4- to 2-fold increase
??
2-3 fold increase
Decreased fractures
No effect
No increased risk
??
??
Summary:
There are potential concerns (breast cancer, venous thrombosis, endometrial cancer, gallstones) and benefits (fewer
menopausal symptoms, decreased GU disorders, improved bone density) associated with hormone replacement
therapy.
For women at risk of osteoporosis with no family history of breast cancer, HRT may have a favorable benefit:risk
ratio.
For other women, the benefit:risk ratio may be less favorable.
12A. Lecture: Screening for prostate cancer
Quick Facts
Most common CA in men
2nd leading cause of CA death
African-Americans at a 2-3 fold higher risk for incidence and mortality
Screening Methods
Digital Rectal Exam
Prostate Specific Antigen (PSA)
Risk Factors
African-American
One 1st degree relative
Two 1st degree relatives
Prior vasectomy?
High fat/red meat diet?
Protective
Tomatoes (lycopenes) ?
Selenium supplementation?
Vitamin E?
Summary
A. No solid evidence early detection of prostate cancer decreases mortality, but no solid evidence it doesn't.
1. ACS recommends offering annual DRE/PSA at age 50 (age 45 with risk factors).
2. CTF, USPSTF do not recommend either DRE or PSA.
3. ACP doesn't recommend routine PSA
B. Information value of PSA is lower in BPH (benign prostatic hyperplasia).
C. DRE and PSA are complementary, if the goal is finding more cancers (but biopsying everyone would be the
best!).
D. The proportion of men who will have a suspicious DRE or PSA is higher than for other commonly-used tests for
the early detection.
E. Should respond to PSA's in the mildly elevated (4-10 ng/ml) range.
Recommendations
A. In the absence of evidence that early detection of prostate cancer and aggressive treatment of localized cancer
does more good than harm, such screening should be optional pending results of controlled
trials.
B. Cutoff age is a controversial point even among advocates of screening; for older men, localized cancers
become less likely to cause death given "competing hazards". Many urologists recommend screening only
men with a minimum 10 year life expectancy (about age 74 with average health).
C. Recommendations by ACS create medicolegal concerns among primary care physicians...one approach is to
explain pros and cons of prostate cancer screening and try to help the patient make an
individualized decision, and document the discussion. This is the approach recommended by the
ACP.
D. Information value of PSA is poor in the setting of symptomatic BPH; however, for A same medicolegal reasons,
discussing the availability of the test with those patients is a common-sense strategy.
12B. Screening for disease
Breast Cancer
Burden:
Breast Cancer - a malignant proliferation of epithelial cells lining the ducts or lobules
 192,000 cases in ’01; 40,600 deaths in ‘01
 96% 5 yr survival if no spread to lymph nodes at diagnosis (vs. 21% 5 yr survival for metastatic cancers at
diagnosis)
 Lifetime risk of dying from breast cancer is 3.6%
 Risk Factors: female, N. America/Europe residence, age, late age of first pregnancy, nulliparity, radiation
exposure, family history
Screening:
There are 3 ways to screen for breast cancer: mammography, breast self exam (BSE), and clinical breast exam
(CBE)
BSE:
 Essentially no data
CBE:
 Sensitivity = 40-63%
 Increased sensitivity when used in conjunction with mammography
Mammography:
 Anterior and lateral X-ray of the breast; efficacy increases as women age
 Sensitivity = 83-95% (changes according to age group)
 Specificity = >90%
 Cost = $51,700-105,000 per yr of life saved
Early Detection:
 18% reduction in mortality with mammography alone
Recommendation:
 American Cancer Society: mammogram every 1-2 yrs & annual CBE beginning at 40; annual
mammogram and CBE beginning at 50
 Begin screening at an earlier age if the patient has a first-degree relative with breast cancer (because 2-3
fold increased risk)
Colorectal Screening
Burden of Suffering: Colorectal cancer has the highest mortality rate of any cancer in the US. It is also frequently
diagnosed, so that over all mortality is high. Treatment is also associated with morbidity. Lifetime risk is 2.6%.
Screening Tests (in increasing order of sophistication):
(1)
(2)
(3)
(4)
Digital Rectal Examination
a. Sensitivity: Less than 10%, as finger only examines small region of rectal mucosa.
b. Specificity: Not reported.
c. Cost: Not reported. Expected small, if done as part of routine examination.
FOBT
a. Sensitivity: 26-92% (Huge range in literature)
b. Specificity: 90-99%
c. Cost: Performed yearly, $5-10.
d. Important issues: When FOBT performed on entire population, the majority of positives will be
false. (i.e. an individual receiving FOBT yearly from age 50-75 has a 45% cumulative chance of a
false positive).
e. Effectiveness: Mortality reduced by 45% vs. no screening.
Sigmoidoscopy:
a. Sensitivity: Depends on particular type of sigmoidoscope employed, with length of
sigmoidoscope having direct effect on sensivity:
i. 35cm: 50-55% of polyps
ii. 60cm: 65-70% of polyps
iii. 105cm: Not routinely employed at present – some indication of not much more
effectiveness.
b. Specificity: Related to reporting benign polyps as malignant. Depending on type of polyp, 5-40%
become malignant (so specificity is 60-95%).
c. Cost: Performed every 5 years.
d. Effectiveness: Reduces mortality by 59%.
Colonoscopy and barium enema.
a.
b.
c.
d.
Sensitivity: 75-95%
Specificity: Not reported.
Cost: Highest – requires sedation and hospital suite, but performed only once per decade. $1,736
per test.
Effectiveness: Assumed greater than 59%.
“Guide to Clinical Preventive Services” recommendations for screening: Should be offered to all individuals:
FOBT yearly, sigmoidoscopy every 5 years, and colonoscopy evert decade starting at age 50 for both men and
women without significant family history. “Significant family history” (meaning first degree relative) patients
should be offered screening one decade earlier. Genetic-predisposing syndromes such as FAP, HNPCC require
more frequent screening.
13A. Exercise and Disease Prevention
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Physical inactivity leads to 200,000 deaths / year (12% of all deaths) – major public health problem
Inactivity has an increased risk of CV disease similar to DM, hypertension, high cholesterol, and smoking
~2/3 Americans are not regularly active
Risk group for inactivity – women, blacks/Hispanics, elderly, low-income
Physical activity declines with age in children
Benefits of exercise – improves metabolism, cardiac output, pulmonary function, insulin sensitivity,
reduces periphal resistance, decreases risk of heart disease, DM, hypertension, colon cancer, obesity, and
osteoporosis
Risks of exercise – arrhythmias, MI, sudden death, rhabdomyolysis, bronchoconstriction
Pre-exercise medical evaluation – needed in men > 40, women > 50, chronic disease, DM, HTN, smoking,
cardiac family Hx, hyperlipidemia
Controversy whether evaluation needs stress test – high false positive
Counseling – outline goals, maintaining life-long activity, assess social support – recommended duration of
exercise - 30 mins (cumulative) /day most days / week
Currently only 34% of Americans are counseled about exercise
Studies show counseling is not very effective, more effective in women than men
Physicians need to improve counseling: written counseling more effective – key points: start slow, make it
fun, incorporate exercise whenever you can, address barriers, prevent injury, reinforce message, follow-up
13B. Tony Sanchez (Diabetes - prevention issues)
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Type II DM (NIDDM: Non-Insulin Dependent DM)  hyperglycemia resulting from increased insulin
resistance mediated by:
o Decreased cell membrane insulin receptors
o Post-receptor dysfunction (impaired intracellular carrier proteins)
o Impaired processing of proinsulin to insulin
Complications: retinopathy, nephropathy, neuropathy, peripheral vascular disease; increased risk for stroke
and coronary heart disease
NIDDM has an 8% prevalence in US (20% in people > 60 years). Risk factors:
o Age; obesity (BMI > 27); lack of physical activity; family history; women with prior gestational
diabetes, polycystic ovarian syndrome, or delivery of baby weighing > 9 lbs.; race / ethnicity
(Black, Hispanic, Native American, Asian); HTN (> 140/90); HDL < 35 mg/dl; Triglycerides >
250; previously identified IFG (impaired fasting glucose) or IGT (impaired glucose tolerance)
Often asymptomatic in early stages  possibility for screening
o Screening is generally performed if: important disease that has a significant burden on the
population, has a recognizable preclinical asymptomatic stage that can be detected with tests,
treatment after early detection yields benefits relative to delayed treatment, screening costs are
reasonable, screening will be a systematic ongoing process
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Best screening test: FPG (fasting plasma glucose)  no food/beverage consumption (except water) for 8
hours before test; FPG > 126 indicates retesting and suggests diabetes; 110 < FPG < 126 mg/dl is
considered impaired fasting glucose (IFG)  risk factor for future diabetes
75g Oral Glucose Tolerance (OGT) test can also be done; if plasma glucose is
200 mg/dl two hours post-glucose load, suggestive of diabetes;
140 < 2 hours post load < 200  considered impaired glucose tolerance (IGT)
Diabetes Prevention Program (DPP) Clinical Trial: trial comparing diet and exercise to treatment with
metformin (Glucophage) in obese people (average age 51; average BMI 34) with impaired glucose
tolerance (IGT: 140-200 post 2 hrs); third group was placebo drug
Participants randomly assigned to intensive lifestyle intervention reduced their risk of getting type 2
diabetes by 58 percent. On average, this group maintained their physical activity at 30 minutes per day,
usually with walking or other moderate intensity exercise, and lost 5-7 percent of their body weight.
Participants randomized to treatment with metformin reduced their risk of getting type 2 diabetes by 31
percent.
Results: About 29 percent of the DPP standard group (placebo) developed diabetes during the average
follow-up period of 3 years. In contrast, 14 percent of the diet and exercise arm and 22 percent of the
metformin arm developed diabetes. Volunteers in the diet and exercise arm achieved the study goal, on
average a 7 percent--or 15-pound-- weight loss, in the first year and generally sustained a 5 percent total
loss for the study’s duration.
Contributors:
Aaron Kuzin
Alisa Land
Andrew Scott
Arif Nathoo
Aya Kuribayashi
Ben White
Boris Spektor
Cullen Taniguchi
Elizabeth Baca
Jeff Velez
Jesus Vazques
Joe Ladapo
Julie Levison
Kate Creskoff
Markella Zanni
Michele Lee
Michelle Tang
Pardis Sabeti
Raj Gopalakrishnan
Ryan Egeland
Sabrina Vineberg
Samira Brown
Savita Dandapani
Scott Weiss
Shannon McDonald
Supinda Bunyavanich