View
219
Download
0
Category
Tags:
Preview:
Citation preview
®
BiomarkersBiomarkers
of of
WellnessWellness
®
““What Gets Measured-What Gets Measured-
Gets Managed” Gets Managed”
Peter DruckerPeter 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
®
®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
®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)
®
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 #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)
®
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
®
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
Cannot be synthesized in adequate quantities
®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.
®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
®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
®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.
®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.
® 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.
®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.
®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
®
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
®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.
®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
®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
®
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
®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
®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)
®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
®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
®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
®
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
®
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
®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
®
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)
®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.
®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
®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.
®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.
®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)
®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
®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
®Liberty + Responsibility = Freedom
Recommended