® biomarkersofwellness. ® what gets measured- gets managed gets managed peter drucker

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® Biomarkers Biomarkers of of Wellness Wellness

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Page 1: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®

BiomarkersBiomarkers

of of

WellnessWellness

Page 2: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®

““What Gets Measured-What Gets Measured-

Gets Managed” Gets Managed”

Peter DruckerPeter Drucker

Page 3: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®

Page 4: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®Body Mass Index (BMI)Body Mass Index (BMI)

BMI = BMI = WeightWeight (in kg)(in kg) Height Height22 (in meters)(in meters)

Lbs/ inchesLbs/ inches22 x 703 x 703

A BMI of A BMI of <25 <25 = = desirabledesirable25 – 29.9 25 – 29.9 = = overweightoverweight>30 >30 = = obeseobese

Page 5: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®

Page 6: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®Relationship of BMI to Relationship of BMI to

Excess Mortality 20-40yoaExcess Mortality 20-40yoa

300Age at Issue

Bray GA. Overweight is risking fate. Definition, classification, prevalence and risks. Ann NY Acad Sci 1987;499:14-28.

20-29250

Mort

alit

y R

ati

o

Body Mass Index (kg/[m2])

200

150

100

50

150

30-39

20 25 30

LowRisk

4035

High

Risk

ModerateRisk

Page 7: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®BMI & Obesity

Sample size and weight

status

NHES I1960-

1962

NHANES I

1971-1974

NHANES II1976-1980

NHANESIII

1988-1994

NHANES

1999-2000

NHANES

2001-2002

NHANES

2003-2004

NHANES

2005-2006

NHANES

2007-2008

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

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)

Page 8: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®

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

Page 9: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®#1 Biomarker of Aging #1 Biomarker of Aging

““. . . no decline with age is as . . . no decline with age is as dramatic or potentially more dramatic or potentially more significant than the decline in significant than the decline in lean body mass.”lean body mass.”J Nutr 127:990S-991S (1997)

Page 10: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®

Over a lifetime 30% of Over a lifetime 30% of muscle mass is lostmuscle mass is lost

From age 20, women lost From age 20, women lost 5 – 7 lbs of muscle @ 5 – 7 lbs of muscle @ decadedecade

25% weight loss on a 25% weight loss on a typical diet is muscletypical diet is muscle

One lb of muscle burns at One lb of muscle burns at least 3Xs the calories as least 3Xs the calories as one lb of fatone lb of fat

Body FatBody Fat

Page 11: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®

Biochemistry of Vitamin D

Page 12: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®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

Cannot be synthesized in adequate quantities

Page 13: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®Vitamin D, on the other hand…

Can be synthesized in the body Has receptors and target tissues…More accurately characterized as a pro-hormone

Since it is synthesized by the body from cholesterol, it is not necessarily “essential” that it be supplied by diet.

Page 14: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®Historical understanding of vitamin D

Fundamental to calcium and phosphorus metabolism

Deficiencies/insufficiencies related to: Rickets Osteomalacia Osteoporosis

400 IU/day is currently the RDI The amount shown to prevent rickets

Page 15: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®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:

10-15 minutes of sun exposure Hands, forearms and face 3-5 times per week Spring, summer fall months only

Page 16: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®Dietary vitamin D is found in two forms:

Vegetable• Ergocalciferol/D2

• Manufactured from the plant sterol ergosterol• Synthetic form of the vitamin

Animal• Cholecalciferol/D3 • Manufactured from cholesterol

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.

Page 17: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®Look a bit closer and vitamin D gets more

interesting…

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.

Page 18: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

® 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.

Page 19: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®There’s more…

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.

Page 20: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®Today, a number of factors have contributed to what one researcher calls a “deficiency pandemic” of vitamin D

Aggressive campaign to use sunscreen has led to a significant segment of the population with vitamin D deficiency

Use of sunscreen results in a 99% reduction of vitamin D production Fewer people get out in the sun regularly

Fear of skin cancer Work location/habits (garage to car to office to car to garage) Changing perceptions of beauty

Aging and skin tone reduce the efficiency of vitamin D synthesis People of color require 5-10 times longer sun exposure compared to

Caucasians to make the same amount of vitamin D

Page 21: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®

Vitamin D levels in our society

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

Page 22: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®Current requirements:Current requirements:

<20 ng/mL: <20 ng/mL: deficientdeficient 21-29 ng/mL:21-29 ng/mL: insufficientinsufficient >30 ng/mL:>30 ng/mL: adequateadequate

If insufficient or deficient, it may take >10,000 IU/day If insufficient or deficient, it may take >10,000 IU/day to attain adequate levels.to attain adequate levels.

Page 23: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®To sum up…

“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

Page 24: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®Waist/Hip RatioWaist/Hip Ratio Waist/Hip RatioWaist/Hip Ratio

Ideal: .70<.80 Woman and <.95 ManIdeal: .70<.80 Woman and <.95 Man 50 years ago the average women’s was 27” and today 50 years ago the average women’s was 27” and today

it’s 34”it’s 34” A size 8 in 1950 is a size 4 todayA size 8 in 1950 is a size 4 today

Adipose Tissue is the largest endocrine gland in the Adipose Tissue is the largest endocrine gland in the body and produce:body and produce:

• Inflammatory chemicalsInflammatory chemicals• EstrogenEstrogen• CortisolCortisol

Page 25: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®

What Does the Adipocyte What Does the Adipocyte Secrete?Secrete?

Heber D: Heber D: PCRI InsightsPCRI Insights, May 2004 Vol 7, No.4, May 2004 Vol 7, No.4

Page 26: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®Blood PressureBlood Pressure Blood PressureBlood Pressure

Systolic less than or equal to 110mm-GoodSystolic less than or equal to 110mm-GoodDiastolic equal to or less than 70mm-GoodDiastolic equal to or less than 70mm-GoodGreater than 130/85mm is Mildly HypertensiveGreater than 130/85mm is Mildly Hypertensive

Page 27: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®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)

Page 28: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®2006 Top 10 DrugsDrug Name

Sales in Billions

Drug Use

1 Lipitor 14,385 Cholesterol

2Advair, Seretide

6,129 Asthma

3 Plavix, Iscover 6,057 Thrombotic events

4 Nexium 5,182 Gastrointestinal disorders

5 Norvasc 4,866 Hypertension

6 Remicade 4,428Crohn's disease, Rheumatoid arthritis

7 Enbrel 4,379 Rheumatoid arthritis

8 Zyprexa 4,364 Psychosis

9 Diovan 4,223 Hypertension10 Risperdal 4,183 Psychosis

Page 29: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®In case you were wondering

9 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

Page 30: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®Sugar BiomarkersSugar Biomarkers Diabetes is the seventh leading cause of death listed on Diabetes is the seventh leading cause of death listed on

U.S. death certificates. U.S. death certificates. Cardiovascular disease is the leading cause of death among Cardiovascular disease is the leading cause of death among

people with diabetes — about 68 percent die of heart people with diabetes — about 68 percent die of heart disease or stroke. disease or stroke.

Total health care and related costs for the treatment of Total health care and related costs for the treatment of diabetes run about $174 billion annually. diabetes run about $174 billion annually.

Actos world wide drug sales are $2.5 Billion, the 9Actos world wide drug sales are $2.5 Billion, the 9thth best best selling drug in America. selling drug in America.

In 1967, 3000 tons of HCFS were produced and 2007 over In 1967, 3000 tons of HCFS were produced and 2007 over 9,000,000 tons of HCFS were produced9,000,000 tons of HCFS were produced

Page 31: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®

How much sugar is in your body

100mg x 10 dl X 5 liters X 1 grams = 5 grams = 1 teaspoon

dl liter 1000 mg

Normal Fasting Glucose: 80-100 mg/dl

Page 32: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®

A BMJ 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. Sept. 7, 2010

Page 33: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®HbA1CHbA1C Equal to % of RBCs that are glycatedEqual to % of RBCs that are glycated You can run but you can’t hide from HbA1C You can run but you can’t hide from HbA1C

because once a RBC is glycated, it stays that because once a RBC is glycated, it stays that way.way.

““The predictive value of HbA1C for total The predictive value of HbA1C for total mortality was stronger than that documented mortality was stronger than that documented for cholesterol concentration, body mass index for cholesterol concentration, body mass index and blood pressure.” and blood pressure.” BMJ 2001BMJ 2001

Page 34: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®

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)

Page 35: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®InsulinInsulin Fasting InsulinFasting Insulin

Increased insulin production causes insulin resistanceIncreased insulin production causes insulin resistance Hyperinsulinemia is associatd with inflammastion in the Hyperinsulinemia is associatd with inflammastion in the

brain and triggers increase in plaques that are hallmark brain and triggers increase in plaques that are hallmark of Alzheimer’s (JAMA 2006)of Alzheimer’s (JAMA 2006)

The neurodengeration that occurs in AD is linked with The neurodengeration that occurs in AD is linked with abnormal insulin signaling (J Alzheimers Disease 2005)abnormal insulin signaling (J Alzheimers Disease 2005)

Insulin resistance also linked to depression, bipolar Insulin resistance also linked to depression, bipolar disease, autism, and schizophrenia.disease, autism, and schizophrenia.

Page 36: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®Lipid BiomarkersLipid Biomarkers

Total Cholesterol = HDL + LDL + VLDLTotal Cholesterol = HDL + LDL + VLDL HDL = 33% protein, 30% cholesterol, carries HDL = 33% protein, 30% cholesterol, carries

cholesterol from the body to the livercholesterol from the body to the liver LDL = 25% protein, 50% cholesterol, carries LDL = 25% protein, 50% cholesterol, carries

cholesterol to the body from the livercholesterol to the body from the liver

Page 37: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®Tidbits 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.

Page 38: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®More Tidbits 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 cholesterol-lowering drugs.

Page 39: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®Lipid BiomarkersLipid Biomarkers

Lipids, fractionated lipidsLipids, fractionated lipids• Total Cholesterol-under 200Total Cholesterol-under 200• Triglycerides-under 150, preferably under 100Triglycerides-under 150, preferably under 100• HDL-over 50 (male) and over 60 (female)HDL-over 50 (male) and over 60 (female)• LDL-under 130LDL-under 130• Trig/HDL ratio- under 2.0 Trig/HDL ratio- under 2.0 • Chol/HDL ratio- under 3.0Chol/HDL ratio- under 3.0

High Tri/HDL – predicts heart attack 17X often High Tri/HDL – predicts heart attack 17X often (AHA 1995)(AHA 1995)

Page 40: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®C – reactive protein 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

Page 41: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®Rank Drug Maker $$$(B) Use1 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

Page 42: ® BiomarkersofWellness. ® What Gets Measured- Gets Managed Gets Managed Peter Drucker

®Liberty + Responsibility = Freedom