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Phar 722 Pharmacy Practice III Obesity and Weight Control


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Title: Phar 722 Pharmacy Practice III Obesity and Weight Control

Phar 722 Pharmacy Practice III Obesity and
Weight Control
  • Spring 2006

Study Guide for the Material on Obesity
  • 1. For obesity, know
  • a. causes
  • b. reasons for the increase in numbers of
    obese individuals
  • c. role in maintaining good health
  • d. potential role of peroxisomes and
    hormonal/cytokine control.
  • 2. What are the problems with maintaining desired
  • For reducing diets, know
  • a. their biochemical validity, where applicable
  • b. their relative nutritional value
  • c. properly designed liquid diets
  • d. criteria for determining if a diet is a fad
  • For artificial sweeteners and fat replacements,
  • a. their underlying chemistry (peptide,
    carbohydrate, heterocycle, etc.)
  • b. the underlying chemistry of the fat
  • 5. Be able to state the medical outcomes from
    bariatric surgery and liposuction.

Nothing is Really New!
  • It is a commonly received notion that
    hard study is the unhealthy element of college
    life. But from tables of mortality of Harvard
    University, collected by Professor Pierce from
    the last triennial catalogue, it is clearly
    demonstrated that the excess of deaths for the
    first 10 years after graduation is found in that
    portion of each class inferior in scholarship.
    Every one who has seen the curriculum knows that
    where Æschylus and political economy injures one,
    late hours and rum punches use up a dozen, and
    that the two little fingers are heavier than the
    loins of Euclid. Dissipation is a swift and sure
    destroyer, and every young man who follows it is,
    as the early flower, exposed to untimely frost.
    A few hours of sleep each night, high living and
    plenty of smashes make war upon every function of
    the human body. The brain, the heart, the lungs,
    the liver, the spine, the limbs, the bones, the
    flesh, every part and faculty are over tasked,
    worn and weakened by the terrific energy of
    passion loosed from restraint until, like a
    dilapidated mansion, the earthly house of this
    tabernacle falls into ruinous decay.
  • Scientific American, September 1918

Not all fat is created equal.
  • Saturated, unsaturated, whats the
    difference?...You cant pack as much fat into a
    serving of food made with unsaturated fats and
    you cant store as much extra weight in your body
    when the triglycerides are kinky. With fats,
    kinky is good, straight is bad.
  • Chemical Engineering News, August 12, 2002,
    p 64.

Obesity Trends Among U.S. Adults BRFSS, 1985
(BMI 30, or 30 lbs overweight for 5 4 woman)
Obesity Trends Among U.S. Adults BRFSS, 1986
(BMI 30, or 30 lbs overweight for 5 4 woman)
Obesity Trends Among U.S. Adults BRFSS, 1987
(BMI 30, or 30 lbs overweight for 5 4 woman)
Obesity Trends Among U.S. Adults BRFSS, 1988
(BMI 30, or 30 lbs overweight for 5 4 woman)
Obesity Trends Among U.S. Adults BRFSS, 1989
(BMI 30, or 30 lbs overweight for 5 4 woman)
Obesity Trends Among U.S. Adults BRFSS, 1990
(BMI 30, or 30 lbs overweight for 5 4 woman)
Obesity Trends Among U.S. Adults BRFSS, 1991
(BMI 30, or 30 lbs overweight for 5 4 woman)
Obesity Trends Among U.S. Adults BRFSS, 1992
(BMI 30, or 30 lbs overweight for 5 4 woman)
Obesity Trends Among U.S. Adults BRFSS, 1993
(BMI 30, or 30 lbs overweight for 5 4 woman)
Obesity Trends Among U.S. Adults BRFSS, 1994
(BMI 30, or 30 lbs overweight for 5 4 woman)
Obesity Trends Among U.S. Adults BRFSS, 1995
(BMI 30, or 30 lbs overweight for 5 4 woman)
Obesity Trends Among U.S. Adults BRFSS, 1996
(BMI 30, or 30 lbs overweight for 5 4 woman)
Obesity Trends Among U.S. Adults BRFSS, 1997
(BMI 30, or 30 lbs overweight for 5 4 woman)
Obesity Trends Among U.S. Adults BRFSS, 1998
(BMI 30, or 30 lbs overweight for 5 4 woman)
Obesity Trends Among U.S. Adults BRFSS, 1999
(BMI 30, or 30 lbs overweight for 5 4 woman)
Obesity Trends Among U.S. Adults BRFSS, 2000
(BMI 30, or 30 lbs overweight for 5 4 woman)
Obesity Trends Among U.S. Adults BRFSS, 2001
(BMI 30, or 30 lbs overweight for 5 4 woman)
No Data lt10 1014
1519 2024 25
Obesity Trends Among U.S. Adults BRFSS, 2002
(BMI 30, or 30 lbs overweight for 5 4 woman)
(BMI ?30, or 30 lbs overweight for 54 person)
No Data lt10 1014
1519 2024 25
Source Behavioral Risk Factor Surveillance
System, CDC
Obesity Trends Among U.S. Adults BRFSS, 2003
(BMI ?30, or about 30 lbs overweight for 54
No Data lt10 1014
1519 20-24 ?25
Source Behavioral Risk Factor Surveillance
System, CDC
Obesity is a Global Problem!
What is Historical Ideal Weight?
  • Examine the female figure in the Renaissance-era
  • They would not be hired as todays fashion
  • Who were the ideal male and female, particularly
    in the lower economic groups?
  • Male Somewhat overweight (paunch) because it
    meant the male could afford food.
  • Female Husky because she could bear children
    and return to farmwork or maintain the household.

What is Ideal Weight-Today?
  • In the United States, this concept was originally
    developed by the Metropolitan Life Insurance Co.
    who developed a set of tables that were the
    standard used by physicians and dieticians.
    These may be too conservative. The body mass
    index (BMI) is the current standard, but the
    numbers for all indices are based on
    retrospective studies.

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Womens Health Initiative Results
  • Among post menopausal women, a low-fat dietary
    pattern did not result in a statistically
    significant reduction in invasive breast cancer
    risk over an 8.1 year average follow-up period.
  • JAMA, 295 629-642, 2006
  • In this study, a low-fat dietary pattern
    intervention did not reduce the risk of
    colorectal cancer in postmenopausal women during
    8.1 years of follow-up.
  • JAMA, 295 643-654, 2006
  • Over a mean of 8.1 years, a dietary intervention
    that reduced total fat intake of vegetables,
    fruits and grains did not significantly reduce
    the risk of CHD, stroke, or CVD in post
    menopausal women and achieved only modest effects
    on CVD risk factor, suggesting that more focused
    diet and lifestyle interventions may be neededto
    improve risk factors and reduce CVD risk.
  • JAMA, 295 655-666, 2006

Why so many diseases associated with obesity?
  • Adipocytes make fat a very dynamic tissue.
  • Every adipocyte is serviced by capillaries.
  • Found in adipose tissue is a large concentration
    of macrophages.
  • Between the adipocytes and macrophages, there is
    formation and release of
  • Leptin
  • Resistin
  • TNF-a (Tissue Necrosis Factor)
  • IL-6 (Interleukin-6)
  • Adipocyte contain peroxisome-linked steroid

Alternate Measure of Obesity
  • Waist to Hip Ratio
  • Narrowest area of waist in inches
  • Widest area of hips in inches
  • Guidelines state the male WHR should be less
    than 0.95 and female less than 0.80. Some
    research shows that people with apple-shaped
    bodies (with more weight around the waist) have
    visceral fat and face more health risks such as
    Type 2 Diabetes, hypercholesterolemia, and heart
    disease as compared with those with pear-shaped
    bodies who carry more weight around the hips and
    have subcutaneous fat.
  • NOTE Liposuction does not normally remove
    visceral fat.

Visceral versus Subcutaneous Fat
Keep a Sense of Perspective
  • Several health professionals now are looking at
    weight as one of several health variables. Other
    variables include
  • Normal or elevated serum lipid levels
  • Maintain an active physical life style
  • Normal blood pressure
  • Does NOT smoke
  • Does NOT show a family history of type 2 diabetes
    or heart disease
  • This person may not have to be concerned even if
    the height-weight tables or the persons BMI
    indicate being overweight. The type of food
    being consumed is important.
  • Weight reduction is indicated for people with the
    listed risk factors.

Causes of Obesity
  • Excess Adipose Tissue
  • This is based on a model which states that the
    number of adipocytes will stay constant. The
    more adipocytes people form as youngsters, the
    more will be the problems with weight control.
    Adipocytes can be thought of as fuel storage
    tanks. They are designed to store triglycerides
    (fat). We can empty them and, thereby, lose
    weight, but the empty adipocytes will fill back
    up with consumption of excess calories.
  • There is lack of agreement as to the age when the
    number of adipocytes becomes critical. At one
    time pregnant women were told that they should
    not gain more than 20 lbs during their pregnancy.
    Sometimes this limitation led to malnourished
    infants. After birth, the first two years may
    not be critical although eating habits and taste
    development may be important variables.

Causes of Obesity-Continued
  • Shifts in Eating Habits
  • On the average Americans have increased their
    caloric consumption by about 100 Calories (kcal)
    each day. Paralleling this increase is a
    decrease in physical activity or increase in
    sedentary lifestyle. This is happening to both
    adults and children.
  • See picture from our local newspaper.

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100 Cal/day excess
  • Do the following calculation
  • 100 Cal/day x 365 days/year 36,500 Cal/year
  • 36,500 Cal/year 7,000 Cal/lb 5 lbs/year
  • 5 lbs/year x 20 years 100 lbs weight gain
  • Exacerbating Variable
  • As we age, we need fewer daily calories to
    maintain our weight. (See later slide.)

Impact of Sedentary Behavior
  • Science (307, 530-531, January 28, 2005) carried
    a report that sedentary behavior in individuals
    prone to gain weight can result in an excess of
    350 Calories per day.

Note decrease in dietary calcium.
Fructose has been Implicated as a cause of
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Causes of Obesity-Continued
  • Social Class
  • This is controversial, but the facts are that
    individuals in the lower economic classes have a
    greater problem with controlling body weight than
    those in the upper economic class. There are a
    variety of explanations ranging from a poor
    understanding of good eating habits, lack of
    access to a variety of foods particularly in the
    inner city where there is a shortage of large
    food markets, to other medical problems which may
    make it difficult to earn a decent wage and have
    the money to purchase a variety of nutritious

Causes of Obesity-Continued
  • Ethnicity (Genetics?)
  • There is evidence that within the United States,
    obesity is more likely found in specific ethnic
    groups. Part of this may be related to economic
    social class described in the preceding section.
    This is not the complete answer.
  • Others argue from an evolutionary viewpoint.
    These groups are better able to survive famine
    because they use their food calories more
    efficiently. Some call this the thrifty gene
    theory. When foods become more readily
    available, their metabolism still behaves as if
    famine is eminent.

Causes of Obesity-Continued
  • Hormone Imbalances
  • This can be quite complex and range from
    hypothyroidism, pituitary imbalances, diabetes,
    estrogen imbalances, etc.

Genetics and Obesity
  • Overweight parents produce overweight children
  • It must be remembered that it is only in recent
    human history that we have had an abundance of
    food whenever we want it. Thus, our ancestors
    who had adipose tissue had better chances of
    surviving a famine. Heavier women had enough
    resources to nurse their infants and survive to
    care for the child and give birth to another
    infant. Remember that the location of body fat
    (adipocytes) is important. Adipose tissue in the
    hips, buttocks and thighs cause fewer
    complications than adipose tissue in the
    abdominal region. This is an example of the
    thrifty gene model.

Genetics and Obesity-Continued
  • Fat Gene Model
  • It has been observed that individuals consuming
    identical diets and participating in identical
    physical activity will not produce the same
    weight gain or loss. Based on the brown fat
    model in rodents, it has been assumed that humans
    can "burn off" excess calories rather than always
    storing them as triglycerides in adipocytes.
  • Recently, there are reports of a gene that
    controls the proton flux across the mitochondrion
    inner membrane. When excess calories are
    consumed, a protein that uncouples oxidative
    phosphorylation is synthesized. Remember that in
    uncoupling oxidative phosphorylation, the
    respiratory chain continues to receive electrons
    from aerobic glycolysis, ß-oxidation and the
    Krebs Cycle and reduce oxygen, but no ATP is
    produced. The oxidative reactions continue
    because there is no ATP build up to inhibit the
    ATP synthetase enzymes and stop the reaction.
  • Individuals lacking the ability to make this
    protein produce ATP which, as ATP concentration
    increases, stops the Krebs Cycle by feedback
    control. Thus, in these individuals excess food
    is converted to triglycerides rather than being
    "burned off."

Possible Key Receptors
  • Peroxisome proliferator-activated receptors
  • What are Peroxisomes?
  • These are subcellular organelles.
  • What are the functions of Peroxisomes?
  • glycerolipid synthesis
  • cholesterol biosynthesis
  • cholesterol breakdown forming bile acids
  • fatty-acid ß-oxidation (w/o ATP production)

Classification of PPARs
  • PPARa
  • Found in cardiac muscle cells and those organs
    where gluconeogenesis occurs (liver, intestine,
    renal cortex)
  • Prefers polyunsaturated fatty acids.
  • Leukotriene B4 (LTB4) is a potent natural
    ligand. (NOTE LTB4 is an integral part of the
    inflammatory process.)
  • Has anti-inflammatory properties.
  • The fibric acids (indicated for
    hypertriglyceridemia) - gemfibrozil (Lopid)
    and fenofibrate (Tricor) - act at this receptor.

Classification of PPARs-continued
  • PPARß
  • Activated by fatty acids, but its function(s)
    is/are not well understood.
  • .PPAR?
  • Found in white adipose tissue and immune cells.
  • Considered to be the master regulator of
    adipocyte differentiation.
  • Has antiinflammatory properties.
  • The thiazolidinediones (indicated for insulin
    resistant type 2 diabetes) - rosiglitazone
    (Avandia) and pioglitazone (Actos) act at this

More on PPARs
  • PPAR? Coactivator 1 (PGC-1)
  • (R. Taylor, New England Journal of Medicine,
    3507, 639-641, February 13, 2004.)
  • A polymorph of the coactivator has been found in
    patients with type 2 diabetes. Overwight people
    with a family history of type 2 diabetes have
    decreased expression of PGC-1 even when glucose
    tolerance still is normal.
  • One manifestation of the PGC-1 polymorph is
    significantly reduced mitochondria activity.
    This leads to lipid accumulation and might
    partially explain insulin resistance.

Hormones/Cytokines and Obesity
  • Insulin required for
  • Transport of glucose into muscle and adipose
  • Muscle Glucose either is stored as glycogen or
    metabolized in the aerobic and anaerobic
    glycolytic pathways.
  • Adipocyte Glucose can be aerobically
    metabolized, converted to triglyceride or
    interconverted via the pentose phosphate
  • Required for release of dietary triglycerides
    from chylomicrons and endogenous triglycerides
    from VLDL.
  • Hypertriglceridemia is one of the complications
    seen in uncontrolled diabetes

Hormones/Cytokines and Obesity-continued
  • NOTE Much of the work with cytokine role in
    obesity is done with mice. There have been
    problems extrapolating the mice results with
    pharmacological studies in humans.
  • Leptin
  • This cytokine (adipokine) is synthesized
    primarily in adipose tissue and released from
    that tissue. It travels to the hypothalamus to
    inform the body about the quantity of fat
    stores in the body. In mice, leptin suppresses
    appetite. Unfortunately, the situation appears
    more complicated in humans. Nevertheless, some
    forms of obesity may be caused by defects in the
    gene that forms leptin or in the cytokines
    ability to communicate with the hypothalamus.
  • Resistin
  • This cytokine (adipokine) is synthesized in
    adipose tissue in mice and macrophages in humans.
    It maintains blood glucose levels during
    fasting. In obesity, it may contribute to
    insulin resistance seen in Type 2 Diabetes.
  • Ghrelin
  • First discovered in 1999, it is secreted
    primarily by the stomach and duodenum. In
    contrast with leptin whose release appears to be
    constant, ghrelin is secreted in a pulsatile
    manner. It is released when food is needed and
    then falls off with the intake of food. It is
    elevated in patients on low calorie diets causing
    to desire food. Its production is reduced after
    gastric bypass surgery which may explain
    satiation in these patients.

Weight Control and Reduction
  • It aint easy!!!
  • It is difficult to lose excess weight!
  • Once lost, it is difficult to maintain the
    desired weight. (See next slide.)
  • It is difficult to maintain current weight,
    particularly as one ages.
  • Methods include
  • Drugs (not too successful, but the American goal
    is take a pill and all will be well.

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Weight Control-Drug Therapy
  • Phentermine (Ionamin)
  • Approved in1959 for short term appetite
    suppression. It was part of the infamouse
    phen-fen or phen-dexfen combination.
    Fenfluramine was approved in 1973 followed by
    dexfenfluramine (Redux). The combination of
    phentermine and either one of the other drugs was
    never approved by the FDA, especially for long
    term control of weight. One of the main adverse
    reactions to this combination developed
    abnormalities of the heart valve. Some were
    asymptomatic, others required surgery and some
    died. Additional work indicated that
    fenfluramine/dexfenfluramine were the causative
    agents, not phentermine. It was part of the
    phen-fen combination. Both drugs inhibit
    serotonin release.
  • The prototype design for phentermine is
    amphetamine/dextroamphetamine (Dexadrine) and is
    a centrally acting sympathomimetic

Drug Therapy-Continued
  • Sibutramine (Meridia)
  • It acts by inhibiting reuptake of serotonin and
    norepinephrine. Its pharmacology is complicated
    because two of the metabolites also are active.
    There are significant cardiovascular problems
    including hypertension. Italy has removed the
    drug from its market. However, a European Union
    committee concluded that the drugs benefits
    outweigh the risks.

Drug Therapy-Continued
  • Orlistat (Xenical-prescription, AlliTM-otc)
  • It inhibits lipase in the intestinal tract
    preventing triglyceride digestion and absorption.
    While of limited effectiveness (2 - 5 greater
    weight loss that diet along), it causes
    intestinal discomfort including steatorrhea.
    Patients are advised to take vitamin supplement
    containing the fat soluble vitamins (A, D, E, K)
    when taking Orlistat. (A patient probably should
    take a vitamin supplement when on any
    weight-reduction program.

Drug Therapy-Continued
  • Bupropion (Wellbutrin)
  • It is an antidepressant that might help patients
    who eat excessively when depressed. The results
    are mixed.
  • Topiramate (Topamax)
  • This drug is indicated for seizures also seems to
    cause weight loss.
  • Metformin (Glucaphage)
  • This is one of the leading drugs dispensed in the
    United States for Type 2 Diabetes. Weight loss
    has been reported by patients taking this drug.

Drug Therapy-Continued
  • Mesotherapy
  • This is an unapproved therapy that is popular in
    Europe and South American and becoming more used
    in the United States. The patient receives 100 -
    500 skin deep injections of aminophylline,
    isoproteranol and a sweet clover extract directly
    into adipose tissue, usually in the hips and
    thighs. It is supposed to melt the fat which
    then is released slowly into the body where it
    either is oxidized in the lipid metabolic cycles
    or excreted, probably in the bile. Most
    mesotherapists require diet and exercise programs.

Drug Therapy-Concluded
  • Rimonabant (Acompilia)

More on Rimonabant
  • Rimonabant was developed based on one of the
    cannabinoid receptors. Ligands for these
    receptors seem to treat addiction and satiation.
  • This experimental drug has been evaluated for
    both smoking cessation and obesity. Related
    compounds are being evaluated as agents for
    positron emission tomography (PET) scans of the
    central nervous system.
  • Its Log P and Log D (pH 7.0) is 4.81, meaning
    that it is very lipophilic.
  • Approval has been delayed.
  • In recent reports, the positive results must be
    weighed against the fact that fewer than 2/3 of
    patients completed the trial (NEJM, 353 2121-34,
    2005) or 50 completed (JAMA, 295 761-775, 2006)
  • Clinical trials also reported some incidences of
    depression in patients.

Weight Control-Diet
  • Diet requires great patience.
  • Peer support is very helpful.
  • For most diet will work.
  • The trick is to not fall for the fad diets.
  • Most valid diets tend towards complex
    carbohydrate and high bulk for several reasons.
  • Taking a vitamin-mineral supplement might be
    advised for the lower calorie diet. It has been
    estimated that it is very difficult for people to
    obtain their vitaminmineral RDA on a diet of
    1,200 Calories or less.

Diet-Calorie Calculations
  • Carbohydrate 4 Calories (kcal)/g
  • Lipid 9 Calories (kcal)/g
  • Protein 4 Calories (kcal)/g
  • Multiple the weight in grams/serving size for
    each biochemical food group by their respective
    calories per gram, total and round to the nearest
    five calories. You should obtain the same number
    as found in the table.

Are complex carbohydrate, high bulk diets the
most effective?
  • There are fewer calories per gram (4 Calories/gm
    versus 9 Calories/gm for lipids).
  • The number of calories could even be less/gm
    depending on the amount of poorly digestible
    fiber present in the food.
  • These diets help lower serum lipid levels. This
    is important for people with hyperlipidemias.

So why dont we demand this type of diet?
  • It must be remembered that we like the texture of
    lipid containing foods sliding over our tongues.
  • This is considered to be an evolutionary
  • Our ancestors who consumed lipid containing foods
    received more Calories per gram and, therefore,
    gained weight. This allowed them to better
    survive famines.

Valid versus Fad Diet?
  • Biochemical Valid Diets
  • They make sense biochemically and nutritionally.
  • Weight loss averages 1 - 2 lbs per week.
  • It recognizes that the a persons former excess
    weight will return unless the person monitors
    what is eaten and maintains an active life

Valid versus Fad Diet?-continued
  • Fad Diet Characteristics (One or more of these
    will be the focus of the diet.)
  • Magic or miracle foods that burn fat.
  • Bizarre quantities of only one food or type of
  • Rigid menus involving a limited selection of
    foods that must be eaten.
  • Specific food combinations.
  • Rapid weight loss (more than 2 lbs per week).
  • Lack of medical warnings (i.e. diabetics and
    hypertensives should seek medical advice before
    beginning the diet program).
  • No emphasis on physical activity.

Examples of Fad Reducing Diets-1
  • The New Beverly Hills Diet
  • Combine or separate certain foods so your body
    will thoroughly digest every nutrient in each
    food (This diet claims that this will make you
    leaner because your stomach and intestines wont
    create any fatty buildup.)
  • A limited number of food groups, including just
    fruits and baked potatoes for the first three
  • Promises to take off up to 15 pounds in 35 days
    (up to 3 lbs/week)

Examples of Fad Reducing Diets-2
  • Sugar Busters (authored by three physicians -
    so it must be valid - right? Wrong! The nutrition
    training of physicians and nurses is worse than
    that of pharmacists.)
  • Too much sugar is the major reason for weight
    gain due to insulins regulatory effects on body
    fat storage. (Remember, insulin is fat sparing,
    but lets not carry this to extremes.)
  • Calories do not regulate weight gain or loss.
    (Calories have a major role unless there is an
    endocrine disorder. Even where there is a
    genetic predisposition for obesity, caloric
    intake and expenditure are important variables.)
  • Promises that you can eat most foods in normal
    quantities or even larger quantities than you
    presently consume. Carbohydrate containing foods
    should be reduced.

Examples of Fad Reducing Diets-3
  • Mastering the Zone (authored by a Ph.D. - so it
    must be valid - right? Wrong?)
  • Most people suffer from an insulin imbalance that
    causes them to gain excess weight.
  • By eating protein, carbohydrates and fat in the
    proportions described in the Zone guidelines, the
    insulin imbalance will be corrected, leading to
    weight loss.
  • Promises that the dieter can indulge in food
    usually considered taboo such as red meat and
    fatty foods.
  • Protein 30 Carbohydrate 40 and Fat 30.

Examples of Fad Reducing Diets-4
  • Dr. Atkins New Diet Revolution
  • South Beach Diet
  • The South Beach Diet can be considered another in
    the series of low carbohydrate diets. The focus
    is not so much reduction of all dietary
    carbohydrate, but a reduction in foods with high
    glycemic indices. The author of this diet (an
    M.D.) states that there is greater insulin
    release and, therefore, rapid intake of glucose
    into the adipose tissue, when eating foods with a
    high glycemic index. (In the adipocyte, glucose
    is converted into triglycerides.)

Atkins South Beach Diets-continued
  • Weight gain is caused by eating a diet high in
    sugar and refined carbohydrate that boosts
    insulin production which converts these foods
    into body fat. (There is some truth to this
  • The diet focuses on increased intake of protein.
  • By avoiding carbohydrates and sugars, your body
    will automatically burn fat for energy.
    (Remember that the body needs glucose for brain
    metabolism and for a multitude of other uses. It
    also uses glucose for quick energy. The new
    Atkins Diet and South Beach Diet does have
    some carbohydrate in it.)
  • No hunger in-between meals.
  • Significant improvements in cholesterol and blood
    pressure. (Most weight loss regimens will show
    improvements in these conditions.)
  • Protein 30 Carbohydrate 40 and Fat 30.

Liquid Protein Diets
  • These products provide approximately 400 Calories
    per day and consist of hydrolyzed, protein with a
    high biological value. The purpose is to keep
    the patient in positive nitrogen balance. There
    is little insulin produced with this type of
    product. They are indicated for the severe obese

Fat Substitutes
  • Add the smooth feel we like in our foods.
  • Salatrim (Nabisco)
  • An artificial triglyceride composed of stearic
    acid and short chain fatty acids. Because
    stearic acid is poorly absorbed and the short
    chain fatty acids contain less calories, Salatrim
    is claimed to have only 5 Calories/gm.
  • Problem It is not suitable for frying foods
  • Olestra (Proctor and Gamble)
  • This product is not a triglyceride, but it is a
    non-digestible product consisting of a mixture of
    sucrose esterified with six to eight fatty acids.
  • Advantage Because it is non-digestible, it is
  • free.
  • It can be used in frying.

Fat Substitutes-concluded
  • Simplesse (NutraSweet Company)
  • A dried milk protein extracted from whey. The
    protein has been "engineered" into very small
    spherical particles that slide by each other like
    ball bearings and mimic the feel of fat.
  • Advantage It has the "feel" of fat in the mouth.
    It has only 1.5 Calories/gm.
  • Problem Being a protein, it cannot carry flavors
    that normally dissolve in fat and are
    released when eaten.

Artificial Sweeteners
  • These originally were marketed to patients
    diagnosed with diabetes mellitus. Their
    marketing in low and zero calorie products is
    fairly recent.
  • The first group show that a sugars are not the
    only structure that can ellicit a strong response
    from the taste receptors that detect sweetness.

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Bariatric Surgery
  • Removal of a section of the small intestine.
  • Except for malignancies and scar tissue (Crohns
    Disease, etc) from chronic inflammatory diseases,
    removal a section of the small intestine for the
    treatment of obesity is rarely done. What
    results is a variety of malabsorption syndromes
    and liver disease.
  • Intestinal bypass
  • This is not often done and is considered
    temporary. A section of the small intestine was
    bypassed for a period of time. When the desired
    weight was obtained, the bypassed section was
    reconnected. Obviously, each of these procedures
    is major surgery with long recovery times.

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NEJM 35126, 2683-93, December 22, 2004
Figure 3. Incidence of Hypertriglyceridemia, Low
HDL-C and Hypercholesterolemia. NEJM, 35126,
2683-93, December 22, 2004.
Figure 4. Recovery from Hypertriglyceridemia, Low
HDL-C and Hypercholesterolemia. NEJM, 35126,
2683-93, December 22, 2004
NEJM, 35126, 2683-93, December 22, 2004.
Bariatric Surgery-continued
  • Meta-analysis based on 136 published studies on
    22,094 patients.
  • 61.2 lost excess weight
  • Type 2 Diabetes completely resolved 76.8
  • Hyperlipidemia improved in 70
  • Hypertension resolved in 61.7
  • Obstructive sleep apnea resolved in 85.7
  • The article did not indicate years following
    surgery for the above results.
  • JAMA, 29214, 1724-1737, October 13, 2004

Bariatric Surgery-1 year later
  • Among Medicare beneficiearies, the risk of early
    death after bariatric surgery is considerably
    higher than previously suggested and associated
    with advancing age, male sex and lower surgeon
    volume of bariatric procedures. Patients aged 65
    years or older had a substantially higher risk of
    death within the early postoperative period than
    younger patients.
  • JAMA, 294 1903-1908, October 19, 2005

Bariatric Surgery-1 year later
  • Increases in hospital use after surgery appear to
    be related to the use Roux-en-Y gastric bypass.
    Payers, clinicians, and patients must consider
    the not-inconsequental (consequental?) rate of
    rehospitalization after this surgery.
  • JAMA, 294 1918-1924, October 19, 2005

Bariatric Surgery-Continued Possible Effect on
Drug Absorption
  • Most drug absorption is in the small intestine
    with its greater surface area.
  • Some speculation that prodrugs relying on acid
    hydrolysis might be affected may have varied
    absorption because of decreased gastric acid in
    the pouch.
  • No significant clinical problems reported.
  • Drug dosing based on body weight may need to be
    monitored as weight is lost.
  • No definitive studies on drug absorption have
    been done with a population of bariatric surgery
  • Drugs that normally are monitored regularly
    (coumadin, digoxin, etc) should be followed
    closely following bariatric surgery.
  • The drug therapy for most bariatric surgical
    patients usually can be monitored based on
    therapeutic outcome.

Bariatric Surgery-Continued Possible Effect on
Nutrient Absorption
  • Recognized need for vitamin B12 (cyanocobalamin)
    supplements either by injection, nasal or 25,000
    units orally. B12 requires instrinsic factor
    produced in the stomach for its absorption.
  • Iron deficiency common in menstruating women
    because iron absorption occurs in the lower

Bariatric Surgery-concluded
  • These procedures can be done laproscopically and
    are considered successful if done by a properly
    trained surgeon. From 1992 to 2003 the estimated
    number of the latter type of surgery has
    increased from 18,000 to about 103,000
    procedures. There is money to be made!
  • Remember, it appears that ghellin release is
    reduced following gastric bypass surgery causing
    reduced appetite in these patients.

Any Benefits from Liposuction??
  • Liposuction does NOT seem to be beneficial in
    terms of common markers most likely because it
    removes subcutaneous fat.
  • Plasma glucose
  • Insulin resistance
  • Hyperlipidemia
  • Hypertension
  • Onset of Type 2 Diabetes
  • NEJM, 35025, 2542-2544, 2549-57, June 16, 2004

Exercise and Weight Reduction
  • It is not as straight forward as one might
  • There are at least three reasons for a program of
    regular exercise or physical activity.
  • Cardiovascular fitness
  • A major component of weight control
  • A feeling of well being and feeling good about
    ones self.
  • There is a biochemical reason why the
    recommendation is to schedule 30 60 minutes of
    exercise daily along with keeping physically
    active throughout the day.

Exercise and Weight Reduction-continued Respirator
y Exchange Ratio (RER)
RER 0.7 for 100 percent oxidation of palmitate.
RER 1.0 for 100 percent oxidation of glucose
Exercise and Weight Reduction-continued
  • Biochemical Facts
  • At rest (sedentary life style)
  • Body prefers to metabolize triglyceride (9
    Cal/gm) rather than carbohydrate (4 Cal/gm).
  • Sudden increase in physical activity
  • Body begins to oxidize carbohydrate. Why?
  • 0.7 L of O2 required to oxidize one gm of
  • 2.03 L of oxygen required to oxidize one gm of

Exercise and Weight Reduction-continued
  • Implication
  • Heart and lungs CANNOT "instantly" adjust to the
    increased oxygen demand required to oxidatively
    metabolize triglyceride.
  • Fatty acids are not "instantly" available. Fatty
    acids are obtained by hydrolysis of triglycerides
    stored in the adipocytes. Then the fatty acids
    must be attached to serum albumin for the trip to
    the skeletal muscle. In contrast, muscle
    glycogen quickly provides glucose as an "instant
  • It is estimated that during the first few minutes
    of exercise, up to 80 percent or more of fuel
    used may be glycogen with metabolism dropping
    from 100 percent of the fuel for a resting muscle
    to 20 percent for initial activity.
  • Over about 45 minutes, the carbohydrate/fatty
    acid ratio shifts from 80/20 to about 50/50.
    After about 60 minutes the ratio shifts to about
    20/80 as the body protects its now diminished
    glycogen stores.

Weight Reduction-continued
  • Summary
  • The "fuel" consumed in an hour of endurance
    activity will be about 30 percent triglyceride
    and 70 percent carbohydrate.
  • Implications for weight control
  • Goal Remove one lb. of body fat.
  • Requires 3,500 Cal (kcal) of activity if only
    triglycerides are metabolized.
  • In Reality Because of the carbohydrate
    consumption that occurs during physical
    activity, the total caloric expenditure will
    be 11,700. To meet this goal, the person would
    have to run about 120 miles and eat no fat.
  • Conclusion
  • Moderate exercise will consume more body
    triglyceride than intense exercise because the
    latter's oxygen requirement will cause the body
    to start using carbohydrate for fuel.
  • The amount of dietary fat must be monitored