Transcript 8 WEEKS TO WELLNESS GIVE US 8 WEEKS AND WE`LL CHANGE

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Biomarkers
of
Wellness
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“What Gets MeasuredGets Managed”
Peter Drucker
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Body Mass Index (BMI)
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BMI = Weight (in kg)
Height2 (in meters)
 Lbs/ inches2 x 703
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A BMI of
<25
25 – 29.9
>30
= desirable
= overweight
= obese
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Relationship of BMI to
Excess Mortality 20-40yoa
300
250
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Age at Issue
20-29
30-39
200
150
100
Low
Risk
50
0
15
20
25
30
High
Moderate
Risk
35
Risk
40
Body Mass Index (kg/[m2])
Bray GA. Overweight is risking fate. Definition, classification,
prevalence and risks. Ann NY Acad Sci 1987;499:14-28.
BMI & Obesity
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NHE
SI
1960
1962
NHANE
SI
19711974
NHANE
S II
19761980
NHANE
S
III
19881994
NHANE
S
19992000
NHANE
S
20012002
NHANE
S
20032004
NHANE
S
20052006
NHANE
S
20072008
Sample (n)
6,126
12,911
11,765
14,468
3,603
3,916
3,756
3,835
4,881
Overweight
(25 ≤ BMI <
30)
31.5
32.3
32.1
32.7
33.6
34.4
33.4
32.2
33.6
Obese
(BMI ≥ 30)
13.4
14.5
15.0
23.2
30.9
31.3
32.9
35.1
34.3
Extremely
obese
(BMI ≥ 40)
0.9
1.3
1.4
3.0
5.0
5.4
5.1
6.2
6.0
Sample size
and weight
status
The 773 morbidly obese female members had used a mean of $11,145 in
medical insurance expenses in the year 2003 versus a mean of $8,096 for the
other 106,908 adult women (27% higher). Similar values for the men were
$16,720 for the 138 morbidly obese men versus $5,943 for the other 82,490
men. (64% higher)
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While BMI certainly tells us how unhealthy a
person is, it doesn’t tell us how healthy a person
is. Example, a skinny fat person aka sarcopenic
obesity
#1 Biomarker of Aging
“. . . no decline with age is as
dramatic or potentially more
significant than the decline in
lean body mass.”
J Nutr 127:990S-991S (1997)
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Body Fat
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Over a lifetime 30% of
muscle mass is lost
From age 20, women lost
5 – 7 lbs of muscle @
decade
25% weight loss on a
typical diet is muscle
One lb of muscle burns at
least 3Xs the calories as
one lb of fat
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Biochemistry of Vitamin D
What is a vitamin?
Organic compound
 Required to support life
 Generally a co-factor for enzyme activation (most B
vitamins) or antioxidant (E and C)
 Must be obtained from the diet
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Cannot be synthesized in adequate quantities
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Vitamin D, on the other hand…
Can be synthesized in the body
 Has receptors and target tissues
…More accurately characterized as a pro-hormone
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Since it is synthesized by the body from cholesterol,
it is not necessarily “essential” that it be supplied by
diet.
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Historical understanding of vitamin D
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Fundamental to calcium and phosphorus metabolism
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Deficiencies/insufficiencies related to:
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Rickets
Osteomalacia
Osteoporosis
400 IU/day is currently the RDI
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The amount shown to prevent rickets
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Vitamin D is called the “sunshine” vitamin
It is manufactured in the skin from cholesterol upon
exposure to UV radiation.
 Healthy (RDI) levels of vitamin D production can be
achieved by:
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10-15 minutes of sun exposure
Hands, forearms and face
3-5 times per week
Spring, summer fall months only
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Dietary vitamin D is found in two forms:
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Vegetable
• Ergocalciferol/D2
• Manufactured from the plant sterol ergosterol
• Synthetic form of the vitamin
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Animal
• Cholecalciferol/D3
• Manufactured from cholesterol
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Both can be converted to active hormone 1,25-(OH)2
D3, (also called calcitriol) via a two-step hydroxylation
first in the liver, then in the kidneys.

May also be hydroxylated in the colon, breast, lungs and
prostate.
Look a bit closer and vitamin D gets more
interesting…
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Vitamin D regulates uptake of calcium from the gut through
stimulation of gene expression

Activating the production of calcium-binding proteins such as
calbindin that increase calcium absorption.
Upwards of 200 genes are believed to be regulated by
Vitamin D, most of which are not involved in mineral
metabolism.
 Essentially every tissue and cell in the body has a vitamin D
receptor.
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Blood levels of vitamin D below 20 ng/mL led to 30-50%
increased risk of developing and dying from various cancers
(colorectal, breast, prostate etc.)
Low 25(OH)D levels are associated with all-cause mortality and
even more pronounced with cardiovascular mortality
Women with blood vitamin D level <12 ng/mL had a 253%
increased risk of colerectal cancer
Highest levels of vitamin D consumption correlated with a 50%
lower risk of breast cancer.
Teenagers with frequent sun exposure had a 35-40% reduced
risk of breast cancer as adults.
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There’s more…
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Low sun exposure for the first 10 years of life doubles the risk to
multiple sclerosis development.
Children receiving ~2000 IU of vitamin D daily had 78% reduced
risk to development of type I diabetes.
Vitamin D lowered BP to normal levels
Low blood vitamin D level is associated with depression,
autoimmune disease, osteoarthritis, increased susceptibility to
infection, even postulated as a cause of seasonal cold and flu.
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Today, a number of factors have contributed to what one researcher calls a
“deficiency pandemic” of vitamin D
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Aggressive campaign to use sunscreen has led to a significant segment of the
population with vitamin D deficiency
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Use of sunscreen results in a 99% reduction of vitamin D production
Fewer people get out in the sun regularly
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Fear of skin cancer
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Work location/habits (garage to car to office to car to garage)
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Changing perceptions of beauty
Aging and skin tone reduce the efficiency of vitamin D synthesis
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People of color require 5-10 times longer sun exposure compared to
Caucasians to make the same amount of vitamin D
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Vitamin D levels in our society
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An estimated 1 billion people worldwide are thus considered
deficient
Adults >65
52% of postmenopausal women
36% of young adults 18-29 had vit D levels <20 ng/mL at the end
of winter, in spite of consuming fortified milk or multivitamin
daily.
In a group of 40 mother-infant pairs tested at birth, 76% of the
mothers and 81% of the infants had vit D <20 ng/mL
Current requirements:
<20 ng/mL:
 21-29 ng/mL:
 >30 ng/mL:
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deficient
insufficient
adequate
If insufficient or deficient, it may take >10,000
IU/day to attain adequate levels.
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To sum up…
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“Vitamin D has evolved into a hormone that is active throughout
the body, not only to regulate calcium and bone metabolism,
but to control cellular growth, regulate immune function, and
control production of insulin and renin among other
hormones.
All healthcare professionals should be alert to the vitamin D
deficiency pandemic.”
Michael Holick, University of Boston
Waist/Hip Ratio
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Waist/Hip Ratio
Ideal: .70<.80 Woman and <.95 Man
50 years ago the average women’s was 27” and today
it’s 34”
A size 8 in 1950 is a size 4 today
Adipose Tissue is the largest endocrine gland in the
body and produce:
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•
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Inflammatory chemicals
Estrogen
Cortisol
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What Does the Adipocyte
Secrete?
Heber D: PCRI Insights, May 2004 Vol 7, No.4
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Blood Pressure
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Blood Pressure
Systolic less than or equal to 110mm-Good
Diastolic equal to or less than 70mm-Good
Greater than 130/85mm is Mildly Hypertensive
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Any why you should care
 ALLHAT
compared 4 BP drug classes
 study proved diuretics is just as good as
the other 3 more expensive class of drugs
 Top 50 drugs for seniors in 2001, Norvasc
is #2.
 Diuretics were # …… >50
 37/hr for diuretics; $715/yr Norvasc (2002)
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2006 Top 10 Drugs
Drug Name
Sales in
Billions
Drug Use
1
Lipitor
2
Advair,
Seretide
6,129 Asthma
3
Plavix, Iscover
6,057 Thrombotic events
4
Nexium
5,182 Gastrointestinal disorders
5 Norvasc
14,385 Cholesterol
4,866 Hypertension
Crohn's disease, Rheumatoid
arthritis
6
Remicade
4,428
7
Enbrel
4,379 Rheumatoid arthritis
8
Zyprexa
4,364 Psychosis
9 Diovan
10 Risperdal
4,223 Hypertension
4,183 Psychosis
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In case you were wondering
9
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billion dollars will buy
3,409,090 8 Weeks to Wellness Programs in
our office
2,141,051 8 Weeks to Wellness Programs in
Dr. Prakash’s office
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Sugar Biomarkers
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Diabetes is the seventh leading cause of death listed on U.S. death
certificates.
Cardiovascular disease is the leading cause of death among people
with diabetes — about 68 percent die of heart disease or stroke.
Total health care and related costs for the treatment of diabetes run
about $174 billion annually.
Actos world wide drug sales are $2.5 Billion, the 9th best selling drug
in America.
In 1967, 3000 tons of HCFS were produced and 2007 over
9,000,000 tons of HCFS were produced
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How much sugar is in your body
100mg x 10 dl X 5 liters X 1 grams
dl
liter
Normal Fasting Glucose:
80-100 mg/dl
1000 mg
= 5 grams = 1 teaspoon
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A
investigation into the top-selling
diabetes drug rosiglitazone (Avandia)
raises concerns about its safety and
the whole system by which drugs are
evaluated, regulated, and promoted
around the world.
B
M
J
S
e
p
t
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7
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2
0
1
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HbA1C
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Equal to % of RBCs that are glycated
 You can run but you can’t hide from HbA1C
because once a RBC is glycated, it stays that
way.
 “The predictive value of HbA1C for total
mortality was stronger than that documented
for cholesterol concentration, body mass index
and blood pressure.” BMJ 2001
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HbA1C
(%)
(mg/dL)
5
97 (76–120)
6
126 (100–152)
7
154 (123–185)
8
183 (147–217)
9
212 (170–249)
10
240 (193–282)
11
269 (217–314)
12
298 (240–347)
Insulin
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Fasting Insulin
Increased insulin production causes insulin resistance
Hyperinsulinemia is associatd with inflammastion in the
brain and triggers increase in plaques that are hallmark
of Alzheimer’s (JAMA 2006)
The neurodengeration that occurs in AD is linked with
abnormal insulin signaling (J Alzheimers Disease 2005)
Insulin resistance also linked to depression, bipolar
disease, autism, and schizophrenia.
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Lipid Biomarkers
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Total Cholesterol = HDL + LDL + VLDL
 HDL = 33% protein, 30% cholesterol, carries
cholesterol from the body to the liver
 LDL = 25% protein, 50% cholesterol, carries
cholesterol to the body from the liver
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Tidbits
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Cholesterol Endogenous > Exogenous
South African egg farmers consume 1,240 mg per day,
their average cholesterol is 181.4 (RDA is 300 mg)
NEJM reported on a 88 year old man who ate 25 eggs
per day for 30 years, weighed 185 at 6’2” and had a
normal cholesterol level.
On the island of Crete, the incidence of CVD is lowest in
the world and the average serum cholesterol is over 200.
Cholesterol is a necessary molecule in the body and
accounts for over half the weight of the brain’s cortex.
At least 5% - 7% of statin users experience significant
muscle problems.
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More Tidbits
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Cardiomyopathy (serious weakening of the heart muscle) is a known
adverse and often not reported side effect of statin therapy.
Cholesterol is the precursor to all hormones and, therefore, is vital to the
many functions of the endocrine system including sexual function.
Cholesterol is found in the cell wall of each one of the 70 trillion cells in your
body.
When cholesterol gets too low, you could suffer from memory loss, sexual
dysfunction, low blood pressure leading to dizziness, and loss of libido.
Reducing the manufacture of cholesterol in the liver simultaneously reduces
the production of Co-Enzyme Q10 - a vital anti-oxidant essential for healthy
heart function. (Rather counter productive, don’t you think?)
Cholesterol is a precursor to serotonin -- a key hormone to feeling good and
sleeping well.
And last but certainly not least…these cholesterol-lowering drugs DO NOT
reduce the deaths due to heart disease. If you don’t believe this, just look
for this disclaimer on the ads and website of the leading cholesterollowering drugs.
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Lipid Biomarkers
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Lipids, fractionated lipids
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Total Cholesterol-under 200
Triglycerides-under 150, preferably under 100
HDL-over 50 (male) and over 60 (female)
LDL-under 130
Trig/HDL ratio- under 2.0
Chol/HDL ratio- under 3.0
High Tri/HDL – predicts heart attack 17X often
(AHA 1995)
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C – reactive protein
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CRP is a protein found in the blood, the levels of which rise in response to
inflammation.
CRP rises up to 50,000-fold in acute inflammation, such as infection. It rises
above normal limits within 6 hours, and peaks at 48 hours. Its level is mainly
determined by the rate of production (and hence the severity of the
precipitating cause).
Levels above 2.4 mg/l has been associated with a doubled risk of a
coronary event compared to levels below 1 mg/l.
CRP & Statins: "the number of patients who would need to be treated with
Crestor for 2 years to prevent the occurrence of one primary end point is 95,
and the number needed to treat for 4 years is 31." In other words, after four
years of treatment, out of every 31 patients, one cardiovascular event would
be prevented.
Physical fitness is inversely related to CRP level in children and that this
relationship is more pronounced in boys than in girls. (Pediatrics 2003)
Insulin resistance and C-reactive protein (CRP) levels are strongly
correlated in adults
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Rank Drug
Maker
$$$(B) Use
1
Lipitor
Pfizer
5.36
Cholesterol
2
Nexium
AZ
5.02
Acid Reflux
3
Plavix
BMS
4.22
Blood thinner
4
Advair
GSK
3.65
Asthma/COPD
5
Serequel
AZ
3.12
Depression/Anxiety
6
Abilify
BMS
3.08
Depression/Anxiety
7
Singular
Merck
3.02
Asthma/COPD
8
Oxycontin
Purdue
3.01
Pain
9
Actos
Takeda
2.5
Diabetes
10
Prevacid
Takeda
2.3
Acid Reflux
Liberty + Responsibility = Freedom
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