Phar 722 Pharmacy Practice III Obesity and Weight Control

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Phar 722Pharmacy Practice IIIObesity and
Weight Control

• Spring 2006

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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
  weight?
• 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
  diet.
• For artificial sweeteners and fat replacements,
  know
• a. their underlying chemistry (peptide,
  carbohydrate, heterocycle, etc.)
• b. the underlying chemistry of the fat
  replacements.
• 5. Be able to state the medical outcomes from
  bariatric surgery and liposuction.

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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

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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.

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Obesity Trends Among U.S. AdultsBRFSS, 1985
(BMI 30, or 30 lbs overweight for 5 4 woman)
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Obesity Trends Among U.S. AdultsBRFSS, 1986
(BMI 30, or 30 lbs overweight for 5 4 woman)
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Obesity Trends Among U.S. AdultsBRFSS, 1987
(BMI 30, or 30 lbs overweight for 5 4 woman)
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Obesity Trends Among U.S. AdultsBRFSS, 1988
(BMI 30, or 30 lbs overweight for 5 4 woman)
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Obesity Trends Among U.S. AdultsBRFSS, 1989
(BMI 30, or 30 lbs overweight for 5 4 woman)
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Obesity Trends Among U.S. AdultsBRFSS, 1990
(BMI 30, or 30 lbs overweight for 5 4 woman)
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Obesity Trends Among U.S. AdultsBRFSS, 1991
(BMI 30, or 30 lbs overweight for 5 4 woman)
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Obesity Trends Among U.S. AdultsBRFSS, 1992
(BMI 30, or 30 lbs overweight for 5 4 woman)
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Obesity Trends Among U.S. AdultsBRFSS, 1993
(BMI 30, or 30 lbs overweight for 5 4 woman)
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Obesity Trends Among U.S. AdultsBRFSS, 1994
(BMI 30, or 30 lbs overweight for 5 4 woman)
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Obesity Trends Among U.S. AdultsBRFSS, 1995
(BMI 30, or 30 lbs overweight for 5 4 woman)
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Obesity Trends Among U.S. AdultsBRFSS, 1996
(BMI 30, or 30 lbs overweight for 5 4 woman)
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Obesity Trends Among U.S. AdultsBRFSS, 1997
(BMI 30, or 30 lbs overweight for 5 4 woman)
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Obesity Trends Among U.S. AdultsBRFSS, 1998
(BMI 30, or 30 lbs overweight for 5 4 woman)
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Obesity Trends Among U.S. AdultsBRFSS, 1999
(BMI 30, or 30 lbs overweight for 5 4 woman)
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Obesity Trends Among U.S. AdultsBRFSS, 2000
(BMI 30, or 30 lbs overweight for 5 4 woman)
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Obesity Trends Among U.S. AdultsBRFSS, 2001
(BMI 30, or 30 lbs overweight for 5 4 woman)
No Data lt10 1014
1519 2024 25
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Obesity Trends Among U.S. AdultsBRFSS, 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
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Obesity Trends Among U.S. AdultsBRFSS, 2003
(BMI ?30, or about 30 lbs overweight for 54
person)
No Data lt10 1014
1519 20-24 ?25
Source Behavioral Risk Factor Surveillance
System, CDC
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Obesity is a Global Problem!
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What is Historical Ideal Weight?

• Examine the female figure in the Renaissance-era
  paintings.
• They would not be hired as todays fashion
  models.
• 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.

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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

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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
  receptors.

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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.

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Visceral versus Subcutaneous Fat
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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.

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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.

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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.)

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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.

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Note decrease in dietary calcium.
Fructose has been Implicated as a cause of
obesity.
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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
  foods.

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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.

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Causes of Obesity-Continued

• Hormone Imbalances
• This can be quite complex and range from
  hypothyroidism, pituitary imbalances, diabetes,
  estrogen imbalances, etc.

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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.

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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."

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Thermogenesis
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Possible Key Receptors

• Peroxisome proliferator-activated receptors
  (PPAR)
• 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)

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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.

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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
  receptor.

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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.

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Hormones/Cytokines and Obesity

• Insulin required for
• Transport of glucose into muscle and adipose
  tissue.
• 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
  pathways.
• Required for release of dietary triglycerides
  from chylomicrons and endogenous triglycerides
  from VLDL.
• Hypertriglceridemia is one of the complications
  seen in uncontrolled diabetes

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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.

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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

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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.

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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.

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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.

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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.

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Drug Therapy-Concluded

• Rimonabant (Acompilia)

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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.

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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.

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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.

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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.

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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
  adaptation.
• Our ancestors who consumed lipid containing foods
  received more Calories per gram and, therefore,
  gained weight. This allowed them to better
  survive famines.

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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
  lifestyle.

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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
  food.
• 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.

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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
  days.
• Promises to take off up to 15 pounds in 35 days
  (up to 3 lbs/week)

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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.

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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.

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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.)

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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
  statement.)
• 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.

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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
  patient.

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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
  "calorie
• free.
• It can be used in frying.

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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.

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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
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Figure 3. Incidence of Hypertriglyceridemia, Low
HDL-C and Hypercholesterolemia. NEJM, 35126,
2683-93, December 22, 2004.
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Figure 4. Recovery from Hypertriglyceridemia, Low
HDL-C and Hypercholesterolemia. NEJM, 35126,
2683-93, December 22, 2004
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NEJM, 35126, 2683-93, December 22, 2004.
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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

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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

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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

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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
  patients.
• 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.

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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
  stomach.

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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.

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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

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Exercise and Weight Reduction

• It is not as straight forward as one might
  assume.
• 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.

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Exercise and Weight Reduction-continuedRespirator
y Exchange Ratio (RER)
RER 0.7 for 100 percent oxidation of palmitate.
RER 1.0 for 100 percent oxidation of glucose
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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
  carbohydrate.
• 2.03 L of oxygen required to oxidize one gm of
  triglyceride.

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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
  fuel.
• 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.

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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
  carefully.